MONICA Manual, Part I: Description and

Organization of the Project

Section 1: Objectives and Outline

Protocol
November 1990

This section provides information about the background, objectives, hypotheses, major
components, organization and management, of the Multinational Monitoring of Trends
and Determinants in Cardiovascular Disease (MONICA Project).

Contents
• Introduction
• 1. Objectives
• 2. Hypotheses
• 3. General structure
• 4. Choice of MONICA populations and Reporting Units
o 4.1 Reporting Units
o 4.2 Size of population
o 4.3 Autonomy and centralization of medical services and records
o 4.4 Stability of population
o 4.5 Definition of the study population
• 5. Optional studies
• References

© Copyright World Health Organization (WHO) 1998. All rights reserved.

• Copyright notice
• Manual acknowledgements
• Document identification:
o URL:http://www.ktl.fi/publications/monica/manual/part1/i-1.htm
o URN:NBN:fi-fe19981147

Queries and comments on this section to be addressed

to:
MONICA Management Centre
Cardiovascular Diseases Programme
Division of Noncommunicable Diseases
World Health Organization
CH1211 Geneva 27
Fax: +41 22 791 4151;
E-mail: mendiss@who.int or pricea@who.int

Introduction
Although cardiovascular disease accounts for approximately half of all deaths in
developed countries, the mortality rates show wide variation from one country to another.
In the past considerable research effort has been expended, with rich results, on
investigating national, regional, ethnic and individual differences in cardiovascular risk
considered as a static attribute. Yet mortality rates are changing. In several countries a
major decline in coronary heart disease mortality has occurred since the 1960s and
smaller declines have occurred in a few other countries while rates elsewhere are
stationary or rising.[1,2] Stroke mortality is declining in many countries but the trends
vary considerably. In most cases these trends in mortality rates are isolated observations
unsupported by any validation of death certificates, or by data on trends in non-fatal
cardiovascular disease (or incidence), or by systematic observations on cardiovascular
risk factor levels, or socio-cultural behaviour such as diet and exercise. It is not possible,
therefore, to attribute changes in mortality with confidence either to a change in disease
incidence or to a change in its natural history; yet such information is fundamental to the
development and monitoring of strategies for prevention and control.

The purpose of the Multinational Monitoring of Trends and Determinants in

Cardiovascular Disease (MONICA Project) is to complement the older cross-sectional
studies of differences in disease rates by longitudinal investigation of the dynamics of
change. The MONICA Project will initiate the simultaneous monitoring of cardiovascular
mortality, morbidity, case fatality, risk-factor levels and social and behavioural trends
within defined communities over a period of years so that these variables may be
interrelated. By replicating the same core of observations in many contrasting
communities, and by thus monitoring multiple similar and dissimilar trends, there is a
potential for the investigation of the determinants of cardiovascular disease which would
be beyond the scope of any single research unit or nation acting alone.

This manual covers the minimum core requirements for a Collaborating Centre that are
obligatory.

1. Objectives
The objectives of the MONICA Project are to measure the trends in cardiovascular
mortality and coronary heart disease and cerebrovascular disease morbidity and to assess
the extent to which these trends are related to changes in known risk factors, daily living
habits, health care, or major socioeconomic features measured at the same time in defined
communities in different countries. Collaborating Centres may wish to cover all these
areas, but the basic protocol covers key items only, leaving the rest as local options.

2. Hypotheses
Changes in cardiovascular mortality rates might be related to: a change in disease
incidence, or change in case fatality, or change in both disease incidence and case
fatality. The alternative explanations, therefore, relate to whether the trends in fatal and
non-fatal incidence attack rates are parallel, convergent or divergent, and whether the
resultant case fatality rate is changing or not.

A change in incidence could be related to known etiological factors such as:

a. Cigarette smoking behaviour and attempts to modify it.

b. Community blood pressure levels changing with environmental factors and/or as
the result of detection and treatment of hypertensive people.
c. Community serum cholesterol levels.
d. Dietary changes involving changes in total food energy intake, and major
components such as saturated and polyunsaturated fats, cholesterol and salt.
e. Change in weight and exercise.
f. Combinations of any or all of the above factors, or changes in other unrecorded
factors.

A change in case-fatality rates could be related to changes either in medical care in the
population affected, or in the natural history of the disease, or in both.

The MONICA study will involve measurement of:

a. Incidence rates
b. Case fatality rates
c. Risk factor levels
d. Medical care

These four variables can be used to test six possible associations:

i. Risk factors versus incidence

ii. Medical care versus case fatality
iii. Incidence versus case fatality
iv. Medical care versus incidence
v. Risk factors versus case fatality
vi. Medical care versus risk factors.
The replication of the study in several contrasting Centres with different trends should
demonstrate the consistent associations despite the varying experiences; something that
studies within one country, where trends may be uniform, are less likely to achieve.

Although the six associations described previously can be tested within the MONICA
Project for both coronary heart disease and stroke, a small number of main null
hypotheses have been formulated:

CORONARY HEART DISEASE

Main null hypothesis: For the population reporting units there is no relationship
between:

• 10-year trends in the major CVD risk factors of serum cholesterol, blood pressure
and cigarette consumption; and
• 10-year trends in incidence rate1 (fatal plus non-fatal attack rates) of coronary
heart disease.

Second main null hypothesis: For the population reporting units there is no relationship
between:

• 10-year trends in case fatality rate (percentage of attacks that are fatal within 28
days); and
• 10-year trends in acute coronary care.

STROKE

Main null hypothesis: For the population reporting units there is no relationship
between:

• 10-year trends in the major CVD risk factors of serum cholesterol, blood pressure
and cigarette consumption; and
• 10-year trends in incidence rate1 of stroke.

Second main null hypothesis: For the population reporting units there is no difference in
10-year trends in event rates or mortality rates between stroke and coronary events.

Note: 1The phrase "incidence rate" more typically refers to first-ever events, while
"attack rate" refers to the occurrence of an event, recurrent or not. In terms of assessing
causality, it would be preferable to analyse changes in the rate of occurrence of first
events; however, the complete and accurate documentation required to differentiate
between first and subsequent events will not always be available for all events for all
Centres. Thus, it will be necessary to analyse the data on attack rates and also, where the
data permit, on "incidence rates for first event."
3. General structure of the core study
Four basic sources of information are to be utilized in the core study over a period of 10
years, three involving special studies:

1. Routinely available administrative data on the study population, from local

government and local medical sources. Some of this would be available annually
and some from Decennial Censuses taking place in 1980 and 1981 in most
Centres and again ten years later.
2. Investigation of medically recognized cardiovascular events, fatal and non-fatal,
using medical and medico-legal sources and validating the original diagnoses
using MONICA criteria.
3. Continuous or intermittent monitoring of the acute care of coronary and stroke
events.
4. Population surveys to monitor levels of risk factors and health-related behaviour.

For the defined population each Centre should be able to obtain:

a. Census data defining the population by size, sex and age distribution in standard 5
year age groups.
b. Intercensal annual estimates of the mid-year population allowing for births,
deaths, immigration and emigration from year to year.
c. Numbers of deaths by 5 year age/sex group 25-64 or 74 for each year of the study
and classified according to ICD 3-digit codes, 8th or 9th Revision, into standard
disease groupings. It is important that, in general, Centre personnel do not recode
these certificates as these will demonstrate how far local mortality trends reflect
the national picture, and will also show the competing causes of death.
d. Coronary heart disease deaths (including sudden death) age 25-64 (men and
women) each coded and classified according to study criteria.
e. Stroke deaths age 25-64 (men and women) each coded and classified according to
study criteria.
f. Other cardiovascular deaths (certain diagnoses only) age 25-64 reviewed and
validated and considered as potential coronary or stroke deaths as above.
g. Non-fatal myocardial infarction age 25-64 coded and classified according to study
criteria.
h. Non-fatal stroke age 25-64 coded and classified according to study criteria.
Although strokes are in the core study it is recognized that not all Centres are able
to include them.
i. Population surveys at at least 2 points in the 10-year study period (beginning and
end), each data point encompassing a new random sample of at least 200 (see
Section 2) individuals in each 10 year age and sex group between 35 and 64, and
preferably between 25 and 64, covering at a minimum:
o Smoking
o Blood pressure
 o Blood cholesterol
o Weight
o Height
j. Additional data on acute care of coronary events and stroke (where relevant) on
two or more occasions during the study period, or monitored continuously.
k. Annual data on health services.

4. Choice of MONICA populations and Reporting Units

The balance has to be struck between the ideal and the practical. If only one Centre is to
be established in a country it is hoped that the Centre will be typical, in its morbidity and
mortality and risk factors levels and trends, of the country as a whole. Some of this
information will be unavailable when the choice is made, and other considerations such
as the accessibility and compactness of the population may go against the choice of a
particular population, even though its mortality rates are average for the country
concerned.

Where a country has greatly contrasting regions the possibility of setting up several
Centres should be considered. Similarly, if a Centre is being established in a population
in which an intensive campaign of cardiovascular disease control and prevention is being
mounted thought should be given to the study of an additional population elsewhere.
Insofar as mortality, morbidity and risk factor trends within the population studied are
being related to each other, the representativeness of that population of a nation or region
is of less importance to the collaborative study than that a variety of contrasting
populations and trends are included. The choice of a typical or representative population
may, therefore, be more of an issue in obtaining national funding for projects than it is a
primary requirement of the collaborative study. As few Centres in any country can
undertake the present study, populations may be chosen more for their accessibility to the
Collaborating Centre and the local knowledge and contacts already made.

4.1 Reporting Units

Reporting Units are the population group for which trends in cardiovascular and
cerebrovascular disease and risk factors will be directly measured. An official MONICA
Reporting Unit is defined as the residents of an area delineated by clear geopolitical
boundaries. It is this area which is the object of the MONICA data collection activities,
i.e. for which annual demographic and mortality data are reported, to which the event
registration process is applied and within which the population survey is conducted. A
given MONICA Collaborating Centre may have more than one official MONICA
Reporting Unit.

4.2 Size of population

The number of subjects screened in the study population will be under the control of the
investigators but the number of morbid or fatal events is determined by the size of the
population and the event rate in the age group concerned. The event rate in most cases for
coronary heart disease will be greater than for stroke, and male mortality will be higher
than female mortality.

In order to monitor mortality trends in middle-age with the same degree of precision, the
study population would need to be much larger for stroke or female coronary heart
disease mortality than for male coronary heart disease mortality.

The problem of the population size for monitoring time trends in event rates is critical
and limits the number of possible Collaborating Centres able to produce very accurate
trend estimates. The annual number of events is what matters, not the population size; in
high incidence Centres smaller populations can be studied and in low incidence Centres
larger ones would be needed.

No Centre will be rejected from the project just because the population size is rather
small but this factor will be considered with any others that might make a Centre
unsuitable. In populations generating less than 200 fatal coronary events in men per year,
it will be difficult to establish trends in fatal event rates with confidence.

4.3 Autonomy and centralization of medical services and records

The study population should be an administrative unit or units both for local government
and for medical services. This will ensure that routinely collected information on the size
and age and sex breakdown, emigration and immigration, and provision and utilization of
medical services apply to the same population as that being investigated; Collaborating
Centres should not have to conduct their own censuses but should take advantage of the
available information.

4.4 Stability of the population

Diurnal. Populations are enumerated on the basis of residence but may be composed of
commuters working elsewhere. Study populations should be investigated to find methods
of finding victims of vascular illnesses who fall ill while at work outside the study area.
This problem arises particularly if part of a city is being studied; it is less important if a
total community is involved.

Seasonal. Migration to the country for holidays or other purposes may affect recording of
events. Methods for tracing both deaths and illnesses occurring at distant places should be
investigated.

Permanent migration in and out. The turnover of the population does not create the
same problems for the core study as it would for registration and long-term follow-up of
persons or for the interpretation of the results of record linkage. However, there are
potential problems in populations with a high turnover, namely:
 • denominator problems: The census data may become inaccurate very rapidly
and the intercensal estimates will only be validated at the time of the next
decennial census.
• numerator problems: A high proportion of potential events may be in new
arrivals or those in the process of moving out of the area so that there may be
doubts as to whether they should be included.

4.5 Definition of the study population

The denominator for the study will be persons with their chief residence in the study
area, which will be defined geographically to correspond with administrative and census
boundaries. The decennial censuses in 1980 or 1981 will be used to provide the age and
sex breakdown of the population. These figures should be revised to give the best
available estimates of the midyear (30 June) population size and structure for each year of
the study. It is possible that the 1990 and 1991 census results will be employed to
validate these estimates retrospectively as inaccurate population trends could account for
spurious trends in mortality and morbidity rates. Populations for which it is not possible
to obtain census data or intercensal estimates cannot be used.

The numerator will be persons with their chief residence in the study area, however
recently they have moved in, who suffer an illness or death satisfying study criteria after
arrival. Events in non-residents occurring in the study area or admitted to hospital in the
area do not qualify. Events in residents occurring out of the area do qualify. Efforts must
be made to find them; or to estimate the potential loss and whether over a period of years
it could be changing and interfering with the validity of the observed trends in rates.

5. Optional studies
Inevitably the core study will be extended to include data of local interest. Additionally
there are areas of general interest which are not included in the core study. The core study
has concentrated on basic items which can be standardized cross-culturally. Many of the
local options are of great importance, but the lack of a good method of investigation (or
the presence of too many competing ones which are not standardized for international
use) prevented their inclusion as an obligatory component of the core study.

Centres interested in specific items will be encouraged to develop new methods and to
share their techniques, and for certain key items to report on local methods of
measurement and on trends. Reference Centres have been established for diet, exercise
and drug monitoring, and the WHO Regional Office for Europe in Copenhagen is
responsible for coordinating studies on socioeconomic and behavioural factors.

References
1. Uemura K, Pisa Z. Recent trends in cardiovascular disease mortality in 27
industrialized countries. World Health Stat Q 1985;38:142-162.
 2. Uemura, Pisa Z. Trends in cardiovascular disease mortality in industrialized
countries since 1950. World Health Stat Q 1988;41:155-178.

MONICA Manual, Part I: Description and

Organization of the Project

Section 2: Organization and Management

of the WHO MONICA Project

Amendments to this section since 2004

After publication of the main results of the MONICA Project, it was decided that the
MONICA Manual will no longer be revised, but any changes will be included as
amendments to the Manual. To the extent of the amendments, parts of the MONICA
Manual, although of historical relevance, will be superseded:

• Amendment 1: Management of the MONICA Project

• Amendment 2: Publication rules

February 1999

This section of the MONICA Manual describes the organization and management of the
WHO MONICA Project. It can only be altered by the MCCs at a meeting of the CPI or
through a postal or other form of ballot (see Annex 1).

Proposals for changes to the Manual can be made by anyone in MONICA. The MSC will
review the relevance of such proposals and, where appropriate, submit them to a ballot in
which the MCCs only will be eligible to vote. Decisions on change of MONICA rules
will be valid if there is a 65% majority of those voting and the total vote is 80% of MCCs
eligible to vote. Eligibility of MCCs to vote will depend on their continuing involvement
with the WHO MONICA Project. Those Centres which have persistently failed to
respond to communications over a period of three months before the ballot and have been
deemed to be non-operational for that reason by the MSC will not be counted in the
MONICA denominator for ballots.

Contents
 • 1. Working language
• 2. Membership
• 3. Policy and management
o 3.1 Council of Principal Investigators (CPI)
o 3.2 MONICA Steering Committee (MSC)
o 3.3 MONICA Management Centre (MMC)
o 3.4 MONICA Data Centre (MDC)
o 3.5 MONICA Quality Control Centres (MQC)
o 3.6 MONICA Reference Centres (MRC)
• 4. MONICA Collaborating Centres (MCC)
• 5. Reporting
• 6. Communication procedures
• 7. Publication rules (see Amendment 2 for revised Publication rules)
o 7.1 Publication policy
o 7.2 Rules for centrally generated Collaborative Publications
o 7.3 Rules for data release
o 7.4 Ownership of collaborative data
o 7.5 Citation of Collaborative Publications
o 7.6 Publication Plan
o 7.7 Cumulative list of publications and presentations
• 8. Site visits
• Annex 1 Conducting postal ballots

Forms
• Publication proposal form

© Copyright World Health Organization (WHO) 1999. All rights reserved.

• Copyright notice
• Manual acknowledgements
• Document identification:
o URL:http://www.ktl.fi/publications/monica/manual/part1/i-2.htm
o URN:NBN:fi-fe19981148

Queries and comments on this section to be addressed

to:
MONICA Management Centre
Cardiovascular Diseases Programme
Division of Noncommunicable Diseases
World Health Organization
CH1211 Geneva 27
Fax: + 41 22 791 4151
E-mail: mendiss@who.int or pricea@who.int

Earlier versions
• WHO MONICA Project. MONICA Manual. CVD/MNC/Version 1.1, December
1986; Sect. 12.
• WHO MONICA Project. MONICA Manual. Geneva: World Health Organization,
Cardiovascular Diseases Unit; November 1990; Part I, Sect. 2.
• WHO MONICA Project. Revision of Part I, Sect. 2 of MONICA Manual.
MONICA Memo 244; July 1993.
• WHO MONICA Project. Revision of Part I, Sect. 2 of MONICA Manual.
MONICA Memo 282; October 1994.
• WHO MONICA Project. MONICA Manual, Part I: Description and Organization
of the Project, Section 2: Organization and Management of the WHO MONICA
Project. (August 1998). An annotated copy, showing the changes from the
previous version is available from: URL:
http://www.ktl.fi/publications/monica/manual/part1/i-2oct94.htm

The August 1998 revision was made in recognition of the changes in governance that
were likely to occur with the conclusion of data collection phase of the Project. In
particular it was recognised that as future Councils of Principal Investigators were
unlikely, or at best unpredictable, the previous procedures for changing the rules
governing the project or electing new members to the MONICA Steering Committee,
would no longer apply. There will nevertheless be an ongoing requirement to oversee the
ongoing publication of results and other reports from the Project and to regulate the use
of the MONICA Archive.

The current (February 1999) version differs from the August 1998 version only in Annex
1, where the rules for counting postal votes in the election of MSC members have been
revised to cover all situations.

1. Working language
The working language is English.

2. Membership
There are two types of membership:

(i) Full membership

 Centres which fulfil the criteria set out in Section 4 will be accorded full
membership so long as they continue to meet the requirements for the Project, as
judged by the Steering Committee. They are known as MONICA Collaborating
Centres.
(ii) Associate membership
Centres conducting projects comparable to the WHO MONICA Project, but not
meeting all the requirements of the MONICA Protocol, may request Associate
Membership from the Steering Committee. This entitles them to receive copies of
unclassified Project documentation and to attend meetings of the Council of
Principal Investigators at their own expense. No central data analysis, or quality
control evaluation or measures, are normally provided. Associate Members may
not use the name MONICA and will not participate in pooled data analyses.

3. Policy and management

The WHO MONICA Project is a partnership between the World Health Organization and
the MONICA Principal Investigators. Between the infrequent meetings of the MONICA
parliament - the Council of Principal Investigators - the running of the project is carried
on by designated MONICA Centres as described below.

The World Health Organization acts as project sponsor and co-ordinator, assists in
acquiring funds, and executes financial and other contracts whenever necessary. The
general management and coordination of the WHO MONICA Project are carried out
from WHO Headquarters by the Cardiovascular Diseases Programme within the Division
of Noncommunicable Diseases, the MONICA Management Centre. Responsibility for
the management of the major technical aspects has been assigned to different centres with
expertise in the specific fields. The area of responsibility and the terms of reference for
each of the different centres are stated in the relevant sections below.

The policy making and management structure of the WHO MONICA Project, is made up
of the following components:

• Council of Principal Investigators - CPI

• Principal Investigators - PI
• MONICA Steering Committee - MSC
• MONICA Management Centre - MMC
• MONICA Data Centre - MDC
• MONICA Quality Control Centres - MQC
• MONICA Collaborating Centres - MCC
• MONICA Reference Centres - MRC

Throughout the text only the abbreviations given above are used. An organizational chart
is shown below.
3.1 Council of Principal Investigators (CPI)

a. The CPI is composed of the designated PIs (responsible scientific officer(s) of

each full member centre) from each MCC. The CPI is the highest policy and
decision-making body of the WHO MONICA Project.
b. Meetings of the CPI are held as often as funding permits. The meetings are
attended by:
i. PIs or their representatives
ii. MONICA country coordinators1
iii. Ex-officio staff including heads of the MMC, MDC, MQCs and MRCs
iv. Principal investigators from associate member centres
v. Team members from MONICA Centres
vi. Consultants, whenever necessary, appointed by WHO
vii. MSC members.
Only category i) has the right to vote at CPI meetings. Each MCC has only one vote,
even if it has two PIs.

Note: 1 A chief scientific officer designated by a country to coordinate activities of

MONICA Collaborating Centres within that country.

The Council has the following functions:

• reviewing, deciding and planning the execution of the MONICA Project

• monitoring and evaluating progress
• exchanging experience and information
• reviewing the recommendations of the MSC
• charging the MSC with specific assignments, if necessary
• electing new members of the MSC
• agreeing upon timetables

Funding: To the extent that funds are available, the costs of participation of the Principal
Investigator (or his/her nominated alternate), the Heads of the MMC, MDC, MQCs and
MRCs, as well as coopted advisers will be borne by WHO. In the case of joint PIs, the
WHO will cover the cost of one PI for each MCC, except where one of the PIs is head of
a management body (MMC, MDC, MQCs, MRCs).

Organization: Meetings of the CPI are organized by the MMC, the MSC and, where
relevant, any local co-ordinator.

3.2 MONICA Steering Committee (MSC)

The MSC is a committee of the CPI with the following constitution:

i. Three members elected by the CPI from among members of the MCCs;
ii. Five ex-officio members
o Responsible Officer, Cardiovascular Diseases, WHO/HQ
o Regional Officer, Chronic Diseases, EURO
o Chief, MONICA Data Centre, Helsinki
o Rapporteur, who shall also be rapporteur for the CPI
o MONICA Biomed project grant Coordinator(s) during the currency of the
grant(s)2
o The coordinators of other significant grants held on behalf of the Project
as agreed to by the MSC
iii. Coopted advisers appointed by the MMC after consultation with the MSC on an
ad hoc basis.
Note: 2 MONICA is partially supported under Concerted Action funding granted by the
European Union for a 3-year period from 1 June 1996, and a Shared Cost Action for a 3-
year period from 1 May 1998.

Prior to the CPI meeting in October 1997, elected members of the MSC served for a
period of three terms, where the terms were defined as the periods between two CPI
meetings. After the 1997 CPI meeting, a term is defined as an 18-month period, ending
on 31 March or 30 September. In principle the longest serving elected member shall
retire at the end of each term. Vacancies due to the retirement of elected members shall
be filled by the CPI; should an elected PI-member of the MSC resign, the alternate
elected at the previous election shall serve in his/her place.

Procedure for election of MSC members

Until October 1997 one new member of the MSC was elected at each meeting of the CPI.
Thereafter the appointment of the elected members of MSC can be by postal ballot. A
ballot to elect a new member will be held at the end of each term. Elections will be held
in March or September of the appropriate year.

Prior to October 1997, eligibility to serve on the MSC was restricted to MCC PIs or co-
PIs. Post October 1997, eligibility is defined as:

• Any member of an MCC is eligible for membership of the MSC except that at any
time only one member of an MCC can be an elected member of the MSC.
• Past members of the MSC are eligible for re-election after standing down for one
term.
• A second member of an MCC can only be elected to the MSC after the first
elected member has stood down for one term.

Rules for postal voting:

See Annex 1.

Chair and Rapporteur

The Chair of the MSC shall be elected by the MSC from among the three members
elected by the CPI. The Chair shall hold office for one term. The Rapporteur, who serves
both the MSC and CPI, shall be appointed by WHO in consultation with the MSC for a
period of 3 years, and shall be subject to re-appointment.

Publications Coordinator (PC)

The PC shall be appointed by the MSC from its elected PI members. In general the PC
will serve for one electoral term, and can be re-elected. The PC has the responsibility for:

• assessing MONICA Publication Proposals for centrally generated collaborative

MONICA publications and advising the MSC on which of these should be
accepted as 'Agreed Publications'
• proposing to the MSC the Manuscript Groups and their Leaders charged with the
development of draft manuscripts
• assuring timely and efficient processing of analysis proposals and manuscripts
(see Section 7).

Quorum

A total of four, including two elected members and two ex-officio members shall form a
quorum.

Voting

Each member of the MSC (except coopted advisers) shall be eligible to vote. However,
the three elected members, when voting together, shall have power of veto over the ex-
officio members.

Attendance

PIs who are not members of the MSC may be invited to attend MSC sessions but are not
entitled to vote. Technical staff of the management organizations, including the MQCs,
may also be invited to participate in MSC sessions when required. Observers may be
permitted at the discretion of WHO after consultation with the Chair.

Secretariat

CVD Programme, WHO/HQ, serves as Secretariat to the MSC.

Responsibilities

The MSC is charged with the following responsibilities:

1. To carry forward the work of the project on behalf of the CPI.

2. To propose changes to the MONICA Manual whenever necessary.
3. To approve and monitor measures for quality control that will be managed by the
MDC and MQCs.
4. To monitor and evaluate the performance and activities of the MMC, MDC and
the MQCs.
5. To review performance of MCCs and decide on termination of membership of
any centre failing to meet performance criteria.
 6. To assist the MMC and MDC in the management and administration of the
project and in planning meetings of the CPI.
7. To advise and assist in fund raising.
8. To decide on associate membership.
9. To request site visits to evaluate MCC, MQC, MDC and MMC performance.
10. To keep the MCCs and MQCs informed on the current management of the
Project.
11. To promote and develop guiding principles for future international collaborative
research arising from the MONICA Project or from the collaboration of MCCs
(but not necessarily confined to such Centres).

3.3 MONICA Management Centre (MMC)

Cardiovascular Diseases Programme

World Health Organization
CH - 1211 Geneva 27

The Cardiovascular Diseases Programme (CVD), within the Division of

Noncommunicable Diseases (NCD), WHO Headquarters, is responsible for the day-to-
day management and coordination of the WHO MONICA Project in accordance with
WHO policy and directives. The MMC has the following functions:

1. General management and coordination of the Project, including:

o Keeping detailed records of MONICA Project membership, lists of
collaborating centre team members, copies of local manuals, etc.;
o Ensuring regular information dissemination exchange through the
MONICA Memo (MNM) system and liaison among the MCCs;
o Maintaining MONICA mailing lists;
o Preparing and distributing project documentation.
2. In collaboration with the MDC and MQCs, maintenance of quality assurance
procedures, including:
o Organization of site visits in consultation with the MSC, MDC and MQCs;
o Arranging the recruitment of consultants for specific ad hoc assignments
whenever necessary.
3. Monitoring the work of the MDC, MQCs and MRCs.
4. Acting as Secretariat to the CPI and MSC.
5. In consultation with the MSC, appointing the rapporteur of the MSC who serves
both the MSC and CPI.

3.4 MONICA Data Centre (MDC)

Department of Epidemiology
National Public Health Institute
Mannerheimintie l66
00300 Helsinki, Finland
The MDC is jointly sponsored by WHO, through a technical services agreement, and by
the National Public Health Institute of Finland, and is supported through a Biomed grant
from the European Union. The MDC is concerned with the management and analysis of
the core data of the WHO MONICA Project. Under the overall direction of the MSC and
of WHO, the MDC shall:

1. Prepare data collection methodology and instruments for the core study data;
2. Receive core study data from the MCCs in an agreed format and ensure its
security and confidentiality;
3. Provide analyses and reports of the MONICA core study data in a format decided
and approved by the MSC;
4. Assist in the development and implementation of an appropriate quality assurance
programme;
5. Advise MCCs on MONICA data collection and management procedures;
6. Assist in preparing MONICA Project publications of results from the MONICA
Project;
7. Report to the CPI, the MSC and the MMC, at minimum six-monthly intervals and
whenever requested;
8. Collaborate closely in management of the MONICA Project with the MSC and
the MMC.

Organization

The tasks of the MDC are defined by the MSC in accordance with the requirements of the
MONICA Manual.

All MCCs and MQCs will have direct communication with the MDC regarding data flow
and related technical matters.

The MDC is a separate unit within the Department of Epidemiology of the National
Public Health Institute of Finland, and is not part of FINMONICA.

3.5 MONICA Quality Control Centres (MQC)

Centres nominated by WHO in consultation with the MSC to provide expertise on

specified areas of the core project. There are four Quality Control Centres with specific
tasks:

A. MONICA Quality Control Centre for Lipid Measurements:

WHO Collaborating Centre for Blood Lipid Research in Atherosclerosis and Ischaemic
Heart Disease (usually known as the WHO Lipid Reference Centre)
Laboratory for Atherosclerosis Research
Institute for Clinical and Experimental Medicine (IKEM)
Videnska 800, PO Box 10
14000 Prague 4, Czech Republic:
Aim: To ensure comparability of data collection in the MONICA Project by testing the
performance of Centres in lipid measurements.

Terms of Reference: In close cooperation with the MSC and MMC, the Prague Centre
will provide the following services:

1. Procure quality control pools for lipid measurements at the MCCs.

2. Establish and execute a reference programme for testing the total cholesterol,
HDL-cholesterol and thiocyanate methods.
3. Respond to queries on MONICA lipid measurement procedures and laboratory
standardization.
4. Maintain appropriate documentation on MONICA lipid and thiocyanate
measurement procedures and laboratory standardization.
5. Provide periodic summary reports on the performance of the lipid laboratories at
the various MCCs.
6. Ensure comparability at regular intervals against the WHO Collaborating Centre
for Blood Lipid Standardization at the Centres for Disease Control, Atlanta,
Georgia, USA.
7. Assist the MMC in taking appropriate action when the performance of an
individual lipid laboratory is not satisfactory.
8. Present status and progress reports at regular intervals to the MSC.
9. Respect confidentiality of all data received from MCCs.
10. Communicate direct with individual MCCs on technical matters, or through the
MONICA Memo system.

B. Quality Control Centre for ECG Coding

National Institute of Cardiology

IX Haman Kato Ut 29
PO Box 88
1450 Budapest, Hungary

Aim: To standardize the interpretation of ECG according to Minnesota coding in order to

improve diagnostic performance in assigning MONICA ECG categories.

Terms of reference: In close cooperation with the MSC, the MMC and the MQC for
Event Registration, Dundee (Dundee Centre), the MONICA Quality Control Centre for
ECG Coding, Budapest (Budapest Centre) will provide the following services:

1. Preparation of standard sets of ECG tracings for distribution to Centres to assess

differences in ECG coding. Official MONICA reference codes will be established
in consultation with the Dundee Centre using the algorithm produced by the
Dundee Centre.
2. Reports, including statistical analysis and commentary, will be prepared and
circulated. The attention of each centre will be drawn to their weak points and
suggestions for improved performance will be put forward.
 3. The Budapest Centre will provide the official Minnesota reference codes for the
ECG tracings included in the sets of specimen case histories elaborated by the
Dundee Centre and will agree the official MONICA categories with Dundee.
4. The Budapest Centre will provide consultation services and organize training
courses in ECG coding as needed and appropriate.
5. The Budapest Centre will maintain a programme of standardization for its own
ECG coding activities with the Minnesota Coding Laboratory at the University of
Minnesota, Minneapolis, whilst such a link remains in being, but will also
establish an external panel of expert coders, or task force, who will provide and
code test material and standardize the Centre.
6. Status and progress reports will be presented to the MMC and the MSC at regular
intervals.
7. Respect confidentiality of all data received.
8. Communicate direct with individual MCCs on technical matters with copies to
MMC, or through the MONICA Memo system.

C. Quality Control Centre for Event Registration

Cardiovascular Epidemiology Unit

Ninewells Hospital and Medical School
University of Dundee
Dundee DD1 9SY, Scotland

Aim: To standardize the coding and classification of coronary and stroke events
according to the MONICA Protocol in order to improve comparability and stability
within and between Centres, thereby maximizing the chances of detecting true time
trends in event rates and minimizing the likelihood of spurious trends.

Terms of reference: In close cooperation with the MSC, the MMC and the MQC
Budapest, the Dundee Centre is responsible for the following areas:

1. Preparation and circulation of sample case histories and other material covering
both coronary and stroke events, to be followed up with general commentaries
and specific reports.
2. Answering queries on the MONICA event registration process.
3. Assisting, as appropriate, Centres having problems with this process.
4. Developing an operational definition for coronary and stroke events leading to
diagnostic algorithms and, where appropriate, computer programs based on these.
5. Presenting status and progress reports to the MMC and the MSC at regular
intervals.
6. Respecting confidentiality of all information received from MCC, MMC or MDC.
7. Final interpretation of the criteria (e.g. in a dispute between the Dundee Centre
and an MCC) rests with the MSC.
8. Communicating direct with MCCs on technical matters, or through the MONICA
Memo System in Geneva.
 9. Collaborate with the MDC, MSC and MCCs in preparing reports on the quality of
event data sent to the MDC and its interpretation.

Links between the Dundee Centre and the Budapest Centre: ECG diagnoses will be
agreed with the MQC for ECG Coding, Budapest, this centre taking primary
responsibility for Minnesota coding and Dundee for any problems with diagnostic
algorithms. Other procedures are to be agreed with the MMC and the MDC concerning
distribution, analysis and commentaries.

D. Quality Control Centre for Health Services

Department of Public Health

University of Western Australia
Western Australia 6907, Australia

Aim: To develop methods for the collection and quality assessment of standardised data
on provision of health services and selected aspects of medical and surgical care for the
management of cardiovascular disease in MONICA Collaborating Centres.

Terms of Reference: In close cooperation with the MSC, MDC, MMC and MQC for
Event Registration, the Perth Centre is responsible for the following areas:

1. Developing and testing, in consultation with the MONICA Data Centre and the
Steering Committee, the data instruments to ensure collection of comparable data
for health services assessment within the WHO MONICA Project.
2. Monitoring and evaluating the progress and effectiveness of this component of the
WHO MONICA Project.
3. Maintaining, in liaison with the MONICA Data Centre, the MONICA Manual
section for this data component.
4. Assisting, as appropriate, Centres having problems in health services data
collection.
5. Communicating direct with MCCs on technical aspects of this component, or
through the MONICA memo system in Geneva.
6. In close liaison with the MSC through the Publications Coordinator (PC, see 3.2),
supervision of MONICA collaborative publications in this area.
7. Respecting confidentiality of all data received.
8. Presenting, in collaboration with the MDC if necessary, progress reports to the
MSC and the MMC at regular intervals.

3.6 MONICA Reference Centres (MRC)

MRCs deal only with optional studies carried out within the framework of the WHO
MONICA Project. They coordinate and advise on their specific areas of speciality as
follows:

1. Act as resource centres in areas in which they have special expertise or interest.
 2. Help to develop common protocols and provide a focus for the relevant optional
studies.
3. Coordinate any collaborative studies and plan any joint analyses.
4. Advise their collaborators on any methodological or quality control problems
whenever necessary.
5. Organize data management for the respective optional study.
6. Keep the MMC informed of all activities through six-monthly reports.
7. Follow international development in the respective field, help with necessary
contacts with other related studies and advise Centres on possible additional
activities in the field in question.

MRC Nutrition (MRC-NUT)

Department of Chronic Diseases and Environmental Epidemiology
National Institute of Public Health and the Environment
P.O. Box 1
NL-3720 BA Bilthoven, The Netherlands
MRC Vitamins
Vitamin Unit
Institute for Biochemistry and Molecular Biology
University of Bern
Bühlstrasse 28
3000 Bern 9, Switzerland
MRC Physical Activity (MOSPA)
Behavioral Epidemiology and Evaluation Branch
Division for Health Education
Centers for Disease Control
Atlanta, Georgia 30333, USA
MRC Psychosocial Studies Office of Chronic Diseases (MOPSY)
WHO Regional Office for Europe
8 Scherfigsweg
DK - 2100 Copenhagen
MRC Drugs (MRC-DRG)
Bremer Institut für Präventionsforschung und Sozialmedizin (BIPS)
St Jürgen Str. 1
D - 2800 Bremen 1
MRC Haemostatic Factors and CHD (MRC-HFC)
Division of Epidemiology
The Queens University of Belfast
Mulhouse Building
Grosvenor Road
Belfast BT12 6BJ

4. MONICA Collaborating Centres (MCC)

The following conditions form the basis for recruitment, continuing participation and
quality assurance of individual Centres.
Expertise:

a. Centres should have recognized epidemiological experience, or should be

supported, backed or assisted by a centre with documented experience.
b. Centres should maintain standardization in accordance with the criteria
established by the MSC for lipid measurements, ECG coding and event
registration, and for any other techniques determined by the MSC within the time
limits established, providing the MMC and MQCs with information whenever
requested in the format required.

Population to be monitored: See Section I.1.

Local procedures:

a. MCCs should comply with the rules given in this document and should prepare
their own local protocols and manuals of operation based on the present
document.
b. The local protocol and manual of operations should be translated where necessary
into English and submitted for approval to the MSC through the MMC at WHO as
should any subsequent revisions.
c. Any variation in procedure from the approved Protocol and Manual of Operations
must be discussed with the MMC, as should any difficulties in adhering to the
Protocol.

Coordination:

a. MCCs should provide the MMC with details of the study population in the format
requested.
b. MCCs should provide data at the frequency and in the format required by the
MDC, the MMC and the MSC.
c. MCCs should provide the MMC with
i. a list of principal MONICA project team members with their individual
responsibilities, reviewed annually. Each MCC should have one or two
Principal Investigators (PIs) and/or are encouraged to designate one or
more Co-Principal Investigators in addition to the PI;
ii. a list of the optional studies carried out locally and whether they are being
carried out according to a collaborative protocol;
iii. an annual progress report by 30 June each year for review by the MSC.
This should include a list of publications and reprints.
d. MCCs should accept periodic visits from groups of experts sent by the MMC and
the MSC to review their data and procedures.
e. Encourage exchange of information and problem sharing.

Local responsibilities:

a. Responsibility for local funding.

 b. Support of the collaborative MONICA project and compliance with organization
and management procedures according to Protocol and Manual.
c. Ensuring that MONICA activities fulfil local and international criteria of medical
ethics, e.g. in ensuring confidentiality of data.

5. Reporting
The various Centres of the MONICA Project are required to provide formal written
reports regularly as follows and, in addition, whenever requested for ad hoc specific
purposes:

Centre/group Reports to Timing

MCC MMC Annually by 30 June
MSC CPI Every meeting
MMC MSC Every meeting
MDC MMC 30 June and 30 December
MSC Every meeting
MQC MMC 30 June and 30 December
MRC MMC 30 June and 30 December

Reports should contain the following information:

1. Administrative changes affecting the activity of the centre, such as changes in

personnel or facilities, or budgetary issues;
2. Activities since the previous report;
3. Current activities and problems;
4. Activities planned for the next reporting period;
5. (For MCCs) Optional study activities;
6. Two copies of publications issued since the previous report (including summary
or abstract in English).

Reports should be signed by the designated PIs or the head of the centre concerned.

6. Communication procedures
Procedures to be followed by MMC, MDC and MQCs.

a. MONICA Memoranda (MNM):

i. All MNM to be transmitted by priority mail and outside Europe by
airmail.
ii. Draft MNM to be sent to MMC at least one month before the date of
distribution to MCCs to allow adequate time for reproduction and mailing.
 iii. All MNM to be marked with an appropriate statement concerning action
required by MCC.
iv. All MNM to be marked with realistic deadlines and a priority statement.
b. For other communication, electronic mail (E-mail) and the World Wide Web
(WWW) whenever available and appropriate are preferred to telefax and ordinary
mail.
c. Forthcoming deadlines to be reviewed at each MSC meeting.
d. Compliance with deadlines to be monitored by MMC, MDC and MQCs and
discussed at each MSC meeting.
e. MMC and MDC and MQCs to acknowledge receipt of all "action"
communications form MCC and to provide a statement of date of expected action.

Procedures to be followed by MCCs:

a. MCC Principal Investigators to take responsibility for ensuring that MONICA

documents reach appropriate personnel efficiently.
b. Additional MCC personnel (and address) for MNM mailing list to be sent by PI to
MMC (or additional number of copies to be sent direct to PI).
c. MCC to acknowledge receipt of all "action" MNM and all important
communications and quality control materials from MMC, MDC and MQC and to
provide an expected date for completeness of required actions.
d. MCC to send communication by E-mail whenever appropriate. Otherwise telefax,
priority mail and outside Europe airmail should be used.
e. Each MCC to keep master file of all MNMs with note of action taken and date.

Procedures for communication by E-mail and the WWW:

a. Up-to-date procedures are described in the WWW at

"http://www.ktl.fi/monica/internal/". This includes
i. Addresses.
ii. Instructions for transfer of documents by E-mail.
iii. Instructions for commenting and annotating documents transferred by E-
mail.
iv. Procedures for distributing documents through WWW.
v. Rules for E-mail discussion by the MSC.
b. All MONICA Centres should pay particular attention to preventive measures
against computer viruses. Executable computer programs or documents in the
internal format of sophisticated text processing systems should be transferred only
in special cases. In such cases, both the sender and the receiver should check the
program or document against viruses.

7. Publication rules
(These publication rules have been superseded by those given in Amendment 2.)

7.1 Publication Policy

7.1.1 General statement

The MONICA publication policy is designed to encourage scientific publication of all

types, while maintaining the high quality of these publications and ensuring the
legitimate interests of all MONICA participants.

The policy refers to written or oral presentations of unpublished MONICA core data
(including data accepted for publication but not yet published). No such data can be
presented or published without the consent of each PI. As a general rule, consent should
be received within 4 weeks; failure to reply within this time will be taken to mean
consent ('The 4-week rule' starts from the date the document is e-mailed, faxed or
posted).

MONICA publications are coordinated by the PC (see 3.2).

7.1.2 Publications from individual MCCs

Individual MONICA Centres are encouraged to present and publish results that are based
on the data from their own centre, subject to acknowledgement that they are derived from
the WHO MONICA Project. Publications which refer to the WHO MONICA Project in
the title must be approved by the MSC before publication.

7.1.3 Publications from several MCCs

Publications from MCCs based on mutual agreement among participating PIs are
encouraged. This applies to Optional Studies.

Interested Centres can directly pool their own data.

If core data from the MDC are used for such a publication, a formal request for data
release, accompanied by the approval of all MCCs concerned, must be sent to the MMC.
The MSC decides on the data release.

If collaborative publications from several MCCs refer to the WHO MONICA Project in
the title, or if more than six Centres are included, approval by the MSC must be obtained
before the manuscript is submitted for publication. For such approval the manuscript
should be sent to the MMC. Approval from the MSC must also be obtained when four or
more MCCs wish to explore the interrelationships of tenyear data on trends in events,
case fatality, risk factors or medical care. A paper from up to three Centres exploring
these relationships must carry the statement that it cannot, for reasons of power and
geographical representation, test the main MONICA hypotheses.

The authors have full responsibility for the appropriate use and accuracy of the data
reported in such a publication.

7.2 Rules for centrally generated Collaborative Publications

7.2.1 Rules for Publication Proposals

Anybody can propose MONICA collaborative publications (The Proposer). The proposal,
including the Publication Proposal Form (Form SA) as a cover sheet, should give
purpose, outline, target journal and time schedule and be submitted to the PC (see Figure
1). Whenever possible, a proposal for authorship should be made.

The PC assesses the appropriateness, priority and proposed leadership of the publication
(see 7.2.2 below) possibly with the help of reviewers of his selection and the Head of the
MDC. The PC advises the MSC which decides whether the manuscript should be
accepted as a MONICA collaborative 'Agreed Publication', its priority, and who should
be its Leader. If the MSC does not reply within 7 days, it is assumed that the proposal of
the PC is accepted. The PC informs the Proposer of the decision and the Chief of the
MDC updates the MONICA Publication Plan (see 7.6) as appropriate.

7.2.2 Rules for Preparation of Manuscripts

The manuscript is prepared by a Manuscript Group. Anyone from a MONICA centre can
volunteer to join a Manuscript Group. This group will carry out the analysis and prepare
the manuscript. The Group, with its Leader should include the necessary expertise in
epidemiology, statistics and programming, and whichever other skills may be required.
Priority will be given to those in MONICA who have indicated their interest to work on a
particular manuscript.
The Leader is crucial to the success of the MONICA Publication Plan as he or she is
responsible for organising the Manuscript Group, for overseeing the preparation of the
manuscript, and for ensuring that the Agreed Publication is produced to an appropriately
high standard within the agreed timetable. The Leader will report to the PC on a regular
basis. The essential prerequisite for becoming a Leader is an ability to meet deadlines and
to motivate others to do the same. The Leader may delegate some if not all the writing of
the paper to another member of the Manuscript Group but in this case the delegated
person's name should appear first in the authorship statement.

Authors other than the Leader and/or the first author should be significant contributors to
the design of the paper, data preparation, analysis and/or writing. They should be
consulted by the Leader and/or first author at key stages in the paper's development and
should have seen and approved the final draft before it is submitted to the PC. In the eyes
of journal editors they are responsible and answerable for the accuracy of the data and
conclusions contained in the paper. Co-authors are not necessarily those who
volunteered, or were volunteered by others when the paper was first proposed - they must
have contributed substantially when work on the paper was in progress. The final
authorship list may therefore be different from the original manuscript group. Names of
co-authors should be agreed by the Leader and first author involving the PC and the MSC
if there is any difficulty or ambiguity.

The PC maintains regular contact with the Leaders of the Manuscript Groups to ensure
that deadlines are met and on the basis of this keeps the Publication Plan up-to-date. If
MONICA core data are used for a publication, the data must be obtained from the MDC,
the analysis must be carried out under the control of the MDC, and the results must be
verified by the MDC (see also 7.3.2). If and when this is no longer possible, appropriate
checks will be organized by the MSC through the PC.

Such publications appear with the authorship statement as follows:

Name(s) of author(s) for the WHO MONICA Project (1),

Title:................................

Text:.................................

(1) Annex: Sites and key personnel of the WHO MONICA Project

The Annex includes:

• Sites, PIs and key personnel

o Only MCCs whose results appear in the paper will be listed.
o Names of key personnel should be restricted to those involved in the data
component(s) considered in the publication.
o Names should be those who would be named in locally published papers,
rather than being a complete list of everyone working in the project.
 o Although the listing for each MCC is at the discretion of the PI, the lead
author and/or PC may wish to indicate to MCCs whether this is a major
report supporting a detailed annex or a minor one in which an annex of
reduced length might be more appropriate.
• MSC, MMC, MDC, MQCs, national coordinating centres (where applicable)
o Only MQCs involved in the data used for the publication will be listed.
• Consultants.

The list is drafted by the Manuscript Group and corrected when necessary by the PIs at
the same time as they approve the manuscript.

The letter to the editor on submission should include this sentence displayed prominently
and the accompanying statement on a separate sheet:

"Please Note: Publication of WHO MONICA Project data is subject to WHO

MONICA Project publication rules. Please see accompanying statement"

Accompanying Statement.

"WHO MONICA Project Publication Rules

Ownership of MONICA data is vested in the WHO MONICA Project Principal

Investigators who have resolved that publication of results should be restricted to those
journals which accept the WHO MONICA Project publication rules. These appear
reasonable to us and are accepted by major scientific journals. However, we wish to draw
these to your attention now to prevent delays or disputes later in the publication process.
Within these constraints the author of the accompanying letter is authorized by the WHO
MONICA Project to negotiate publication with you. We will presume acceptance of these
rules if you acknowledge this paper and forward it for refereeing. If you do not accept
these rules please return the manuscripts immediately so that it can be submitted
elsewhere without further delay. Thank you for your co-operation.

The publication rules cover three specific items:

1. The authorship line (as in the accompanying manuscript)

2. Citation of previous MONICA publications (as in the accompanying manuscript)
3. Publication of the list of MONICA sites and key personnel as an annex to the
paper.

The format and print size are at the discretion of the journal."

Whenever reasonable, the paper should have "WHO MONICA Project" in the title.

The publication must have an acknowledgement paragraph in a format consistent with

WHO MONICA Project policy and sources of funding. The wording of this should be
obtained by the Leader of the Manuscript Group from the PC who will have agreed it
with the MMC and MSC. This acknowledgement may need to be updated during the
development of the paper and is subject to final revision when the paper is approved by
the MSC.

The acknowledgement paragraph may have added to it the names of internal MONICA
reviewers who have made what is judged to be substantial contributions in the reviewing
process. This can be agreed by the lead author and the PC prior to submission to a
journal.

7.2.3 Rules for Agreed Publications

On completion the Manuscript is sent to the PC who sends it to three reviewers, at least
one of whom should be a statistician. (see Figure 2).The reviewers of MONICA
manuscripts will be chosen among PIs and staff members as well as among scientists
outside MCCs who have proven specific knowledge in the field. The PC also informs the
MSC about the manuscript and the reviewers. The MSC may appoint additional
reviewers within 7 days. The PC may ask the authors to send copies of the manuscript
directly to the reviewers to speed up this process.

The reviewers consider the appropriateness of the manuscript for publication and report
back to the PC within 3 weeks.

On the basis of the reviews, the PC either returns the manuscript for revision to the
authors or sends it with the reviewers' reports to the MSC.

In special cases (e.g. the stroke publications which concern only a part of the MCCs) the
MSC may decide on a review process different from the one described above, if it can be
expected to streamline the publication process.

The MSC considers the manuscript for approval as a MONICA collaborative publication
and hence for distribution to the MCCs for approval. If the manuscript is not acceptable,
the MSC decides on how to proceed further. If the MSC does not reply within 7 days, it is
assumed that the proposal of the PC is accepted.

The manuscript is distributed to the MCCs, relevant MQCs and the MDC by the MMC,
together with the list of key personnel.

The MCCs (PIs) approve the manuscript for publication and/or send their comments to
the PC or the person(s) specified in the covering letter of the manuscript. This must be
forthcoming within four weeks, and if no response is obtained the publication will
proceed.

Any minor modifications that may be necessary, including the list of key personnel,
should be made to the manuscript, before submission. After approval the manuscript will
be submitted for publication.
The leader of the manuscript group and the first author should agree between themselves
as to who will be responsible for submitting the paper to the agreed journal, for dealing
with reviewers/ editorial comment, for checking the proofs and for ordering reprints. The
decision on responsibility should be communicated to the PC. Anything other than minor
corrections arising from the editorial-review process should be discussed with other
members of the Manuscript group and with the PC. Whoever is responsible for the proofs
must inform the PC immediately on receipt of the proofs if there is any problem with the
journal carrying out MONICA publication policy on authorship, citations or listing of
sites and key personnel, so that they can agree how to take the matter up with the journal
editor. Whoever is responsible for obtaining the reprints must send copies to other
members of the authorship group and the remainder to the MMC for distribution. The
number and funding of reprints should be discussed at the time of ordering with the PC.

The MMC is responsible for providing reprints of the published paper to the MCCs,
MQCs and the MDC.
7.2.4 Rules for Internal Documents

Internal documents are subject to the same review procedures as for publications and
require a Publication Proposal Form (Form SA), giving purpose, outline and timetable.

7.2.5 Rules for Oral Presentations

Abstracts submitted for oral presentation based on unpublished MONICA collaborative

data will be sent to the MMC which will distribute them to the MSC (see Figure 3).
Abstracts will be approved solely by the MSC, the only exception being when mention of
specific MCCs is made in the abstract, in which case, explicit permission will be sought
from the MCCs concerned by the presenter and evidence of this furnished to the MMC.
Failure to reply within 4 weeks by the MCCs concerned will be taken to mean consent.
Approved abstracts will be circulated by the MMC to all MCCs, MQCs and MDC. On
approval by the MSC the PC informs the presenter that MSC approval has been given.

7.2.6 Rules for Invited Presentations

In addition to the above, no person invited to speak "on behalf of the WHO MONICA
Project" should do so without prior approval of the MSC. If an abstract is required, the
Person Invited should follow the rules for oral presentations (see Figure 4) and give
details concerning the source of the invitation. If no abstract is required, the Person
Invited should send details to the MMC. If the MSC gives approval, the PC will inform
the Person Invited who should then proceed with the presentation but must send a
summary to the MMC for distribution to the MCCs, MQCs and MDC for information. If
any proceedings are subsequently published the Rules for Agreed Publications apply (see
7.2.3).
7.2.7 Additional rule for stroke studies

All the above rules apply, except that only PIs from MCCs participating in stroke
registration have to give their consent for publications involving stroke.

7.3 Rules for data release

7.3.1 Data Analysis in the MDC for Agreed Publications

The individual data analyses for all Agreed Publications are considered for acceptance by
the Chief of the MDC. Quality control analyses can be accepted by the Chief of the MDC
even if they are not part of an Agreed Publication. Any statistical computing will be
performed, documented and reviewed according to the MDC procedures.

7.3.2 Data analysis of Agreed Publications outside the MDC

In certain circumstances, approval of the analysis of collaborative data outside the MDC
is permissible. If an MCC wishes to undertake analysis concerning an Agreed Publication
it should, after consultation with the MDC, send an application to the MMC which will
be referred to the MSC (see Figure 5). The application must give full justification for the
reasons for decentralising the analysis, give a firm time-table, specify the data records
and items needed, with a signed commitment by the PI of the MCC that the data will be
used for the specified purpose only. If the MSC gives approval a sub-set of the MONICA
core data can then be transferred from the MDC to the MCC. All MCCs and MQCs will
be informed about the release of the data for such decentralised analysis by the MMC.
After the analysis has been completed, the MCC will provide the MDC with a full
briefing of the analysis, including source code of the data analysis programs and output
listings of the results which have been used in the manuscript for publication. For this
briefing, which will include details of statistical inferences, a visit to the MDC may be
necessary. All resulting publications are subject to MONICA Publication Rules. On
completion of the agreed analysis, the MCC must not use the data for any purpose, unless
further clearances are given by the MSC.

7.4 Ownership of collaborative data

By definition, collaborative data are those collected using the routine procedures of the
WHO MONICA Project and sent to the MDC as part of the required data transfer
procedures. These data form a part of the WHO MONICA database and are owned by the
MONICA Council of PIs, and the MQCs (for quality control data).

7.5 Citation of Collaborative Publications

Collaborative MONICA publications must be cited in the following format in both local
and collaborative MONICA publications. This format should be applied both to recent
and to older papers published using earlier MONICA authorship formats. All in
MONICA should encourage colleagues who quote MONICA papers to cite them in the
same way when they are asked to comment on or to referee papers.

Examples of citations according to MONICA publication rules:

 i. Vancouver style (may vary with journal):

Pajak A, Kuulasmaa K, Tuomilehto J, Ruokokoski E for the WHO MONICA

Project. Geographical variation in the major risk factors of coronary heart disease
in men and women aged 3564. Wld Hlth Statist Quart 1988; 41 (3/4):115140.

ii. Harvard style (may vary with journal):

Pajak A, Kuulasmaa K, Tuomilehto J, Ruokokoski E for the WHO MONICA

Project (1988). Geographical variation in the major risk factors of coronary heart
disease in men and women aged 3564. Wld Health Statist Quart, 41, 115140.

If the sub-editor tries to change this format in the proofs, the author should change it back
and inform the journal that this is the WHO MONICA Project format.

7.6 Publication Plan

The MONICA Publication Plan outlines all MONICA collaborative Agreed Publications
and reports arising from checking, quality assessment, and analysis of the collaborative
MONICA data. For each of the component data sets it describes the anticipated
progression from compilation of data books to generation of quality assessment reports
and the drafting of papers for publication in scientific journals. For each subject, there is,
in general, a series of reports relating to baseline, mid-term and final results.

For each Agreed Publication and report, the Publication Plan identifies the Leader, other
members of the Manuscript Group, target journal or a mention that it will be an internal
report of the project, and the current status.

The Chief of the MDC, in consultation with the PC, has the responsibility for maintaining
the Publication Plan. The Plan is available in the internal MONICA site in the World
Wide Web. The MMC distributes the plan regularly to the MCCs and MQCs.

7.7 Cumulative list of publications and presentations

A complete list of all publications and presentations relating to the WHO MONICA
Project is kept by the MMC. All MCCs, MQCs and the MDC should notify the MMC
about their publications, and two copies of each publication (including an English
summary and/or abstract, together with the title of the article and the journal) should be
submitted together with the MCC Annual Report. A list of MONICA publications and
presentations should be included as an annex to the MMC Annual Report.

8. Site visits
Site visits are part of the quality control programme of the WHO MONICA Project and
are planned to add an external point of view to local procedures which may result in
higher quality data.
Purpose

a. To ascertain the extent to which MCCs and/or other MONICA Centres adhere to
the requirements of the standardized methods of the MONICA Project or their
MONICA remits.
b. To identify possible sources of systematic bias and variation which may have
slipped through local quality control measurements.
c. To clarify sources of errors detected in the core data which cannot be dealt with
through postal channels.
d. To provide data for central analysis which could help to explain unexpected
results.
e. To discuss possibilities for improving data collection.
f. To provide information for central management.

Each of the following activities should be reviewed in detail:

1. collection of population demographic and mortality data

2. population survey activities
3. collection of coronary and stroke event register data
4. collection of medical care data
5. data handling
6. local management.

In each data component, special attention should be paid to local quality control and to
procedural changes within the study period.

Follow-up

After the visit, a report must be submitted to the MMC with a copy to the MCC
concerned, within one week of the site visit. The MMC then reviews the report and
prepares follow-up recommendations, in consultation with the MDC, MQCs and MCC if
necessary. A copy of the recommendations is sent to all management centres, including
the MSC, as well as to the MCC concerned.

Based on the review, the MSC may need to decide on what action, if any, might be
needed to improve local procedures, and may also need to make a decision on the status
of the MCC within the MONICA Project. If the decision of the MSC is unacceptable to
the MCC, the matter should be referred to the Council of Principal Investigators.

Follow-up procedures for site-visits to the MDC, MQC and the MMC are related to their
original remits.

Annex 1: Conducting postal ballots

1. Alteration of the rules of the MONICA Project

The MSC should determine the most efficient way of conducting the ballot. The
procedure for a postal ballot is described below, but at the time of writing this, the use of
an electronic voting system is being explored.

Postal ballots will be conducted by the MMC:

• Proposals for changes to the MONICA rules, together with supporting arguments
must be distributed to MCCs by MMC in the form of a MONICA Memorandum
• MCCs will have two weeks in which to indicate that they wish to distribute a
rejoinder opposing the proposed change; and four weeks to provide this in writing
to the MMC.
• At the end of four weeks from the date of distribution of the initial Memorandum,
the MMC will:
a. If no counter arguments are received, proceed with the ballot OR
b. Distribute any counter arguments opposing the changes in a second
memorandum. Two weeks after distribution of the second memorandum,
MMC will then proceed with the ballot.

2. Election of MSC members by postal ballot

• Postal ballots for membership of MSC will be conducted by the MMC.

• A call for nominations will be circulated four weeks before the date for closure of
nominations.
• The proposer and seconder of a nominated candidate must obtain the written
agreement of the nominee.
• Ballot papers for the election will be distributed by MMC as soon as possible after
the closing date. The candidates will be encouraged to provide a personal
statement indicating their current research interests and reasons for standing for
membership, which will be circulated with the ballot papers.
• A double envelope system will be used for returning completed ballot papers to
the MMC. The ballot paper will be first placed in a non-identified envelope. This
will then be placed within the second envelope that will have the MCC name and
number written on the back. This will also be signed by the PI.
• To avoid multiple rounds of voting, an 'optional preferential' ballot system will be
used:
o Voting: PIs will be asked to place the figure '1' in the box opposite the
name of the preferred candidate and then to continue numbering boxes in
descending order of preference. The voter may, but is not obliged, to
indicate a preference for all of candidates. If the same number has been
written against the name of more than one candidates, only the preferences
above that number will be valid.
o Counting of votes:
1. Any candidate with an absolute majority (i.e. in excess of 50%) of
first preference votes is elected.
 2. If, after the first preference votes have been counted, no candidate
has obtained an absolute majority of votes, then the candidate with
the fewest number of first preference votes is excluded. That
excluded candidate's second preference votes are then distributed
to the remaining candidates. (Whenever a ballot paper shows a
void preference for a continuing candidate, that ballot paper is said
to be exhausted.)
3. Any candidate with an absolute majority of those votes remaining
in the count is elected. If no candidate has obtained an absolute
majority of votes, the next remaining candidate with the fewest
votes is excluded and all of his/her votes are distributed to the
remaining candidate (i.e. each first preference vote or vote
received from the first excluded candidate is given to the next
preference candidate).
4. The above process is continued until one candidate obtains an
absolute majority of the remaining votes.
5. If, at any exclusion, the next available preference is for a
previously excluded candidate, then that preference is disregarded
and the vote is distributed to the continuing candidate for whom
the next available preference is shown.
6. If at any stage there is a tie for the fewest votes (i.e. for the
candidate to be excluded), the original first preference votes (i.e.
first preference votes before anyone was excluded) will be used to
break the impasse. If the tie persists, the original second preference
votes will be used, and so on. If the impasse remains after the votes
of the last preferences have been used, lots will be drawn to break
the tie. (Note that this rule also includes a tie for the first place.)
7. To select the alternate, a similar procedure is used, but excluding
the elected candidate in the beginning.

MONICA Manual, Part I, Section 2: Organization and Management of the WHO

MONICA Project

Amendment 1: Management of the

MONICA Project
April 2004

After publication of the main results of the MONICA Project, it was thought necessary to
revise the way MONICA is managed. Following the response of the Principal
Investigators (PI) to MONICA Memo 394E in May 2002, the MONICA Steering
Committee concluded that there was agreement on the following changes. It was also
agreed that the MONICA Manual will not be revised, but the changes will be included as
amendments to the Manual. To the extent of this amendment, parts of the MONICA
Manual, although of historical relevance, will be superseded and no longer valid after
March 2004.

1. Ownership of the MONICA name and logo

The World Health Organization (WHO) and the WHO MONICA Project Investigators
will together retain the ownership of the MONICA name and logo.

2. Ongoing contact and decision-making mechanisms

MONICA Management Centre at the WHO Headquarter in Geneva is replaced by a
contact person for MONICA-related matters. His or her tasks are mainly to deal with
MONICA-WHO interactions and to direct people who are interested in MONICA to the
right persons.

MONICA Data Centre is replaced by a contact person at KTL, Helsinki, with the task of
co-ordinating data issues.

A long-term MONICA Steering Committee (MSC) with five members was elected by the
MONICA PIs to serve for a period of five years, starting on 1st January 2003. The
members of the MSC may within themselves elect a chairman and a rapporteur. Contact
persons at WHO and KTL serve as ex officio members of the MSC.

After the 5-year term, the MSC will decide whether or not there is a need for a
prolongation of its mandate. The responsibilities of the MSC are:

1. To carry forward the work of the Project on behalf of the PIs.

2. To propose changes to the MONICA Manual whenever necessary.
3. To assist WHO and KTL in the management and administration of the Project.
4. To raise funds for its own activities.
5. To keep the PIs and MQCs informed on the current management of the Project. A
major task will be to co-ordinate the network of former MCCs (WHO MONICA
Collaboration) and to edit the network website.
6. To promote and develop guiding principles for future international collaborative
research arising from the MONICA Project or from the collaboration of MCCs
(but not necessarily confined to them).

It is anticipated that most communication within the MSC in future will be by e-mail.

3. Ownership of the MONICA collaborative data

The WHO MONICA Project Investigators and the MQCs retain the formal ownership of
the MONICA collaborative data. The PIs retain the right to take major decisions
concerning ownership and use of the MONICA collaborative data. The MONICA
Steering Committee may delegate the contact person at KTL to deal with practical issues
concerning access to the data.

4. Storage of the MONICA database and other material

As decided earlier, a copy of the database will be kept at KTL and WHO (see
http://www.ktl.fi/monica/internal/archive_root/archive.htm).

5. Access to the collaborative data - who and how?

The MSC has the task of encouraging use, and preventing misuse, of the collaborative
data, which has now been made available to all MONICA Collaborating Centres, under
agreed rules (see Publication Policy). A random sample (20%) of most data from most
centres was placed in the public domain with the publication of the MONICA
Monograph and Multimedia Sourcebook and its accompanying CD-ROMs in 2003.

The MSC will decide if and when to propose that the current restrictions on use and
access to the Basic Analysis Data Set of the MONICA Archive (which includes all
primary data) should be relaxed. This could be done by placing it completely in the
public domain or by licensing its use to specified groups of users. Individual PIs retain
the right to decide on access to data from their own MCCs. They will be consulted and
their agreement sought before any change is made to the rules on use and access to the
data.

MONICA Manual, Part I, Section 2: Organization and Management of the WHO

MONICA Project

Amendment 2: Publication rules

September 2004

Contents
• 7. Publication rules
o 7.1 Publication Policy
▪ 7.1.1 General statement
▪ 7.1.2 Publications for the WHO MONICA Project
 ▪7.1.3 Publications from individual or groups of MCC
▪7.1.4 Publications from individuals/groups not affiliated with
WHO MONICA
o 7.2 Rules for Collaborative Publications
▪ 7.2.1 Rules for Publication Proposals
▪ 7.2.2 Rules for Preparation of Manuscripts
▪ 7.2.3 Rules for Internal Manuscript Review
▪ 7.2.4 Submission of the manuscript to the journal
▪ 7.2.5 Rules for Oral/Poster Presentations
▪ 7.2.6 Rules for Invited Presentations
▪ 7.2.7 Additional rule for stroke studies
o 7.3 Rules for data release
▪ 7.3.1 Ownership of collaborative data
▪ 7.3.2 Data Release to MCCs
▪ 7.3.3 Data Release to Individuals/Groups outside the WHO
MONICA Project
o 7.4 Citation of Collaborative Publications
o 7.5 Publication Plan

After publication of the main results of the MONICA Project, a copy of the Basic
Analysis Data Set of the MONICA Archive was distributed to the MONICA
Collaborating Centres (MCC), and the Publication Rules were revisited. The Principal
Investigators decided on new Publication Rules, which are given in this amendment. In
May 2002 it was agreed that the MONICA Manual will no longer be revised but any
changes will be included as amendments to the Manual. The old publication rules of
Subsection 7 of Section 2 of Part I of the MONICA Manual, although of historical
reference, will be superseded and are no longer valid after September 2004.

7. Publication rules
7.1 Publication Policy

7.1.1 General statement

The MONICA publication policy is designed to encourage scientific publication of all

types, while maintaining the high quality of these publications and ensuring the
legitimate interests of all MONICA participants.

The policy covers:

1. written or oral/poster collaborative presentations that are prepared ", for the WHO
MONICA Project" and are referred to as Collaborative Publications
2. written or oral/poster presentations by one or more MCCs, using MONICA data
not in the public domain or using the term "WHO MONICA Project" in the title
 3. written or oral/poster presentations, using MONICA data not in the public
domain, by individuals/groups that are not affiliated with any MONICA
Collaborating Centre. Their access to the MONICA data was obtained through an
agreement that commits them to adhering to the MONICA Publication Rules

The principles of the MONICA Publication Rules are:

1. All papers that use MONICA data must acknowledge the WHO MONICA
Project.
2. The applicable rules are summarized in the following table and detailed in
subsequent sections. Their aims are to protect the interest of the MCCs and to
provide a credible process for authors to justify their claim vs. journal editors that
they write for the WHO MONICA Project.

Does the paper claim to represent the whole MONICA group?

(i.e. authorship line includes ", for the WHO MONICA Project" or equivalent terms)
No
• Consent has to be obtained from
MCCs whose data are to be used.
• Acknowledgement requirements
have to be observed.
• Recommended citation formats
should be followed.
Yes
• Publication proposal must be
submitted to and approved by the
MSC.
• MSC informs MCCs.
• MSC guides the manuscript through
the internal review process.
• MSC request approval of the final
manuscript from MCCs.

MONICA publications are coordinated by the Publication Coordinator PC (see

http://www.ktl.fi/monica/public/msc.html).

7.1.2 Publications for the WHO MONICA Project

No such publications can occur without the consent of each PI or his/her representative.
As a general rule, consent should be received within 4 weeks; failure to reply within this
time will be taken to mean consent (The 4-week rule starts from the date the document is
e-mailed, faxed or posted). Presentations require only the approval of the MSC, but PIs or
their representatives have to be informed of the content and location of the presentation
prior to the date of the presentation.

The rules for these publications are described in detail in Section 7.2 below.

7.1.3 Publications from individual or groups of MCC

MONICA Centres are encouraged to present and publish results that are based on the data
from their own centre(s), acknowledging data collection under the protocol and
adherence to quality control of the WHO MONICA Project. It is advisable that proposers
keep all MCCs whose data are to be used informed about the proposal and involve them
as much as feasible. Publications that refer to the WHO MONICA Project in the title
should be approved by the MSC before publication.

7.1.4 Publications from individuals/groups not affiliated with WHO MONICA

If the publications are based on MONICA data not in the public domain they have to
include the statement:

"The data have been collected by the WHO MONICA investigators (for list see
http://www.ktl.fi/publications/monica/investigators.htm) and have been made available
for this publication by the WHO MONICA Project. Views expressed in this paper are
those of the authors and may not reflect those of individual WHO MONICA Principal
Investigators".

7.2 Rules for Collaborative Publications

7.2.1 Rules for Publication Proposals

Anybody with approved access to the WHO MONICA database can propose MONICA
collaborative publications (the Proposer). Before preparation of the manuscript, approval
should be sought from the MSC, by submitting a proposal to the PC, including the
Publication Proposal Form (Form SA) as a cover sheet, giving outline, target journal and
time schedule, and whenever possible suggested authors. The list of authors must end
with the term ", for the WHO MONICA Project".

The PC assesses the appropriateness of the proposal, possibly with the help of reviewers
of his choice. The PC advises the MSC that decides whether the proposed paper should
be accepted as a MONICA Collaborative Publication. If the MSC does not reply within 7
days, it is assumed that the proposal of the PC is accepted. The PC informs the Proposer
of the decision and the KTL contact person updates the MONICA Publication Plan (see
Section 7.5) as appropriate.

MCCs will be informed of the proposed manuscript through e-mail. The note to the
MCCs will include the following statement:

"It is hoped that data from as many populations as possible can be included in the
analysis. However, if you want to exclude your data from the analysis, please inform the
PC and the Proposer within 28 days of receiving this message."

The PC will monitor the progress of the manuscript development. If no noticeable

progress is made within four months, he/she will inform the Proposer that the approval
for the proposal will be withdrawn and the entry in the Publication Plan will be deleted.
MCCs will be informed of the deletion through e-mail.
7.2.2 Rules for Preparation of Manuscripts

It is the responsibility of the Proposer to assemble a group of potential authors that

represent the necessary expertise and are prepared to devote the required effort for a
successful and timely completion of the proposed manuscript. The group of authors will
select a lead author. As much as possible, MCCs should be given an opportunity to
participate in the writing groups. Authors must be significant contributors to design of the
paper, data preparation, analysis and/or writing. They should be consulted by the lead
author at key stages in the manuscript's development and should have seen and approved
the final draft before it is submitted to the PC. In the eyes of journal editors they are
responsible and answerable for the accuracy of the data and conclusions contained in the
manuscript.

Such publications appear with the authorship statement as follows:

Name(s) of author(s), for the WHO MONICA Project (1),

Title:................................

Text:.................................

Whenever the publication rules of the target journal allow it, the following format should
be used for footnote (1):

(1) Annex: Sites and key personnel for the WHO MONICA Project.

The Annex includes:

• Sites, PIs and key personnel

o Only MCCs whose results appear in the paper will be listed.
o Names of key personnel should be restricted to those involved in the data
component(s) considered in the publication.
o Names should be those who would be named in locally published papers,
rather than being a complete list of everyone working in the project.
o Although the listing for each MCC is at the discretion of the PI, the lead
author and/or PC may wish to indicate to MCCs whether this is a major
report supporting a detailed annex or a minor one in which an annex of
reduced length might be more appropriate.
• MSC, MMC, MDC, MQCs, national coordinating centres (where applicable)
o Only MQCs involved in the data used for the publication will be listed.
• Consultants.

The list is drafted by the authors and corrected when necessary by the PIs at the same
time as they approve the manuscript.
If the publication rules of the target journal preclude the use of the full Annex, an
alternative format of footnote (1) is:

(1) For participants in the WHO MONICA Project see http://www.ktl.fi/monica/...

The hyperlink points to the list of MCCs and key personnel, MSC, MMC, MQS, and
consultants relevant to the manuscript. The exact URL should be requested from the KTL
contact person, and he should be provided with the list.

Collaborative papers should be cited as specified in Section 7.4 below.

Papers should include the following disclaimer:

"This publication was approved by the MONICA centres whose data were used.
However, the views expressed in this paper are those of the authors and may not reflect
the views of individual WHO MONICA investigators."

The publication has to include the following acknowledgement statement:

"The MONICA Centres were funded by regional and national governments, research
councils, charities, and other local sources. Central coordination was the responsibility
of the World Health Organization (WHO), assisted by the MONICA Data Centre (MDC)
at the National Public Health Institute (KTL) in Helsinki. Initial funding for the MDC
came from WHO, KTL, and NHLBI (USA) and later from two BIOMED grants from the
European Commission. The latter supported completion of the project, along with grants
from pharmaceutical companies and medical charities."

The acknowledgement paragraph may have added to it the names of internal MONICA
reviewers who have made what is judged to be substantial contributions in the reviewing
process. This can be agreed by the lead author and the PC prior to submission to a
journal.

7.2.3 Rules for Internal Manuscript Review

On completion, the manuscript is sent to the PC who sends it to three internal reviewers,
at least one of them should be a statistician. The reviewers of MONICA manuscripts will
be chosen among PIs and staff members as well as among scientists outside MCCs who
have proven specific knowledge in the field. The PC informs the MSC about the
manuscript and the reviewers. The MSC may appoint additional reviewers within 7 days.

The internal reviewers consider the appropriateness of the manuscript for publication and
report back to the PC within 3 weeks. Reviewers should comment on:

1. Clarity of objectives
2. Is target journal appropriate?
3. Are the data suitable for answering the objectives?
 4. Are the methods clearly described?
5. Are the methods adequate for answering the objectives?
6. Are results presented in clear fashion?
7. Is the use of Figures/Tables excessive or inadequate?
8. Are conclusions supported by results?
9. Does the discussion only restate the findings or are the results put into perspective
and inferences and implications drawn?
10. Are similar studies cited and discussed?
11. General comments on writing style.

On the basis of the internal reviews, the PC either returns the manuscript for revision to
the authors or sends it with the reviewers' reports to the MSC.

In special cases the MSC may decide on a review process different from the one
described above, if it can be expected to streamline the publication process.

The MSC considers whether the manuscript qualifies for distribution to the MCCs for
approval. If the manuscript is not acceptable, the MSC decides on how to proceed further.
If the MSC does not reply within 7 days, it is assumed that the proposal of the PC is
accepted.

The representative of KTL distributes the manuscript to the MCCs and relevant MQCs.

The MCCs (PIs) approve the manuscript for publication on the internal MONICA
website and/or send their comments to the PC or the person(s) specified in the covering
letter of the manuscript. This must be forthcoming within four weeks, and if no response
is obtained the publication will proceed.

Any minor modifications suggested by the MCCs should be made to the manuscript
before submission. After approval, the manuscript will be submitted for publication. If a
MCC refuses approval, the MSC will attempt to mediate.

7.2.4 Submission of the manuscript to the journal

The authors should agree among themselves as to who will be responsible for submitting
the paper to the agreed journal, for dealing with reviewers/editorial comments, and for
checking the proofs. The decision on responsibility should be communicated to the PC.

The letter to the editor on submission should include this section displayed prominently,
with the accompanying statement on a separate sheet:

Please Note: WHO MONICA Project manuscripts are prepared and submitted according
to collaborative project rules on authorship and citation. Journal editorial staff should be
aware of, and honour these rules when considering and preparing such manuscripts for
publication. Please see the accompanying statement.
Accompanying Statement.

WHO MONICA Project collaborative rules on authorship and citation

The WHO MONICA Project Principal Investigators, who own the MONICA data, have
developed over many years a policy on authorship and citation in the preparation and
publication of manuscripts that they ask journal editorial staff to honour. This policy is
designed to give appropriate recognition both to the collaborative enterprise and
constituent centres, and to those identified as primarily responsible for preparing a
particular manuscript and therefore answerable for its validity. These rules comply with
current international requirements on authorship for publication and citation. They have
been followed in our major publications by many prestigious journals (eg Lancet,
Circulation). Journals in the past that deviated had to make changes in proof, or to
publish corrections with apologies. It is for this reason that we bring these rules to your
attention.

Submission of this manuscript by the manuscript leader is authorized by the WHO

MONICA Project on the understanding that these rules will be honoured by the journal
to which it is submitted.

The publication rules cover three specific items

1. The authorship line, as in the accompanying manuscript:

"A Author, B Author, C Author,(etc), for the WHO MONICA Project."
2. Citation of authorship of previous MONICA publications, as in the accompanying
manuscript:
"Author A, Author B, Author C, (etc), for the WHO MONICA Project."
3. Publication of a list of MONICA sites and key personnel as an annex to the paper.

Format and print size are obviously at the discretion of the journal. Items 1 and 2 are
essential to all collaborative papers, and 3 to major publications. 3 is subject to
compromise for short papers or families of papers when reference to a related issue or a
web-based annex may be agreed for MONICA. If a journal has a specific problem with
any aspect of MONICA publication policy the manuscript leader will need to involve the
MONICA Publications Coordinator and the Steering Committee. We trust that most
journals agree that the above rules are reasonable and that they enhance rather than
detract from the publication of our manuscripts. These rules have been admired and
copied by colleagues involved in other similar large collaborative studies.

If a journal requires assignment of royalties, KTL should usually be specified. KTL will
ensure that such royalties will be applied to coordination of MONICA publications and
data activities without charging overhead. In such a case, the representative of KTL and
the PC should be contacted for further instructions.

Anything other than minor corrections arising from the editorial-review process should
be discussed with other authors and with the PC. Whoever is responsible for the proofs
must inform the PC immediately on receipt of the proofs if there is any problem with the
journal carrying out MONICA publication policy on authorship and citations, so that they
can agree how to take the matter up with the journal editor.

If the manuscript has been accepted for publication its reference will be published on the
MONICA website http://www.ktl.fi/monica by the representative of KTL.

7.2.5 Rules for Oral/Poster Presentations

Abstracts intended for oral/poster presentation and based on MONICA collaborative data
will be sent to the PC who will distribute them to the MSC. Abstracts will be approved
solely by the MSC, the only exception being when specific MCCs are mentioned in the
abstract, in which case explicit permission will be sought from the MCCs concerned by
the presenter and evidence of this furnished to the PC. Failure to reply within 4 weeks by
the MCCs concerned will be taken as consent. The MSC makes its decision within two
weeks after receiving the abstract and the PC informs the presenter. Presenters will
inform the PC if an abstract has been accepted for presentation and the KTL
representative will distribute the abstract to all MCCs and MQCs prior to presentation.

7.2.6 Rules for Invited Presentations

In addition to the above, no person invited to speak "on behalf of the WHO MONICA
Project" should do so without prior approval of the MSC. If an abstract is required, the
person invited should follow the rules for oral presentations. Otherwise, the MSC should
be informed about the source of the invitation. If the MSC gives approval, the PC will
inform the person invited who should then proceed with the presentation but must send a
summary to the KTL representative for distribution to the MCCs and MQCs.

7.2.7 Additional rule for stroke studies

All the above rules apply, except that only PIs from MCCs participating in stroke
registration have to give their consent for publications involving stroke.

7.3 Rules for data release

7.3.1 Ownership of collaborative data

see Amendment 1: Management of the MONICA Project, section 3

7.3.2 Data Release to MCCs

The MCCs have been provided with a MONICA Archive CD-ROM of the collaborative
data (Version: 29 August 2003).

7.3.3 Data Release to Individuals/Groups outside the WHO MONICA Project

Terms and modality to be decided by MSC.

7.4 Citation of Collaborative Publications

In order to assure accurate listing of MONICA publications in citation indices

collaborative MONICA publications must be cited in the following format in both local
and collaborative MONICA publications. This format should be applied both to recent
and to older papers published using earlier MONICA authorship formats. All in
MONICA should encourage colleagues who quote MONICA papers to cite them in the
same way when they are asked to comment on or to referee papers.

Examples of citations according to MONICA publication rules:

1. Vancouver style (may vary with journal):

Stewart AW, Kuulasmaa K, Beaglehole R, for the WHO MONICA Project.

Ecological analysis of the association between mortality and major risk factors of
cardiovascular disease. Int J Epidemiol 1994;23:505-16.

2. Harvard style (may vary with journal):

Stewart AW, Kuulasmaa K, Beaglehole R, for the WHO MONICA Project (1994).
Ecological analysis of the association between mortality and major risk factors of
cardiovascular disease. Int J Epidemiol, 23, 505-16.

If the editor tries to change this format in the proofs, the author should change it back and
inform the journal that this is the WHO MONICA Project format.

7.5 Publication Plan

The MONICA Publication Plan outlines all MONICA collaborative Agreed Publications
and reports arising from checking, quality assessment, and analysis of the collaborative
MONICA data. For each of the component data sets it describes the anticipated
progression from compilation of data books to generation of quality assessment reports
and the drafting of papers for publication in scientific journals. For each subject, there is,
in general, a series of reports relating to baseline, mid-term and final results.

For each Agreed Publication and report, the Publication Plan identifies the Proposer,
other suggested authors, target journal or a mention that it will be an internal report of the
project, and the current status.

The representative of KTL on the MSC, in consultation with the PC, maintains the
Publication Plan. The Plan is available in the internal MONICA site in the World Wide
Web (http://www.ktl.fi/monica/internal/publ/pplan/).

MONICA Manual, Part III: Population Survey

 Section 1: Population Survey Data
Component
December 1997

This section provides the equivalent of a manual of operations for the collection and
processing of data for this MONICA data component.

Contents
• Introduction
• 1.Sample selection procedures (including sample size requirements)
o 1.1 Sample size
o 1.2 Sample selection
o 1.3 Frequency of screening
• 2.Survey serial numbers
o 2.1 Survey serial number inventory
• 3.Eligibility for the sample, respondents and non-respondents
• 4.Procedures for respondents
o 4.1 Smoking history
o 4.2 Blood pressure and arm circumference measurement
o 4.3 Serum cholesterol
o 4.4 Serum thiocyanate
o 4.5 Expired air carbon monoxide measurement
o 4.6 Height, weight, waist and hip measurement
o 4.7 Core data transfer form and instructions
o 4.8 Quality assurance procedures
o 4.9 Error correction
• 5.Procedures for non-respondents
• References

Forms
• Smoking questionnaire
• Survey serial number inventory format
o Current version (Version 3)
o Former version (Version 2) used for data transfer to the MONICA Data
Centre
• Survey core data transfer format
 o Current version (Version 7)
o Former versions (Version 3 and Version 6) used for transfer of data to the
MONICA Data Centre
• Non-respondent data transfer format
o Current version (Version 3)
o Former version (Version 2) used for data transfer to the MONICA Data
Centre

© Copyright World Health Organization (WHO) 1998. All rights reserved.

• Copyright notice
• Manual acknowledgements
• Document identification:
o URL:http://www.ktl.fi/publications/monica/manual/part3/iii-1.htm
o URN:NBN:fi-fe19981151

Queries and comments on this section to be addressed to:

Professor Alun Evans

Division of Epidemiology
The Queen's University of Belfast
Mulhouse Building
Grosvenor Road
Belfast, Northern Ireland BT12 6BJ
Fax + 44 1232 236 298
Email: a.evans@qub.ac.uk

Earlier versions
• Proposal for the multinational monitoring of trends and determinants in
cardiovascular disease and protocol (MONICA Project). WHO/MNC/82.1 Rev.1;
May 1983.
• Multinational monitoring of trends and determinants in cardiovascular diseases -
MONICA Project. Manual of operations. WHO/MNC/82.2, Draft MOO;
November 1983.
• Description of data collection procedures for the MONICA Project. MONICA
Memo 49; June 1985.
• WHO MONICA Project. MONICA Manual. CVD/MNC/Version 1.1, December
1986; Sect. 3.
• WHO MONICA Project. MONICA Manual. Geneva: World Health Organization,
Cardiovascular Diseases Unit; November 1990; Part III, Sect. 1.
• Revision of MONICA Manual, Part III, Sect. 1, March 1992. MONICA Memo
214; May 1992.
Changes made after March 1992 revision

• Misprints corrected
• Instructions for blood pressure measurement (Subsection 4.2) rewritten. The old
instructions were difficult to follow. The current instructions correspond to the
procedures taught in MONICA training seminars for risk factor measurement.
• An inconsistency between Subsections 4.6 and 4.8 in checking of scales used for
measurement of weight has been corrected.

Introduction
The population survey data, collected on separate random samples, on at least two
different occasions during the ten-year period of the MONICA Project, will provide
estimates of the levels and changes of known cardiovascular disease risk factors. The
core study is concerned with the three major risk factors: blood cholesterol, blood
pressure, and smoking habits, as well as height and weight.

1.Sample selection procedures

(INCLUDING SAMPLE SIZE REQUIREMENTS)

1.1 Sample size

Statistical calculations indicate that 200 subjects are needed in each age and sex group to
show the expected changes of risk factor levels, in most situations.

The total sample size should be 1200 or 1600, depending on whether or not the youngest
age group (optional) is included or not.

Age Males Females

25-34 200 200
35-44 200 200
45-54 200 200
55-64 200 200
Total 800 (or 600) 800 (or 600)
Grand total: 1600 (or 1200)

Such estimates assume 100% participation which is usually unrealistic. Therefore, each
centre must estimate the expected participation on the basis of previous experience and/or
of a pilot study and enlarge the sample size accordingly. It must be stated that every
effort should be expended on achieving as high a response rate as possible and therefore
it is preferable to select fewer subjects and see as many of them as possible, rather than
drawing a larger sample and screening a smaller proportion of subjects. The following
points are also important:

a. in general, within the specified age groups, a lower participation rate may be
expected in younger people, and in men as compared with women;
b. the self selection resulting from low participation rates may introduce biases in
the estimation of means and rates, and their trends.

1.2 Sample selection

For sample selection each of the following points should be taken into account:

1. Samples for the different surveys must be independent. This means that the
sample for the second or the third survey should be selected irrespective of
whether or not individuals were included in previous surveys.
2. Within an age/sex group, simple random sampling, or systematic random
sampling if the ordering of the sampling frame can be regarded as random, is
preferred. In practice, simple random sampling may pose serious organizational
problems. Multistage sampling (where first a set of clusters is selected and then
individuals are selected within the clusters) or some other complex sampling is
often easier for logistic or organizational purposes. Such a sampling technique can
be used, but the number of individuals selected should be increased. When
multistage sampling or some other complicated sampling technique is used, the
final method must be reviewed by the statistician at the MONICA Data Centre
(MDC).
3. The sampling frame and the sample selection procedure used, corresponding to
point 2 above, must be documented in detail. The document must be included in
the local manual of operations and a copy must be sent to the MDC.
4. Great care must be taken when planning, not to use a sampling scheme for the 2nd
and the 3rd survey which differs from that for the previous surveys. Such a
situation should be avoided, but if it is unavoidable, the planned change should be
discussed with the statistician of the MDC.

1.3 Frequency of screening

Since a ten-year collection of mortality and morbidity data is required, it is recommended

that screening occurs at the beginning (year 1), at the middle (year 5) and at the end (year
10). However, if the entry screening cannot take place at year 1 because the centre is
unable to start screening and monitoring at the same time, the screening can be carried
out at years 2 and 3; then at years 5 and 6; and then at years 8 and 9. The middle survey is
optional.

Two years are indicated each time as the screening of 1600 or more people may involve
field work lasting longer than a 12-month period. In any case the subsequent screening
should cover the same seasons of the year as they did previously.
2.Survey serial numbers
Every individual selected in a sample must be issued a Survey Serial Number by the
MCC. The serial number consists of six digits. Each serial number must be unique within
each MONICA Reporting Unit and within each of the two or three surveys. Different
MONICA Reporting Units may use the same serial numbers.

Log books of serial number histories: The MCC must keep a log book of the history of
every serial number issued. The items of the SURVEY SERIAL NUMBER
INVENTORY FORM should be included in the log book. The log book can be part of
the checklist.

Correctness of the serial number: The serial number is one of the key items of a survey
record. The Form Identification, MONICA Collaborating Centre Code, MONICA
Reporting Unit Code, Number of the Population Survey and Serial Number are all
necessary in order to identify an individual uniquely. Each MCC should have some kind
of security system to help ensure that the serial number is error free. One possibility is to
have the last digit of the serial number as a check digit which is used to control the
correctness of the other digits, at least until the individual record has been computerized.

A check digit needs to be calculated when the serial number is issued. It is useful only if
this is done correctly. This can be guaranteed by letting the computer generate the serial
numbers with the check digits and print the numbers on stickers or labels which are then
fixed on log books and data collection forms.

2.1 Survey serial number inventory

As a final check that no data have been lost during the various stages of data flow
between the sample selection and inclusion of data in the master file of the MDC, the
MCC should submit the serial number inventory data to the MDC. The data should be
submitted for each individual selected in the original sample in the Survey Serial Number
Inventory Format.

3. Eligibility for the sample, respondents and non-

respondents
For data collection purposes, those selected for the original sample will fit into one of
three categories: ineligibles, respondents and non-respondents. Every individual selected
for the original sample belongs to only one of these three categories.

Ineligibles

In principle, the sample should be selected from the 25-64 (25-34 optional) year old
residents of the MONICA Reporting Units. In practice, such sample selection is not
usually possible because the sampling frame is not fully updated at the time of the sample
selection. The individuals selected in the original sample who died or moved out of the
reporting unit area before the survey examination are called ineligibles. No survey
examination should be done on the ineligibles, and no survey respondent or non-
respondent data should be collected for them.

Note, however, that if a person selected for the age group 25-64 (25-34 optional) of the
original sample does not meet the age criteria on the day of examination because it was
not possible to assess the exact date of survey examination at the time when the sample
was selected, the person should be regarded as eligible for the sample.

The MCC should document the reason for ineligibility for every ineligible.

Respondents and non-respondents

It is important to try to get the full survey core data from as many persons selected and
eligible for the sample as possible. Each MCC should develop an algorithm to decide for
each subject when sufficient attempts have been made. After the result of the attempts are
known, the persons should be classified as respondents and non-respondents according to
the following definition:

A non-respondent is a person selected and eligible in the original sample who could not
be found or contacted, or a person who did not provide questionnaire data at the clinic or
during a home visit.

Those eligible for the sample who are not non-respondents are classified as respondents.

The data requirements will be considered separately for respondents and non-
respondents.

4.Procedures for respondents

4.1 Smoking history

The smoking questionnaire appended to this section is part of the general questionnaire
and was produced in its near final form by the October 1981 Geneva Working Group.

It represents a compromise among different proposals and is derived from the WHO
Cardiovascular Survey Methods questionnaire [1]. It can be self administered if it is sent
to the home of the invited persons together with the invitation to the examination; or it
can be administered by a technician or nurse at the screening site.

The same procedure, however, should be applied throughout the study in the same centre.

In the case of self-administered procedures, the questionnaire should be checked by a

technician or a nurse for completeness and consistency of answers.
In the case of direct administration, some general rules should be followed:

• use the same wording as written in the questionnaire;

• ask the questions a second time and in the same way if on the first occasion the
subject does not answer or appears not to have understood;
• ask the questions a third time using different wording but having the same
meaning if the subject again does not answer or understand;
• do not induce certain answers;
• ask all questions and record all answers, unless otherwise stated.

Interviewers should be trained and their performance evaluated and tested for precision
and accuracy.

The smoking questionnaire should be validated by expired air carbon monoxide, serum
cotinine or serum thiocyanate measurement on 100% of subjects. While serum
thiocyanate estimation remains an option it is no longer part of the core study and the
quality control procedures have been withdrawn. Carbon monoxide measurement is
cheap, gives an instant readout, has a comparatively short half-life, shows diurnal
variation in smokers and is confounded to some extent by environment or an
occupational exposure to carbon monoxide [2]. Cotinine is very specific, sensitive but
expensive [3]. Measurement only in sub-samples should be avoided if possible, but the
minimum requirement in such an event is 10% of subjects, irrespective of their smoking
history. Instructions for carbon monoxide measurement are given in subsection 4.5.
Standardization of serum thiocyanate measurements is described in Part III, Section 3.

4.2 Blood pressure and arm circumference measurement

It is important that measurement of blood pressure BP) is as precise as possible. This is

essential for valid comparisons to be drawn. Therefore a strict routine for BP
measurement should be adhered to. The measurement should be planned to precede any
painful or anxiety producing procedures such as blood taking or electrocardiography;
ideally it should follow the administration or checking of the questionnaire.

1. The subject should be instructed to avoid the following activities for at least one
hour before the BP measurement: strenuous exercise, eating, drinking of anything
other than water, smoking, drugs that affect the blood pressure; a full bladder
affects the blood pressure and patients should be advised accordingly. Most
MONICA surveys are done with the subject non-fasting; taking blood pressure in
patients who have fasted for a long time for blood lipid estimations will result in
poor comparability with other survey populations.
2. The participant should have removed outer garments, jackets, etc. The sleeve of
shirts, blouses, etc. should be rolled up so that the upper right arm is bare for the
blood pressure cuff. The garment should not be constrictive and the blood
pressure cuff should not be over the garment. Garments must be removed if
obstructing and a short-sleeved jacket provided.
3. The examination should take place in a quiet room with comfortable temperature.
The room temperature should be recorded routinely.
4. The recommended instrument is the random-zero sphygmomanometer, although a
standard mercury sphygmomanometer is admissible. In any case Centres should
adhere to the instrument used in earlier surveys. It is now generally accepted that
the key to good blood pressure measurement in MONICA is in training,
certification of the measurers, constant monitoring of performance and feedback.
5. The cuff size (bladder-size) should be 12-13 cm wide and sufficiently long
(recommended length: width-ratio >2:1) to surround at least two thirds of the
upper arm. The centre of the inflatable part of the cuff (bladder) must be
positioned over the brachial artery of the inner side of the upper arm. The cuff
should neither be applied too loosely or too tightly in order to avoid over or under
estimation of the pressure required to obliterate the artery.

NOTE: The MCC should not change the size(s) of a cuff used for blood pressure
measurement between the surveys. If several cuff sizes are used, the rule for using
each should also be kept unchanged and the information recorded.

6. The BP should be measured after resting with no change of position for at least 5
minutes, in a sitting position and using the right arm - unless there is a deformity.
When seated the subject's arm should be allowed to rest on a desk so that the
antecubital fossa is level with the heart. To achieve this either the chair should be
adjusted, or the arm may be raised or lowered on a comfortable support. The
subject must always be in an upright position and feel comfortable.
7. Measure the upper arm circumference with a tape, and record the value, rounded
to the nearest centimetre. The upper arm circumference is measured with the arm
in the normal blood pressure measurement position, i.e. forearm resting on the
table and the antecubital fossa at the level of the heart. Read the measurement
tape at the greatest circumference of the upper arm with the arm relaxed.
8. It is recommended that the bell of the stethoscope should be used, even if the
diaphragm was used in earlier surveys. The lower edge of the cuff should be 2-3
cm. above the cubital fossa, to allow sufficient room for the bell of the
stethoscope. The top edge of the cuff should not be restricted by clothing.
9. The observer should be in a comfortable position in relation to the examination
table. The sphygmomanometer's mercury column should be in a perfectly upright
position, the centre of it at the eye level of the examiner. The mercury column
should face the observer and should not be visible to the subject.

The cuff should now be connected to the sphygmomanometer.

10. A. Blood Pressure Measurements with the Random Zero Sphygmomanometer

i. The subject should rest for 5 minutes in a sitting position - during which
the whole process of BP measurement should be explained to him/her. If
the subject is spoken to during the period of resting before the
measurement, the staff involved should speak quietly and calmly. The
 subject should not be involved in animated conversation, joking or teasing
as this will give a high blood pressure reading.
ii. Locate the brachial pulse. The bell of the stethoscope should be placed
immediately below the cuff at the point of maximal pulsation. If it is not
possible to feel the brachial pulse, the bell of the stethoscope should be
placed over the area of the upper arm immediately inside the biceps
muscle tendon. The bell should not touch the cuff, rubber or clothing.
iii. Ensure that the mercury reservoir valve is in the operating position, i.e.
turned fully to the right and extending past the right side of the case
(applies only to older devices). Turn the bellows cock on the face of the
device to the position marked OPEN.
iv. Turn the thumb wheel at the right side of the device, by gently stroking it
twice in the same direction with the thumb of the right hand. If the wheel
is not free to spin in either direction, the bellows are not completely
deflated and the bellows check position should be rechecked.
v. Before each measurement, the observer has to make sure that the mercury
column is precisely at the RZ baseline level.
vi. Feel the subject's radial pulse with the fingers of your left hand.
vii. Close the valve of the inflation bulb and the valve at the bottom of the
device's case. Looking at the manometer with the centre of the scale at eye
level, and the column perfectly upright, inflate the cuff rapidly to a
pressure equal to the peak inflation level, that is, 30 mmHg above the level
where the radial pulse disappears. Hold the pressure at this level for five
seconds (count to five slowly), and then turn the bellows cock to the
position marked CLOSE.
viii. By carefully controlling the valve at the bottom of the device's case, with
the bell of the stethoscope over the brachial artery, deflate the cuff at 2
mm/second. Continue to reduce pressure steadily at this rate until the
occurrence of the systolic level and the phase 5 diastolic level, i.e. the
disappearance of Korotkoff sounds. Continue to deflate until the mercury
is 4 to 6 mm below the diastolic level.
ix. Then open the inflation bulb valve fully, allowing the mercury to fall to its
zero level for this reading.
x. Record the systolic and 5th phase diastolic readings, uncorrected.
xi. Read the zero level for this reading and record it on the form in the spaces
provided beneath the uncorrected systolic and 5th phase diastolic readings.
Subtract the zero level to obtain the correct readings and record them on
the form.
xii. Blood pressure values should be recorded to the nearest 2 mmHg (reading
from the top of the rounded meniscus). If the top of the meniscus falls half
way between two markings, choose the marking immediately above. The
subject should not be informed about the blood pressure value at this
point.
xiii. Wait for at least 30 seconds to allow the distribution of the blood in the
forearm to return to normal. Furthermore, the arm may be raised for about
5 seconds to reduce venous congestion resulting from reactive
 hyperaemia. Then repeat the measurement in exactly the same way that
the first one was carried out. This includes resetting of the thumb wheel on
the right side of the manometer case. Whenever experiencing difficulties
in hearing the sounds, the cuff must be completely deflated and at least 30
seconds must elapse before making the next measurement.
xiv. Record the value of both measurements.

10. B. Blood Pressure Measurement with the Standard Mercury Sphygmomanometer

i. The subject should rest for 5 minutes in a sitting position - during which
the whole process of BP measurement should be explained to him/her. If
the subject is spoken to during the period of resting before the
measurement, the staff involved should speak quietly and calmly. The
subject should not be involved in animated conversation, joking or teasing
as this will give a high blood pressure reading.
ii. Locate the brachial pulse. The bell of the stethoscope should be placed
immediately below the cuff at the point of maximal pulsation. If it is not
possible to feel the brachial pulse, the bell of the stethoscope should be
placed over the area of the upper arm immediately inside the biceps
muscle tendon. The bell should not touch the cuff, rubber or clothing.
iii. Feel the subject's radial pulse. Inflate the cuff rapidly until the radial pulse
disappears. Inflate the cuff by a further 30 mmHg . This is called the 'peak
inflation level' and it is the level to which the pressure should be raised for
each of the ensuing blood pressure measurements.
iv. Wait for at least 30 seconds to allow the distribution of the blood in the
forearm to return to normal. Furthermore, the arm may be raised for about
5 seconds to reduce venous congestion resulting from reactive
hyperaemia.
v. Looking at the manometer with the centre of the scale at eye level, and the
column perfectly upright, inflate the cuff rapidly to a pressure equal to the
peak inflation level. Then let the column of mercury fall at a rate of 2
mmHg per second.
vi. Continue to reduce pressure steadily at this rate until the occurrence of the
systolic level and the phase 5 diastolic level, i.e. the disappearance of
Korotkoff sounds. Then deflate the cuff rapidly by fully opening the valve
of the inflation bulb.
vii. Blood pressure values should be recorded to the nearest 2 mmHg (reading
from the top of the rounded meniscus). If the top of the meniscus falls half
way between two markings, choose the marking immediately above. The
subject should not be informed about the blood pressure value at this
point.
viii. Wait for at least 30 seconds to allow redistribution of blood in the forearm.
In addition, the arm may be raised for about five seconds to further reduce
venous congestion in the forearm resulting from reactive hyperaemia.
Then repeat the measurement in exactly the same way that the first one
was carried out. Whenever experiencing difficulties in hearing the sounds,
 the cuff must be completely deflated and at least 30 seconds must elapse
before making the next measurement.
ix. Record the value of both measurements.

NOTE: It may well be that the European Union will ban the use of Mercury
sphygmomanometers of all types for health reasons. This will have implications for
cardiovascular epidemiology. Therefore, the use of reliable automatic devices which are
validated against the reference method of sphygmomanometry may become necessary.

4.3 Serum cholesterol

The procedures for serum cholesterol measurement are given in Part III, Section 2:
Standardization of Lipid Measurements.

4.4 Serum thiocyanate (Optional)

The procedures for thiocyanate measurements are given in Part III, Section 3.

4.5 Expired air carbon monoxide measurement (Optional)

Carbon monoxide (CO) is a gas produced by incomplete combustion and is commonly

present in the environment as a result of smoking, car exhaust, gas appliances, etc.

Since everybody is exposed to trace amounts of CO as well as producing small amounts

by metabolism, it is normal to have a concentration of CO in expired air in the range of 2-
8 parts per million (ppm). Individuals who have been exposed to relatively high doses of
CO from inhaling cigarette smoke typically have levels in the range of 9-40 ppm.

A portable carbon monoxide monitor should be used [4]. It is a cheap, quick- to-use
instrument which runs on batteries. The following instructions are relevant for one such
instrument: the Bedfont EC50.

1. The monitor is switched on and the observer ensures that the reading is at zero.
2. A disposable mouthpiece is attached to the monitor.
3. The subject is asked to hold the monitor and an explanation of the procedure is
given:
a. Breathe out fully
b. Breathe in deeply
c. Hold breath for 15 seconds
d. Blow out fully into the mouthpiece.
4. Carry out the procedure.
5. Record the reading.
6. Repeat the procedure to obtain a second reading.
7. Record the average of the two readings.
8. The disposable mouthpiece is removed and discarded.
4.6 Height, weight, waist and hip measurement

HEIGHT - Procedure:

1. Height is measured in conjunction with the weight measurement. It may precede

or follow this procedure.
2. The height rule must be taped vertically to a hard flat surface, with no moulding
(skirting board), with the base at floor level. A carpenter's level should be used to
ensure vertical placement of the rule.

NOTE: The correct position of the height rule should be checked daily and
corrected as necessary. If the position of the height rule is found to be inaccurate
by more than 1 cm, the measurements taken since the rule was last checked
should not be used or reported to the MDC.

3. The floor surface must be hard (tile, cement, etc.) and must not be carpeted or be
covered with other soft materials. If only a carpeted surface is available, a wooden
platform should be laid down to serve as a floor.
4. The participant is asked to remove his/her shoes and heavy outer garments.
5. To measure height, the participant should stand with his/her back to the height
rule. The back of the head, back, buttocks, calves and heels should be touching
the upright, feet together. The top of the external auditory meatus (ear canal)
should be level with the inferior margin of the bony orbit (cheek bone). The
position is aided by asking participant to hold the head in a position where he/she
can look straight at a spot, head high, on the opposite wall.
6. Place the triangle on the height rule and slide down to the head so that the hair (if
present) is pressed flat.
7. Record information on survey form to the nearest centimetre. For example, if
187.4, record as 187; if 187.5, record as 188; if 187.6, record as 188.
8. Self-reported heights are not acceptable in mobile participants and should not be
reported (mark as refusal). Only persons who are immobile (e.g. amputees) may
self-report their heights. Be sure to note this on the form.
9. To measure extreme heights, a short rule is used in addition. It is placed at the top
of the long rule and the extra height is added.

WEIGHT - Procedure

The use of balance scales is recommended. If the MCC uses digital scales, testing with
standard weights is of particular importance.

1. The floor surface on which the scale rests must be hard and should not be
carpeted or covered with other soft material.
2. The scale should be balanced with both weights at zero and the balance bar
aligned.
 NOTE: Check the scales using standard weights at least monthly and whenever
the scales are installed at a new location. If the error is more than 1 kg the
measurements taken since the scales were last checked should not be used or
reported to the MDC. Check for the zero level every day before starting
measurement and immediately afterwards. If there is an error of more than 1 kg
the measurements taken since the scales were last checked should not be used or
reported to the MDC.

3. The participant should have removed his/her shoes and heavy outer garments
(jacket, coat, etc.).
4. The participant should stand in the centre of the platform as standing off-centre
may affect measurement.
5. The weights are moved until the beam balances (the arrows are aligned).
6. The weight is read and recorded on the form. Record weights to the nearest 200 g.
7. Self-reported weights are not acceptable in mobile persons. Refusals to be
weighed should be recorded as refusals. Only participants who are immobile (e.g.
amputees) may self-report their weights. Be sure to note this on the form.
Participants must not read the scales themselves.

WAIST CIRCUMFERENCE - Procedures

1. Record the measurement of the circumference at a level midway between the

lower rib margin and iliac crest in cms to the nearest 0.0 or 0.5 cm. Example: If
the exact measurement is 87.7 cm, code the item 0875.
2. The circumference should preferably be measured on subjects while they are
semi-clothed, i.e. waist uncovered with the subjects wearing underclothes only. If
it is not possible to follow this procedure in the MCC, the alternative is to
measure the circumference on subjects without heavy outer garments with all
tight clothing, including the belt, loosened and with the pockets emptied.
3. Participants should stand with their feet fairly close together (about 12- 15 cm)
with their weight equally distributed on each leg. Participants should be asked to
breathe normally and at the time of the reading of the measurement asked to
breath out gently. This will prevent subjects from contracting their muscles or
from holding their breath.
4. A plastic metric tape should be used. The tape should be held firmly and its
horizontal position should be ensured. It is recommended that the observer sits
beside the participant while the readings are taken. The tape should be loose
enough to allow the recorder to place one finger between the tape and the
subject's body. The importance of the tightness of the tape should be emphasized
in training.
5. The length of tape should be checked before starting the survey and the length
should be rechecked against a standard measure at least once a month and
replaced as appropriate.
6. The two sides of the tape should be differently coloured or have a scale only on
one side. If the tape is uniformly coloured, with readings on both sides, one side
should be blanked out.
 7. MCCs which have collected these data in the past, but using a different technique,
should not change their technique but should contact the MDC.

HIP CIRCUMFERENCE - Procedures

1. Record measurement of maximum circumference over the buttocks in cms to the

nearest 0.0 or 0.5 cm. Example: if the exact measurement is 93.2 cm, code the
item 0930.
2. The same general comments made for waist circumference measurement apply to
the measurement of hip circumference.
3. MCCs which have collected hip circumferences in the past, but using a different
technique, should not change their technique but should contact the MDC.

4.7 Core data transfer format and instructions

The survey core data to be sent to the MDC are specified in the Core Data Transfer
Format - Survey Data, which is appended to this section.

4.8 Quality assurance procedures

Training and certification

It is clear that the survey procedures used at the two or three different points in time
within a centre must be comparable so that the trends identified reflect actual changes in
measurements between the samples and not changes in the data collection or
measurement procedures. The general principles described in Cardiovascular Survey
Methods 1982 [1] should be followed.

The reproducibility of the survey methods can be tested in pilot studies and at intervals
throughout the main study. Every effort should be made to maximize the participation of
individuals selected for the survey.

It is necessary to pay attention to the sequence of various measurements in the surveys.

For instance, blood pressure should always be measured before venipuncture.
Furthermore, the sequence as well as the measurement techniques must be identical in
each survey.

Smoking

The standard set of questions should be used and the results of the questionnaire should
be validated by serum thiocyanate, serum cotinine or expired carbon monoxide
measurements. The survey personnel should be trained to check the main questions of the
self-administered questionnaires concerning smoking habits which are needed for the
core study. This checking is aimed at reducing the frequency of missing or inadequate
information, and also at detecting incorrect self- reporting by simply asking the main
questions again.
Blood pressure

The procedures should be described in the local manuals of the MCCs. This description
should include a list of equipment, including cuff sizes. MCCs should send this list to the
MDC together with their survey data.

Training is the most vital part of the quality assurance for blood pressure measurement.

The training course should be organized before each survey and it should deal in detail
with all the elements involved in BP measurement (see subsection 4.2).

1. the principles of Korotkoff sound and their sequence

2. the equipment: (a) stethoscope (with bell); (b) sphygmomanometer (type) and its
maintenance
3. observer: (a) hearing test, (b) digit preference
4. the technique of measurement
5. sources of error: systematic; random

Practical training:

1. Tape recordings:

Among the existing training programmes, the method developed by RJ Prineas is

recommended (the timex can be replaced by 3 stop-watches) [5].

2. Training on subjects:

Measurement with double (Y-tube connected) stethoscopes with each observer

operating the bulb in turn. Comparison should be made between observers
(interobserver variation between supervisor and observer -systematic error - and
between repeated measurements - intraobserver variation). The measurements
should be recorded on training sheets and kept for further comparison.

The method of measuring blood pressure can be learned quickly and it is far from
being a "doctor's job" only. Paramedical personnel can perform it sometimes more
precisely, as they are free from preconceptions. But whoever takes up the task of
measuring BP must be trained and tested beforehand.

Within one MCC, in different MONICA populations and different surveys, if

more than one observer measures blood pressure, they should be as alike as
possible. For example, all of them should be paramedical technicians. (Consider
the likelihood that subjects react differently to nurses than to doctors.)

The aim of a training and retraining programme is to develop maximum precision

and standard recording. This is necessary to avoid both random and systematic
error. Random error will occur if an observer occasionally neglects the
 controllable factors during BP measurement. Systematic error will arise from
actions which consistently result in a higher or lower BP reading. Examples:
severe hearing loss for low frequency sounds, digit preference, prejudice, i.e.
"anticipating a BP", consistently using another technique (left arm, lying position,
etc.). Therefore, constant attention should be paid to BP measurement techniques
and training. During the practical training, the means of measurement are used for
comparison between observers and the supervisor.

If the mean value or range of an observer's measurements differs markedly from

those of other observers, further training is necessary. Retraining and retesting of
observers should be carried out at regular intervals in order to maintain the
validity of BP measurement.

Any observer continually measuring blood pressure should be retested at 6

monthly intervals. Observers with a mean value of measurements differing from
other observers should be retested earlier. Observers with consistent systematic
errors should not be certified for BP measurement. Each MCC should nominate
an investigator to certify and recertify the blood pressure observers. Copies of the
certificates should be kept available.

During the surveys the investigators should continuously track the inter and
intraobserver variation and the last digit preference in order to detect possible
problems.

Serum total and HDL-cholesterol

See Part III, Section 2: Standardization of Lipid Measurements. If plasma cholesterol is

measured, the MDC should be notified.

Body weight

The procedures for measuring body weight must be described in detail in the local
manuals of the MCCs. Only accurate balance scales should be used. All scales should be
checked using standard weights at least monthly and whenever the scales are installed at
a new location. The type of scales used in the surveys in each MCC must be described in
the local manual.

Also, the weight observers require training, as some observers tend towards a last digit
preference in recording body weights; this should be taken into consideration in training.

Local data checking

The MCC should have procedures to ensure that the data collection process is complete
and accurate. This can be accomplished by following the procedures listed below.

Processing check list

Keep a check-list to follow the status of data collection for every subject selected in the
sample. The contents of the check-list may vary between the MCCs, but should record
these items as a minimum:

• Survey Serial Number

• name and address
• eligibility for the survey
• that interview data were received
• that medical examination was performed
• that blood samples were received
• that laboratory results were received
• that data were submitted for keying
• that shipment was made to the MDC.

The check-list may be used to generate the Survey Serial Number Inventory Form.

Keying of data forms

Before submitting the forms for keying

• check that all parts of the form (interview, laboratory results, medical examination
results etc.) are together.
• check the forms visually for completeness and logical flow.

It is preferable to have all data verified or keyed twice to keep keying errors to a
minimum. The method of verification will depend on the MCC's data entry system.
Punched cards can be verified and most data entry programs have the ability to double-
enter the data. As an alternative, two data files can be independently created and
compared.

Check serial numbers

After the data have been keyed and verified, the serial numbers should be checked again
by comparing the keyed value with the original form. The use of a check digit is strongly
recommended since a computerized check of the serial number can then be performed.

Other checks

Before the data are appended to the local master file, checks and other quality control
routines similar to those described in Part V, Section 1.3.3 should be performed. Checks
for duplicate records, missing values, etc., are particularly important at this stage.

When verifying the accuracy of the data, all suspect data items should be checked against
the original documents on which data were collected. Any erroneous values should be
corrected. On the other hand, suspect values which cannot be shown to be erroneous
should not be changed. Instead, such values, even though very unusual, should be
submitted to the MDC.

Store the forms for future reference.

4.9 Error correction

The procedure for correcting errors in data which have already been submitted to the
MDC are described in Part V, Section 1.3.3.

5. Procedures for non-respondents

Even though it is not possible to get the complete data required for the core study for the
non-respondents, the MCC should try to collect information about their age, sex, marital
status, education, smoking history and blood pressure. The objective is to estimate the
selection bias which non-response inflicts on the core study. Age and sex are often
known at the time of the sample selection. For other data, a telephone interview or a
postal questionnaire can be tried. It is recommended that all non-respondents are asked to
provide the information. However, it is acceptable that only a random sample of non-
respondents are investigated in full. The reason for non-response should be recorded in
all cases.

The survey non-respondent data (Form 8: Data transfer format, survey non-respondent
data) should be submitted to the MONICA Data Centre for every non-respondent,
regardless of how much information was received from the non-respondent. In most
cases the MCC should at least elicit the age group, sex and reason for non- response.

References
1. Rose GA, Blackburn H, Gillum RF, Prineas RJ. Cardiovascular survey methods
(Second Edition). World Health Organization, Monograph Series No. 56, 1982
2. Jarvis MJ, Tunstall Pedoe H, Feyerabend C, Vesey C, Saloojee Y. Comparison of
tests used to distinguish smokers from non-smokers. Am J Public Health, 1987;
77:1435-8
3. Feyerabend C, Russell MAH. A rapid gas-liquid chromatographic method for
determination of cotinine and nicotine in biological fluids. J Pharm Pharmcol,
1990; 42:450-2
4. Irving JM, Clark EC, Crombie IK, Smith WCS. Evaluation of a portable measure
of expired-air carbon monoxide. Prev Med 1988; 17:109-115.
5. Prineas RJ. Blood pressure sounds: their measurement and meaning. A training
Manual. Gamma Medical Products Corporation, Philadelphia, 1977

MONICA Manual, Part I: Description and

Organization of the Project
Section 2: Organization and Management
of the WHO MONICA Project

Amendments to this section since 2004

After publication of the main results of the MONICA Project, it was decided that the
MONICA Manual will no longer be revised, but any changes will be included as
amendments to the Manual. To the extent of the amendments, parts of the MONICA
Manual, although of historical relevance, will be superseded:

• Amendment 1: Management of the MONICA Project

• Amendment 2: Publication rules

February 1999

This section of the MONICA Manual describes the organization and management of the
WHO MONICA Project. It can only be altered by the MCCs at a meeting of the CPI or
through a postal or other form of ballot (see Annex 1).

Proposals for changes to the Manual can be made by anyone in MONICA. The MSC will
review the relevance of such proposals and, where appropriate, submit them to a ballot in
which the MCCs only will be eligible to vote. Decisions on change of MONICA rules
will be valid if there is a 65% majority of those voting and the total vote is 80% of MCCs
eligible to vote. Eligibility of MCCs to vote will depend on their continuing involvement
with the WHO MONICA Project. Those Centres which have persistently failed to
respond to communications over a period of three months before the ballot and have been
deemed to be non-operational for that reason by the MSC will not be counted in the
MONICA denominator for ballots.

Contents
• 1. Working language
• 2. Membership
• 3. Policy and management
o 3.1 Council of Principal Investigators (CPI)
o 3.2 MONICA Steering Committee (MSC)
o 3.3 MONICA Management Centre (MMC)
 o 3.4 MONICA Data Centre (MDC)
o 3.5 MONICA Quality Control Centres (MQC)
o 3.6 MONICA Reference Centres (MRC)
• 4. MONICA Collaborating Centres (MCC)
• 5. Reporting
• 6. Communication procedures
• 7. Publication rules (see Amendment 2 for revised Publication rules)
o 7.1 Publication policy
o 7.2 Rules for centrally generated Collaborative Publications
o 7.3 Rules for data release
o 7.4 Ownership of collaborative data
o 7.5 Citation of Collaborative Publications
o 7.6 Publication Plan
o 7.7 Cumulative list of publications and presentations
• 8. Site visits
• Annex 1 Conducting postal ballots

Forms
• Publication proposal form

© Copyright World Health Organization (WHO) 1999. All rights reserved.

• Copyright notice
• Manual acknowledgements
• Document identification:
o URL:http://www.ktl.fi/publications/monica/manual/part1/i-2.htm
o URN:NBN:fi-fe19981148

Queries and comments on this section to be addressed

to:
MONICA Management Centre
Cardiovascular Diseases Programme
Division of Noncommunicable Diseases
World Health Organization
CH1211 Geneva 27
Fax: + 41 22 791 4151
E-mail: mendiss@who.int or pricea@who.int

Earlier versions
 • WHO MONICA Project. MONICA Manual. CVD/MNC/Version 1.1, December
1986; Sect. 12.
• WHO MONICA Project. MONICA Manual. Geneva: World Health Organization,
Cardiovascular Diseases Unit; November 1990; Part I, Sect. 2.
• WHO MONICA Project. Revision of Part I, Sect. 2 of MONICA Manual.
MONICA Memo 244; July 1993.
• WHO MONICA Project. Revision of Part I, Sect. 2 of MONICA Manual.
MONICA Memo 282; October 1994.
• WHO MONICA Project. MONICA Manual, Part I: Description and Organization
of the Project, Section 2: Organization and Management of the WHO MONICA
Project. (August 1998). An annotated copy, showing the changes from the
previous version is available from: URL:
http://www.ktl.fi/publications/monica/manual/part1/i-2oct94.htm

The August 1998 revision was made in recognition of the changes in governance that
were likely to occur with the conclusion of data collection phase of the Project. In
particular it was recognised that as future Councils of Principal Investigators were
unlikely, or at best unpredictable, the previous procedures for changing the rules
governing the project or electing new members to the MONICA Steering Committee,
would no longer apply. There will nevertheless be an ongoing requirement to oversee the
ongoing publication of results and other reports from the Project and to regulate the use
of the MONICA Archive.

The current (February 1999) version differs from the August 1998 version only in Annex
1, where the rules for counting postal votes in the election of MSC members have been
revised to cover all situations.

1. Working language
The working language is English.

2. Membership
There are two types of membership:

(i) Full membership

Centres which fulfil the criteria set out in Section 4 will be accorded full
membership so long as they continue to meet the requirements for the Project, as
judged by the Steering Committee. They are known as MONICA Collaborating
Centres.
(ii) Associate membership
Centres conducting projects comparable to the WHO MONICA Project, but not
meeting all the requirements of the MONICA Protocol, may request Associate
 Membership from the Steering Committee. This entitles them to receive copies of
unclassified Project documentation and to attend meetings of the Council of
Principal Investigators at their own expense. No central data analysis, or quality
control evaluation or measures, are normally provided. Associate Members may
not use the name MONICA and will not participate in pooled data analyses.

3. Policy and management

The WHO MONICA Project is a partnership between the World Health Organization and
the MONICA Principal Investigators. Between the infrequent meetings of the MONICA
parliament - the Council of Principal Investigators - the running of the project is carried
on by designated MONICA Centres as described below.

The World Health Organization acts as project sponsor and co-ordinator, assists in
acquiring funds, and executes financial and other contracts whenever necessary. The
general management and coordination of the WHO MONICA Project are carried out
from WHO Headquarters by the Cardiovascular Diseases Programme within the Division
of Noncommunicable Diseases, the MONICA Management Centre. Responsibility for
the management of the major technical aspects has been assigned to different centres with
expertise in the specific fields. The area of responsibility and the terms of reference for
each of the different centres are stated in the relevant sections below.

The policy making and management structure of the WHO MONICA Project, is made up
of the following components:

• Council of Principal Investigators - CPI

• Principal Investigators - PI
• MONICA Steering Committee - MSC
• MONICA Management Centre - MMC
• MONICA Data Centre - MDC
• MONICA Quality Control Centres - MQC
• MONICA Collaborating Centres - MCC
• MONICA Reference Centres - MRC

Throughout the text only the abbreviations given above are used. An organizational chart
is shown below.
3.1 Council of Principal Investigators (CPI)

a. The CPI is composed of the designated PIs (responsible scientific officer(s) of

each full member centre) from each MCC. The CPI is the highest policy and
decision-making body of the WHO MONICA Project.
b. Meetings of the CPI are held as often as funding permits. The meetings are
attended by:
i. PIs or their representatives
ii. MONICA country coordinators1
iii. Ex-officio staff including heads of the MMC, MDC, MQCs and MRCs
iv. Principal investigators from associate member centres
v. Team members from MONICA Centres
vi. Consultants, whenever necessary, appointed by WHO
vii. MSC members.
Only category i) has the right to vote at CPI meetings. Each MCC has only one vote,
even if it has two PIs.

Note: 1 A chief scientific officer designated by a country to coordinate activities of

MONICA Collaborating Centres within that country.

The Council has the following functions:

• reviewing, deciding and planning the execution of the MONICA Project

• monitoring and evaluating progress
• exchanging experience and information
• reviewing the recommendations of the MSC
• charging the MSC with specific assignments, if necessary
• electing new members of the MSC
• agreeing upon timetables

Funding: To the extent that funds are available, the costs of participation of the Principal
Investigator (or his/her nominated alternate), the Heads of the MMC, MDC, MQCs and
MRCs, as well as coopted advisers will be borne by WHO. In the case of joint PIs, the
WHO will cover the cost of one PI for each MCC, except where one of the PIs is head of
a management body (MMC, MDC, MQCs, MRCs).

Organization: Meetings of the CPI are organized by the MMC, the MSC and, where
relevant, any local co-ordinator.

3.2 MONICA Steering Committee (MSC)

The MSC is a committee of the CPI with the following constitution:

i. Three members elected by the CPI from among members of the MCCs;
ii. Five ex-officio members
o Responsible Officer, Cardiovascular Diseases, WHO/HQ
o Regional Officer, Chronic Diseases, EURO
o Chief, MONICA Data Centre, Helsinki
o Rapporteur, who shall also be rapporteur for the CPI
o MONICA Biomed project grant Coordinator(s) during the currency of the
grant(s)2
o The coordinators of other significant grants held on behalf of the Project
as agreed to by the MSC
iii. Coopted advisers appointed by the MMC after consultation with the MSC on an
ad hoc basis.
Note: 2 MONICA is partially supported under Concerted Action funding granted by the
European Union for a 3-year period from 1 June 1996, and a Shared Cost Action for a 3-
year period from 1 May 1998.

Prior to the CPI meeting in October 1997, elected members of the MSC served for a
period of three terms, where the terms were defined as the periods between two CPI
meetings. After the 1997 CPI meeting, a term is defined as an 18-month period, ending
on 31 March or 30 September. In principle the longest serving elected member shall
retire at the end of each term. Vacancies due to the retirement of elected members shall
be filled by the CPI; should an elected PI-member of the MSC resign, the alternate
elected at the previous election shall serve in his/her place.

Procedure for election of MSC members

Until October 1997 one new member of the MSC was elected at each meeting of the CPI.
Thereafter the appointment of the elected members of MSC can be by postal ballot. A
ballot to elect a new member will be held at the end of each term. Elections will be held
in March or September of the appropriate year.

Prior to October 1997, eligibility to serve on the MSC was restricted to MCC PIs or co-
PIs. Post October 1997, eligibility is defined as:

• Any member of an MCC is eligible for membership of the MSC except that at any
time only one member of an MCC can be an elected member of the MSC.
• Past members of the MSC are eligible for re-election after standing down for one
term.
• A second member of an MCC can only be elected to the MSC after the first
elected member has stood down for one term.

Rules for postal voting:

See Annex 1.

Chair and Rapporteur

The Chair of the MSC shall be elected by the MSC from among the three members
elected by the CPI. The Chair shall hold office for one term. The Rapporteur, who serves
both the MSC and CPI, shall be appointed by WHO in consultation with the MSC for a
period of 3 years, and shall be subject to re-appointment.

Publications Coordinator (PC)

The PC shall be appointed by the MSC from its elected PI members. In general the PC
will serve for one electoral term, and can be re-elected. The PC has the responsibility for:

• assessing MONICA Publication Proposals for centrally generated collaborative

MONICA publications and advising the MSC on which of these should be
accepted as 'Agreed Publications'
• proposing to the MSC the Manuscript Groups and their Leaders charged with the
development of draft manuscripts
• assuring timely and efficient processing of analysis proposals and manuscripts
(see Section 7).

Quorum

A total of four, including two elected members and two ex-officio members shall form a
quorum.

Voting

Each member of the MSC (except coopted advisers) shall be eligible to vote. However,
the three elected members, when voting together, shall have power of veto over the ex-
officio members.

Attendance

PIs who are not members of the MSC may be invited to attend MSC sessions but are not
entitled to vote. Technical staff of the management organizations, including the MQCs,
may also be invited to participate in MSC sessions when required. Observers may be
permitted at the discretion of WHO after consultation with the Chair.

Secretariat

CVD Programme, WHO/HQ, serves as Secretariat to the MSC.

Responsibilities

The MSC is charged with the following responsibilities:

1. To carry forward the work of the project on behalf of the CPI.

2. To propose changes to the MONICA Manual whenever necessary.
3. To approve and monitor measures for quality control that will be managed by the
MDC and MQCs.
4. To monitor and evaluate the performance and activities of the MMC, MDC and
the MQCs.
5. To review performance of MCCs and decide on termination of membership of
any centre failing to meet performance criteria.
 6. To assist the MMC and MDC in the management and administration of the
project and in planning meetings of the CPI.
7. To advise and assist in fund raising.
8. To decide on associate membership.
9. To request site visits to evaluate MCC, MQC, MDC and MMC performance.
10. To keep the MCCs and MQCs informed on the current management of the
Project.
11. To promote and develop guiding principles for future international collaborative
research arising from the MONICA Project or from the collaboration of MCCs
(but not necessarily confined to such Centres).

3.3 MONICA Management Centre (MMC)

Cardiovascular Diseases Programme

World Health Organization
CH - 1211 Geneva 27

The Cardiovascular Diseases Programme (CVD), within the Division of

Noncommunicable Diseases (NCD), WHO Headquarters, is responsible for the day-to-
day management and coordination of the WHO MONICA Project in accordance with
WHO policy and directives. The MMC has the following functions:

1. General management and coordination of the Project, including:

o Keeping detailed records of MONICA Project membership, lists of
collaborating centre team members, copies of local manuals, etc.;
o Ensuring regular information dissemination exchange through the
MONICA Memo (MNM) system and liaison among the MCCs;
o Maintaining MONICA mailing lists;
o Preparing and distributing project documentation.
2. In collaboration with the MDC and MQCs, maintenance of quality assurance
procedures, including:
o Organization of site visits in consultation with the MSC, MDC and MQCs;
o Arranging the recruitment of consultants for specific ad hoc assignments
whenever necessary.
3. Monitoring the work of the MDC, MQCs and MRCs.
4. Acting as Secretariat to the CPI and MSC.
5. In consultation with the MSC, appointing the rapporteur of the MSC who serves
both the MSC and CPI.

3.4 MONICA Data Centre (MDC)

Department of Epidemiology
National Public Health Institute
Mannerheimintie l66
00300 Helsinki, Finland
The MDC is jointly sponsored by WHO, through a technical services agreement, and by
the National Public Health Institute of Finland, and is supported through a Biomed grant
from the European Union. The MDC is concerned with the management and analysis of
the core data of the WHO MONICA Project. Under the overall direction of the MSC and
of WHO, the MDC shall:

1. Prepare data collection methodology and instruments for the core study data;
2. Receive core study data from the MCCs in an agreed format and ensure its
security and confidentiality;
3. Provide analyses and reports of the MONICA core study data in a format decided
and approved by the MSC;
4. Assist in the development and implementation of an appropriate quality assurance
programme;
5. Advise MCCs on MONICA data collection and management procedures;
6. Assist in preparing MONICA Project publications of results from the MONICA
Project;
7. Report to the CPI, the MSC and the MMC, at minimum six-monthly intervals and
whenever requested;
8. Collaborate closely in management of the MONICA Project with the MSC and
the MMC.

Organization

The tasks of the MDC are defined by the MSC in accordance with the requirements of the
MONICA Manual.

All MCCs and MQCs will have direct communication with the MDC regarding data flow
and related technical matters.

The MDC is a separate unit within the Department of Epidemiology of the National
Public Health Institute of Finland, and is not part of FINMONICA.

3.5 MONICA Quality Control Centres (MQC)

Centres nominated by WHO in consultation with the MSC to provide expertise on

specified areas of the core project. There are four Quality Control Centres with specific
tasks:

A. MONICA Quality Control Centre for Lipid Measurements:

WHO Collaborating Centre for Blood Lipid Research in Atherosclerosis and Ischaemic
Heart Disease (usually known as the WHO Lipid Reference Centre)
Laboratory for Atherosclerosis Research
Institute for Clinical and Experimental Medicine (IKEM)
Videnska 800, PO Box 10
14000 Prague 4, Czech Republic:
Aim: To ensure comparability of data collection in the MONICA Project by testing the
performance of Centres in lipid measurements.

Terms of Reference: In close cooperation with the MSC and MMC, the Prague Centre
will provide the following services:

1. Procure quality control pools for lipid measurements at the MCCs.

2. Establish and execute a reference programme for testing the total cholesterol,
HDL-cholesterol and thiocyanate methods.
3. Respond to queries on MONICA lipid measurement procedures and laboratory
standardization.
4. Maintain appropriate documentation on MONICA lipid and thiocyanate
measurement procedures and laboratory standardization.
5. Provide periodic summary reports on the performance of the lipid laboratories at
the various MCCs.
6. Ensure comparability at regular intervals against the WHO Collaborating Centre
for Blood Lipid Standardization at the Centres for Disease Control, Atlanta,
Georgia, USA.
7. Assist the MMC in taking appropriate action when the performance of an
individual lipid laboratory is not satisfactory.
8. Present status and progress reports at regular intervals to the MSC.
9. Respect confidentiality of all data received from MCCs.
10. Communicate direct with individual MCCs on technical matters, or through the
MONICA Memo system.

B. Quality Control Centre for ECG Coding

National Institute of Cardiology

IX Haman Kato Ut 29
PO Box 88
1450 Budapest, Hungary

Aim: To standardize the interpretation of ECG according to Minnesota coding in order to

improve diagnostic performance in assigning MONICA ECG categories.

Terms of reference: In close cooperation with the MSC, the MMC and the MQC for
Event Registration, Dundee (Dundee Centre), the MONICA Quality Control Centre for
ECG Coding, Budapest (Budapest Centre) will provide the following services:

1. Preparation of standard sets of ECG tracings for distribution to Centres to assess

differences in ECG coding. Official MONICA reference codes will be established
in consultation with the Dundee Centre using the algorithm produced by the
Dundee Centre.
2. Reports, including statistical analysis and commentary, will be prepared and
circulated. The attention of each centre will be drawn to their weak points and
suggestions for improved performance will be put forward.
 3. The Budapest Centre will provide the official Minnesota reference codes for the
ECG tracings included in the sets of specimen case histories elaborated by the
Dundee Centre and will agree the official MONICA categories with Dundee.
4. The Budapest Centre will provide consultation services and organize training
courses in ECG coding as needed and appropriate.
5. The Budapest Centre will maintain a programme of standardization for its own
ECG coding activities with the Minnesota Coding Laboratory at the University of
Minnesota, Minneapolis, whilst such a link remains in being, but will also
establish an external panel of expert coders, or task force, who will provide and
code test material and standardize the Centre.
6. Status and progress reports will be presented to the MMC and the MSC at regular
intervals.
7. Respect confidentiality of all data received.
8. Communicate direct with individual MCCs on technical matters with copies to
MMC, or through the MONICA Memo system.

C. Quality Control Centre for Event Registration

Cardiovascular Epidemiology Unit

Ninewells Hospital and Medical School
University of Dundee
Dundee DD1 9SY, Scotland

Aim: To standardize the coding and classification of coronary and stroke events
according to the MONICA Protocol in order to improve comparability and stability
within and between Centres, thereby maximizing the chances of detecting true time
trends in event rates and minimizing the likelihood of spurious trends.

Terms of reference: In close cooperation with the MSC, the MMC and the MQC
Budapest, the Dundee Centre is responsible for the following areas:

1. Preparation and circulation of sample case histories and other material covering
both coronary and stroke events, to be followed up with general commentaries
and specific reports.
2. Answering queries on the MONICA event registration process.
3. Assisting, as appropriate, Centres having problems with this process.
4. Developing an operational definition for coronary and stroke events leading to
diagnostic algorithms and, where appropriate, computer programs based on these.
5. Presenting status and progress reports to the MMC and the MSC at regular
intervals.
6. Respecting confidentiality of all information received from MCC, MMC or MDC.
7. Final interpretation of the criteria (e.g. in a dispute between the Dundee Centre
and an MCC) rests with the MSC.
8. Communicating direct with MCCs on technical matters, or through the MONICA
Memo System in Geneva.
 9. Collaborate with the MDC, MSC and MCCs in preparing reports on the quality of
event data sent to the MDC and its interpretation.

Links between the Dundee Centre and the Budapest Centre: ECG diagnoses will be
agreed with the MQC for ECG Coding, Budapest, this centre taking primary
responsibility for Minnesota coding and Dundee for any problems with diagnostic
algorithms. Other procedures are to be agreed with the MMC and the MDC concerning
distribution, analysis and commentaries.

D. Quality Control Centre for Health Services

Department of Public Health

University of Western Australia
Western Australia 6907, Australia

Aim: To develop methods for the collection and quality assessment of standardised data
on provision of health services and selected aspects of medical and surgical care for the
management of cardiovascular disease in MONICA Collaborating Centres.

Terms of Reference: In close cooperation with the MSC, MDC, MMC and MQC for
Event Registration, the Perth Centre is responsible for the following areas:

1. Developing and testing, in consultation with the MONICA Data Centre and the
Steering Committee, the data instruments to ensure collection of comparable data
for health services assessment within the WHO MONICA Project.
2. Monitoring and evaluating the progress and effectiveness of this component of the
WHO MONICA Project.
3. Maintaining, in liaison with the MONICA Data Centre, the MONICA Manual
section for this data component.
4. Assisting, as appropriate, Centres having problems in health services data
collection.
5. Communicating direct with MCCs on technical aspects of this component, or
through the MONICA memo system in Geneva.
6. In close liaison with the MSC through the Publications Coordinator (PC, see 3.2),
supervision of MONICA collaborative publications in this area.
7. Respecting confidentiality of all data received.
8. Presenting, in collaboration with the MDC if necessary, progress reports to the
MSC and the MMC at regular intervals.

3.6 MONICA Reference Centres (MRC)

MRCs deal only with optional studies carried out within the framework of the WHO
MONICA Project. They coordinate and advise on their specific areas of speciality as
follows:

1. Act as resource centres in areas in which they have special expertise or interest.
 2. Help to develop common protocols and provide a focus for the relevant optional
studies.
3. Coordinate any collaborative studies and plan any joint analyses.
4. Advise their collaborators on any methodological or quality control problems
whenever necessary.
5. Organize data management for the respective optional study.
6. Keep the MMC informed of all activities through six-monthly reports.
7. Follow international development in the respective field, help with necessary
contacts with other related studies and advise Centres on possible additional
activities in the field in question.

MRC Nutrition (MRC-NUT)

Department of Chronic Diseases and Environmental Epidemiology
National Institute of Public Health and the Environment
P.O. Box 1
NL-3720 BA Bilthoven, The Netherlands
MRC Vitamins
Vitamin Unit
Institute for Biochemistry and Molecular Biology
University of Bern
Bühlstrasse 28
3000 Bern 9, Switzerland
MRC Physical Activity (MOSPA)
Behavioral Epidemiology and Evaluation Branch
Division for Health Education
Centers for Disease Control
Atlanta, Georgia 30333, USA
MRC Psychosocial Studies Office of Chronic Diseases (MOPSY)
WHO Regional Office for Europe
8 Scherfigsweg
DK - 2100 Copenhagen
MRC Drugs (MRC-DRG)
Bremer Institut für Präventionsforschung und Sozialmedizin (BIPS)
St Jürgen Str. 1
D - 2800 Bremen 1
MRC Haemostatic Factors and CHD (MRC-HFC)
Division of Epidemiology
The Queens University of Belfast
Mulhouse Building
Grosvenor Road
Belfast BT12 6BJ

4. MONICA Collaborating Centres (MCC)

The following conditions form the basis for recruitment, continuing participation and
quality assurance of individual Centres.
Expertise:

a. Centres should have recognized epidemiological experience, or should be

supported, backed or assisted by a centre with documented experience.
b. Centres should maintain standardization in accordance with the criteria
established by the MSC for lipid measurements, ECG coding and event
registration, and for any other techniques determined by the MSC within the time
limits established, providing the MMC and MQCs with information whenever
requested in the format required.

Population to be monitored: See Section I.1.

Local procedures:

a. MCCs should comply with the rules given in this document and should prepare
their own local protocols and manuals of operation based on the present
document.
b. The local protocol and manual of operations should be translated where necessary
into English and submitted for approval to the MSC through the MMC at WHO as
should any subsequent revisions.
c. Any variation in procedure from the approved Protocol and Manual of Operations
must be discussed with the MMC, as should any difficulties in adhering to the
Protocol.

Coordination:

a. MCCs should provide the MMC with details of the study population in the format
requested.
b. MCCs should provide data at the frequency and in the format required by the
MDC, the MMC and the MSC.
c. MCCs should provide the MMC with
i. a list of principal MONICA project team members with their individual
responsibilities, reviewed annually. Each MCC should have one or two
Principal Investigators (PIs) and/or are encouraged to designate one or
more Co-Principal Investigators in addition to the PI;
ii. a list of the optional studies carried out locally and whether they are being
carried out according to a collaborative protocol;
iii. an annual progress report by 30 June each year for review by the MSC.
This should include a list of publications and reprints.
d. MCCs should accept periodic visits from groups of experts sent by the MMC and
the MSC to review their data and procedures.
e. Encourage exchange of information and problem sharing.

Local responsibilities:

a. Responsibility for local funding.

 b. Support of the collaborative MONICA project and compliance with organization
and management procedures according to Protocol and Manual.
c. Ensuring that MONICA activities fulfil local and international criteria of medical
ethics, e.g. in ensuring confidentiality of data.

5. Reporting
The various Centres of the MONICA Project are required to provide formal written
reports regularly as follows and, in addition, whenever requested for ad hoc specific
purposes:

Centre/group Reports to Timing

MCC MMC Annually by 30 June
MSC CPI Every meeting
MMC MSC Every meeting
MDC MMC 30 June and 30 December
MSC Every meeting
MQC MMC 30 June and 30 December
MRC MMC 30 June and 30 December

Reports should contain the following information:

1. Administrative changes affecting the activity of the centre, such as changes in

personnel or facilities, or budgetary issues;
2. Activities since the previous report;
3. Current activities and problems;
4. Activities planned for the next reporting period;
5. (For MCCs) Optional study activities;
6. Two copies of publications issued since the previous report (including summary
or abstract in English).

Reports should be signed by the designated PIs or the head of the centre concerned.

6. Communication procedures
Procedures to be followed by MMC, MDC and MQCs.

a. MONICA Memoranda (MNM):

i. All MNM to be transmitted by priority mail and outside Europe by
airmail.
ii. Draft MNM to be sent to MMC at least one month before the date of
distribution to MCCs to allow adequate time for reproduction and mailing.
 iii. All MNM to be marked with an appropriate statement concerning action
required by MCC.
iv. All MNM to be marked with realistic deadlines and a priority statement.
b. For other communication, electronic mail (E-mail) and the World Wide Web
(WWW) whenever available and appropriate are preferred to telefax and ordinary
mail.
c. Forthcoming deadlines to be reviewed at each MSC meeting.
d. Compliance with deadlines to be monitored by MMC, MDC and MQCs and
discussed at each MSC meeting.
e. MMC and MDC and MQCs to acknowledge receipt of all "action"
communications form MCC and to provide a statement of date of expected action.

Procedures to be followed by MCCs:

a. MCC Principal Investigators to take responsibility for ensuring that MONICA

documents reach appropriate personnel efficiently.
b. Additional MCC personnel (and address) for MNM mailing list to be sent by PI to
MMC (or additional number of copies to be sent direct to PI).
c. MCC to acknowledge receipt of all "action" MNM and all important
communications and quality control materials from MMC, MDC and MQC and to
provide an expected date for completeness of required actions.
d. MCC to send communication by E-mail whenever appropriate. Otherwise telefax,
priority mail and outside Europe airmail should be used.
e. Each MCC to keep master file of all MNMs with note of action taken and date.

Procedures for communication by E-mail and the WWW:

a. Up-to-date procedures are described in the WWW at

"http://www.ktl.fi/monica/internal/". This includes
i. Addresses.
ii. Instructions for transfer of documents by E-mail.
iii. Instructions for commenting and annotating documents transferred by E-
mail.
iv. Procedures for distributing documents through WWW.
v. Rules for E-mail discussion by the MSC.
b. All MONICA Centres should pay particular attention to preventive measures
against computer viruses. Executable computer programs or documents in the
internal format of sophisticated text processing systems should be transferred only
in special cases. In such cases, both the sender and the receiver should check the
program or document against viruses.

7. Publication rules
(These publication rules have been superseded by those given in Amendment 2.)

7.1 Publication Policy

7.1.1 General statement

The MONICA publication policy is designed to encourage scientific publication of all

types, while maintaining the high quality of these publications and ensuring the
legitimate interests of all MONICA participants.

The policy refers to written or oral presentations of unpublished MONICA core data
(including data accepted for publication but not yet published). No such data can be
presented or published without the consent of each PI. As a general rule, consent should
be received within 4 weeks; failure to reply within this time will be taken to mean
consent ('The 4-week rule' starts from the date the document is e-mailed, faxed or
posted).

MONICA publications are coordinated by the PC (see 3.2).

7.1.2 Publications from individual MCCs

Individual MONICA Centres are encouraged to present and publish results that are based
on the data from their own centre, subject to acknowledgement that they are derived from
the WHO MONICA Project. Publications which refer to the WHO MONICA Project in
the title must be approved by the MSC before publication.

7.1.3 Publications from several MCCs

Publications from MCCs based on mutual agreement among participating PIs are
encouraged. This applies to Optional Studies.

Interested Centres can directly pool their own data.

If core data from the MDC are used for such a publication, a formal request for data
release, accompanied by the approval of all MCCs concerned, must be sent to the MMC.
The MSC decides on the data release.

If collaborative publications from several MCCs refer to the WHO MONICA Project in
the title, or if more than six Centres are included, approval by the MSC must be obtained
before the manuscript is submitted for publication. For such approval the manuscript
should be sent to the MMC. Approval from the MSC must also be obtained when four or
more MCCs wish to explore the interrelationships of tenyear data on trends in events,
case fatality, risk factors or medical care. A paper from up to three Centres exploring
these relationships must carry the statement that it cannot, for reasons of power and
geographical representation, test the main MONICA hypotheses.

The authors have full responsibility for the appropriate use and accuracy of the data
reported in such a publication.

7.2 Rules for centrally generated Collaborative Publications

7.2.1 Rules for Publication Proposals

Anybody can propose MONICA collaborative publications (The Proposer). The proposal,
including the Publication Proposal Form (Form SA) as a cover sheet, should give
purpose, outline, target journal and time schedule and be submitted to the PC (see Figure
1). Whenever possible, a proposal for authorship should be made.

The PC assesses the appropriateness, priority and proposed leadership of the publication
(see 7.2.2 below) possibly with the help of reviewers of his selection and the Head of the
MDC. The PC advises the MSC which decides whether the manuscript should be
accepted as a MONICA collaborative 'Agreed Publication', its priority, and who should
be its Leader. If the MSC does not reply within 7 days, it is assumed that the proposal of
the PC is accepted. The PC informs the Proposer of the decision and the Chief of the
MDC updates the MONICA Publication Plan (see 7.6) as appropriate.

7.2.2 Rules for Preparation of Manuscripts

The manuscript is prepared by a Manuscript Group. Anyone from a MONICA centre can
volunteer to join a Manuscript Group. This group will carry out the analysis and prepare
the manuscript. The Group, with its Leader should include the necessary expertise in
epidemiology, statistics and programming, and whichever other skills may be required.
Priority will be given to those in MONICA who have indicated their interest to work on a
particular manuscript.
The Leader is crucial to the success of the MONICA Publication Plan as he or she is
responsible for organising the Manuscript Group, for overseeing the preparation of the
manuscript, and for ensuring that the Agreed Publication is produced to an appropriately
high standard within the agreed timetable. The Leader will report to the PC on a regular
basis. The essential prerequisite for becoming a Leader is an ability to meet deadlines and
to motivate others to do the same. The Leader may delegate some if not all the writing of
the paper to another member of the Manuscript Group but in this case the delegated
person's name should appear first in the authorship statement.

Authors other than the Leader and/or the first author should be significant contributors to
the design of the paper, data preparation, analysis and/or writing. They should be
consulted by the Leader and/or first author at key stages in the paper's development and
should have seen and approved the final draft before it is submitted to the PC. In the eyes
of journal editors they are responsible and answerable for the accuracy of the data and
conclusions contained in the paper. Co-authors are not necessarily those who
volunteered, or were volunteered by others when the paper was first proposed - they must
have contributed substantially when work on the paper was in progress. The final
authorship list may therefore be different from the original manuscript group. Names of
co-authors should be agreed by the Leader and first author involving the PC and the MSC
if there is any difficulty or ambiguity.

The PC maintains regular contact with the Leaders of the Manuscript Groups to ensure
that deadlines are met and on the basis of this keeps the Publication Plan up-to-date. If
MONICA core data are used for a publication, the data must be obtained from the MDC,
the analysis must be carried out under the control of the MDC, and the results must be
verified by the MDC (see also 7.3.2). If and when this is no longer possible, appropriate
checks will be organized by the MSC through the PC.

Such publications appear with the authorship statement as follows:

Name(s) of author(s) for the WHO MONICA Project (1),

Title:................................

Text:.................................

(1) Annex: Sites and key personnel of the WHO MONICA Project

The Annex includes:

• Sites, PIs and key personnel

o Only MCCs whose results appear in the paper will be listed.
o Names of key personnel should be restricted to those involved in the data
component(s) considered in the publication.
o Names should be those who would be named in locally published papers,
rather than being a complete list of everyone working in the project.
 o Although the listing for each MCC is at the discretion of the PI, the lead
author and/or PC may wish to indicate to MCCs whether this is a major
report supporting a detailed annex or a minor one in which an annex of
reduced length might be more appropriate.
• MSC, MMC, MDC, MQCs, national coordinating centres (where applicable)
o Only MQCs involved in the data used for the publication will be listed.
• Consultants.

The list is drafted by the Manuscript Group and corrected when necessary by the PIs at
the same time as they approve the manuscript.

The letter to the editor on submission should include this sentence displayed prominently
and the accompanying statement on a separate sheet:

"Please Note: Publication of WHO MONICA Project data is subject to WHO

MONICA Project publication rules. Please see accompanying statement"

Accompanying Statement.

"WHO MONICA Project Publication Rules

Ownership of MONICA data is vested in the WHO MONICA Project Principal

Investigators who have resolved that publication of results should be restricted to those
journals which accept the WHO MONICA Project publication rules. These appear
reasonable to us and are accepted by major scientific journals. However, we wish to draw
these to your attention now to prevent delays or disputes later in the publication process.
Within these constraints the author of the accompanying letter is authorized by the WHO
MONICA Project to negotiate publication with you. We will presume acceptance of these
rules if you acknowledge this paper and forward it for refereeing. If you do not accept
these rules please return the manuscripts immediately so that it can be submitted
elsewhere without further delay. Thank you for your co-operation.

The publication rules cover three specific items:

1. The authorship line (as in the accompanying manuscript)

2. Citation of previous MONICA publications (as in the accompanying manuscript)
3. Publication of the list of MONICA sites and key personnel as an annex to the
paper.

The format and print size are at the discretion of the journal."

Whenever reasonable, the paper should have "WHO MONICA Project" in the title.

The publication must have an acknowledgement paragraph in a format consistent with

WHO MONICA Project policy and sources of funding. The wording of this should be
obtained by the Leader of the Manuscript Group from the PC who will have agreed it
with the MMC and MSC. This acknowledgement may need to be updated during the
development of the paper and is subject to final revision when the paper is approved by
the MSC.

The acknowledgement paragraph may have added to it the names of internal MONICA
reviewers who have made what is judged to be substantial contributions in the reviewing
process. This can be agreed by the lead author and the PC prior to submission to a
journal.

7.2.3 Rules for Agreed Publications

On completion the Manuscript is sent to the PC who sends it to three reviewers, at least
one of whom should be a statistician. (see Figure 2).The reviewers of MONICA
manuscripts will be chosen among PIs and staff members as well as among scientists
outside MCCs who have proven specific knowledge in the field. The PC also informs the
MSC about the manuscript and the reviewers. The MSC may appoint additional
reviewers within 7 days. The PC may ask the authors to send copies of the manuscript
directly to the reviewers to speed up this process.

The reviewers consider the appropriateness of the manuscript for publication and report
back to the PC within 3 weeks.

On the basis of the reviews, the PC either returns the manuscript for revision to the
authors or sends it with the reviewers' reports to the MSC.

In special cases (e.g. the stroke publications which concern only a part of the MCCs) the
MSC may decide on a review process different from the one described above, if it can be
expected to streamline the publication process.

The MSC considers the manuscript for approval as a MONICA collaborative publication
and hence for distribution to the MCCs for approval. If the manuscript is not acceptable,
the MSC decides on how to proceed further. If the MSC does not reply within 7 days, it is
assumed that the proposal of the PC is accepted.

The manuscript is distributed to the MCCs, relevant MQCs and the MDC by the MMC,
together with the list of key personnel.

The MCCs (PIs) approve the manuscript for publication and/or send their comments to
the PC or the person(s) specified in the covering letter of the manuscript. This must be
forthcoming within four weeks, and if no response is obtained the publication will
proceed.

Any minor modifications that may be necessary, including the list of key personnel,
should be made to the manuscript, before submission. After approval the manuscript will
be submitted for publication.
The leader of the manuscript group and the first author should agree between themselves
as to who will be responsible for submitting the paper to the agreed journal, for dealing
with reviewers/ editorial comment, for checking the proofs and for ordering reprints. The
decision on responsibility should be communicated to the PC. Anything other than minor
corrections arising from the editorial-review process should be discussed with other
members of the Manuscript group and with the PC. Whoever is responsible for the proofs
must inform the PC immediately on receipt of the proofs if there is any problem with the
journal carrying out MONICA publication policy on authorship, citations or listing of
sites and key personnel, so that they can agree how to take the matter up with the journal
editor. Whoever is responsible for obtaining the reprints must send copies to other
members of the authorship group and the remainder to the MMC for distribution. The
number and funding of reprints should be discussed at the time of ordering with the PC.

The MMC is responsible for providing reprints of the published paper to the MCCs,
MQCs and the MDC.
7.2.4 Rules for Internal Documents

Internal documents are subject to the same review procedures as for publications and
require a Publication Proposal Form (Form SA), giving purpose, outline and timetable.

7.2.5 Rules for Oral Presentations

Abstracts submitted for oral presentation based on unpublished MONICA collaborative

data will be sent to the MMC which will distribute them to the MSC (see Figure 3).
Abstracts will be approved solely by the MSC, the only exception being when mention of
specific MCCs is made in the abstract, in which case, explicit permission will be sought
from the MCCs concerned by the presenter and evidence of this furnished to the MMC.
Failure to reply within 4 weeks by the MCCs concerned will be taken to mean consent.
Approved abstracts will be circulated by the MMC to all MCCs, MQCs and MDC. On
approval by the MSC the PC informs the presenter that MSC approval has been given.

7.2.6 Rules for Invited Presentations

In addition to the above, no person invited to speak "on behalf of the WHO MONICA
Project" should do so without prior approval of the MSC. If an abstract is required, the
Person Invited should follow the rules for oral presentations (see Figure 4) and give
details concerning the source of the invitation. If no abstract is required, the Person
Invited should send details to the MMC. If the MSC gives approval, the PC will inform
the Person Invited who should then proceed with the presentation but must send a
summary to the MMC for distribution to the MCCs, MQCs and MDC for information. If
any proceedings are subsequently published the Rules for Agreed Publications apply (see
7.2.3).
7.2.7 Additional rule for stroke studies

All the above rules apply, except that only PIs from MCCs participating in stroke
registration have to give their consent for publications involving stroke.

7.3 Rules for data release

7.3.1 Data Analysis in the MDC for Agreed Publications

The individual data analyses for all Agreed Publications are considered for acceptance by
the Chief of the MDC. Quality control analyses can be accepted by the Chief of the MDC
even if they are not part of an Agreed Publication. Any statistical computing will be
performed, documented and reviewed according to the MDC procedures.

7.3.2 Data analysis of Agreed Publications outside the MDC

In certain circumstances, approval of the analysis of collaborative data outside the MDC
is permissible. If an MCC wishes to undertake analysis concerning an Agreed Publication
it should, after consultation with the MDC, send an application to the MMC which will
be referred to the MSC (see Figure 5). The application must give full justification for the
reasons for decentralising the analysis, give a firm time-table, specify the data records
and items needed, with a signed commitment by the PI of the MCC that the data will be
used for the specified purpose only. If the MSC gives approval a sub-set of the MONICA
core data can then be transferred from the MDC to the MCC. All MCCs and MQCs will
be informed about the release of the data for such decentralised analysis by the MMC.
After the analysis has been completed, the MCC will provide the MDC with a full
briefing of the analysis, including source code of the data analysis programs and output
listings of the results which have been used in the manuscript for publication. For this
briefing, which will include details of statistical inferences, a visit to the MDC may be
necessary. All resulting publications are subject to MONICA Publication Rules. On
completion of the agreed analysis, the MCC must not use the data for any purpose, unless
further clearances are given by the MSC.

7.4 Ownership of collaborative data

By definition, collaborative data are those collected using the routine procedures of the
WHO MONICA Project and sent to the MDC as part of the required data transfer
procedures. These data form a part of the WHO MONICA database and are owned by the
MONICA Council of PIs, and the MQCs (for quality control data).

7.5 Citation of Collaborative Publications

Collaborative MONICA publications must be cited in the following format in both local
and collaborative MONICA publications. This format should be applied both to recent
and to older papers published using earlier MONICA authorship formats. All in
MONICA should encourage colleagues who quote MONICA papers to cite them in the
same way when they are asked to comment on or to referee papers.

Examples of citations according to MONICA publication rules:

 i. Vancouver style (may vary with journal):

Pajak A, Kuulasmaa K, Tuomilehto J, Ruokokoski E for the WHO MONICA

Project. Geographical variation in the major risk factors of coronary heart disease
in men and women aged 3564. Wld Hlth Statist Quart 1988; 41 (3/4):115140.

ii. Harvard style (may vary with journal):

Pajak A, Kuulasmaa K, Tuomilehto J, Ruokokoski E for the WHO MONICA

Project (1988). Geographical variation in the major risk factors of coronary heart
disease in men and women aged 3564. Wld Health Statist Quart, 41, 115140.

If the sub-editor tries to change this format in the proofs, the author should change it back
and inform the journal that this is the WHO MONICA Project format.

7.6 Publication Plan

The MONICA Publication Plan outlines all MONICA collaborative Agreed Publications
and reports arising from checking, quality assessment, and analysis of the collaborative
MONICA data. For each of the component data sets it describes the anticipated
progression from compilation of data books to generation of quality assessment reports
and the drafting of papers for publication in scientific journals. For each subject, there is,
in general, a series of reports relating to baseline, mid-term and final results.

For each Agreed Publication and report, the Publication Plan identifies the Leader, other
members of the Manuscript Group, target journal or a mention that it will be an internal
report of the project, and the current status.

The Chief of the MDC, in consultation with the PC, has the responsibility for maintaining
the Publication Plan. The Plan is available in the internal MONICA site in the World
Wide Web. The MMC distributes the plan regularly to the MCCs and MQCs.

7.7 Cumulative list of publications and presentations

A complete list of all publications and presentations relating to the WHO MONICA
Project is kept by the MMC. All MCCs, MQCs and the MDC should notify the MMC
about their publications, and two copies of each publication (including an English
summary and/or abstract, together with the title of the article and the journal) should be
submitted together with the MCC Annual Report. A list of MONICA publications and
presentations should be included as an annex to the MMC Annual Report.

8. Site visits
Site visits are part of the quality control programme of the WHO MONICA Project and
are planned to add an external point of view to local procedures which may result in
higher quality data.
Purpose

a. To ascertain the extent to which MCCs and/or other MONICA Centres adhere to
the requirements of the standardized methods of the MONICA Project or their
MONICA remits.
b. To identify possible sources of systematic bias and variation which may have
slipped through local quality control measurements.
c. To clarify sources of errors detected in the core data which cannot be dealt with
through postal channels.
d. To provide data for central analysis which could help to explain unexpected
results.
e. To discuss possibilities for improving data collection.
f. To provide information for central management.

Each of the following activities should be reviewed in detail:

1. collection of population demographic and mortality data

2. population survey activities
3. collection of coronary and stroke event register data
4. collection of medical care data
5. data handling
6. local management.

In each data component, special attention should be paid to local quality control and to
procedural changes within the study period.

Follow-up

After the visit, a report must be submitted to the MMC with a copy to the MCC
concerned, within one week of the site visit. The MMC then reviews the report and
prepares follow-up recommendations, in consultation with the MDC, MQCs and MCC if
necessary. A copy of the recommendations is sent to all management centres, including
the MSC, as well as to the MCC concerned.

Based on the review, the MSC may need to decide on what action, if any, might be
needed to improve local procedures, and may also need to make a decision on the status
of the MCC within the MONICA Project. If the decision of the MSC is unacceptable to
the MCC, the matter should be referred to the Council of Principal Investigators.

Follow-up procedures for site-visits to the MDC, MQC and the MMC are related to their
original remits.

Annex 1: Conducting postal ballots

1. Alteration of the rules of the MONICA Project

The MSC should determine the most efficient way of conducting the ballot. The
procedure for a postal ballot is described below, but at the time of writing this, the use of
an electronic voting system is being explored.

Postal ballots will be conducted by the MMC:

• Proposals for changes to the MONICA rules, together with supporting arguments
must be distributed to MCCs by MMC in the form of a MONICA Memorandum
• MCCs will have two weeks in which to indicate that they wish to distribute a
rejoinder opposing the proposed change; and four weeks to provide this in writing
to the MMC.
• At the end of four weeks from the date of distribution of the initial Memorandum,
the MMC will:
a. If no counter arguments are received, proceed with the ballot OR
b. Distribute any counter arguments opposing the changes in a second
memorandum. Two weeks after distribution of the second memorandum,
MMC will then proceed with the ballot.

2. Election of MSC members by postal ballot

• Postal ballots for membership of MSC will be conducted by the MMC.

• A call for nominations will be circulated four weeks before the date for closure of
nominations.
• The proposer and seconder of a nominated candidate must obtain the written
agreement of the nominee.
• Ballot papers for the election will be distributed by MMC as soon as possible after
the closing date. The candidates will be encouraged to provide a personal
statement indicating their current research interests and reasons for standing for
membership, which will be circulated with the ballot papers.
• A double envelope system will be used for returning completed ballot papers to
the MMC. The ballot paper will be first placed in a non-identified envelope. This
will then be placed within the second envelope that will have the MCC name and
number written on the back. This will also be signed by the PI.
• To avoid multiple rounds of voting, an 'optional preferential' ballot system will be
used:
o Voting: PIs will be asked to place the figure '1' in the box opposite the
name of the preferred candidate and then to continue numbering boxes in
descending order of preference. The voter may, but is not obliged, to
indicate a preference for all of candidates. If the same number has been
written against the name of more than one candidates, only the preferences
above that number will be valid.
o Counting of votes:
1. Any candidate with an absolute majority (i.e. in excess of 50%) of
first preference votes is elected.
 2. If, after the first preference votes have been counted, no candidate
has obtained an absolute majority of votes, then the candidate with
the fewest number of first preference votes is excluded. That
excluded candidate's second preference votes are then distributed
to the remaining candidates. (Whenever a ballot paper shows a
void preference for a continuing candidate, that ballot paper is said
to be exhausted.)
3. Any candidate with an absolute majority of those votes remaining
in the count is elected. If no candidate has obtained an absolute
majority of votes, the next remaining candidate with the fewest
votes is excluded and all of his/her votes are distributed to the
remaining candidate (i.e. each first preference vote or vote
received from the first excluded candidate is given to the next
preference candidate).
4. The above process is continued until one candidate obtains an
absolute majority of the remaining votes.
5. If, at any exclusion, the next available preference is for a
previously excluded candidate, then that preference is disregarded
and the vote is distributed to the continuing candidate for whom
the next available preference is shown.
6. If at any stage there is a tie for the fewest votes (i.e. for the
candidate to be excluded), the original first preference votes (i.e.
first preference votes before anyone was excluded) will be used to
break the impasse. If the tie persists, the original second preference
votes will be used, and so on. If the impasse remains after the votes
of the last preferences have been used, lots will be drawn to break
the tie. (Note that this rule also includes a tie for the first place.)
7. To select the alternate, a similar procedure is used, but excluding
the elected candidate in the beginning.

MONICA Manual, Part III: Population Survey

Section 2: Standardization of lipid

measurements
May 1998

This section provides details on the methods to be used for measurement of lipids in the
WHO MONICA Project and their standardization.
Contents
• List of abbreviations
• 1. Obligatory and voluntary biochemical measurements
• 2. Sample collection and initial processing
• 3. Storage of serum/plasma samples
• 4. Recommended analytical procedures for total cholesterol and HDL-cholesterol
measurement
• 5. Calibration of methods
• 6. Units of reporting
• 7. Internal (intralaboratory) quality control (IQC)
• 8. External quality assessment (EQA)
• 9. Recording and reporting MONICA and quality control results
• 10. Actions if performance with required accuracy and/or precision cannot be
achieved in a laboratory
• Bibliography
• Figure 1. Recommended sequence of N specimens in a run
• Appendix 1. Example of calculation of the pool mean and standard deviation.

© Copyright World Health Organization (WHO) 1998. All rights reserved.

• Copyright notice
• Manual acknowledgements
• Document identification:
o URL:http://www.ktl.fi/publications/monica/manual/part3/iii-2.htm
o URN:NBN:fi-fe19981152

Queries/comments on this section should be addressed

to:
Dr D. Grafnetter and Assist. Prof. R. Poledne (Chief)
Laboratory for Atherosclerosis Research
Institute for Clinical and Experimental Medicine (IKEM)
Videnska 800
14000 Praque-4
Czech Republic
Email: rudolf.poledne@medicon.cz

Earlier versions
• WHO MONICA Project. Manual of operations - standardization of lipid
measurements. WHO/MNC/82.2, Annex I Rev. 1; May 1983.
 • WHO MONICA Project. MONICA Manual. CVD/MNC/Version 1.1, December
1986; Sect. 6.
• WHO MONICA Project. MONICA Manual. Geneva: World Health Organization,
Cardiovascular Diseases Unit; November 1990; Part III, Sect. 1.

Changes made after November 1990 version

• The language has been edited and misprints have been corrected.

List of abbreviations
Apo-B Apoprotein B
CDC Centers for Disease Control, Atlanta, Georgia 30333, USA
EDTA Ethylene diamine tetraacetic acid
EQA External quality assessment
G Gravity
HDL High density lipoproteins
HDL-C High density lipoprotein cholesterol
IKEM Institute for Clinical and Experimental Medicine, Prague, Czechoslovakia
IQC Internal quality control
LDL Low density lipoproteins
LRC Lipid Research Clinics
MDC MONICA Data Centre
MMC MONICA Management Centre
MQC MONICA Quality Control Centre
OD Optical Density
QA Quality Assurance
R.p.m. Revolutions per minute
RV Reference value
SCN Serum thiocyanate
St Total standard deviation
TC Total cholesterol
TG Triglycerides (Triacylglycerols)
VLDL Very low density lipoproteins
WHO- WHO Headquarters
HQ
WHO-
WHO-Kaunas-Rotterdam Intervention Study
KRIS
WHO-
WHO Lipid Workshop (Prague, 26-28 January 1982)
LW
WHO- World Health Organization Regional Lipid Reference Centre (WHO
RLRC Collaborating Centre for Blood Lipid Research In Atherosclerosis and
Ischaemic Heart Disease at the Institute for Clinical and Experimental
Medicine (IKEM), Budejovicka 800, 14000 Prague-4, Czech Republic)

1. Obligatory and voluntary biochemical measurements

1.1 Total cholesterol (TC) is an obligatory blood (serum, plasma) measurement in the
MONICA surveys. Wherever possible, samples should also be analysed for HDL-C.
Laboratory directors who attended WHO-LW agreed upon HDL-C measurements. Serum
thiocyanate (SCN) (for SCN see Part III, Section 3) was originally an obligatory
parameter, but became optional after the initial survey.

1.2 Other optional but complementary measurements might include, e.g.: triacyglycerols
(triglycerides), lipoprotein typing and composition (electrophoresis, ultracentrifugation,
ultrafiltration and nephelometry, chromatography of lipoproteins, etc.), apoprotein
concentrations [12] (immuno-electrophoretic, radial-diffusion and/or nephelometric
methods), glucose, uric acid, urea, electrolytes, creatinine, thyroxine, haemoglobin,
carboxyhaemoglobin, and in certain situations, trace elements.

2. Sample collection and initial processing

2.1 Centres should collect MONICA blood samples in each survey over the same
seasons to prevent seasonal variations in the levels of serum/plasma parameters. MCC
collecting MONICA blood samples over the course of the entire year should randomize
blood taking to ensure equal representation of age and sex subgroups over time.

Lipid laboratories may want to measure lipoprotein fractions and triglycerides and so
requires a 16-hour fast. For epidemiological purposes such as in MONICA, where the
primary lipid of interest is serum total cholesterol and secondarily high density
lipoprotein cholesterol (HDL-C), blood can be taken at any time of day with the subject
non- fasting; this facilitates the scheduling appointments at the survey clinic. For
comparability with other MONICA centres it is desirable that blood pressure
measurements be spread throughout the day and made in non-fasting subjects: for this
reason any MCC that wishes to measure fasting lipid specimens should consider doing
this separately from the routine survey clinic where blood pressure is measured.

For the purposes of longitudinal comparisons, the methods of measurement of lipids

should be consistent between one MONICA survey and another. Any proposed changes
such as of time of day and fasting/non-fasting status should be avoided or tested in pilot
studies to ensure that they do not introduce bias.

2.1.1 Venipunctures should be carried out with the subject or patient in a sitting position.
Prolonged venous occlusion can cause changes in the apparent concentrations of blood
constituents [3]. Use of a tourniquet should therefore be avoided. If a good flow cannot
be obtained in some subjects and the tourniquet has to be used, it must be released before
the withdrawal of blood.

Standardization of the position (sitting position is recommended) is necessary since

plasma volume changes occur when a standing subject assumes a recumbent position
[20,3].

2.2 Serum should be used in preference to plasma. It is realized that the group of
laboratories standardized with CDC may have to continue using these methods for
MONICA. It follows that these laboratories may continue using EDTA plasma prepared
according to the LRC instructions [20].

2.2.1 Either 10 ml vacuum tubes or syringes and glass tubes may be used to collect blood.
Glass tubes should be equipped with stoppers made from material which does not react
with blood constituents. When vacuum tubes are used, the type with stoppers un-
lubricated with glycerol should be selected (glycerol causes interference with TG assays
in enzymatic methods).

2.2.2 The use of vacuum tubes containing EDTA is recommended if plasma is used (the
group of laboratories following LRC methods).

2.3 For serum preparation, blood samples are allowed to clot at not more than 20°C
usually for up to one hour before centrifugation. There is evidence (personal
communication from the Helsinki Centre) that this period can be prolonged by up to three
hours.

Blood specimens should be centrifuged at a temperature of not more than 20°C (warning:
Prolonged running of a non-refrigerated centrifuge may result in considerable warming of
the centrifuge compartment and centrifuged samples) at a minimum of 1500 G for at least
10 minutes to separate serum from the clot. If a refrigerated centrifuge is unavailable, it
may be necessary to cool blood samples before centrifugation (for instance, in a
refrigerator or on melting ice). With a refrigerated centrifuge, centrifugation should be
preferably done at 4°C. Whole blood samples must not be frozen during processing (this
will cause haemolysis).

2.4 For plasma preparation the tube(s) filled with blood must be stoppered immediately
(if vacuum tubes are not used) and inverted gently about 10 times to ensure prompt and
thorough mixing of blood sample(s) with EDTA. Mixing should not be vigorous.
According to LRC recommendations the blood samples are then cooled on melting ice.
Within 3 hours (and preferably within one hour) the tubes should be centrifuged at 4°C in
a refrigerated centrifuge at 1500 G for 30 minutes. If a refrigerated centrifuge is not
available within 3 hours of collection, the samples may be centrifuged at room
temperature within 1 hour of collection, and the plasma stored at 4°C.

2.5 After centrifugation, the serum/plasma should be promptly separated from clot or
cells and transferred to a clean tube. The white cell layer (buffy coat) is not transferred
with the plasma.

2.6 Haemolytic serum/plasma samples should be discarded and fresh samples should be
taken from the subjects and analysed.

3. Storage of serum/plasma samples

3.1 It is recommended that the TC and HDL-C levels should be estimated on the day of
sample collection.

3.2 Samples can be stored for up to four days at +4°C [1,3,5]. If analyses of TC cannot be
performed within 4 days the serum or plasma samples should be immediately stored at -
20°C or lower in tightly stoppered glass vials [1].

3.3 Precipitation of Apo-B containing (LDL + VLDL) lipoproteins (see 4.5) should
preferably be done on fresh (non-frozen) serum aliquots on the day of blood collection.
Should it prove impossible to perform precipitation on fresh samples, the serum or
plasma for HDL-C determination should be immediately frozen at -20°C or lower [1,3].
Precipitation should then be performed within 14 days. The sample should be thawed
only once and well mixed. It should be recognized, however, that freezing may introduce
a systematic error of up to 4% in HDL-C measurements [3].

3.4 Storage of serum/plasma samples for other purposes than immediate analysis of TC,
HDL-C and SCN: if samples are to be stored for voluntary analysis, laboratories must
select adequate storage conditions at which the measured parameters' concentrations
would be stable.

3.5 Despite the problems associated with storage, MONICA centres are encouraged to
archive replicate samples of serum as an insurance. If the laboratory's external quality
control proves to be seriously deficient, the replicate samples give the opportunity for
providing valid data, if the results from the primary specimens are disqualified.

4. Recommended analytical procedures for TC and

HDL-C measurement
4.1 It is recommended that an enzymatic cholesterol method with practically 100%
cholesterol ester hydrolysis be used. Advantages include non-corrosive reagents, easy and
fast operational steps, specificity, the possibility of using automated methods as well as
manual methods with inexpensive instruments, the standardization of methodology in
MONICA, etc. However, it is realized that a group of laboratories standardized with CDC
using LRC methods based on extraction into isopropanol, and several laboratories using
so called "direct methods" (see also 4.3) may continue using their methods for MONICA
if the purpose of their own research should require such continuity.

4.2 The use of a number of commercial brands of enzymatic reagents for cholesterol
analysis might diminish comparability of results between laboratories due, for example,
to non-homogeneity of production lots or due to loss of kit enzyme activities on storage.
Information collected at the WHO-LW showed that most of the participating laboratories
have worked, or are going to work with the same commercial brand which is widely used
in Europe. This is fortunate for the Project. The suitability of selected enzymatic methods
will be checked by means of the EQA.

4.3 It is possible that a few laboratories taking part in MONICA may be unable to
comply, for local reasons, with the recommendation to use an enzymatic method. These
laboratories probably will continue to use the so-called "direct", "one- step",
"Liebermann-Burchard" method(s) in manual or automated version(s), etc. The WHO-
RLRC will circulate a questionnaire concerning analytical and associated procedures to
be used in the different centres, with the aim of obtaining full information on the use of
alternatives to LRC or enzymatic methods. It is the policy of MONICA to accept, in
exceptional cases, participants not able to use the recommended methods. In such cases
particular attention to methods for ensuring comparability will be necessary if
performance within allowable EQA limits is unattainable with use of primary pure
standards. The laboratories concerned may have to calibrate with serum calibrators
provided by the WHO-RLRC (MQC).

4.4 Every participating laboratory should provide a detailed description of their entire
procedure of sample collection and analysis to the MMC (WHO - Cardiovascular
Diseases Unit) and to Dr D. Grafnetter (WHO-RLRC) at least six months before analysis
of MONICA samples begins in the MCC concerned. An example of a recommended
sequence of quality control standardization and participant samples for total cholesterol
and HDL-cholesterol determination are shown in Figure 1.

4.5 Isolation of the HDL-fraction:

4.5.1 It was recommended before the start of MONICA that laboratories should use a
"Phosphotungstate-Mg2+" (PT) precipitation method [2, 10, 11, 15, 31, 32, 33] for
isolation of HDL from LDL + VLDL. In this method final concentrations after mixing
serum (or plasma) with precipitation reagent(s) are: 3.6 g/litre for phosphotungstic acid
and 0.045 M for Mg2+ [21, 24]. According to these papers, precipitation of LDL +
VLDL is complete if the pH of the final mixture (serum/plasma + PT reagents) remains
below pH 7.6. This method (see 4.5.2 - 4.5.7.3) was in general use at the time this
Manual was initiated. By 1986, many centres had already switched to a new PT method
described under 4.5.9.
4.5.1.1 Some laboratories, e.g. those with the LRC methodology, may need to continue
with other precipitation techniques (Mg2+ -dextran, Mn2+ -heparin). Acceptance of these
methods is based on the same policy as mentioned under 4.3.

4.5.2 Preparation of PT method [31, 32] reagents for precipitation at pH below 7.6 (for
alternative concentrations and use of PT reagents see subsections 4.5.7-4.5.9):

4.5.2.1 Sodium phosphotungstate, 40.0 g/l, pH 7.4. Dissolve four grams of

phosphotungstic acid (reagent grade) in about 60 ml distilled water. Add gradually while
mixing and using a pH meter as much of 1 mol/l NaOH so as to reach pH 7.4 (usually
somewhat less than 16 ml). Then make the volume up to 100 ml.

4.5.2.2 Magnesium chloride, 2.0 mol/l: Dissolve 40.6 grams of MgCl2·6H2O (analytical
grade) in about 80 ml of distilled water and make the volume up to 100 ml.

4.5.2.3 Reagents should be kept at 4°C in between use and can be kept for up to 6
months, provided they show no bacterial growth.

4.5.3 Use of PT reagents is described under 4.5.2.1 and 4.5.2.2:

4.5.3.1 Add 100 µl of the phosphotungstate solution (4.5.2.1) to 1.0 ml of sample and
mix (preferably by vortexing). Add 25 µl of magnesium chloride solution (4.5.2.2) and
again mix well. Let each precipitated sample stand for ten minutes at room temperature
and then centrifuge. For centrifugation conditions see subsection 4.5.4.

4.5.3.2 Volumes of sample and reagents could be reduced (e.g. halved) for the
precipitation step.

4.5.3.3 It is also permissible to use the pre-mixed reagent. This is prepared and used as
follows: phosphotungstate and magnesium chloride solutions are mixed on the day of use
in the ratio of 100:25 (e.g. 4 ml + 1 ml). Then 125 µl of the pre-mixed reagent are added
to 1.0 ml of sample and the solution is mixed well.

4.5.4 Centrifugation after precipitation: Since centrifugation at +4°C on one hand and
+20°C on the other can lead to certain differences in HDL-C levels in some reconstituted
lyophilized quality control materials (observations made in the WHO-RLRC) but not in
fresh sera, it is recommended (for all but the LRC methods laboratories) to centrifuge
"HDL samples" after PT precipitation of Apo-B containing lipoproteins at room
temperature (not below +15°C or above +25°C) at 2000 G for 30 minutes.

4.5.5 After centrifugation the supernatant should be immediately transferred to a clean

and dry tube.

4.5.5.1 The HDL-C concentration obtained after the colorimetric measurement in the
supernatants has to be multiplied by 1.125 (due to sample dilution by the precipitant).
4.5.6 With study samples, only clear (non-turbid) supernatants should be used for
subsequent cholesterol analysis. With the PT method (if TG are elevated) the supernatant
may occasionally show some turbidity. In this case the precipitation step should be
repeated with the serum/plasma sample diluted 1:1 with 0.9% sodium chloride solution in
distilled water (saline, physiological solution). This usually results in a clear supernatant
(but the precision of the cholesterol assay is decreased; remember that the result must be
multiplied by two if the 1:1 diluted sample is used - see also subsection 4.6.4). Should the
dilution of serum/plasma sample not give clear supernatants after precipitation and
centrifugation, do not proceed. Any such irregularity and/or difficulty in obtaining clear
supernatants should be recorded on the results form.

4.5.6.1 In some lyophilized quality control materials slight turbidity of supernatants may
be unavoidable. The WHO-RLRC will distribute instructions for use of pools with
individual shipments of EQA sets.

4.5.7 Alternative concentrations and use of PT method reagents:

Special (adjustable or constriction) pipettes are necessary to deliver the unusual volumes
(e.g. 25 µl or 125 µl) of the above "classical" PT method reagents (see 4.5.1-4.5.6.1). The
following modified reagent concentrations [33] and their use (see sections 4.5.7.1, 4.5.7.2
and 4.5.7.3) yield the same result but enable the use of normal precision pipettes:

4.5.7.1 Sodium phosphotungstate, 48.0 g/l, pH 7.4: dissolve 4.8 grams of

phosphotungstic acid (reagent grade) in about 50 ml distilled water. Add gradually while
mixing, and using a pH meter, as much of 1 mol/1 NaOH as necessary to reach pH 7.4.
Then make the volume up to 100 ml.

4.5.7.2 Magnesium chloride, 3.0 mol/l: dissolve 60.9 grams of MgCl2·6H2O (analytical
grade) in about 80 ml of distilled water and make the volume up to 100 ml.

4.5.7.3 Use of the modified PT method reagents:

Precipitation reagent is prepared by mixing 5 parts of sodium phosphotungstate (4.5.7.1)

with one part of magnesium chloride (4.5.7.2) solution (e.g. 5 ml + 1 ml) on the day of
use. Then 100 µl of the premixed reagent are added to 1.0 ml of serum/plasma sample
and the whole is mixed well. Further steps (centrifugation, etc.) are the same as those
starting at section 4.5.4. However, the multiplication (dilution) factor will be 1.1 in this
case (not 1.125 as in 4.5.5.1).

4.5.8 Some laboratories have used a commercial PT precipitation kit and followed its
working instructions, and they may wish to continue doing so. This is possible if results
obtained with the use of such a kit are found compatible with the EQA criteria.

4.5.9 A modified precipitation method [35, 36] for determination of HDL- cholesterol
using PT was developed and has been commercially available for several years (kit
"HDL-cholesterol. Precipitant", Cat. no. 543004; Boehringer Mannheim GmbH). This
technique is described in detail in the operation sheet inserts with each kit. The method
has been shown to compare well with the reference ultracentrifugation method. It uses a
precipitant solution with decreased phosphotungstic acid and magnesium chloride
concentrations; only 200 µl of sample are required for one determination on a sample
using the semimicro version of the method. Samples become more diluted than in the
conventional PT method(s); thus, turbid supernatants occur only very exceptionally. In
short, the procedure is as follows:

500 µl (or 200 µl in the semi-microversion) of sample are mixed with 1000 µl (500 µl) of
the reagent. In the semimicro version the precipitant solution must be diluted with water
(4 + 1 volumes) to obtain the precipitation reagent. After mixing, the mixture is left to
stand 10 minutes at room temperature and then centrifuged for 10 minutes at 4000 r.p.m.
or 2 minutes at 12 000 r.p.m. Cholesterol is determined in the supernatant using the
enzymatic method (e.g. Monotest Cholesterol or Peridochrom, Boehringer Mannheim
GmbH). 200 µl of sample (or blank, or standard) supernatant are mixed with 2000 µl of
the Monotest or Peridochrom reagent in the conventional manual method (one can also
use proportionally less of sample and reagent in the automated methods, or where
allowed by the cuvette volume of the photometric instrument). After mixing and 10
minute incubation at 20°C - 25°C (or 5 minutes at 37°C) the developed colour is
measured at Hg 546nm or at 500nm, using a 1 cm cuvette. Concentration is calculated on
the basis of "water soluble" standard(s) (e.g. Preciset Cholesterol; Boehringer Mannheim
GmbH), or using the manufacturer's factor if the kit procedure is followed exactly as
described in the insert, of a factor derived from use of a certified serum calibrator.

The Precipitant solution used in this method contains phosphotungstic acid (0.55 mmol/l)
and magnesium chloride (25 mmol/l) in distilled water. For use in the semimicro version
of the method (200 µl sample + 500 µl reagent), the Precipitant should be diluted as
mentioned above, i.e. 4 + 1 (4 volumes Precipitant + 1 volume distilled water). This
method yields good results not only on fresh serum or plasma material, but also on many
non-outdated lyophilized control materials. Its use makes control of HDL-cholesterol
methods by means of lyophilized control sera easier [35].

4.6 Determination of cholesterol in the HDL containing supernatant:

4.6.1 The determination should preferably be made shortly after precipitation of

LDL+VLDL and the centrifugation step (on the same day). If it is necessary to store
samples, analysis is recommended within 4 days if stored at +4°C. Prolonged storage
requires at least -20°C. Storage is recommended in small volume glass tubes (vials) with
leak-proof stoppers to prevent volume and concentration changes (evaporation, freezing
out). After storage and before analyses the samples should be brought to room
temperature and gently mixed.

4.6.2 Cholesterol should be determined in the HDL-containing supernatants by the same

method as used in the laboratory concerned with the TC estimation. Should the methods
sensitivity be low (optical density readings in unreliably low range) it might be necessary
to use a photometric cuvette with greater optical length and/or to increase the supernatant
sample volume. Reliability of the method must be checked carefully in such cases.

4.6.3 When serum/plasma sample is diluted 1:1 before use (see section 4.5.6) again the
results must be multiplied by two to obtain the final serum/plasma HDL-C concentration.

4.6.4 Duplicate or single TC and HDL-C measurements: If possible, all MONICA

serum/plasma samples should be analysed in duplicate. For the analysis of cholesterol by
extraction chemical methods, two separate extracts will be required for duplication (do
not perform two analyses on one extract). For HDL-C analysis duplicate LDL+VLDL
precipitations will be required. Mean results are reported if analyses are performed in
duplicate. (The MDC must be notified as to whether single analysis or mean values are
reported, the "power" of the means is greater in statistical evaluations.)

4.6.5 For IQC and EQA samples all analyses are performed in duplicate (but mean
values are not reported to the MQC, both values are recorded and reported).

4.6.6 The IQC rules shown below (see section 7.7) give criteria for each single
measurement result on control samples, from which the maximal allowable difference
between side-by-side duplicates is in fact also defined. Daily use of IQC information is of
prime importance for maintaining good precision, since EQA information is only
retrospective and primarily devoted to following interlaboratory comparability.

It is recommended in addition that laboratories analyzing not only control, but also
MONICA Project samples in duplicate, should reanalyse the samples with duplicates
differing more than 0.40 mmol/l for TC (15.0 mg/dl), or 0.20 mmol/l (8.0 mg/dl) for
HDL-C. Should duplicate results frequently differ that much, the method should be
revised and every effort be made to improve precision.

5. Calibration of methods
Recommendation: Primary standards and/or secondary serum/plasma calibrators are used
in duplicate at least for calibration.

5.1.0 Each participating laboratory is responsible for its own analytical primary
standards and/or secondary serum calibrators.

5.1.1 It is assumed that all participating laboratories will use the purest and most
appropriate substances and method reagents. The cholesterol substance used for
preparation of standards should be of more than 99% purity.

5.1.2 Secondary (serum) calibrators should preferably be prepared and/or labelled with
correct TC and/or HDL-C concentrations in the WHO-RLRC and/or CDC. It is
understood, however, that staffing and budgetary restraints may be a limiting factor in
such an undertaking.
5.1.3 The WHO-RLRC distributed during the pre-standardization period a set of three
cholesterol standards for use in testing linearity over the working range. There was a
shipment of a commercial cholesterol standards pack (6 standards with concentrations of
50-400 mg/dl/1.3-10.4 mmol/l) to each laboratory. Such sets should enable control of
linearity and at the same time calibration of several enzymatic and/or extraction
cholesterol methods. Some cholesterol methods (the so-called "direct" Liebermann-
Burchard chemical methods) cannot be calibrated by these "water soluble" standards
(falsely high results may be obtained without special arrangements), but the linearity
response of these methods can be judged on the basis of these standards.

5.1.4 Each standard (calibrator) should be run at least in duplicate.

5.1.5 Each laboratory should perform tests on linearity over the usual working range (0.5
- 10.0 mmol/l of TC), even if the WHO-RLRC or other body is not able to supply them
free with appropriate control material for this purpose.

5.1.6 It is essential that linearity should be checked repeatedly during the

prestandardization period. During the study linearity should be checked regularly, and
particularly if greater than allowable imprecision and/or inaccuracy (allowable limits on
accuracy and precision - see 8.3.8) is detected. Ideally, linearity should be checked with
at least three standards in each run in which MONICA samples are analysed. It is
understood, however, that this will not always be possible in all laboratories and that it
may not be necessary to use standards to judge linearity where adequate data can be
obtained from IQC and EQA samples (see 7.3.2). Laboratories are free to check on
linearity by any reasonable method guaranteeing acceptable results within the limits of
accuracy and precision.

It is understood that linearity enabling the use of a mean calculation factor (which
requires calibration line passing through the X,Y intercept after subtraction of the reagent
blank) may not be attainable in some participating laboratories (e.g. because of
limitations in the photometric equipment available for the assay). Non-linearity need not
necessarily mean wrong results. Linearity must be checked, and every effort should be
made to attain it. If unattainable the laboratory should derive results mathematically from
regression equations or graphically from standard curves covering the working range of
the method. (Enzymatic cholesterol methods can usually provide linearity up to
11.5 mmol/l. When a higher serum/plasma cholesterol concentration is expected, analysis
should be repeated after appropriate dilution of the sample according to the instructions
of the manufacturer of the enzymatic kit).

5.1.7 More detailed information on checking on linearity, calibration, and QA can be

found in the literature [4, 14, 19, 20].

6. Units of reporting
Recommendation: All results should ideally be reported to 2 decimals in the International
SI Units [23].
However, the older units (e.g. mg/dl) are still used in some laboratories because
continuity of methods is desirable until certain related projects are finished. In the
MONICA Project results for TC and HDL-C will therefore be accepted both in mmol/l
and mg/dl since units can easily be converted by computer.

6.1 Results obtained in mmol/l should be calculated and reported to two decimals.

6.2 Results obtained in mg/dl should be calculated to one decimal, but TC concentrations
should then be reported, rounded off to whole numbers and HDL-C concentrations as
calculated, i.e. to one decimal.

6.3 The conversion factor for cholesterol from mg/dl to mmol/l is: 0.025864. The
conversion factor for triglyceride from mg/dl to mmol/l is: 0.0114.

Example: (250mg/dl) x (0.025864) = 6.466 = 6.47 mmol/l for TC.

(250mg/dl) x (0.0114) = 2.85 mmol/l for TG.

7. Internal (Intra-laboratory) Quality Control (IQC)

Recommendation: At least two serum control pools are used for IQC. The preparation,
checking, and use of these pools are described under 7.3 and 7.7.

7.1 Performance of methods within IQC limits is a prerequisite for successful

participation in the EQA programme and for reliable analysis of MONICA samples.

7.2 The following recommendations on the preparation of IQC pools and how to proceed
with IQC represent the views of the WHO-LW on the desirable methods of quality
control. It is understood however that some laboratories will not be in a position to
comply with all of these recommendations, and others will already have instituted
adequate but different quality control procedures, which they are unable to change. In
these cases each participating laboratory should inform the WHO-RLRC centre of their
quality control and standardization methods. In other words, systems other than the
recommended internal quality control system are permissible as long as there is
adequate indication that analytical results, as judged by IQC and EQA, are within
the IQC and EQA control limits described below. It follows that use of self-made
and/or commercial frozen or lyophilized internal quality control materials is allowed. If
lyophilized material is used for HDL-C, it should be material specifically designed for
this purpose.

7.3 Establishment of pools: Each laboratory should establish at least two control serum
pools for internal quality control. Each pool should last through the whole of one survey
phase of MONICA and in any case should be sufficient to last for one year of normal
operations. The pools under 7.3.1 and 7.3.2 are the only two pools that are strictly
required for MONICA.
7.3.1 TC + HDL-C pool: This pool should be prepared from non-turbid human serum
containing "normal" TC and TG concentrations. The pool should be distributed in
suitable aliquots into tightly closed glass vials and ideally kept frozen at -60°C or below1.
Should it prove impossible to use a self-made or commercial frozen serum pool, a
lyophilized pool could be used. In the latter cases, there should be a guarantee that the
pool was prepared only from human sera, without use of additives or enrichments which
could affect TC and HDL-C determinations, and it should be suitable for the HDL-C
determination. The TC + HDL-C pool would be used both for TC and HDL-C method
control, including the precipitation step in the latter case (the quality control specimen
should be treated in exactly the same way as the test samples). Lyophilized pools do not
require -60°C for storage. Even +4°C to +6°C may be satisfactory for a defined expiry
period.

Note1: CDC laboratories found -20°C unsatisfactory for long term storage (personal
communication). However, a number of MONICA laboratories may only have storage at
-20°C. In such cases the TC + HDL-C pool should be periodically checked for HDL-C
concentration stability in runs containing EQA samples.

7.3.2 Low total cholesterol pool (LTC pool): This pool should contain 1.30-1.60 mmol/l
cholesterol and it should be used for control in the low TC range. It could be prepared
from a human serum pool diluted to the appropriate cholesterol concentration with 0.15m
NaCL. Alternatively, animal (bovine, horse) serum pool, eventually slightly diluted to the
desired CH concentration level, could be used.

7.3.2.1 The appropriately diluted TC + HDL-C pool (under 7.3.1) could be used as a LTC
pool with the advantage that both pools could also be used for linearity checking (plot of
absorbance against concentrations or dilution factors should result in a line passing
through the X, Y intercept). This checking will work only with enzymatic and/or
extraction cholesterol methods. In the direct chemical cholesterol methods the
concomitant dilution of interference (by bilirubin, tryptophane, proteins, etc.), as well as
changed viscosity in automated versions, may result in non-proportionality of
absorbances to dilution.

7.4 Some laboratories may elect to establish a further (or several more) pool(s) for TC
and/or HDL-C measurements, e.g. one with the cholesterol concentration in the upper
part of the working range. The HDL-C pool(s) should have a low TG concentration
(under 1.5 mmol/l).

7.5 Useful information concerning the preparation of self-made pools can be found in the
literature [13, 14, 16, 17, 18, 22, 26, 27, 28, 29].

7.6 Use of IQC material to ensure analytical precision for TC and HDL-C analysis:
7.6.1 Once opened, an ampoule (vial) of quality control materials should not be used for
more than one day's operations. Accurate reconstitution of lyophilized materials must be
ensured (to prevent introduction of errors unrelated to the method itself). If a lyophilized
pool is used for HDL-C control (precipitation included) each laboratory concerned should
standardize the time period between reconstitution and analysis.

7.6.2 Each analytical run should begin with calibration standard(s). This could be the
primary standard(s) and/or secondary serum calibrator(s) (see example in Appendix I).

7.6.3 IQC samples should follow. All quality control samples should be analysed in side-
by-side duplicates. The results obtained from quality control samples following the
standard(s) are used to indicate whether the run is in control and whether the analysis of
study samples can be begun (for criteria see 7.7).

7.6.4 When a new pool is introduced both the next and the old pool should be in use
together (overlap period) for at least the number of runs (analyses) required to establish
the starting mean (see 7.6.6), to ensure adequate calibration of the new pool and method
control.

7.6.5 Control of drift in a run:

In each analytical run (or part of analytical run) containing MONICA samples, quality
control material should be placed in every tenth position among the samples (to monitor
within-run stability). This can be other than the LTC+HDL-C or LTC pool material and
need not necessarily be of human origin nor accurately calibrated because it serves only
for monitoring within-run reproducibility (see Figure 1).

7.6.6 Before a pool is introduced, its starting concentration mean must be established.
This is done as follows: at least 40 values are collected on at least 20 pool vials randomly
distributed in independent analytical runs over at least 20 days (do not use 40 times in
one run). Finally, the whole set of values should be examined for potential outliers [19].
If any value differs from the overall mean ( ) by a number greater than 3.3 St (i.e. if
any Xi > + 3.3 St), the pair of results in which it occurs is discarded and
recalculated. Only one such outlier is permissible. Should there be more outliers, the
method should be revised and complemented with further runs and checks on outliers as
above.

(St is calculated only for the purpose of checking for outliers; it is not needed for IQC in
MONICA, common control limits are stated below.)

Total (overall) standard deviation (St) is calculated on the basis of individual repeated
measurements as follows:
where Xi = individual measurements results

= the mean of all measurements

n = the number of measurements

= the sum of the measurements results.
Relative standard deviation (coefficient of variation-C.V.) is calculated:

For an example of mean and St calculation see Appendix 1.

7.7 IQC criteria for acceptability of the run: Once the acceptable pool mean ( ) is
obtained, the precision control limits are defined as follows (for an example of the quality
control chart for visual follow-up of method performance see Figure 2):

Warning limits for TC (levels above 2.60 mmol/l or 100 mg/dl)

±3% from the mean (±0.03 ).
Example: at a 5.17 mmol/l (200 mg/dl) level:
 • the lower warning limit = 5.02 mmol/l (194 mg/dl)
• the upper warning limit = 5.33 mmol/l (206 mg/dl)

Maximum allowable limits for TC measurements (levels above 2.6 mmol/l or

100 mg/dl):
±4.5% from the mean (±0.045 )
Example: at a 5.17 mmol/l (200 mg/dl) level:

• the lower allowable limit = 4.94 mmol/l (191 mg/dl)

• the upper allowable limit = 5.41 mmol/l (209 mg/dl)

Warning limits for HDL-C: ±6% from the mean (±0.06 )

Maximum allowable limits for HDL-C: ±9% from the mean (±0.09 ).

7.7.1 Ideally, in runs containing MONICA samples, no single quality control pool value
(not the mean of a duplicate) should surpass the warning limits. Should this occur, and
the result be still within maximum allowable limits, the run result can be used but it is a
strong signal that method(s) should be checked (see standards, calibrator(s), reagents, OD
reading instrument(s), pipettes, dispensers, quality control pool expiry dates (see 7.3),
eventual microbial growth, possible calculation errors, etc.). The best quality volumetric
glass, dispensers, and measurement instruments are recommended.

7.7.2 In no case should single control value(s) fall beyond the maximum allowable limits.
If this occurs, the run must be stopped, results cannot be used, the cause of trouble must
be eliminated, and the method must be brought under control before MONICA samples
are started.

8. External Quality Assessment (EQA)

Recommendation: the WHO-RLRC is responsible for sending the EQA samples.

8.1 EQA is complementary to the IQC and its main purpose will be to check on accuracy
(assessment of bias), although it will also supply laboratories with evaluations concerning
overall, between-day (between-run) and within-run variability. (Regular use of IQC is a
prerequisite for successful participation in the EQA programme.)

8.2 EQA will be carried out from the MQC at the WHO-RLRC (Chief: Dr R. Poledne
(former chief: Dr D. Grafnetter), Institute for Clinical and Experimental Medicine
(IKEM), Videnska 800, PO Box 10, 140 00 Prague 4, Czech Republic).

8.3 EQA assistance to participating laboratories:

8.3.1 1982 was considered as a pre-checking (pre-calibration, pre- standardization)

period. Each laboratory assigned to analyse MONICA samples (all addresses should be
made available to the WHO-RLRC by WHO/HQ, see also 4.4) were expected before the
start of the proper EQA to analyse with "blind" samples (concentration unknown to the
laboratories) in one or two self-evaluation sets (concentrations known) provided by the
WHO-RLRC. Self-evaluation sets contain vials with control sera selected from
lyophilized pools. They are provided, if needed, with instructions for use and with the list
of reference TC, HDL-C, TG (and possibly also Apoprotein AI and B) concentrations.
Self-evaluation sets enable a check on methods and/or their calibration.

After the "open" period, a "blind" EQA system was started to evaluate laboratory
performances. Its principles and methods were explained in detail to the laboratory
directors who attended the WHO-LW. Others who are interested or who join the Project
later may obtain information from the literature [6, 7, 8, 9]. It is only necessary to
mention here that the system has been based on repeated analysis of control sera shipped
at regular intervals as lyophilizate to laboratories ("sets" composed of 14-21 samples).
This system of "blind" EQA sets will be used throughout MONICA.

8.3.2 Sets are sent periodically to participating laboratories with clear instructions for use,
as well as with relevant information, reporting forms, and eventually also questionnaires.
Samples contained in the shipments may originate from commercial pools, as well as
from pools prepared in the WHO-RLRC or elsewhere. It is the responsibility of the
WHO-RLRC to check, in cooperation with CDC or other bodies, the suitability of pools.

8.3.3 Control samples should be used in the laboratories according to the accompanying
instructions (reconstitution, sequence of samples, etc.). Each sample should be analysed
in side-by-side duplicates on the day of reconstitution. If more measurements are
performed, only the first two should be reported to the WHO-RLRC. The rest may serve
for internal purposes, e.g. analysis of drift.

8.3.4 The decision on how many samples (or sets) should be distributed to individual
laboratories should be made on an individual basis, depending on the questionnaires
completed and results reported by the laboratories. In most cases 4-5 EQA sets per year
should be distributed to each laboratory during the respective survey period. Each set
should contain about 20 samples, sufficient for about 2 months.

8.3.5 Some laboratories may wish to analyse MONICA survey samples (each survey
covers approximately 1600 samples) in batches separated by intervals of days or weeks,
while others may spread their analyses over year(s). Frequency of EQA sets should be
adjusted to their needs. Only sets falling into the survey periods of sample analyses (not
collection and/or storage) will be used for evaluation of MONICA results.

Laboratories will be requested to complete analysis of individual sets and report results
within 2 months, at the latest . Failure to do so may mean that a further set will not be
received, since only the receipt of results will be a signal to the WHO-RLRC to
indicate that a further set should be sent. Failure of a laboratory to undertake
sufficient EQA control may result in elimination of its TC and HDL-C results from
MONICA evaluations.
8.3.6 Based upon the EQA results received, the WHO-RLRC will as soon as possible
supply the participating laboratory (and WHO-HQ if needed) with information on the
analysis of the EQA set, i.e. on the calculated overall, between-run and within-run
standard deviation, and on bias, from which acceptability of results for the different pools
and methods can be judged. Performance acceptability criteria are shown in Table 1 and
discussed under 8.3.8.

8.3.7. Reference values (RV) will be obtained in the WHO-RLRC as before by the
modified Abell Kendall method [18], in cooperation with CDC. CDC will be requested to
analyse the EQA pools and make results available to the WHO-RLRC, to ensure
comparability between WHO-CDC and WHO-RLRC evaluations. As a secondary check
in obtaining the RVs a CHOD-PAP enzymatic cholesterol method with practically 100%
cholesterol-ester hydrolysis may be used by WHO-RLRC. For LDL+VLDL precipitation
in the HDL-C reference value estimation the PT reagents and procedures described in
sections 4.5 and 4.6 will be used.

8.3.8 Performance acceptability criteria in EQA (limits on maximum allowable

inaccuracy and imprecision) (see Table 1):

Total cholesterol: for any of the control pools, calculated bias (based on the EQA set
mean and on RV) should not be greater than +5%. At the same time st should be smaller
than that shown for individual reference values in Table 1. Table 2 shows allowable
limits for CV% according to increasing levels of cholesterol concentration.

HDL-cholesterol: for any control pool, calculated bias (based on the EQA set mean and
RV) should not be greater than +7.5%. At the same time St should be smaller than that
shown for individual reference values in Table 2 (i.e. CV<6.5%).

Table 1. Performance acceptability criteria in EQA (limits on maximum allowable

inaccuracy and imprecision).

Individual standard deviations can be obtained for any RV concentration by interpolation.

Reference Maximum allowable Maximum allowable
value(RV) overall standard deviation of set
deviation (St) pool mean from RV (bias)*
mmol/l mg/dl mmol/l mg/dl
TOTAL 2.5864 100 0.1681 6.5 ±5%
CHOLESTEROL 5.1728 200 0.1940 7.5 ±5%
7.7592 300 0.2198 8.5 ±5%
10.3456 400 0.2457 9.5 ±5%

HDL- 0.5173 20 0.0336 1.3 ±7.5%

CHOLESTEROL 1.0346 40 0.0672 2.6 ±7.5%
1.5518 60 0.1009 3.9 ±7.5%
2.0691 80 0.1345 5.2 ±7.5%

*Calculated by comparing the average of all determinations for a given pool in a set to
the reference value for that pool, i.e. with 0.05×RV (total cholesterol) or 0.075×RV
(HDL-cholesterol)

Table 2. MONICA - Total Cholesterol Limits on maximal allowable imprecision

Overall Coefficient Overall Coefficient

Reference Reference
standard of standard of
value value
deviation variation deviation variation
mmol/l mmol/l
mmol/l % mmol/l %
2.6 0.1682 6.5 6.4 0.2062 3.2
2.7 0.1692 6.3 6.5 0.2072 3.2
2.8 0.1702 6.1 6.6 0.2082 3.2
2.9 0.1712 5.9 6.7 0.2092 3.1
3.0 0.1722 5.7 6.8 0.2102 3.1
3.1 0.1732 5.6 6.9 0.2112 3.1
3.2 0.1742 5.4 7.0 0.2122 3.0
3.3 0.1752 5.3 7.1 0.2132 3.0
3.4 0.1762 5.2 7.2 0.2142 3.0
3.5 0.1772 5.1 7.3 0.2152 2.9
3.6 0.1782 5.0 7.4 0.2162 2.9
3.7 0.1792 4.8 7.5 0.2172 2.9
3.8 0.1802 4.7 7.6 0.2182 2.9
3.9 0.1812 4.6 7.7 0.2192 2.8
4.0 0.1822 4.6 7.8 0.2202 2.8
4.1 0.1832 4.5 7.9 0.2212 2.8
4.2 0.1842 4.4 8.0 0.2222 2.8
4.3 0.1852 4.3 8.1 0.2232 2.8
4.4 0.1862 4.2 8.2 0.2242 2.7
4.5 0.1872 4.2 8.3 0.2252 2.7
4.6 0.1882 4.1 8.4 0.2262 2.7
4.7 0.1892 4.0 8.5 0.2272 2.7
4.8 0.1902 4.0 8.6 0.2282 2.7
4.9 0.1912 3.9 8.7 0.2292 2.6
5.0 0.1922 3.8 8.8 0.2302 2.6
5.1 0.1932 3.8 8.9 0.2312 2.6
5.2 0.1942 3.7 9.0 0.2322 2.6
5.3 0.1952 3.7 9.1 0.2332 2.6
5.4 0.1962 3.6 9.2 0.2342 2.5
5.5 0.1972 3.6 9.3 0.2352 2.5
 5.6 0.1982 3.5 9.4 0.2362 2.5
5.7 0.1992 3.5 9.5 0.2372 2.5
5.8 0.2002 3.5 9.6 0.2382 2.5
5.9 0.2012 3.4 9.7 0.2392 2.5
6.0 0.2022 3.4 9.8 0.2402 2.5
6.1 0.2032 3.3 9.9 0.2412 2.4
6.2 0.2042 3.3 10.0 0.2422 2.4
6.3 0.2052 3.3

8.4 Laboratories should not begin analysis of MONICA samples before they are able to
show that their analyses of at least two successive blind EQA sets are within the limits of
acceptability (see 8.3.8) for every control pool. In order to allow time for all this,
participating laboratories should begin standardization at least six months before
MONICA population survey work begins, and this should be repeated before each further
MONICA population survey. In order to detect trends in serum cholesterol level, the
laboratory must be well standardized on all occasions.

8.4.1 If EQA results suggest trouble with a method a decision will have to be made on the
admissibility of data from the laboratory. It is strongly recommended that assistance be
provided to help solve such problems with the laboratory concerned, using QA
information, including IQC data. Laboratories should keep good records on their IQC
data and be able to present them upon request.

8.4.2 A situation might arise, however, when a laboratory demonstrates greater than
permissible but fairly stable analytical bias with acceptable precision (small s t). In such a
case the WHO MONICA appointed adviser, who receives evaluation copies from WHO-
RLRC through WHO-HQ, should consider the case and advise the laboratory and WHO-
RLRC immediately on the course to be followed. (Results might perhaps be corrected
mathematically provided that the bias was practically the same at different concentration
levels in successive tests, and that st did not surpass allowable limits). Once st is above
the acceptable limit no allowance for bias consideration can be made, and the laboratory
will be requested to revise and correct the method before proceeding with the MONICA
study samples.

8.5 To help overcome problems of retrospectivity in EQA, the WHO-RLRC will include
in sets, if possible, a pool with nominated RVs to be made known to participating
laboratories for continual self-evaluation.

9. Recording and reporting MONICA and quality

control results
9.1 MONICA results reported to WHO-HQ and/or an outside adviser elsewhere will be
analysed under the auspices of WHO. WHO staff will design forms for data reporting
suitable for computer analysis.
9.2 Laboratories should at all times indicate whether they report single measurements
results or means.

9.3 WHO-RLRC will provide laboratories with reporting forms prepared for EQA sets.

9.3.1 Laboratories will be identified in the EQA system by code numbers which will not
be made publicly available without written consent from the respective laboratories.
However, the code will be open for WHO-HQ and for MONICA appointed advisers (who
are also bound to keep it confidential) and WHO MONICA meetings.

10. Actions if performance with required accuracy

and/or precision cannot be achieved in a laboratory
Initial action should be to make every effort to bring the method(s) into the required
performance limits, with the use of information obtained and with special samples for
method calibration. WHO-RLRC or CDC should be advised about the problem.

If all efforts fail, WHO may assist in nominating and supporting a visit of a consultant to
the laboratory concerned.

Laboratories are advised to store replicate samples under good conditions. Should quality
control results be poor and the fault cannot be found, these replicates can then be
processed by a well-standardized laboratory elsewhere. If the local laboratory's problems
are solved, it can process the replicates itself.

BIBLIOGRAPHY

1. Albers JJ, Warnick GR, Johnson N, Bachorik PS, Muesing R, Lippel K &
Williams, OD (1980) Quality control of plasma high-density lipoprotein
cholesterol measurement methods. The Lipid Research Clinics Programme
Prevalence Study. Circulation, Part II, Volume 62, No. 4, November 1980.
American Heart Association Monograph Number 73, pp IV-9 to IV-18.
2. Assmann G, Schriewer H, Schopohl B & Funke H (1979) Investigation of the
Specificity of the HDL-cholesterol test. In: Greten H, Lang PD & Schettler G
(Eds) Lipoproteins and coronary heart disease. New aspects of the diagnosis and
therapy of disorders of lipid metabolism. International Symposium, Vienna, May
12-13, 1979. Gerhard Witzstrock Publishing House, Baden Baden, 1980, pp 43-
45
3. Bachorik PS (1979) Factors that affect HDL-cholesterol measurements: sample
preparation and storage at refrigerator and freezer temperatures. In: Lippel K
(Ed): Report of the high density lipoprotein methodology workshop. San
Francisco, California, 12-14 March 1979. US Department of Health, Education,
and Welfare, NIH publication no. 79-1661, August 1979: pp 164-177
4. Boerma GJM (1979) Studies in standardization - Serum cholesterol analysis
performed for epidemiological investigations. Erasmus University, Rotterdam
5. Girault A, Loiseau D & Girault M (1980) Quantitative determination of
apolipoprotein A in human serum by laser nephelometry. Medical Laboratory,
Volume 9, Medical Diagnostics "E.V. Behring", pages 11-20. Die Medizinische
Verlagsgesellschaft GmbH, 3550 Marburg, West Germany, POB 1732
6. Grafnetter D (1977) World Health Organization (WHO) coordinated quality
control in the lipid laboratory. Giorn. Aterioscl., Vol. 2, 113-128
7. Grafnetter D (1978) External quality control carried out by WHO European Lipid
Reference Center in Prague. In: Carlson LA et al. International Conference on
Atherosclerosis, Raven Press, New York, 1978
8. Grafnetter D (1979) International standardization of lipid methods, experience
and trends. In: Proceedings of the 3rd Dresdner Lipid Symposium, 14Í16 May
1979, pp 362-367
9. Grafnetter D (1980) WHO lipid reference programme. A quality control substudy
in socialist countries with use of the Precilip and Precilip EL samples. Paper
presented at the symposium on Lipid Methods and Their Quality Control, Prague,
8 September 1980. Boehringer Mannheim, GmbH, Mannheim, West-Germany.
10. Greten H, Lang PD & Schettler G (Eds) (1980) Lipoproteins and coronary heart
disease. New aspects in the diagnosis and therapy of disorders of lipid
metabolism. International Symposium, Vienna, May 12-13, 1979. Gerhard
Witzstrock Publishing House, Baden Baden.
11. Grove TH (1979) Effect of reagent pH on determination of high-density
lipoprotein cholesterol by precipitation with sodium phosphotungstate-
magnesium. Clinical Chemistry, Vol. 25, No. 4, 560-564
12. Kostner GM (1980) Lipoproteins and atherosclerosis: Influence of the diet.
Medical Laboratory, Volume 9, Medical Diagnostice "E.V. Behring", pp 1-10.
Die Medizinische Verlagsgesellschaft mbH, 3550 Marburg, West Germany, POB
1732
13. Kuchmak M, Taylor L & Olansky AS (1981) Low lipid level reference sera with
human serum matrix. Clinica Chimica Acta, 116, 125-130
14. Lippel K (Ed): Report of the high density lipoprotein methodology workshop. San
Francisco, California, 12-14 March 1979. US Department of Health, Education,
and Welfare. NIH publication no. 79-1661, August 1979
15. Seigler L & Wu WT (1981) Separation of serum high-density lipoprotein for
cholesterol determination: Ultracentrifugation vs. precipitation with sodium
phosphotungstate and magnesium chloride. Clinical Chemistry, Vol. 27, No. 6,
838- 841
16. Tyroler HA (Ed) Epidemiology of plasma high-density lipoprotein cholesterol
levels. The Lipid Research Clinics Program Prevalence Study. Circulation, Part II,
Volume 62, No. 4, November 1980. American Heart Association Monograph
Number 73.
17. US Department of Health and Human Services, Centers for Disease Control: CDC
Survey of High Density Lipoprotein Cholesterol Measurement: A Report. CDC
Clinical Chemistry Division, 1980.
18. US Department of health and Human Services, Centers for Disease Control:
Manual of instructions and protocols for laboratory quality control in the Lipid
Research Clinics Program. March 1978.
19. US Department of Health and Human Services, Centers for Disease Control -
National Heart, Lung, and Blood Institute High Density Lipoprotein Cholesterol
Standardization Program. CDC, 15/10/80.
20. US National Heart and Lung Institute: Lipid Research Clinics Program Manual of
Laboratory Operations, Volume 1: Lipid and lipoprotein analysis. DHEW
Publication No. (NIH) 75-628, May 1974
21. Warnick GR & Albers JJ (1979) HDL cholesterol quantitation: Comparison of six
precipitation methods and ultracentrifugation. In: Lippel K (Ed): Report of the
High Density Lipoprotein Methodology Workshop. San Francisco, California, 12-
14 March 1979. US Department of Health, Education, and Welfare, NIH
publication no. 79-1661, August 1979: pp 53-69
22. Warnick GR, Mayfield C & Albers JJ (1981) Evaluation of quality-control
materials for high-density-lipoprotein cholesterol quantitation. Vol. 27, No. 1,
116-123.
23. World Health Organization (1977) The SI for the Health Professions, WHO,
Geneva.
24. Draeger B, Wahlefeld A (1979) Development of the test for determination of
HDL-cholesterol precipitation. In: Greten H, Lang PC & Schettler G (Eds)
Lipoproteins and coronary heart disease. New aspects in the diagnosis and therapy
of disorders of lipid metabolism. International Symposium, Vienna, May 12-13,
1979. Gerard Witzstrock Publishing House, Baden Baden, 1980, pp 38-42.
25. Williams JH, Taylor L, Kuchmak M & Witter RF (1970) Preparation of
hypercholesterolemic and/or hypertriglyceridemic sera for lipid determinations.
Clin. Chim. Acta 28, 247-253
26. Kuchmak M, Williams JH, Taylor L & Witter RF (1973) Alcohol precipitation
and 1000 x centrifugation preparation of hypercholesterolemic and
hypertriglyceridemic sera as lipid determination control. US Patent No. 3, 764,
556
27. Kuchmak M, Taylor L & Williams JH (1981) Preparation of reference sera with
desired levels of cholesterol and triglyceride. Clin. Chim Acta 114, 127-135
28. Proksch GH & Bonderman DP (1976) Preparation of optically clear lyophilized
human serum for use in preparing control material. Clin. Chem. 22, 456-460
29. Proksch GJ & Bonderman DP (1979) Development of a stable lipoprotein diluent
for use of reconstituting lyophilized human serum for the preparation of clear
hyperlipidemic quality-control materials. Clin. Chem. 25, 1377-1380
30. van Kampen EJ & Zijlstra WG (1965) General requirements for Hb determination
and standardization. In: Hemoglobin and its derivatives. Advances in Clinical
Chemistry, Part 8. Academic Press, New York.
31. Burstein M, Scholnick HR & Morfin R (1970) Rapid method for isolation of
lipoproteins from human serum by precipitation with polyanions. J. Lip. Res.,
11:583.
32. Lopes-Virella MF, Sonte P, Ellis S & Caldwell JA (1977) Cholesterol
determination in high density lipoproteins separated by three different methods.
Clin. Chem., 23:882-885.
33. Test-combination HDL-cholesterol Precipitant No. 400971, Boehringer
Mannheim, GmbH.
 34. Henderson LO, Saritelli AL, LaGarde E, Herbert PN & Schulman RS (1980)
Minimal within-day variation of high density lipoprotein cholesterol and
apolipoprotein cholesterol and apolipoprotein A-I levels in normal subjects.
Journal of Lipid Research, Vol. 21, 7, 953-955.
35. Assmann G, Schriewer H, Schmitz G & Hagele O (1983) Quantification of high-
density-lipoprotein cholesterol by precipitation with phosphotungstic acid/mgCl,
Clin. Chem., 29/12, 2026-2030.
36. HDL-cholesterol Precipitant. Cat. No. 543004. Boehringer Mannheim, GmbH.

MONICA Manual, Part IV:Event Registration

Section 2: Stroke event registration data

component
November 1990

This section provides the equivalent of a manual of operations for the collection and data
processing for this component of the MONICA Project.

Contents
• Introduction
• 1. Coronary and stroke registration
o 1.1 Criteria for inclusion and exclusion of events
o 1.2 Identification of suspect coronary or stroke events
• 2. Registration of stroke events
o 2.1 Data collection
o 2.2 Diagnostic classification
• 3. Core data transfer form and instructions for stroke events
• 4. Error correction
• 5. Stroke serial numbers

Forms
• Stroke events core data transfer format
• Stroke serial number inventory format

© Copyright World Health Organization (WHO) 1999. All rights reserved.

 • Copyright notice
• Manual acknowledgements
• Document identification:
o URL:http://www.ktl.fi/publications/monica/manual/part4/iv-2.htm
o URN:NBN:fi-fe19981155

Queries and comments on this section to be addressed

to:
Dr Kjell Asplund
Department of Medicine
University Hospital
S - 901 85 Umeå
Fax: +46 90 10 26 34
Email: Kjell.Asplund@medicin.umu.se

Earlier versions
• Proposal for the multinational monitoring of trends and determinants in
cardiovalscular disease and protocol (MONICA Project). WHO/MNC/82.1 Rev.1;
May 1983.
• Multinational monitoring of trends and determinants in cardiovascular diseases -
MONICA Project. Manual of operations. WHO/MNC/82.2, Draft MOO;
November 1983.
• Report of the MONICA Principal Investigators' meeting, Geneva, 28 February - 1
March 1984, Annexes III-VII. CVD/MNC/84.1, Draft. MONICA Memo 30; May
1984.
• Description of data collection procedures for the MONICA Project. MONICA
Memo 49; June 1985.
• WHO MONICA Project. MONICA Manual. CVD/MNC/Version 1.1, December
1986; Sect. 4.
• WHO MONICA Project. MONICA Manual. Geneva: World Health Organization,
Cardiovascular Diseases Unit; November 1990; Part IV, Sect. 2.

Introduction
The MONICA core study is concerned with coronary and stroke events (and not with
persons) and with two characteristics of the events, apart from their diagnostic category,
which are whether they are (a) first or recurrent, and (b) fatal or non- fatal. Each episode
must have a defined duration. In the MONICA core study a period of 28 days is used to
establish the case-fatality and to distinguish two events from each other.
The Protocol (WHO/MNC/82.1 Rev. 1) was the first document describing the principles
of event registration. Modifications and clarifications have been agreed by the Council of
Principal Investigators and these were included in MONICA MEMOs 30, 40, 41, 49
and 57. This Manual contains the latest information which should always be used.

It is important that event registration procedures are similar throughout the entire study
period in each MCC or in each Reporting Unit. There are some differences causing
systematic bias between MCC's which cannot be avoided and, therefore, the data from
different centres will not be fully comparable. If this systematic bias within each MCC is
kept unchanged, it will be possible to compare trends in incidence and case-fatality both
between and within centres because the changes over time will then be independent of the
systematic bias. The most important source of systematic bias in estimating incidence is
related to the coverage of event registration. The aim of event registration is to get as near
to 100% coverage as possible, i.e. to ascertain the maximum number of coronary events
and stroke events in the study population.

Certain factors may influence the detection of events and calculation of the event rates
such as instability of the population, seasonal migration and permanent migration in and
out of the study area. Populations for event registration must be the same as the defined
Reporting Units in each MCC. The denominator must be the same for event registration
and for the population surveys. The population size estimates for each Reporting Unit
must be reported annually to the MDC from the MCC using the Population
Demographics Reporting Form.

1. Coronary and stroke registration

1.1 Criteria for inclusion and exclusion of events

For an event to qualify for inclusion in the MONICA study:

1. the subject must be a resident of a MONICA Reporting Unit area aged between
25 and 64 years when the onset of the event occurred. This means that events
which begin in subjects who are aged under 25 years or 65 or over do not qualify
(although they may be studied as a local option);
o Residence should be defined in the same way as is done for ascertaining
the resident population of the Reporting Unit. Events occurring in non-
residents do not qualify. Conversely attempts should be made to discover
events, fatal and non-fatal which occur in residents of the area who are
elsewhere in the country or in other countries at the time they occur and
are treated outside the Reporting Unit. Each MCC should develop
standard procedures for dealing with the exclusion of non-residents and
inclusion of out-of-area events and should describe these procedures in
their local manuals.
2. the event must have had its apparent onset within the study period and more than
28 days from any preceding recorded coronary or stroke event in the same
subject;
 o Special rules apply when a subject has a stroke and a coronary event
recorded within 28 days of each other (see Subsection 1.2.4).
3. the event must satisfy the criteria for Definite or Possible Myocardial Infarction or
Ischaemic Cardiac Arrest or Definite stroke, or, if fatal, must satisfy these criteria
or those for death from coronary heart disease or cerebrovascular stroke.
Alternatively the case must have been definitively diagnosed clinically as
myocardial infarction, or coronary death, or stroke and must then be registered as
a false positive coronary or stroke or a case with inadequate data;
o In other words, the study is not concerned with cases initially
considered to be cases of myocardial infarction or stroke where such a
diagnosis has been excluded by clinical investigation and a different
pathology found. However, it is concerned with cases that continue to
have these diagnoses, even if they do not satisfy MONICA criteria, as
these `false positives' contribute to the routinely reported morbidity
and mortality trends for the Reporting Unit and they should therefore
be registered even if the MONICA diagnostic category is Not or
Inadequate data.
4. the event must have been detected and diagnosed with 28 days of onset.
o The MONICA study therefore excludes coronary and stroke events which
were not clinically recognised and investigated within 28 days of onset.
This excludes `silent' myocardial infarction and stroke and possible cases
that came to clinical attention and were not investigated but were
misdiagnosed. However desirable it may be to know about these cases, the
study design is such that they cannot be included, and they could be a
source of systematic bias.

1.2 Identification of suspect coronary or stroke events

1.2.1 Sources of Case Finding

The suspect events are collected from death certificates, from hospital medical records
and from community health services. These suspect events are examined for eligibility
into the Coronary and Stroke register. Event finding may be:

1. prospective, identifying and following up suspect cases during the hospitalization

(sometimes called "hot pursuit")
2. retrospective, abstracting information from the medical records, death certificates
and other possible sources without seeing patients at all (sometimes called "cold
pursuit")

Some sources of event finding may provide information a long time only after the actual
event occurred. Typical examples of such situations are: National Hospital Discharge
Registers, Registers for Social Security Purposes and Death Certificate Registers. One to
two years delay may occur. There is no preset time limit for including such events in the
coronary or stroke register if the criteria are otherwise met (e.g. they must have been
clinically recognised within 28 days of onset even if there was a delay in registering
them). However, the Data Centre may have to impose such a time limit at the end of the
study, in order to bring it to an end. These late events can be identified in the database by
using the date of event (DONSET) and the date of registration (DREG) and appropriate
methods of data analysis can be applied. Another problem is that of cases identified
reasonably early for whom case records remain unavailable. Again local policy and
discussion with the Data Centre will determine the optimum policy for balancing
complete registration with completing a year's registrations reasonably quickly.

In each MONICA Reporting Unit an information gathering system will need to be

instituted (1) to gain information on likely events, and (2) to obtain all available
diagnostic and other information.

The sources used must depend on the structure of the local medical and medico-legal
services.

The following sources may be used to identify cases:

• Death certificates
• Hospital admission or discharge records
• Community health centres
• Necropsy and medico-legal records
• General practitioners
• Local newspapers
• ECG records
• Laboratory records
• Social insurance records
• Emergency services (ambulance, para-medic, bed-bureau, GP deputising services)
• Interviews with patients and relatives

The first two sources are obligatory but the others will depend on the local situation.

Once sources and ICD codes have been determined in the MCC or in the Reporting Unit
it is important that methods are not changed over time without measuring the
consequences, as a change of sources may cause a spurious change in event rates.

All death certificates of the residents of the MONICA Reporting Unit areas should be
reviewed at least quarterly or semiannually.

Periodically during the 10-year period a random or stratified sample of hospital cases
should be taken to search for changes in the pattern of cases. Where multiple field
discharge data are available a different set of rules may be applied for main and
subsidiary diagnoses.

1.2.2 Identification and Validation of Fatal Events

While each MCC should attempt to find all the death certificate codes both as immediate,
main and antecedent or underlying causes of death that lead to cases of coronary heart
attack and stroke satisfying the MONICA criteria, at least the following causes of death
should be considered during pilot studies:

Cause of death ICD code

Diabetes 250
Hyperlipidaemia 272
Obesity 278
Cardiovascular
Hypertensive 401-405
Ischaemic 410-414
Other 420-429
Stroke 430-439
Arteries, etc. 440-447
Symptoms, etc. 797-799

It is therefore possible to exclude those deaths that are clearly due to trauma (e.g. contain
a sequence of events including accident, homicide or suicide), chronic obstructive
pulmonary disease, cancer, cirrhosis of the liver, or rheumatic heart disease without
mention of atherosclerotic heart or vascular disease. However, if an atherosclerotic
condition is mentioned in the sequence of events or if the cause of death is attributed to
one of the conditions listed above, the cause of death should be validated. Where deaths
are notified through medico-legal sources all non-violent sudden deaths, hospital "dead
on arrival" and deaths from cardiovascular disease within 24 hours of onset should be
monitored.

Validation is based on any available medical and medico-legal records and, if necessary
(local option) interview of the decedent's next-of-kin or another informant. Medical
records for the period within a minimum of 28 days of death should also be examined for
information that may elucidate the circumstances leading to the death. The interview
should establish the circumstances surrounding the decedent's death.

Deaths should be validated by applying the MONICA diagnostic criteria for coronary
events (see Section 1, subsection 2.2). These are based on the symptom history, ECG's,
cardiac enzymes, necropsy and death certificate data. In positive cases diagnostic
findings should be recorded on the locally used MONICA Coronary Event Registration
Forms. In those centres undertaking stroke registration diagnostic criteria should be
applied for stroke using similar sources of data. In positive cases diagnostic findings
should be recorded on the locally used MONICA Stroke Event Registration Forms.

The list of death certificate codes produced above was for use during the development of
the MONICA Registration procedures in each MONICA Collaborating Centre. Where,
after pilot studies, a more limited list is being monitored, because certain codes were
found to be unproductive, then the full list should be used periodically to see that the
situation has not changed. All deaths with the underlying cause coded to 410-414 must
be registered even if they are found not to be a coronary case on examination.
Stroke registers should register all cases where the ICD code implies acute stroke
(ICD 430-4 and 436) even if they are found not to be strokes alone.

1.2.3 Identification and Validation of Non-fatal Events

In hospital

It is suggested that in the early phases of data collection each MCC collect data on cases
drawn from a broad range of discharge codes which might include stroke assigned to
another category. Examples of these belong to the categories (ICD-9) 430-438 but might
also include hemiplegia (342), "certain symptoms referable to the nervous system and
special senses" (781). Once it has been established that an insignificant proportion of
cases discharged without stroke diagnoses are in fact not stroke, case validation can
proceed on a narrower scale (e.g. 430-436 or 438). Documentation of the adequacy of
such a narrower scale should be repeated every two to five years to make sure that there
has been no change in hospital labelling practice over time.

Out-of-hospital

In communities where patients in the 25-64 age range with stroke are not always treated
in hospital, routine searches outside will be cost effective, but even where hospital
treatment is said to be the norm, this should be confirmed by questioning physicians in
the community in the pilot phase. However, in those countries where stroke is treated at
home, contact must be made with physicians and a protocol established to identify and
collect data on stroke cases. This procedure could take several forms and might include
reviewing charts on a semi- annual basis, providing each office with a log book and a
poster reminding them to log all cases of suspected new stroke, or asking the office nurse
or assistant to notify the project when a new stroke is identified.

1.2.4 Overlapping Coronary and Stroke Registrations

Each coronary and stroke event is defined as lasting for 28 days (unless interrupted by
death) so that any recurrence or exacerbation of the condition within that period is
counted as part of the original episode whereas beyond that time it counts as a new
(recurrent) episode. A special problem arises in those centres who are registering both
coronary and stroke events in dealing with cases who satisfy criteria for both coronary
and stroke events within one 28 day period, or in which the clinical diagnosis is of one
condition, but the diagnostic evidence suggests that the other is more probable. Such
events should be discussed by both registration teams.

Each MCC should lay down its own rules and should adhere to them so that there is no
systematic bias over time. The number of events involved is small and should not have a
big effect on registration numbers whatever method of handling the problem is used. The
following rules are recommended; these should be acceptable to both those centres that
are registering coronary events and strokes and those that are registering coronary events
alone.

Cases satisfying criteria for definite myocardial infarction should be registered as such
whether or not an apparent stroke occurs within 28 days before or afterwards.

Definite strokes should also be registered but if they occur in association with a definite
myocardial infarction (within 28 days before or after), for stroke the diagnostic category
5 can be used, rather than 1. The event would be registered in both the coronary and
stroke registers but could be removed from the latter by excluding category 5 if this was
wanted.

Patients who die from a combined definite myocardial infarction and definite stroke
within 28 days of onset of acute symptoms should be counted as fatal cases in both
registers but again could be removed from the stroke register for certain analyses if
necessary as they would be coded as category 5.

In cases where definite evidence for one of these two diseases is mixed with possible or
inadequate data evidence for the other, the definite diagnosis should take precedence and
the possible diagnosis should not lead to registration unless the secondary diagnosis
appears as the underlying cause of death on the death certificate, or as a major clinical
diagnosis when the case is notified. In these cases the patient would appear in the register
of the definite disease as a Definite case and in the register of the unproven disease as a
Not case, or false positive. In these cases it would be clear from the clinical diagnoses or
the death certificate diagnoses on the record form what had happened to make it a false
positive.

Cases with inadequate data which could be either coronary or stroke events should not be
assigned to both registers as inadequate data but should be allocated the most probable
diagnosis, regardless of what the death certificate diagnosis states. A case diagnosed on
the death certificate as stroke which on investigation is more like a coronary death should
therefore be coded as an inadequate data case in the coronary event register and as
DIACAT 4 in the stroke register.

2. Registration of stroke events

2.1 Data Collection

2.1.1 Data to be collected

The diagnosis of stroke is based on clinical signs which should last more than 24 hours
except in cases of sudden death or if the development of symptoms is interrupted by a
surgical intervention. Therefore, it is important to pay great attention to both symptoms
and duration. Data on subcategories of stroke will also be collected to give more
information about different types of stroke. The classification into subcategories of stroke
should strictly follow the criteria given under Subsection 2.2.4.
2.1.2 28-day survival period

Every stroke event must have its apparent onset within the study period and more than 28
days from any preceding recorded stroke event. Special rules apply where suspected
stroke and coronary events occur within 28 days of each other (see Subsection 1.2.4). The
method of calculating the 28-day survival period in a stroke event is exactly the same as
in coronary events (see Section 1, Subsection 2.1.2).

2.1.3 First or recurrent event

It is important to obtain the best available information about previous stroke in each event
in order to separate first events from recurrent events. The data item "Previous history of
stroke" is the only variable which allows this separation. The previous stroke episode
should be more than 28 days previously, otherwise the present episode would count as a
complication of the previous one and not as a recurrence.

Previous history should be decided on the basis of routine records used consistently
throughout the study such as:

a. records present in the hospital treating the acute index attack

b. a defined number of sources in fatal cases

Previous registration data should NOT be used as this will introduce a bias over the
duration of the study as attacks during an increasing number of previous years will have
been registered. Centres with record linkage should use this as a local option and not use
registration data for the reason given above.

The procedures for the collection of these data should be kept constant throughout the
entire study period.

2.2 Diagnostic Classification

The diagnostic classification is similar to that used in the WHO Stroke Registers.

2.2.1. Definition of Stroke

Stroke is defined as rapidly developed clinical signs of focal (or global1) disturbance of
cerebral function lasting more than 24 hours (unless interrupted by surgery or death),
with no apparent cause other than a vascular origin: it includes patients presenting
clinical signs and symptoms suggestive of subarachnoid haemorrhage, intracerebral
haemorrhage or cerebral ischaemic necrosis. It does not include transient cerebral
ischaemia or stroke events in cases of blood disease (e.g. leukemia, polycythaemia vera),
brain tumour or brain metastases. Secondary stroke caused by trauma should also be
excluded.
Note1 : Global: this applies to patients with subarachnoid haemmorrhage or deep coma
but excluding coma of systemic vascular origin such as shock, Stokes-Adams syndrome
or hypertensive encephalopathy.

Definite focal signs:

• Unilateral or bilateral motor impairment (including dyscoordination)

• unilateral or bilateral sensory impairment
• aphasis/dysphasis (non-fluent speech)
• hemianopia (half-sided impairment of visual fields)
• Diplopia
• Forced gaze (conjugate deviation)
• Dysphagia of acute onset
• Apraxia of acute onset
• Ataxia of acute onset
• Perception deficit of acute onset.

Not acceptable as sole evidence of focal dysfunction

• Dizziness, vertigo
• Localized headache
• Blurred vision of both eyes
• Dysarthria (slurred speech)
• Impaired cognitive function (including confusion)
• Impaired consciousness
• Seizures

(Although strokes can present in this way, these signs are not specific and cannot
therefore be accepted as definite evidence for stroke.)

2.2.2 Timing and Priority of Results

Because each event lasts only 28 days the diagnostic criteria used must be from
investigations or symptoms that refer to what happened within that 28 day period even
though the results (such as necropsy) may be reported later. The definition of the 28-day
survival period has been given earlier.

The most severe findings during the 28-day survival period should always be used to
derive the diagnostic information. If there are recurrent episodes during the 28 day period
the initial episode may not be associated with the same specific diagnostic information as
becomes available later. The date of onset should not be changed for this reason but the
most specific information should be used in deciding on the diagnostic category and type
of stroke.
When a patient dies later than 28 days after onset, and cerebrovascular disease appears
among the death certificate diagnoses, the following procedure is applied. First, check
that death is not caused by a recurrent stroke that should be registered as a separate event.
Then, if death is caused by sequelae of a stroke, and cerebrovascular disease is
considered to be the underlying cause of death, register the initiating event (if registration
has not been done previously) but be sure to code SURVIV = 1 (i.e. survival more than
28 days). In addition, make a new registration relating to the death and be sure to include
stroke as one of CLIND1, CLIND2 or CLIND3, but now code DIACAT = 4 (not stroke),
because the entry criteria are not fulfilled - the event occurred more than 28 days ago. In
this way, discrepancies between the official death registers and the MONICA
registrations are avoided. Deaths caused by the late sequelae of stroke and appearing in
the official registers will be coded as false positive fatal events in the MONICA
registrations but will appear as non-fatal stroke cases.

2.2.3. Diagnostic Categories

There are the following three categories:

(1) = Definite stroke

(4) = Not stroke
(5) = Definite stroke associated with Definite myocardial infarction
(9) = Insufficient data

Allocation of a diagnostic category must follow strictly the definition provided. A strict
watch should be kept over competing causes of death. Note the discussion of competition
and overlap between coronary and stroke event registration in Subsection 1.2.4. Local
rules should be standardized and a record kept of difficult decisions.

Insufficient data should be mainly used for fatal cases, especially for cases of sudden
death without necropsy.

All patients having insufficient supporting evidence of stroke, but for whom the diagnosis
of stroke cannot be entirely excluded, should be classified as insufficient data, e.g. cases
with no necropsy, no documented history of focal neurologic deficits and no other
diagnosis. Living patients can be classified into this category if:

i. it is impossible to say whether the symptoms were from stroke or from some other
disease, e.g. epilepsy, or
ii. patients with symptoms and clinical findings otherwise typical for a stroke but the
duration remaining uncertain.

If the event is classified 1 (definite stroke), 5 (definite stroke associated with definite
myocardial infarction) or 9 (insufficient data) one of the clinical or death certificate
diagnosis codes of CLIND1, CLIND2 or CLIND3 should be between 430-438.

2.2.4. Type of stroke

Subcategories of stroke are given on the form, Item TYPE using the ICD codes (8th or
9th revision).

Codes for specific subcategories of stroke should be used only if the diagnosis has been
confirmed according to the following criteria:

Subarachnoid Haemorrhage ICD 8 or 9 430

Symptoms:
Abrupt onset of severe headache or unconsciousness or both. Signs of meningeal
irritation (stiff neck, Kernig and Brudzinski signs). Focal neurological deficits are
usually not present.

Findings:
At least one of the following must be present additional to typical symptoms.

1. Necropsy - recent subarachnoid haemorrhage and an aneurysm or

arteriovenous malformation
2. CT - blood in the Fissura Sylvii or between the frontal lobes or in the basal
cistern or in cerebral ventricles
3. Cerebrospinal fluid (liquor) bloody (>2 000rbc per cmm) and an aneurysm
or an arteriovenous malformation found on angiography
4. Cerebrospinal fluid (liquor) bloody (>2 000rbc per cmm) and
xanthochromic and the possibility of intra-cerebral haemorrhage excluded
by necropsy or CT-examination

Intracerebral haemorrhage ICD 8 or 9 431

Symptoms:
Usually sudden onset during activities. Often rapidly developing coma, but small
haemorrhage presents no consciousness disturbance.

Findings:
Cerebrospinal fluid often, but not always bloody or xanthochromic. Often severe
hypertension present. Haemorrhage must be confirmed by necropsy or by CT-
examination.

Brain infarction due to occlusion of precerebral arteries ICD 9 433 ICD 8 432

Symptoms:
May vary.

Findings:
The occlusion must be confirmed by angiography or ultrasound or necropsy.

Brain infarction due to cerebral thrombosis ICD 9 434 ICD 8 433

Symptoms:
No severe headache, if at all. Onset acute, sometimes during sleep. Often gradual
progression of focal neurologic deficits. Usually, no, or only slight, disturbance of
consciousness. TIA can often be detected in history. Often other symptoms of
atherosclerosis (CHD, peripheral arterial disease) or underlying diseases
(hypertension, diabetes).

Findings:
Brain infarction in the necropsy or in the CT-examination and no evidence for an
embolic origin.

OR

CT scan of satisfactory quality shows no recent brain lesion although clinical

criteria of stroke are fulfilled.

Embolic brain infarction ICD 9 434 ICD 8 434

Symptoms:
Abrupt onset, usually completion of the neurologic deficits within a few minutes.
Disturbance of consciousness absent or only slight at the onset.

Findings:
As in brain infarction due to cerebral thrombosis, but in addition a source of the
embolus must be detectable. The most common origins are:

• arrhythmia (atrial flutter and fibrillation)

• valvular heart disease (mitral)
• recent AMI (within previous 3 months)

Remarks: If it is impossible to assign to a definite stroke event one of these sub-

categories, the subcategory "Acute, but ill-defined cerebrovascular disease should be
recorded (ICD code 436). Other codes: 435, 437, 438 should not be used in the data item
"TYPE". If the clinical criteria for a stroke are fulfilled but a CT scan (of satisfactory
technical quality) fails to reveal a brain lesion of recent origin, the patient has in all
probability suffered an ischaemic stroke. In this case, type of stroke should be coded as
434 (infarction).

3. Core Transfer Form and Instructions for Stroke

Events
The stroke event registration data to be sent to the MDC are specified in the Core Data
Transfer Format - Stroke Events, which is appended to this section.

4. Error correction
The procedure for correcting errors in data which have already been submitted to the
MDC are described in Part V, Section 1.3.3.

5. Stroke Serial Numbers

Every suspect event should be issued a serial number by the MCC as early as
possible in the identification process, especially in MCCs which register
retrospectively. The minimum requirement is that when the MCC begins to collect data
on a suspect event, it is provided with a serial number. The serial number consists of
seven digits. Each serial number must be unique within each MONICA Reporting Unit
and within each register (i.e. stroke register and coronary register). Different MONICA
Reporting Units and different registers may use the same serial numbers. The serial
numbers within a Reporting Unit and register must be different for different events
throughout the ten-year registration period.

Log-books of serial number histories: The MCCs must keep a log-book of the history
of every Coronary Serial Number and Stroke Serial Number issued. The items of the
Stroke Serial Number Inventory Format should be included in this log-book. The serial
number histories are used to monitor the data flow and time lag in the event registration.

Correctness of the serial number: The serial number is one of the key items of an event
record. The Form Identification, Collaborating Centre Code, Reporting Unit Code and
Serial Number are all necessary in order to uniquely identify an event. Each MCC should
have some kind of security system to help assure that the serial number is error free. One
possibility is to have the last digit of the serial number a check digit which is used to
control the correctness of the other digits at least until the individual record has been
computerized.

A check digit needs to be calculated when the serial number is issued. It is useful only if
this is done correctly. This can be secured by letting a computer generate the serial
numbers with the check digits and print the numbers on stickers or labels which are then
stuck on the log-books and data collection forms.

Serial number inventory data transfer: Serial number inventory data should be sent to
the MDC as instructed in the Stroke Serial Number Inventory Format, which is appended
to this section.

MONICA Manual, Part IV:Event Registration

Section 4: ECG coding quality assurance

methods
 November 1990

This section provides a description of the quality assurance methods to be applied to the
ECG coding in the WHO MONICA Project.

Contents
• Introduction
• 1. Guidelines for Internal Quality Control
• 2. External Quality Control
• Annex

© Copyright World Health Organization (WHO) 1999. All rights reserved.

• Copyright notice
• Manual acknowledgements
• Document identification:
o URL:http://www.ktl.fi/publications/monica/manual/part4/iv-4.htm
o URN:NBN:fi-fe19981159

Queries/comments on this section should be addressed

to:
Professor Hugh Tunstall-Pedoe
Cardiovascular Epidemiology Unit
Ninewells Hospital and Medical School
Dundee DD1 9SY, GB
Fax: +44 1382 644 255
Email: h.tunstallpedoe@dundee.ac.uk

Earlier versions
• WHO MONICA Project. MONICA Manual. CVD/MNC/Version 1.1, December
1986; Sect. 9.
• WHO MONICA Project. MONICA Manual. Geneva: World Health Organization,
Cardiovascular Diseases Unit; November 1990; Part IV, Sect. 3.

Introduction
The reliability of Minnesota coding within the WHO MONICA Project is achieved by
internal and external quality control measures. Internal quality control includes all
measures applied within one MONICA Collaborating Centre aimed at uniform coding by
different coders and consistency in using the code system. External quality control aims
at standardization of Minnesota coding between the MONICA Collaborating Centres and
is carried out by the MONICA Quality Control Centre for ECG Coding, Budapest.

1. Guidelines for internal quality control

1. Each ECG is coded preferably by two independent coders who have previously
been trained in the use of the Minnesota code system, unaware of the results of
each other. The coders should also, ideally, be unaware of the clinical diagnosis
made on the case and the result of any cardiac enzyme determinations. Research
has shown that coders like to agree with the clinicians involved with the case, and
knowledge of the clinical diagnoses and interpretations of the electrocardiogram
biases the coding towards finding more pathological abnormality than is actually
present. The codes established by the two coders separately are compared. If only
one coder is available, all ECGs should be re-coded after a suitable interval.
2. In the case of a discrepancy between the two coders, a third senior coder or
supervisor re-codes the ECG without knowing the codes of the two other coders.
After having established his/her own code, the three coders discuss the case and
come to a final decision.
3. In order to check intra-coder consistency, a random sample of 10% of the ECGs is
re-cycled every year. The results of the two readings are compared and the causes
of discrepancies carefully analysed with the involvement of the supervisor.
4. In the case of more than one Reporting Unit (RU) within one MCC, 20 ECGs are
coded by the supervisors of all RUs every half a year. The two most experienced
supervisor coders previously establish their reference codes. After all the RUs'
supervisors have coded the ECGs, they discuss the discrepancies and come to a
consensus on the codes. The same 20 ECGs are then coded by all the coders
within one RU and the codes discussed by the coders and the supervisor coder.

2. External quality control

1. Training seminars for coders are held regularly by the Quality Control Centre for
ECG Coding according to the needs and requests of the MCCs. The aim is to give
an opportunity to all MCCs to participate in such courses.

The Training Seminars are led by the head of the Quality Control Centre. They
are open to a limited number of participants (preferably not more than 10 to 12 at
each occasion) chosen from those who give notice about their willingness to
participate. The results of the previous test exercises are also taken into
consideration when choosing from candidates. All participants should have some
experience in Minnesota Coding.
 The topic of the Seminars are those items of the Minnesota code system which are
relevant for the MONICA Project. These are 1, 4, 5, 9.2 and suppressing codes.
Both technical and theoretical problems are discussed and great emphasis is
placed on actual coding.

2. A test set of ECGs is collected every year by the Quality Control Centre for ECG
Coding. This set is reproduced and dispatched to the MCCs by the MONICA
Management Centre. The MCCs establish their Minnesota codes of the ECGs in
the set and send the codes back to the Quality Control Centre.

The "reference codes" of the ECG set are established by the Quality Control
Centre in cooperation with the Minnesota Coding Laboratory, and/or a panel of
coders of proven ability. After receipt of the codes from the MCCs, a computer
analysis is carried out - the underlying equations are shown in the appendix. This
is followed by a review of each individual set of codes in comparison to the
reference codes. A short report of the performance of each MCC is prepared and
sent to the respective MONICA Collaborating Centre.

After receipt of the results from each MCC the performance of the individual
Centres is compared. For this purpose formula "B" (see Annex) is used, which
compares the numbered all discrepancies to the total numbered in ECGs with
reference codes. The average of the mistake rates of the three lead groups for Q-
codes is taken and separately the average of averages of the mistake rates for ST
and T codes. Finally, the average of these two values is calculated.

Agreement between the Centre codes and the reference codes is considered good
if the calculated value, i.e. the percentage of discrepancy, is less than 30%, and
acceptable if it is between 30% and 50%. In those cases with disagreement of
more than 50% improvement in Minnesota coding is desirable.

3. The quality control of the MONICA Quality Control Centre itself is provided,
where possible, through the Minnesota Coding Laboratory in Minneapolis. If this
cannot be maintained, it will be done through a panel of external coders of proven
ability, or Task Force, who will help to provide a pool of high quality
electrocardiograms with agreed codes. The panel will help to arbitrate in case of
disagreement between the Quality Control Centre and the individual MCCs.

Annex: Formulas used in ECG quality control

Values were taken from these equations:

(Using code 1)
 Reference Codes
1,0 1,1 1,2 1,3 Total (T1)
(No Q) 1,0 I
(Major Q) 1,1 J
(Moderate Q) 1,2 K
(Minor Q) 1,3 L
(Total T2) N

Formula A = (T1-I) + (T2-I) / (N-I) x 100

extra and missed codes in ECGs with codes

Formula B = (N - I - J - K - L) / (N - I) x 100
extra, missed and codes off by a degree in ECGs with codes

Formula C = (T1 - I) + (T2 - I) / N x 100

extra and missed codes in all ECGs

Formula D = (N - I - J - K - L) / N x 100
extra, missed and codes off by a degree in all ECGs

Formula E = Weaker centre codes by a degree in all ECGs

Formula F = Stronger centre codes by a degree in all ECGs

MONICA Manual, Part IV: Event Registration

Section 1: Coronary Event Registration

Data Component
March 1999

This section provides the equivalent of a manual of operations for the collection and
processing of data for this component of the MONICA Project.
Contents
• Introduction
• 1.Coronary and stroke registration
o 1.1 Criteria for inclusion and exclusion of events
o 1.2 Identification of suspect coronary or stroke events
• 2. Registration of coronary events: diagnostic rules and algorithms
o 2.1 Data collection
o 2.2 Diagnostic classification
o 2.3 Derivation of MONICA diagnostic category for coronary events
o 2.4 Electrocardiographic criteria for coronary events
o 2.5 Diagnostic algorithm for deriving MONICA ECG diagnosis from
Minnesota codes
• 3. Data transfer form and instructions for coronary events
• 4. Acute coronary care
o 4.1 Introduction
o 4.2 Data transfer form and instructions for acute coronary care
o 4.3 Groupings of drugs for MONICA acute coronary care record
• 5. Error correction form and procedures
• 6. Coronary serial numbers
• References
• Annex 1. Dundee diagnostic algorithm
• Annex 2. WHO MONICA Drugs List

Forms
• Coronary events core data transfer format
o Current version (Version 5)
o Former version (Version 3) used for data transfer to the MONICA Data
Centre
• Acute coronary care core data transfer format
o Current version (Version 6)
o Former version (Version 3) used for data transfer to the MONICA Data
Centre
• Coronary serial number inventory format

© Copyright World Health Organization (WHO) 1999. All rights reserved.

• Copyright notice
• Manual acknowledgements
• Document identification:
o URL:http://www.ktl.fi/publications/monica/manual/part4/iv-1.htm
o URN:NBN:fi-fe19981154
Queries and comments on this section to be addressed
to:
Professor Hugh Tunstall-Pedoe
Cardiovascular Epidemiology Unit
Ninewells Hospital and Medical School
Dundee DD1 9SY, GB
Fax: +44 1382 644 255
Email: h.tunstallpedoe@dunde.ac.uk

Earlier versions
• Proposal for the multinational monitoring of trends and determinants in
cardiovascular disease and protocol (MONICA Project). WHO/MNC/82.1 Rev.1;
May 1983.
• Multinational monitoring of trends and determinants in cardiovascular diseases -
MONICA Project. Manual of operations. WHO/MNC/82.2, Draft MOO;
November 1983.
• Report of the MONICA Principal Investigators' meeting, Geneva, 28 February - 1
March 1984, Annexes III-VII. CVD/MNC/84.1, Draft. MONICA Memo 30; May
1984.
• Derivation of MONICA diagnostic categories. A commentary from the MONICA
Quality Control Centre for Event Registration. MONIC Memo 40; February 1985.
• Electrocardiographic coding for MONICA - a diagnostic algorithm and test code
sequences. A commentary from the MONICA Quality Control Centre for Event
Registration. MONICA Memo 41; March 1985.
• Description of data collection procedures for the MONICA Project. MONICA
Memo 49; June 1985.
• Revised coronary event and acute coronary record formats and specific
instructions. MONICA Memo 57; December 1985.
• WHO MONICA Project. MONICA Manual. CVD/MNC/Version 1.1, December
1986; Sect. 4 and 5.
• WHO MONICA Project. MONICA Manual. Geneva: World Health Organization,
Cardiovascular Diseases Unit; November 1990; Part IV, Sect. 1.

Changes made after November 1990 revision

• Small notes on the experience in data collection and use of the data in
collaborative MONICA publications have been added.

Introduction
The MONICA core study is concerned with coronary and stroke events (and not with
persons) and with two characteristics of the events, apart from their diagnostic category,
which are whether they are (a) first or recurrent, and (b) fatal or non- fatal. Each episode
must have a defined duration. In the MONICA core study a period of 28 days is used to
establish the case-fatality and to distinguish two events from each other.

The Protocol (WHO/MNC/82.1 Rev. 1) was the first document describing the principles
of event registration. Modifications and clarifications have been agreed by the Council of
Principal Investigators and these were included in MONICA MEMOs 30, 40, 41, 49 and
57. This Manual contains the latest information which should always be used.

It is important that event registration procedures are similar throughout the entire study
period in each MCC or in each Reporting Unit. There are some differences causing
systematic bias between MCCs which cannot be avoided and, therefore, the data from
different centres will not be fully comparable. If this systematic bias within each MCC is
kept unchanged, it will be possible to compare trends in incidence and case-fatality both
between and within centres because the changes over time will then be independent of the
systematic bias. The most important source of systematic bias in estimating incidence is
related to the coverage of event registration. The aim of event registration is to get as near
to 100% coverage as possible, i.e. to ascertain the maximum number of coronary events
and stroke events in the study population.

Certain factors may influence the detection of events and calculation of the event rates
such as instability of the population, seasonal migration and permanent migration in and
out of the study area. Populations for event registration must be the same as the defined
Reporting Units in each MCC. The denominator must be the same for event registration
and for the population surveys. The population size estimates for each Reporting Unit
must be reported annually to the MDC from the MCC using the Population
Demographics Reporting Form.

1. Coronary and stroke registration

1.1 Criteria for inclusion and exclusion of events

For an event to qualify for inclusion in the MONICA study:

1. the subject must be a resident of a MONICA Reporting Unit area aged between
25 and 64 years when the onset of the event occurred. This means that events
which begin in subjects who are aged under 25 years or 65 or over do not qualify
(although they may be studied as a local option);
o Residence should be defined in the same way as is done for ascertaining
the resident population of the Reporting Unit. Events occurring in non-
residents do not qualify. Conversely attempts should be made to discover
events, fatal and non-fatal which occur in residents of the area who are
elsewhere in the country or in other countries at the time they occur and
are treated outside the Reporting Unit. Each MCC should develop
 standard procedures for dealing with the exclusion of non-residents and
inclusion of out-of-area events and should describe these procedures in
their local manuals.
2. the event must have had its apparent onset within the study period and more than
28 days from any preceding recorded coronary or stroke event in the same
subject;
o Special rules apply when a subject has a stroke and a coronary event
recorded within 28 days of each other (see Chapter 1.2.4).
3. the event must satisfy the criteria for Definite or Possible Myocardial Infarction or
Ischaemic Cardiac Arrest or Definite stroke, or, if fatal, must satisfy these criteria
or those for death from coronary heart disease or cerebrovascular stroke.
Alternatively the case must have been definitively diagnosed clinically as
myocardial infarction, or coronary death, or stroke and must then be registered as
a false positive coronary or stroke or a case with inadequate data;
o In other words, the study is not concerned with cases initially
considered to be cases of myocardial infarction or stroke where such a
diagnosis has been excluded by clinical investigation and a different
pathology found. However, it is concerned with cases that continue to
have these diagnoses, even if they do not satisfy MONICA criteria, as
these `false positives' contribute to the routinely reported morbidity
and mortality trends for the Reporting Unit and they should therefore
be registered even if the MONICA diagnostic category is Not or
Inadequate data.
4. the event must have been detected and diagnosed within 28 days of onset.
o The MONICA study therefore excludes coronary and stroke events which
were not clinically recognised and investigated within 28 days of onset.
This excludes `silent' myocardial infarction and stroke and possible cases
that came to clinical attention and were not investigated but were
misdiagnosed. However desirable it may be to know about these cases, the
study design is such that they cannot be included, and they could be a
source of systematic bias.

1.2 Identification of suspect coronary or stroke events

1.2.1 Sources of Case Finding

The suspect events are collected from death certificates, from hospital medical records
and from community health services. These suspect events are examined for eligibility
into the Coronary and Stroke register. Event finding may be;

1. prospective, identifying and following up suspect cases during the hospitalization

(sometimes called "hot pursuit")
2. retrospective, abstracting information from the medical records, death certificates
and other possible sources without seeing patients at all (sometimes called "cold
pursuit")
Some sources of event finding may provide information a long time only after the actual
event occurred. Typical examples of such situations are: National Hospital Discharge
Registers, Registers for Social Security Purposes and Death Certificate Registers. One to
two years delay may occur. There is no preset time limit for including such events in the
coronary or stroke register if the criteria are otherwise met (e.g. they must have been
clinically recognised within 28 days of onset even if there was a delay in registering
them). However, the Data Centre may have to impose such a time limit at the end of the
study, in order to bring it to an end. These late events can be identified in the database by
using the date of event (DONSET) and the date of registration (DREG) and appropriate
methods of data analysis can be applied. Another problem is that of cases identified
reasonably early for whom case records remain unavailable. Again local policy and
discussion with the Data Centre will determine the optimum policy for balancing
complete registration with completing a year's registrations reasonably quickly.

In each MONICA Reporting Unit an information gathering system will need to be

instituted (1) to gain information on likely events, and (2) to obtain all available
diagnostic and other information.

The sources used must depend on the structure of the local medical and medico- legal
services.

The following sources may be used to identify cases:

• Death certificates
• Hospital admission or discharge records
• Community health centres
• Necropsy and medico-legal records
• General practitioners
• Local newspapers
• ECG records
• Laboratory records
• Social insurance records
• Emergency services (ambulance, para-medic, bed-bureau, GP deputising services)
• Interviews with patients and relatives

The first two sources are obligatory but the others will depend on the local situation.

Once sources and ICD codes have been determined in the MCC or in the Reporting Unit
it is important that methods are not changed over time without measuring the
consequences, as a change of sources may cause a spurious change in event rates.

All death certificates of the residents of the MONICA Reporting Unit areas should be
reviewed at least quarterly or semiannually.

Periodically during the 10-year period a random or stratified sample of hospital cases
should be taken to search for changes in the pattern of cases. Where multiple field
discharge data are available a different set of rules may be applied for main and
subsidiary diagnoses.

1.2.2 Identification and Validation of Fatal Events

While each MCC should attempt to find all the death certificate codes both as immediate,
main and antecedent or underlying causes of death that lead to cases of coronary heart
attack and stroke satisfying the MONICA criteria, at least the following causes of death
should be considered during pilot studies:

Cause of death ICD code

Diabetes 250
Hyperlipidaemia 272
Obesity 278
Cardiovascular
Hypertensive 401-405
Ischaemic 410-414
Other 420-429
Stroke 430-439
Arteries,etc. 440-447
Symptoms, etc. 797-799

It is therefore possible to exclude those deaths that are clearly due to trauma (e.g. contain
a sequence of events including accident, homicide or suicide), chronic obstructive
pulmonary disease, cancer, cirrhosis of the liver, or rheumatic heart disease without
mention of atherosclerotic heart or vascular disease. However, if an atherosclerotic
condition is mentioned in the sequence of events or if the cause of death is attributed to
one of the conditions listed above, the cause of death should be validated. Where deaths
are notified through medico-legal sources all non-violent sudden deaths, hospital "dead
on arrival" and deaths from cardiovascular disease within 24 hours of onset should be
monitored.

Validation is based on any available medical and medico-legal records and, if necessary
(local option) interview of the decedent's next-of-kin or another informant. Medical
records for the period within a minimum of 28 days of death should also be examined for
information that may elucidate the circumstances leading to the death. The interview
should establish the circumstances surrounding the decedent's death.

Deaths should be validated by applying the MONICA diagnostic criteria for coronary
events (see 2.2). These are based on the symptom history, ECGs, cardiac enzymes,
necropsy and death certificate data. In positive cases diagnostic findings should be
recorded on the locally used MONICA Coronary Event Registration Forms. In those
centres undertaking stroke registration diagnostic criteria should be applied for stroke
using similar sources of data. In positive cases diagnostic findings should be recorded on
the locally used MONICA Stroke Event Registration Forms.

The list of death certificate codes produced above was for use during the development of
the MONICA Registration procedures in each MONICA Collaborating Centre. Where,
after pilot studies, a more limited list is being monitored, because certain codes were
found to be unproductive, then the full list should be used periodically to see that the
situation has not changed. All deaths with the underlying cause coded to 410-414 must
be registered even if they are found not to be a coronary case on examination.
Stroke registers should register all cases where the ICD code implies acute stroke
(ICD 430-4 and 436) even if they are found not to be strokes alone.

1.2.3 Identification and Validation of Non-fatal Events

In hospital

It is the experience in some countries that practically all myocardial infarctions are
identified as such but not all cases identified as myocardial infarction meet the criteria for
MONICA coronary events. To ensure that this is the case in all MCCs using discharge
diagnoses ("cold pursuit") as the source of case finding it is suggested that each centre
starts with a range of discharge codes that is broader than 410 and 411 (e.g. codes for
chronic ischaemic heart disease and non- ischaemic heart disease, atherosclerosis,
pulmonary embolism and other syndromes associated with chest pain or undiagnosed
chest pain) and document that an insignificant proportion of cases with a definite
coronary event are included in these discharge codes.

For those centres employing "hot pursuit" on the other hand it is necessary to monitor all
acute medical admission wards as well as hospital laboratory data on cardiac enzymes
and ECGs to be sure that all cases have been detected.

It is suggested that in the early phases of data collection each MCC collect data on cases
drawn from a broad range of discharge codes which might include stroke assigned to
another category. Examples of these belong to the categories (ICD-9) 430-438 but might
also include hemiplegia (342), "certain symptoms referable to the nervous system and
special senses" (781). Once it has been established that an insignificant proportion of
cases discharged without stroke diagnoses are in fact not stroke, case validation can
proceed on a narrower scale (e.g. 430-436 or 438). Documentation of the adequacy of
such a narrower scale should be repeated every two to five years to make sure that there
has been no change in hospital labelling practice over time.

Out-of-hospital
Out-of-hospital treatment of acute myocardial infarction is not common in most cities.
Such cases may be detected from clinical pathology laboratory records for cardiac
enzymes and electrocardiographic laboratory records if these are used in the study
centre's area. In communities where acute myocardial infarction patients may be treated
out of hospital attempts should be made to define the proportion of such events by
questioning physicians in the community. A protocol should be developed as part of the
Manual of Operations of the MCC to identify and collect data on coronary events treated
out of hospital.

In communities where patients in the 25-64 age range with stroke are not always treated
in hospital, routine searches outside will be cost effective, but even where hospital
treatment is said to be the norm, this should be confirmed by questioning physicians in
the community in the pilot phase. However, in those countries where stroke is treated at
home, contact must be made with physicians and a protocol established to identify and
collect data on stroke cases. This procedure could take several forms and might include
reviewing charts on a semi- annual basis, providing each office with a log book and a
poster reminding them to log all cases of suspected new stroke, or asking the office nurse
or assistant to notify the project when a new stroke is identified.

1.2.4 Overlapping Coronary and Stroke Registrations

Each coronary and stroke event is defined as lasting for 28 days (unless interrupted by
death) so that any recurrence or exacerbation of the condition within that period is
counted as part of the original episode whereas beyond that time it counts as a new
(recurrent) episode. A special problem arises in those centres who are registering both
coronary and stroke events in dealing with cases who satisfy criteria for both coronary
and stroke events within one 28 day period, or in which the clinical diagnosis is of one
condition, but the diagnostic evidence suggests that the other is more probable. Such
events should be discussed by both registration teams.

Each MCC should lay down its own rules and should adhere to them so that there is no
systematic bias over time. The number of events involved is small and should not have a
big effect on registration numbers whatever method of handling the problem is used. The
following rules are recommended; these should be acceptable to both those centres that
are registering coronary events and strokes and those that are registering coronary events
alone.

Cases satisfying criteria for definite myocardial infarction should be registered as such
whether or not an apparent stroke occurs within 28 days before or afterwards.

Definite strokes should also be registered but if they occur in association with a definite
myocardial infarction (within 28 days before or after), for stroke the diagnostic category
5 can be used, rather than 1. The event would be registered in both the coronary and
stroke registers but could be removed from the latter by excluding category 5 if this was
wanted.
Patients who die from a combined definite myocardial infarction and definite stroke
within 28 days of onset of acute symptoms should be counted as fatal cases in both
registers but again could be removed from the stroke register for certain analyses if
necessary as they would be coded as category 5.

In cases where definite evidence for one of these two diseases is mixed with possible or
inadequate data evidence for the other, the definite diagnosis should take precedence and
the possible diagnosis should not lead to registration unless the secondary diagnosis
appears as the underlying cause of death on the death certificate, or as a major clinical
diagnosis when the case is notified. In these cases the patient would appear in the register
of the definite disease as a Definite case and in the register of the unproven disease as a
Not case, or false positive. In these cases it would be clear from the clinical diagnoses or
the death certificate diagnoses on the record form what had happened to make it a false
positive.

Cases with inadequate data which could be either coronary or stroke events should not be
assigned to both registers as inadequate data but should be allocated the most probable
diagnosis, regardless of what the death certificate diagnosis states. A case diagnosed on
the death certificate as stroke which on investigation is more like a coronary death should
therefore be coded as an inadequate data case in the coronary event register and as
DIACAT 4 in the stroke register.

2. Registration of coronary events: diagnostic rules and

algorithms
2.1 Data Collection

2.1.1. Data to be collected

In order to define the diagnostic category of a suspect event information about the
following four data items must be collected:

• Symptoms
• Electrocardiogram
• Cardiac enzymes
• Necropsy findings

The rest of the data to be collected by Core Data Transfer Format -Coronary Events are
essential for statistical analysis and quality assurance of the data.

2.1.2 28-day survival period

Every coronary event must have its apparent onset within the study period and more than
28 days from any preceding recorded coronary event in the individual. Secondly, the
event must be detected and diagnosed within 28 days of onset. The actual way of
calculating the 28-day survival period is described in the instructions for CORE DATA
TRANSFER FORMATS - CORONARY EVENTS. The principles are that the day of
onset is day zero and that the difference in calendar days is calculated by subtracting
date of onset from date of death.

Any recurrent event in one individual occurring after midnight between days 27 and 28
must be considered as a separate event.

The starting point for calculating the 28-day survival period is the onset of the first
manifestation of a suspect coronary event (symptoms, ECG, enzymes). If recurrences
happen during the next 28 days they belong to the same event. In coronary events the
most severe findings for symptoms, enzymes and ECG detected during the 28-day
survival period should be reported - for instance if a patient has first atypical symptoms
or enzymes other than abnormal but later on he/she has a recurrent event with typical
symptoms or abnormal enzymes, one should code symptoms typical and enzymes
abnormal. This procedure for the diagnostic findings of recurrent events should not
influence the date of onset of the event.

Because the 28-day survival period is the only basis for the assessment of case- fatality it
is essential that the date of onset of an event is recorded in the same way during the entire
study period. Every MCC should pay special attention to consistency during the study
period.

Maximum effort should be put on the accurate ascertainment of the survival status at 28
days in every event.

2.1.3. First or recurrent event

It is important to obtain the best available information about the previous history of
myocardial infarction in each event in order to separate first events from recurrent events.
The data item "Previous history of myocardial infarction" is the variable which allows
this separation. The procedures for collection of these data should be kept constant
throughout the entire study.

2.2 Diagnostic Classification

2.2.1. Timing and Priority of Results

Because each event lasts only 28 days the diagnostic criteria used must be from
investigations or symptoms that refer to what happened within that 28 day survival period
even though the results (such as necropsy or enzyme tests) may be reported later. The
definition of the 28-day survival period has been given earlier.

The most severe findings during the 28-day survival period should always be recorded.
This means that in case of recurrent events during the 28-day period symptoms should be
coded "typical" if in any of the recurrent attacks the criteria for typical symptoms were
met. Accordingly enzymes should be coded "Abnormal" if in any of the recurrent attacks
the criteria for abnormal enzymes were met. This also means that symptoms, enzymes
and ECG findings may refer to different attacks occurring within the 28-day period.

2.2.2. Diagnostic categories

There are the following categories:

(1) definite acute myocardial infarction

(2) possible acute myocardial infarction or coronary death
(3) ischaemic cardiac arrest with successful resuscitation not fulfilling criteria for definite
or possible myocardial infarction
(4) no acute myocardial infarction or coronary death
(9) fatal cases with insufficient data, subsequently called "unclassifiable deaths" in
collaborative MONICA publications

Allocation of a diagnostic category must follow strictly the definitions provided. The
criteria used for the diagnosis of "definite" and "possible" acute myocardial infarction are
not necessarily those that would be used by a clinician, but rigid definitions are essential
for event analysis.

(1) Definite acute myocardial infarction

a. Definite ECG or
b. Symptoms typical or atypical or inadequately described, together with probable
ECG and abnormal enzymes, or
c. Symptoms typical and abnormal enzymes with ischaemic or non-codable ECG or
ECG not available, or
d. Fatal cases, whether sudden or not, with naked-eye appearance of fresh
myocardial infarction and/or recent coronary occlusion found at necropsy.

(2) Possible acute myocardial infarction or coronary death

a. Living patients: with typical symptoms whose ECG and enzyme results do not
place them in category (1) and in whom there is not good evidence for another
diagnosis for the attack, or
b. Fatal cases whether sudden or not (not in category (1)) where there is no good
evidence for another cause of death, clinically or at autopsy.

i. with symptoms typical or atypical or inadequately described, or

ii. without typical or atypical or inadequately described symptoms but with evidence
of chronic coronary occlusion or stenosis or old myocardial scarring at necropsy;
or
iii. with a good history of chronic ischaemic heart disease such as definite or possible
myocardial infarction, or coronary insufficiency or angina pectoris in the absence
of significant valvular disease or cardiomyopathy.
NOTE: A strict watch should be kept over competing causes of death. Local rules should
be standardized and record kept of difficult decisions.

(3) Ischaemic cardiac arrest with successful resuscitation not fulfilling criteria for
definite or possible myocardial infarction

Spontaneous cardiac arrest not provoked by medical intervention, electrocution,

drowning or other gross physical insults, from presumed primary ventricular fibrillation
secondary to ischaemic heart disease, in the absence of significant valvular disease or
cardiomyopathy.

Note: this category was little used and was excluded from the main MONICA
collaborative analyses.

(4) No acute myocardial infarction

a. Living patients (not in category (1))

i. with combinations of symptoms and tests that do not qualify them for the
definite category and who do not have typical symptoms that might place
them in the possible category, or
ii. where illness episode has been explained by another diagnosis
b. Fatal cases, whether sudden or not, not in category (1) where another diagnosis
has been made (clinically or at autopsy)

NOTE: A strict watch should be kept over competing causes of death. Local rules should
be standardized and a record kept of difficult decisions.

(9) Fatal cases with insufficient data

Cases with no autopsy, no history of typical or atypical or inadequately described

symptoms, no previous history of chronic ischaemic heart disease and no other diagnosis.
Living patients should not be allocated to this category. It is hoped that most centres will
not need this category.

Note: unfortunately this was a vain hope, as this category accounted for a large
proportion of deaths in many centres. It was renamed "unclassifiable deaths" in the main
collaborative papers on coronary events.

2.2.3. How diagnostic categories are combined

(Note added in 1999.)

There are four categories of nonfatal events and three categories of fatal events, each of
which is potentially divisible into a number of sub-categories. It was decided early in the
development of the MONICA protocol that nonfatal definite events (NF1) should be the
main endpoint for nonfatal events for the study as a whole. This was because nonfatal
possibles (NF2) were less well defined, were more likely to be missed, were more
dependent on the source of notification and registration, such as hot pursuit and cold
pursuit, and the ratio of these to definites therefore varied greatly between centres.
Conversely, although fatal events with inadequate data (F9), later called unclassifiable
deaths, had similar problems, they accounted for so many presumed coronary deaths in
many centres that they had to be included. Although the prime definition was Definition
1, discussion on these issues led to the definition of other combinations of MONICA
coronary events for the first cross-sectional publication on coronary events.[1]

MONICA coronary events

Definition 1 = NF1 + F1 + F2 + F9
Definition 2 = NF1 + F1 + F2
Definition 3 = NF1 + NF2 + F1 + F2 + F9

A subsequent cross-sectional analysis of nonfatal possible events, involving most, but not
all, MONICA centres produced MONICA coronary events Definition 4, which was
equivalent to Definition 3, but including only those subcategories of nonfatal possibles in
which there was some diagnostic evidence for coronary heart disease.[2]

Note that the categories NF3 (ischaemic cardiac arrest with survival to 28 days) and NF4
and F4 (no myocardial infarction or coronary event) are not included in any of the above
definitions. Sudden death from coronary heart disease without evidence of acute
myocardial infarction was relatively common (F2 and potentially F9) but the number of
registrations of those successfully resuscitated from cardiac arrest in this situation (F3)
was so small as to be insignificant. This was because they were rare, but the register
process may not have found them all.

2.3 Derivation of MONICA diagnostic category for coronary events

The diagnostic algorithm for coronary events was first circulated from Dundee as
MONICA MEMO 40 (dated 25.2.85) and this Dundee algorithm was adopted into
MONICA MEMO 49 and 57 and officially adopted by the Principal Investigators
Meeting in August 1985. In MONICA MEMO 40, it was stated that a completely
automated diagnosis from the diagnostic criteria was not possible using the information
on the Core Data Transfer Form for Coronary Events. The reason for this is that whether
or not a case involves resuscitation from cardiac arrest and has evidence of coronary
disease (such as coronary angiography) may determine whether a non-fatal case is
categorized as category 3 (Ischaemic cardiac arrest) or category 4 (No myocardial
infarction). This information is not core data. In fatal cases the presence or absence of a
competing diagnosis may determine how a case is coded so that category 4 (No
myocardial infarction) is competing with category 2 (Possible coronary death), and with
category 9 (Inadequate data). Priority of diagnoses could be done by giving an order of
priority to the ICD codes on the death certificate, so that, for example, a diagnosis of
carcinoma precludes a possible coronary death. However, the ICD code diagnosis may be
considered inadequate as a criterion by itself without any indication of severity (for
example, centres who are able to obtain case notes, can tell whether a carcinoma coded
on the death certificate had been radically treated, or whether it was regarded as
metastasizing, advanced and incurable at the time of death). MONICA MEMO 74 took
the diagnostic algorithm a stage further. MEMO 40 contained 24 diagnostic permutations
for non-fatal cases and a description of the process for fatal cases. The present algorithm
has been used to examine all the possibly permutations of the Core Data Transfer items
that determine diagnosis. Most of them will never occur but they enable MCCs to
compare the performance of their own computer programs, and coders without access to
a computer program can use the table printed here to check their coding. This algorithm
is being used in Dundee to check test case histories and in Helsinki by the Data Centre to
check the submitted event data.

DUNDEE DIAGNOSTIC ALGORITHM (Version 3, 9.6.86)

For purposes of analysis many of the different values of the diagnostic criteria are
equivalent in determining the diagnostic category. For the following arguments the = sign
will mean "is equivalent to" for deriving the diagnostic category. (It does not mean that
the codes are interchangeable for other purposes because each code is thought to convey
distinct information). "Effective codes" means codes that are effectively different. For the
diagnostic algorithm convert the equivalent codes into the one with the value specified as
the effective code (but note composite code for history of ischaemic heart disease and
previous myocardial infarction). The permutation list considers these simplified values
only, so you will have to convert other values to these simplified values when making a
comparison.

ITEM NUMBER CODE SIMPLIFICATION

SURVIV 11: 9=1 Effective codes therefore are 1,2 (2 categories)
SYMPT 12: 2=5, 3=4=9 Effective codes therefore are 1, 2, 3 (3 categories)
ECG 13: 3=5=9 Effective codes therefore are 1, 2, 3, 4 (4 categories)
ENZ 14: 2=3=4=5=9 Effective codes therefore are 1, 2 (2 categories)
NECSUM 15: 9=8 Effective codes therefore are 1, 2, 4, 8 (4 categories)
PREMI 22: 1=2=3=4=5, 6=7, effective codes are 1,6,9.
HISIHD 30: 1,2,9.
For diagnostic purposes
HISIHD 1= PREMI 1
HISIHD 2= PREMI 6
HISIHD 9= PREMI 9
Therefore derive variable PREHIS
value 1 where PREMI is 1-5 or IHD is 1
value 2 where PREMI is 6 or 7 and IHD is 2 or 9,
value 9 where PREMI is 9 and IHD is 2 or 9.

Examine diagnostic criteria in the following sequence: (Comments in brackets)

1. Without regard to survival status

If ECG 13 = 1
or NECSUM 15 = 1,
or SYMPT = 1 or 2 and ECG = 2 and ENZ = 1
or SYMPT = 1 and ECG = 3 and ENZ = 1

the DIACAT 16 = 1, Definite, whether patient is alive or dead.(SURVIV 11= 1 or

2)

(Comment: Note that definite criteria in life can take precedence over a negative
necropsy).

2. In remaining cases:

If SURVIV 11 = 1 and SYMPT = 1 and NECSUM = 2. DIACAT = 2

(Comment: this is illogical but the diagnostic category is the same whether the
case was fatal or non-fatal, so that despite the conflict of criteria a diagnostic
category is possible)

3. In remaining cases:

If SURVIV 11 = 1 (and/or was 9) and NECSUM = 2 or 4. Allocate new DIACAT

= 8 and print "Illogical uncodable"

(Comment: this combination is illogical and the diagnostic category would be

affected by which of the conflicting criteria is given precedence so no category is
possible. Code 8 does not officially exist and has been used just for this
algorithm.)

4. In remaining cases:

If SURVIV 11 = 1 and SYMPT = 1, DIACAT = 2

5. Remaining cases where SURVIV 11=1 should all be coded as 4 or 3.

(Comment: it is not possible to decide between 4 and 3 using core data items)

6. For remaining cases where SURVIV 11=2:

If NECSUM 15 = 4, DIACAT = 4
If NECSUM 15 = 2, DIACAT = 2

7. For remaining cases where NECSUM = 8

 If SYMPT 12 = 1, DIACAT = 2
If SYMPT 12 = 2, DIACAT = 2

(Comment: Competing diagnoses prevent the use of symptom codes 1 and 2)

8. For remaining cases where SYMPT = 3

If PREHIS = 1, DIACAT = 2 or 4
If PREHIS = 2 or 9 DIACAT = 4 or 9.

(Comment: presence of competing diagnoses decide whether the category is 4 or

not)

The presentations of all these items are considered in the table of Annex1.

2.4 Electrocardiographic criteria for coronary events

The ECG classification will be based on the reading of records taken in the 28 days
following the acute attack and, if available, records taken immediately before (i.e. within
the previous 28 days). Up to four records should be selected for coding of change and the
choice should be standardized. The following is a recommendation:

• First available ECG in the attack (or one from immediately beforehand)
• The next 2 with different dates from the first and from each other.
• The last available in the record file of the admission.

Local discretion to be used if:

• One or more records specified above are uncodable and codable records are
available. OR
• Acute progressive changes occur later in the period of surveillance (e.g. late
inversion of T waves in the presence of ST elevation)

It is recommended that photostats of ECGs should be obtained wherever possible for

potential duplicate coding and quality control.

ECGs should be coded individually using a combination of the MONICA Protocol

criteria and the Minnesota Code Manual of Electrocardiographic Findings, [3] plus a
transparent ruler and a coding lens. Each record should be coded individually for
Minnesota 1, 4, 5, and 9.2 codes within lead groups (anterolateral I, aVL, V6; posterior
(inferior) II, III and aVF; and anterior V1,V2,V3,V4,V5) and for suppression codes
(listed later). The standard procedure will be that a written record is kept of individual
codes as a method of quality control for duplicate coding and so that the MONICA ECG
classification can be derived by inspection of the sequence of codes. A computer
algorithm is feasible using changes within lead groups to generate a MONICA ECG
classification (see Paragraph 2.5). The MONICA criteria are therefore based on the
sequence of individual codes as described here; and without applying the criteria for
significant serial change described in the Minnesota Code Manual. The ECG records as a
whole should be coded to the most severe class applicable. If in doubt code to the less
severe alternative.

Note that the ECG codes that follow are the two-digit codes used in the computer
algorithm. Only the first digit is used in the coronary event transfer format.

Code 1: Definite ECG

(A) The development in serial records of a diagnostic Q wave (as characterized below)

-AND/OR-

(B) The evolution of an injury current which lasts more then one day. (as characterized
below)

(note: criterion B is included because diagnostic Q waves are already present in the first
ECG recording in many cases. The presence of Q waves is not necessary to satisfy this
criterion)

The interpretation of a minimum of two or sometimes three ECG records is therefore

necessary for the establishment of these categories. (Not more than four to be coded. Four
should be coded ideally if they are available.)

A. Development of Q waves

Progression of Q codes from no Q to a diagnostic Q is sufficient but change from no Q to

an equivocal Q or from equivocal to diagnostic Q must be accompanied by deterioration
in the ST segment or the T wave. A change in a Q code or in a 4, 5 or 9-2 code must
occur within the same lead group but the Q can be in a different lead group to that in
which the 4, 5 or 9-2 code is being followed. Note that Minnesota code 1-2-6 is
equivalent to No Q code.

1.1 No Q or QS code in the first ECG record followed by a record with a diagnostic Q or
QS code (Minn. code 1-1-1 through 1-2-5 plus 1-2-7)

-OR-

1.2 An equivocal Q or QS code (Minn. code 1-2-8 or any 1-3 code) and no major ST
segment depression (No Minn. code 4-1 or 4-2) in the first ECG record followed by
a record with a diagnostic Q code PLUS a major ST segment depression (Minn. code
4-1 or 4-2)

-OR-
1.3 An equivocal Q finding and no ST segment elevation (No Minn. code 9-2) in the
first ECG record followed by a record with a diagnostic Q code PLUS an ST
segment elevation (Minn. code 9-2)

-OR-

1.4 An equivocal Q finding and no major T wave inversion (No Minn. code 5-1 or 5- 2)
in the first ECG record followed by a record with a diagnostic Q code PLUS a major
T inversion (Minn. code 5-1 or 5-2)

-OR-

1.5 No Q code and neither 4-1 nor 4-2 in the first ECG followed by a record with an
equivocal Q code PLUS a 4-1 or 4-2

-OR-

1.6 No Q code and no 9-2 in the first ECG followed by a record with an equivocal Q
code PLUS a 9-2

-OR-

1.7 No Q code and neither 5-1 nor 5-2 in the first ECG followed by a record with an
equivocal Q code PLUS a 5-1 or 5-2

-OR-

B. Evolution of an injury current which lasts more than one day.

1.8 An ST segment Elevation (Minn. code 9-2) lasting more than one day (i.e. present
on consecutive records of different dates)

AND

T wave progression on three or more records from 5-0 to 5-2 or from 5-3 to 5- 1, with a
more abnormal code present on consecutive records of different dates. (See VERBAL
EXPLANATION OF ALGORITHM, definition of DEFINITE 1.8, paragraph 2.5).

Note: The ST segment elevation does not have to be present in the same lead groups as
the T progression, nor does it have to be exactly simultaneous. Q waves will often be
present in the same graphs but they are not necessary to the use of this criterion for
Definite ECG.
Code 2: Probable ECG

Evolution of repolarisation changes

2.1 No major ST segment depression in one ECG record (no 4-1 or 4-2) and another
record with a major ST segment depression (Minn. code 4-1)
2.2 No ST segment elevation in one ECG record (no 9-2) and another record with an ST
segment elevation (Minn. code 9-2)
2.3 No major T wave inversion in one ECG record (no 5-1 or 5-2) and another record
with a major T wave inversion (Minn. code 5-1 or 5-2)

Note: Unlike the criteria in the previous classes, the evolution in this class can go in
either direction, that is the codes can get better or worse.

Note also that the criteria are not identical to those for repolarisation criteria
accompanying the Q classes 1.2 to 1.7 in that the 4 code is more severe; the development
or disappearance of 4-2 does not qualify; it has to be a 4-1.

Code 3: Ischaemic ECG (in one or more records)

Records not satisfying the above criteria which nonetheless show:

3.1 Minnesota codes 1-1-1 to 1-3-6 excluding 1-2-6 for Q and QS codes.

-AND/OR-

3.2 Minnesota codes 4-1 through 4-3 for ST junction (J) and segment depression.

-AND/OR-

3.3 Minnesota codes 5-1 through 5-3 for T wave items.

-AND/OR-

3.4 Minnesota code 9-2 for ST segment elevation.

Code 4: Other ECG

All other ECG findings, including normal ECG but note rules for uncodable ECG below.

Code 5: Uncodable ECG

This class should be used where all the available ECG records taken in the attack are
uncodable for technical reasons or because of the presence of suppression codes. Records
in which suppression codes permit certain Q codes to appear could be used to diagnose
the development of a diagnostic Q code from no Q code (MONICA ECG code 1.1) or to
allocate the code of ischaemic ECG (MONICA ECG code 3.1); supporting evidence from
4, 5, and 9-2 codes are needed for all other MONICA ECG classes. Therefore, unless
codable Q waves are present leading to the diagnostic or ischaemic category, and unless
at least one ECG is available that can be coded for 1, 4, 5 and 9-2 items then the presence
of suppression codes or technically unsatisfactory records should lead to the allocation of
the classification "uncodable". The implications of this rule are that ventricular
conduction abnormalities and arrhythmias occurring in the course of an event are not
used as collateral evidence of ischaemia.

The following Minnesota codes lead to suppression of all or most of these items, and a
set of ECG records in which such findings are present in all records should be considered
uncodable (unless codable Q waves are present, for example in an ECG showing a 7-4)

6-1 Third degree A-V block, suppresses all 1,4,5 and 9-2
6-4-1 Persistent Wolff-Parkinson White Pattern, suppresses all other codes.
6-8 Artificial pacemaker, suppresses all other codes.
7-1-1 Complete left bundle branch block, suppresses 1-2-3,1-2-7,1-2-8, 1-3-2, 1-3-6 and
all 4, 5 and 9-2 codes but the presence of a codable Q downgrades it to 7-4.
7-2-1 Complete right bundle branch block, suppresses 1-2-8, and all 4, 5 and 9-2 codes.
7-4 Intraventricular block suppresses all 4, 5, and 9-2 codes.
8-2-1 Ventricular fibrillation and asystole, suppress all other codes
8-2-2 Idioventricular rhythm, suppresses all other codes.
8-4-1 Supraventricular tachycardia above 140/minute, suppresses all other codes.

Code 9: ECG absent

No ECG available or recorded. (Coded as 9, no data)

2.5 Diagnostic algorithm for deriving MONICA ECG diagnosis from

Minnesota codes

Coding of the electrocardiogram will involve, in the majority of centres, the recording of
the Minnesota codes of consecutive (up to 4) electrocardiograms, followed by the
allocation of a MONICA category based on the MONICA protocol. The derivation of the
MONICA category should be automatic given a particular sequence of Minnesota codes
for the electrocardiograms and a computer algorithm was written in Dundee in BASIC
language and has been made available to other centres on request. (See MONICA Memos
41 and 67; MNM 41 contains examples and MNM 67 contains a listing). The algorithm
was officially adopted by the Principal Investigators at the 1985 meeting.

In deriving the algorithm some ambiguities were discovered in the verbal description of
the ECG codes. In particular for MONICA code 1.8, it was decided to allow the
sequences: 5.0, 5.2,5.2; 5.0,5.3,5.2 and 5.0,5.2,5.3 as being covered by the wording
"progression from 5.0 to 5.2 with a more abnormal code present on consecutive dates"
with 5.0, 5.3,5.3 excluded.

Many of the sequences have explanations. The code numbers are those used in the
MONICA Electrocardiographic criteria (Paragraph 2.4).

VERBAL EXPLANATION OF ALGORITHM

The algorithm as written for the computer has five stages:

1. Initiate the program.

2. Read in the table of codes from the computer keyboard.
3. Change Minnesota codes to simpler values for the analysis.
4. Make the diagnosis (allocate a MONICA ECG code).
5. Stop the program.

The algorithm is based on the following MONICA code definitions:

DEFINITE CODES 1.1 TO 1.7

First record with .......... Followed by a record with.....

DEFINITE 1.1 - NO Q code DIAGNOSTIC Q
DEFINITE 1.2 - EQUIVOCAL Q + NO 4-1 or 4-2 DIAGNOSTIC Q + 4-1 or 4-2
DEFINITE 1.3 - EQUIVOCAL Q + NO 9-2 DIAGNOSTIC Q + 9-2
DEFINITE 1.4 - EQUIVOCAL Q + NO 5-1 or 5-2 DIAGNOSTIC Q + 5-1 or 5-2
DEFINITE 1.5 - NO Q + NO 4-1 or 4-2 EQUIVOCAL Q 4-1 or 4-2
DEFINITE 1.6 - NO Q + NO 9-2 EQUIVOCAL Q + 9.2
DEFINITE 1.7 - NO Q + NO 5-1 or 5-2 EQUIVOCAL Q + 5-1 or 5-2

DEFINITE 1.8 -

9-2 in consecutive records on different dates plus T progression in 3 records 5-0 to 5-2 or
5-3 to 5-1:

Examples:
 5-0, 5-2, 5-2;

5-0, 5-3, 5-2;

5-0, 5-2, 5-3,

or substitute 5-1 for 2nd or third:

5-3, 5-2, 5-1;

5-3, 5-1, 5-2;

5-3, 5-1, 5-1.

PROBABLE One record with ........ Another record with ....

PROBABLE 2-1 NO 4-1 OR 4-2 4-1
PROBABLE 2-2 NO 9-2 9-2
PROBABLE 2-3 NO 5-1 or 5-2 5-1 or 5-2
ISCHAEMIC One record or more with ........
ISCHAEMIC 3-1 1-1-1 TO 1-3-6 EXCLUDING 1-2-6
ISCHAEMIC 3-1 4-1 TO 4-3
ISCHAEMIC 3-3 5-1 TO 5-3
ISCHAEMIC 3-4 9-2
OTHER 4
All other ECGs except where all uncodable or absent

UNCODABLE 5
Uncodable

ABSENT 9
None available or recorded.

1. To initiate the program. Prompt and read in the serial number from the
keyboard. Prompt and read in the number of ECGs coded for this case. The
diagnosis has been set to "undiagnosed" on initiating the program. If the number
of ECGs is 0 then the diagnosis is made, MONICA code is 9 ECG ABSENT
...STOP.
2. The program prompts and reads in the data from the keyboard according to
the Scottish MONICA ECG record. If an attempt is made to enter an illegal code
for a particular field the computer will beep and reprompt.
3. Conversion to simpler internal values. The computer creates an internal table of
derived codes for purposes of analysis. This does not correspond with the
Minnesota convention in that 0 is the normal value but 1,2,3,... represent
increasing levels of severity. (There is some inconsistency with suppression
codes).

FOR Q CODES (1-*-*)

o 0 and 2-6 are recoded as 0 which means "no Q"

o 2-8 and 3-* codes are recoded as 1 which means "equivocal Q"
o I-* codes, 2-1 to 2-5 and 2-7 are recoded as 2 which means "definite Q"

FOR STD (4-*)

o 0 and 4 are recoded as 0

o 3 is recoded as 1
o 2 is recoded as 2
o 1 is recoded as 3

FOR T (5-*)

o 0 and 4 are recoded as 0

o 3 is recoded as 1
o 2 is recoded as 2
o 1 is recoded as 3

FOR STE (9-*)

o 0 is recoded as 0
o 2 is recoded as 1

FOR SUPPRESSION CODES (VARIOUS)

o 0 is recoded as 0
o 7-2-1 is recoded as 1
o 7-1-1 is recoded as 2
o 7-4-0 is recoded as 3
o 6-1-0,6-4-1,6-8-0,8-2-1,8-2-2,8-4-1,9-8-1 are recoded as 4

The program then suppresses the relevant fields or codes in the

electrocardiograms in which suppression codes are present.

Code 4 suppresses all fields, codes 1,2,3 suppress STD, T AND STE fields.

Code 2 suppresses the Q fields whose original values were 2-3,2-7,2-8,3-2 or 3 6.

Code 1 suppresses the Q fields whose original value was 2-8.
4. To make the diagnosis (MONICA ECG code).

If all the converted Q fields in all the ECGs are 0, and they all have a converted
suppression code which is not 0, then the diagnosis is MONICA code 5,
UNCODABLE........STOP

DEFINITE.

For all Q comparisons, the first ECG record is used as the baseline unless the Q
field is suppressed, when the first record in which it is not suppressed is used. If
there is a progression from the first to a subsequent ECG, within a lead group,
from converted Q code 0 to converted Q code 2, then the diagnosis is MONICA
code 1.1 DEFINITE.......STOP

The program then searches for smaller Q progressions and for simultaneous
progression between the first codable and any subsequent ECG of :

BOTH

o Q going from 1 to 2 in the same lead group or

o Q going from 0 to 1 in the same lead group

AND

o STD going from 0 or 1 to 2 or 3 in the same lead group or

o STE going from 0 to 1 in the same lead group or
o T going from 0 or 1 to 2 or 3 in the same lead group

SO THAT BOTH CHANGES OCCUR BETWEEN THE SAME TWO ECGs

If so the MONICA code is DEFINITE.......STOP The sub-code is as follows.

1.2 if Q 1 to 2 and STD progression.
1.3 if Q 1 to 2 and STE progression.
1.4 if Q 1 to 2 and T progression.
1.5 if Q 0 to 1 and STD progression.
1.6 if Q 0 to 1 and STE progression.
1.7 if Q 0 to 1 and T progression.

If more than one of these is present then the algorithm awards the lowest code
number.

If there are two consecutive ECGs of different dates in which the converted STE
field is coded 1 within the same lead group, the program searches for a T
progression on three consecutive graphs of different dates, within the same lead
group showing the sequence: 0, 3, 3 or 0, 2, 3 or 0, 3, 2 or 0, 2, 2 or 0, 1, 2 or 0, 2,
1 or 1, 3, 3 or 1, 3, 2 or 1, 2, 3 (the algorithm subtracts the code of the first graph
from each of the subsequent two and the result is accepted if the value is 1 or
more and the sum of these two subtractions is three or more.) MONICA ECG
code 1.8 DEFINITE.........STOP

PROBABLE.

The algorithm searches for lesser diagnostic categories in those cases not already
diagnosed.

If in any two of the ECGs there is within one lead group an STD field with the
value 3 in one graph and 0 or 1 in another the MONICA code is 2.1 PROBABLE
... ...STOP

If in any two of the ECGs there is within one lead group an STE field with the
value 0 in one graph and 1 in another the MONICA code is 2.2
PROBABLE....STOP

If in any two of the ECGs there is within one lead group a T field with the value
of 2 or 3 in one graph and 0 or 1 in another the MONICA code is 2.3
PROBABLE ......STOP.

As has been demonstrated, the PROBABLE codes are tested for in sequence so
that the lowest value is awarded.

ISCHAEMIC

In those cases not already diagnosed :

Any unsuppressed codable Q field greater than 0 gives MONICA code 3.1
ISCHAEMIC ...STOP

Any unsuppressed codable STD field greater than 0 gives MONICA code 3.2
ISCHAEMIC .......STOP

Any unsuppressed T fields greater than 0 gives MONICA code 3.3

ISCHAEMIC..STOP

Any unsuppressed STE fields greater than 0 give MONICA code 3.4
ISCHAEMIC ...STOP

OTHER

If the record is still not diagnosed then the MONICA code is 4 OTHER ....STOP
 5. The algorithm and program terminate on allocating a MONICA code and as has
been shown the logic of the sequence followed is to test for the codes in the
sequence:

9 ABSENT ECG
5 UNCODABLE
1.1 DEFINITE
1.2 to 1.8 DEFINITE
2.1 to 2.3 PROBABLE
3.1 to 3.4 ISCHAEMIC
4 OTHER

3. Data transfer form and instructions for coronary

events
The coronary event registration data to be sent to the MDC are specified in the Core Data
Transfer Format - Coronary Events, which is appended to this section.

4. Acute coronary care

4.1 Introduction

Version 3 of the Acute Coronary Care Record Format was used for the first period of
acute coronary care monitoring in all MCCs. At that time such monitoring was to be
intermittent and done on 500 consecutive cases near the start and at the end of event
registration. The Principal Investigators Meeting in Augsburg in 1988 agreed that centres
should, if they could, monitor acute coronary care continuously because it was changing
so rapidly and could influence diagnoses through the introduction of thrombolytic
therapy, for example.

The present version 6 of the Acute Coronary Care Record Format has used some of the
spaces left for Future Interventions to code items that Principal Investigators want
included. It should be used on all future coronary event registrations, except those in
which the DIACAT is 4. NOTE: It is a modified version of the format circulated with the
1989 Test Case Histories.

It is inevitable that some MCCs will find it very difficult to complete certain items in all
cases and that there will also be cases in which virtually no information is available.
However, the absence of information does not invalidate a record and records with
missing and incomplete information should be forwarded to the Data Centre without
preselection. However, it is important that all fields are filled and that codes for
inadequate data are used to show where this is so.

When this has been done there should be a complete series of MONICA Coronary
registrations for the MCC, with each routine Coronary Event Record linked with an
Acute Coronary Care Record, unless the DIACAT is 4. It is important that each MCC has
a checking system to ensure that this is so and that the Serial numbers on the two records
correspond.

4.2 Data transfer form and introductions for acute coronary care

The acute coronary care data to be sent to the MDC are specified in the Core Data
Transfer Format - Acute Coronary Care, which is appended to this section.

4.3 Groupings of Drugs for MONICA Acute Coronary Care Record

A list of groupings of drugs for the acute coronary care record is given in Annex 2.

5. Error correction
The procedure for correcting errors which have already been submitted to the MDC are
described in Part V, Section 1.3.3.

6. Coronary Serial Numbers

Every suspect event should be issued a serial number by the MCC as early as
possible in the identification process, especially in MCCs which register
retrospectively. The minimum requirement is that when the MCC begins to collect data
on a suspect event, it is provided with a serial number. The serial number consists of
seven digits. Each serial number must be unique within each MONICA Reporting Unit
and within each register (i.e. stroke register and coronary register). Different MONICA
Reporting Units and different registers may use the same serial numbers. The serial
numbers within a Reporting Unit and register must be different for different events
throughout the ten-year registration period.

Log-books of serial number histories: The MCCs must keep a log-book of the history
of every Coronary Serial Number and Stroke Serial Number issued. The items of the
Serial Number Inventory Format should be included in this log-book. The serial number
histories are used to monitor the data flow and time lag in the event registration.

Correctness of the serial number: The serial number is one of the key items of an event
record. The Form Identification, Collaborating Centre Code, Reporting Unit Code and
Serial Number are all necessary in order to uniquely identify an event. Each MCC should
have some kind of security system to help assure that the serial number is error free. One
possibility is to have the last digit of the serial number a check digit which is used to
control the correctness of the other digits at least until the individual record has been
computerized.

A check digit needs to be calculated when the serial number is issued. It is useful only if
this is done correctly. This can be secured by letting a computer generate the serial
numbers with the check digits and print the numbers on stickers or labels which are then
stuck on the log-books and data collection forms.

Serial number inventory data transfer: Serial number inventory data should be sent to
the MDC as instructed in the Coronary Serial Number Inventory Format, which is
appended to this section.

References
1. Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas A-M, Pajak
A. for the WHO MONICA Project. Myocardial infarction and coronary deaths in
the World Health Organization MONICA Project. Registration procedures, event
rates and case fatality in 38 populations from 21 countries in 4 continents.
Circulation 1994;90:583-612.
2. Salomaa V, Dobson A, Miettinen H, Rajakangas A-M, Kuulasmaa K for the
WHO MONICA Project. Mild myocardial infarction - a classification problem in
epidemiologic studies. J Clin Epidemiol 1997;50:3-13.
3. Prineas R.J., Crow R.S. and Blackburn H. (1982) The Minnesota Code Manual of
Electrocardiographic Findings. Standards and Procedures for Measurement and
Classification. John Wright/PSG Inc, Boston/Bristol/London. ISBN 0 1236 2053
3.

The WHO MONICA Project

The MONICA (Multinational MONItoring of trends and determinants in CArdiovascular
disease) Project was established in the early 1980s in many Centres around the world to
monitor trends in cardiovascular diseases, and to relate these to risk factor changes in the
population over a ten year period. It was set up to explain the diverse trends in
cardiovascular disease mortality which were observed from the 1970s onwards. There
were total of 32 MONICA Collaborating Centres in 21 countries. The total population
age 25-64 years monitored was ten million men and women. The ten year data collection
was completed in the late 1990s, and the main results were published in the following
years. The data are still being used for analysis.

• Objectives
• Data components
• Organization
• Addresses
• List of publications
 • Publications in the World Wide Web
o MONICA Manual
o Quality assessment reports of MONICA data
o Data books of descriptive statistics of the MONICA data
o WWW-appendices to papers published in journals
• MONICA Monograph and Multimedia Sourcebook

Internal MONICA pages

Page last updated on 2009-09-19 by Kari Kuulasmaa (firstname.lastname@thl.fi)

MONICA Manual, Part II: Annual Statistics

Section 1: Population Demographics and

Mortality Data Component
December 1998

This section provides the equivalent of a Manual of Operations for the collection and
processing of data for this MONICA data component.

Contents
• Introduction
• 1. Annual Population Demographics Data
o 1.1 Population Demographics Reporting Form and Instructions
o 1.2 Quality Assurance Procedures
• 2. Annual Population Mortality Data
o 2.1 Annual Population Mortality Reporting Form and Instructions
o 2.2 Quality Assurance Procedures

Forms
• Population demographics reporting form
• Error correction form for population demographics reporting form
• Annual population mortality form (ICD-8)
o Current version (Version 2)
 o Former version (Version 1) used for data transfer to the MONICA Data
Centre
• Annual population mortality form (ICD-9)
o Current version (Version 2)
o Former version (Version 1) used for data transfer to the MONICA Data
Centre
• Annual population mortality form (ICD-10)
• Error correction form for annual population mortality reporting form (ICD-8)
• Error correction form for annual population mortality reporting form (ICD-9)
• Error correction form for annual population mortality reporting form (ICD-10)

© Copyright World Health Organization (WHO) 1999. All rights reserved.

• Copyright notice
• Manual acknowledgements
• Document identification:
o URL:http://www.ktl.fi/publications/monica/manual/part2/ii-1.htm
o URN:NBN:fi-fe19981149

Queries and comments on this section to be addressed

to:
MONICA Data Centre
Department of Epidemiology and Health Promotion
National Public Health Institute
Mannerheimintie 166
SF - 00300 Helsinki
Fax: + 358 9 4744 8338
Email: kari.kuulasmaa@ktl.fi

Earlier versions
• Description of data collection procedures for the MONICA Project. MONICA
Memo 49; June 1985.
• WHO MONICA Project. MONICA Manual. CVD/MNC/Version 1.1, December
1986; Sect. 2.
• Revision of MONICA Manual, Part II, Sect. 1, September 1987. MONICA Memo
126; March 1988.
• WHO MONICA Project. MONICA Manual. Geneva: World Health Organization,
Cardiovascular Diseases Unit; November 1990; Part II, Sect. 1.

Changes made after November 1990 revision

 • The deadline for reporting the data was postponed by one year in 1992.
• Annual Population Mortality Form (ICD-10) and its error correction form were
added in December 1998.

Introduction
The routinely available population demographic and mortality data are to be collected
annually for each MONICA Reporting Unit. The annual population demographic data,
derived from routine census and vital registration data systems, provide the denominator
for the calculations of incidence, prevalence, and mortality rates. The annual mortality
data, also derived from the routine vital registration system, will provide for an important
comparison between this routine system and, with respect to cardiovascular diseases, the
more rigorous MONICA system. The mortality data will also show the competing causes
of death.

1. Annual Population Demographics Data

1.1 Population Demographics Reporting Form and Instructions

The Population Demographics Reporting Form, the procedures for providing the data and
the instructions for completing the form are appended to this section.

1.2 Quality Assurance Procedures

The Population Demographic Reporting Form is to be completed for each Reporting Unit
by the MDC Principal Investigator or by his or her designate. No specific training and
certification procedures are required for personnel completing this form; however, the
instructions should be followed carefully. Further aspects of the required quality
assurance activities for this form are discussed below.

MONICA Collaborating Centre Requirements

Before shipping completed form(s) to the MDC, the following are to be done at the
MCC:

• The person responsible for completing the form is to double check all entries
against the original source of the information.
• An additional person should also check all entries against the original source of
the information.
• All totals should be double checked.
• The values recorded on the form should be compared with some other
information, if available, and anything unusual investigated and resolved.
 • As an additional check, Collaborating Centres with more than one Reporting Unit
should compute totals for the entire Collaborating Centre population.

After this process has been completed, the form(s) should be sent to the MDC so that
they arrive by 31 December each year. The form(s) should be accompanied by a
completed Packing List. At least one copy of the forms should be kept at the MCC as
protection against loss during shipment to the MDC and to assist in addressing any
questions that might later arise.

It is possible that questions about the data may arise during its review at the MDC. In this
case, the MDC will communicate with the centre about these questions through the use of
the appropriate Error Correction Form which is appended to this section. The MCC
should respond as indicated.

MONICA Data Centre requirements

The first step in the MDC's activities is to check to see that a completed Population
Demographic Reporting Form has been received by the deadline of 31 December for
each of the official MONICA Reporting Units. Centres which have not provided
complete information will be contacted to obtain the missing data.

Once the form arrives at the MDC, the following steps will be executed:

• An acknowledgement card will be sent to the MCC.

• The form will be checked for completeness and any apparently missing
information noted.
• The rows and columns will be summed and any discrepancies between these sums
and the recorded totals noted.
• The reasonableness of the entries will be assessed and any unusual entries noted.
This will be done also by making comparisons with the information from the
other populations and with previously provided information for the same
population.

All questions uncovered by this examination are to be communicated using the Problem
Communication Form or the Error Correction Form to the person who submitted the form
to the MDC. This person should then formally address each question and provide an
official response. The authority for changing information on the form lies with the MCC
Principal Investigator or his or her designate, and no changes to the data can be made
without this person's approval.

In addition to the points addressed above, the MDC will:

• store and protect the data according to standard MDC operating procedures.
• prepare an annual summary report by 1 May which describes any problems with
the data as well as tabulating appropriately the information collected.
This summary will be distributed appropriately.

2. Annual Population Mortality Data

2.1 Annual Population Mortality Reporting Form and Instructions

The Annual Population Mortality Reporting Forms for the 8th, 9th and 10th revision of
the International Clarification of Diseases (ICD), the procedures for providing the data
and the instructions for completing the forms are appended to this section:

• Annual Population Mortality Form (ICD-8)

• Annual Population Mortality Form (ICD-9)
• Annual Population Mortality Form (ICD-10)

2.2 Quality Assurance Procedures

The annual Mortality Reporting Forms (one for males and one for females for each
reporting unit) are to be completed by the MONICA Collaborating Centre Principal
Investigator or by his or her designate. No specific training and certification procedures
are required for personnel completing these forms; however, the instructions should be
followed carefully. Further aspects of the required quality assurance activities for this
form are discussed below.

MONICA Collaborating Centre requirements

Before shipping the completed forms to the MDC, the following are to be done at MCC:

• The person responsible for completing the forms is to double check all entries
against the original source of the information.
• An additional person should also check all entries against the original source of
the information.
• All totals should be double checked. Furthermore, there form has summary rows
which include the ICD-categories of a some of the following rows. The entries in
such summary rows must be larger than or equal to the sums of the entries entries
in the following rows.
• The values recorded should be compared with some other information, if
available, and anything unusual investigated and resolved.
• As an additional check, Collaborating Centres with more than one Reporting Unit
should compute totals for the entire Collaborating Centre populations.

After this process has been completed, the forms should be sent to the MDC so that they
arrive by 31 December each year. The forms should be accompanied by a completed
Packing List. At least one copy of each completed form should be kept at the MCC as
protection against loss during shipment to the MDC and to assist in addressing any
questions that might later arise.
It is possible that questions about data may arise during its review at the MDC. In this
case the MDC will communicate with the MCC about these questions through the use of
the appropriate Error Correction Forms:

• Error Correction Form for Annual Population Mortality Reporting Form (ICD-8)
• Error Correction Form for Annual Population Mortality Reporting Form (ICD-9)
• Error Correction Form for Annual Population Mortality Reporting Form (ICD-10)

The MCC should respond to the Error Correction Forms as indicated.

MONICA Data Centre requirements

The first step in the MDC's activities is to check to see that the appropriate numbers of
Annual Mortality Reporting Forms have been received by the deadline of 31 December
from each of the MCCs. Centres which have not provided complete information will be
contacted to obtain the missing data.

Once the forms arrive at the MDC, the following steps will be executed:

• An acknowledgement card will be sent to the MCC.

• Each form will be checked for completeness and any apparently missing
information noted.
• Rows and columns will be summed and any discrepancies between these sums
and the recorded totals noted.
• The reasonableness of the entries will be assessed and any unusual entries noted.
This will be done also by making comparisons with the information from other
Reporting Units and with previously provided information for the same Reporting
Unit.

All questions uncovered by this examination are to be communicated by the use of the
Problem Communication Form or the Error Correction Form process to the person
responsible for completing the form. This person should then formally address each
question and provide an official response. The authority for changing information on the
form lies with the MCC Principal Investigator or his or her designate, and no changes to
the data can be made without this person's approval.

In addition to the points addressed above, the MDC will:

• Store the data according to standard MDC operating procedures.

• Prepare an annual summary report by 1 May which describes any problems with
the data as well as tabulating appropriately the information collected. This
summary will be distributed appropriately.
MONICA COLLABORATIVE
PUBLICATIONS
In addition to the collaborative publications listed here, there are over 600 publications
from the individual MONICA Collaborating Centres or small groups of them.
Collaborative presentations at international meetings and Internal reports of the
WHO MONICA Project are listed on separate pages.

Books
1. Tunstall-Pedoe H, editor. Prepared by Tunstall-Pedoe H, Kuulasmaa K, Tolonen
H, Davidson M, Mendis S with 64 other contributors for The WHO MONICA
Project. MONICA Monograph and Multimedia Sourcebook. Geneva: World
Health Organization; 2003. ISBN 92 4 156223 4.

Original printed articles

1. Tuomilehto J, Kuulasmaa K,Torppa J, for the WHO MONICA Project. WHO
MONICA Project: Geographic variation in mortality from cardiovascular
diseases. World Health Stat Q 1987;40:171-84.
2. Tunstall-Pedoe H, for the WHO MONICA Project. The World Health
Organization MONICA Project (Monitoring Trends and Determinants in
Cardiovascular Disease): A major international collaboration. J Clin Epidemiol
1988;41:105-14.[PubMed]
3. Pajak A, Kuulasmaa K, Tuomilehto J, Ruokokoski E, for the WHO MONICA
Project. Geographical variation in the major risk factors of coronary heart disease
in men and women aged 35-64 years. World Health Stat Q 1988;41:115-40.
4. Tunstall-Pedoe H. Problems with criteria and quality control in the registration of
coronary events in the MONICA study. Acta Med Scan Suppl 1988;728:17-25.
[PubMed]
5. Asplund K, Tuomilehto J, Stegmayr B, Wester PO, Tunstall-Pedoe H. Diagnostic
criteria and quality control of the registration of stroke events in the WHO
MONICA Project. Acta Med Scan Suppl 1988;728:26-39. [PubMed]
6. Asplund K, Tuomilehto J, Kuulasmaa K, Torppa J, for the WHO MONICA
Project. Multinational stroke mortality data at the baseline of the WHO MONICA
Project. In: Meyer JS et al., eds. Cerebral Vascular Disease. Elsevier Science
Publishers, B.V. (Biomedical Division), 1989;7:167-170.
7. Böthig S, for the WHO MONICA Project. WHO MONICA Project: objectives
and design. Int J Epidemiol 1989;18(Suppl 1):S29-S37. [PubMed]
8. Tuomilehto J, Kuulasmaa K, for the WHO MONICA Project. WHO MONICA
Project: Assessing CHD mortality and morbidity. Int J Epidemiol 1989;18(Suppl
1):S38-S45. [PubMed]
9. Keil U, Kuulasmaa K, for the WHO MONICA Project. WHO MONICA Project:
Risk factors. Int J Epidemiol 1989;18(Suppl 1):S46-S55. [PubMed]
10. Tunstall-Pedoe H. Diagnosis, measurement and surveillance of coronary events.
Int J Epidemiol 1989;18(Suppl 1):S169-S173. [PubMed]
11. The WHO MONICA Project. A worldwide monitoring system for cardiovascular
diseases: Cardiovascular mortality and risk factors in selected communities.
World Health Stat A 1989;27-149.
12. Chambless LE, Dobson AJ, Patterson CC, Raines B. On the use of a logistic risk
score in predicting risk of coronary heart disease. Stat Med 1990;9:385-396.
[PubMed]
13. Döring A, Pajak A, Ferrario M, Grafnetter D, Kuulasmaa K, for the WHO
MONICA Project. Methods of total cholesterol measurement in the baseline
survey of the WHO MONICA Project. Rev Epidemiol Sante Publique
1990;38:455-461. [PubMed]
14. Hense HW, Kuulasmaa K, Zaborskis A, Kupsc W, Tuomilehto J, for the WHO
MONICA Project. Quality assessment of blood pressure measurements in
epidemiological surveys. The impact of last digit preference and the proportions
of identical duplicate measurements. Rev Epidemiol Sante Publique 1990;38:463-
468. [PubMed]
15. Dobson A, Kuulasmaa K, Eberle E, Scherer J. Confidence intervals for weighted
sums of Poisson parameters. Stat Med 1991;10: 457-62. [PubMed]
16. Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas A-M, Pajak
A, for the WHO MONICA Project. Myocardial infarction and coronary deaths in
the World Health Organization MONICA Project. Registration procedures, event
rates and case fatality in 38 populations from 21 countries in 4 continents.
Circulation 1994;90:583-612. [PubMed]
17. Stewart AW, Kuulasmaa K, Beaglehole R, for the WHO MONICA Project.
Ecological analysis of the association between mortality and major risk factors of
cardiovascular disease. Int J Epidemiol 1994;23:505-16. [PubMed]
18. Asplund K, Bonita R, Kuulasmaa K, Rajakangas A-M, Feigin V, Schädlich H,
Suzuki K, Thorvaldsen P, Tuomilehto J, for the WHO MONICA Project.
Multinational comparisons of stroke epidemiology - evaluation of case-
ascertainment in the WHO MONICA stroke study. Stroke 1995;26:355-60.
[PubMed]
19. Thorvaldsen P, Asplund K, Kuulasmaa K, Rajakangas A-M, Schroll M, for the
WHO MONICA Project. Stroke incidence, case fatality and mortality in the
WHO MONICA Project. Stroke 1995;26:361-367. [PubMed]
20. Hense HW, Koivisto A-M, Kuulasmaa K, Zaborskis A, Kupsc W, Tuomilehto J,
for the WHO MONICA Project. Assessment of blood pressure measurement
quality in the baseline surveys of the WHO MONICA Project. J Hum Hypertens
1995; 9:935-46. [PubMed]
21. Asplund K, Rajakangas A-M, Kuulasmaa K, Thorvaldsen P, Bonita R, Stegmayr
B, Suzuki K, Eisenblätter D, for the WHO MONICA Project. Multinational
comparison of diagnostic procedures and management of acute stroke - the WHO
MONICA Study. Cerebrovascular Diseases 1996; 6:66-74.
22. Dobson A, Filipiak B, Kuulasmaa K, Beaglehole R, Stewart A, Hobbs M, Parsons
R, Keil U, Greiser E, Korhonen H, Tuomilehto J. Relations of changes in
coronary disease rates and changes in risk factor levels: Methodological issues
and a practical example. Am J Epidemiol 1996, 143:1025-34. [PubMed]
23. Tunstall-Pedoe H. Is acute coronary heart disease different in different countries
in the two sexes: lessons from the MONICA Project. Cardiovascular Risk Factors
1996;6:254-61.
24. Salomaa V, Dobson A, Miettinen H, Rajakangas A-M, Kuulasmaa K, for the
WHO MONICA Project. Mild myocardial infarction - a classification problem in
epidemiologic studies. J Clin Epidemiol 1997;50:3-13. [PubMed]
25. Thorvaldsen P, Kuulasmaa K, Rajakangas A-M, Rastenyte D, Sarti C,
Wilhelmsen L, for the WHO MONICA Project. Stroke trends in the WHO
MONICA Project. Stroke 1997;28:500-506. [PubMed]
26. Stegmayr B, Asplund K, Kuulasmaa K, Rajakangas A-M, Thorvaldsen P,
Tuomilehto J, for the WHO MONICA Project. Stroke incidence and mortality
correlated to stroke risk factors in the WHO MONICA Project. Stroke
1997;28:1367-1374. [PubMed]
27. Molarius A, Seidell JC, Kuulasmaa K, Dobson AJ and Sans S, for the WHO
MONICA Project. Smoking and relative body weight: an international perspective
from the WHO MONICA Project. J Epidemiol Community Health 1997;51:252-
260. [PubMed]
28. Kuulasmaa K, Dobson A, for the WHO MONICA Project. Statistical issues
related to following populations rather than individuals over time. Bulletin of the
International Statistical Institute: Proceedings of the 51st Session; 1997 Aug 18-
26; Istanbul, Turkey.Voorburg: International Statistical Institute; 1997. Book 1;
295-8. Also available from
URL:http://www.ktl.fi/publications/monica/isi97/isi97.htm.
29. Chambless L, Keil U, Dobson A, Mähönen M, Kuulasmaa K, Rajakangas A-M,
Löwel H, Tunstall-Pedoe H, for the WHO MONICA Project. Population versus
clinical view of case fatality from acute coronary heart disease: results from the
WHO MONICA Project 1985-1990. Circulation 1997;96:3849-3859. [PubMed]
30. Jackson R, Chambless L, Higgins M, Kuulasmaa K, Wijnberg L, Williams OD,
for the WHO MONICA Project and ARIC Study. Gender differences in ischaemic
heart disease mortality and risk factors in 46 communities: an ecologic analysis.
Cardiovascular Risk Factors 1997;7:43-54.
31. Wolf HK, Tuomilehto J, Kuulasmaa K, Domarkiene S, Cepaitis Z, Molarius A,
Sans S, Dobson A, Keil U, Rywik S, for the WHO MONICA Project. Blood
pressure levels in the 41 populations of the WHO MONICA project. J Hum
Hypertens 1997;11:733-42. [PubMed]
32. Dobson A, Evans A, Ferrario M, Kuulasmaa K, Moltchanov V, Sans S, Tunstall-
Pedoe H, Tuomilehto J, Wedel H, Yarnell J, for the WHO MONICA Project.
Changes in estimated coronary risk in the 1980s: Data from 38 populations in the
WHO MONICA Project. Annals of Medicine 1998;30:199-205. [PubMed]
33. Evans A, Dobson A, Ferrario M, Kuulasmaa K, Moltchanov V, Sans S, Tunstall-
Pedoe H, Tuomilehto J, Wedel H, Yarnell J, for the WHO MONICA Project. The
WHO MONICA Project: changes in coronary risk in the 1980s. Proceedings of
 the XIth International Symposium on Atherosclerosis; 5-9 October 1997, Paris,
France. Elsevier Science, Atherosclerosis XI, 1998; 49-55.
34. Dobson A, Kuulasmaa K, Moltchanov V, Evans A, Fortmann SP, Jamrozik K,
Sans S, Tuomilehto J, for the WHO MONICA Project. Changes in cigarette
smoking among adults in 35 populations in the mid 1980s. Tobacco Control
1998;7:14-21. [PubMed]
35. Molarius A, Seidell JC, Sans S, Tuomilehto J, Kuulasmaa K, for the WHO
MONICA Project. Waist and hip circumferences, and waist-hip ratio in 19
populations of the WHO MONICA Project. Int J Obes 1999;23:116-125.
[PubMed]
36. Tunstall-Pedoe H, Kuulasmaa K, Mähönen M, Tolonen H, Ruokokoski E,
Amouyel P, for the WHO MONICA (monitoring trends and determinants in
cardiovascular disease) Project. Contribution of trends in survival and coronary-
event rates to changes in coronary heart disease mortality: 10-year results from 37
WHO MONICA Project populations. Lancet 1999;353:1547-57. [PubMed]
37. Molarius A, Seidell JC, Sans S, Tuomilehto J, Kuulasmaa K, for the WHO
MONICA Project. Varying sensitivity of waist action levels to identify subjects
with overweight or obesity in 19 populations of the WHO MONICA Project. J
Clin Epid 1999;52:1213-24. [PubMed]
38. Kuulasmaa K, Tunstall-Pedoe H, Dobson A, Fortmann S, Sans S, Tolonen H,
Evans A, Ferrario M, Tuomilehto J, for the WHO MONICA Project. Estimation
of contribution of changes in classic risk factors to trends in coronary-event rates
across the WHO MONICA Project populations. Lancet 2000:355;675-87.
[PubMed]
39. Tunstall-Pedoe H, Vanuzzo D, Hobbs M, Mähönen M, Cepaitis Z, Kuulasmaa K,
Keil U, for the WHO MONICA Project. Estimation of contribution of changes in
coronary care to improving survival, event rates, and coronary heart disease
mortality across the WHO MONICA Project populations. Lancet 2000:355;688-
700. [PubMed]
40. Ingall T, Asplund K, Mähönen M, Bonita R, for the WHO MONICA Project. A
multinational comparison of subarachnoid hemorrhage epidemiology in the WHO
MONICA stroke study. Stroke 2000;31:1054-1061. [PubMed]
41. Molarius A, Seidell JC, Sans S, Tuomilehto J, Kuulasmaa K, for the WHO
MONICA Project. Educational level, relative body weight, and changes in their
association over 10 years: an international perspective from the WHO MONICA
Project. Am J Public Health 2000;90:1260-68. [PubMed]
42. Molarius A, Parsons RW, Dobson AJ, Evans A, Fortmann SP, Jamrozik K,
Kuulasmaa K, Moltchanov V, Sans S, Tuomilehto J, Puska P, for the WHO
MONICA Project. Trends in cigarette smoking in 36 populations from the early
1980s to the mid 1990s: findings from the WHO MONICA Project. Am J Public
Health 2001;91:206-212. [PubMed]
43. Evans A, Tolonen H, Hense HW, Ferrario M, Sans S, Kuulasmaa K, for the WHO
MONICA Project. Trends in coronary risk factors in the WHO MONICA Project.
Int J Epidemiol 2001;30(Suppl 1):S35-S40. [PubMed]
44. Kulathinal SB, Kuulasmaa K, Gasbarra D. Estimation of an errors-in-variables
regression model when the variances of the measurement errors vary between the
observations. Stat Med 2002;21:1089-1101. [PubMed]
45. Tolonen H, Mähönen M, Asplund K, Rastenyte D, Kuulasmaa K, Vanuzzo D,
Tuomilehto J, for the WHO MONICA Project. Do trends in population levels of
blood pressure and other cardiovascular risk factors explain trends in stroke event
rates? Comparisons of 15 populations in 9 countries within the WHO MONICA
Stroke Project. Stroke 2002;33:2367-2375.[PubMed]
46. Truelsen T, Mähönen M, Tolonen H, Asplund K, Bonita R, Vanuzzo D, for the
WHO MONICA Project. Trends in stroke and coronary heart disease in the WHO
MONICA Project. Stroke 2003;34:1346-1352. [PubMed]
47. Sarti C, Stegmayr B, Tolonen H, Mähönen M, Tuomilehto J, Asplund J, for the
WHO MONICA Project. Are changes in mortality from stroke caused by changes
in stroke event rates or case fatality? - Results from the WHO MONICA Project.
Stroke 2003;34:1833-1841. [PubMed]
48. Silventoinen K, Sans S, Tolonen H, Monterde D, Kuulasmaa K, Kesteloot H,
Tuomilehto J, for the WHO MONICA Project. Trends in obesity and energy
supply in the WHO MONICA Project. Int J Obes 2004;28:710-718. [PubMed]
49. Lundberg V, Tolonen H, Stegmayr H, Kuulasmaa K, Asplund K, for the WHO
MONICA Project. Use of oral contraceptives and hormone replacement therapy
in the WHO MONICA Project. Maturitas 2004;48:39-49. [PubMed]
50. Merlo J, Asplund K, Lynch J, Råstam L, Dobson A, for the WHO MONICA
Project. Population effects on individual systolic blood pressure: a multilevel
analysis of the World Health Organization MONICA Project. Am J Epidemiol
2004;159:1168-1179. [PubMed]
51. Gostynski M, Gutzwiller F, Kuulasmaa K, Döring A, Ferrario M, Grafnetter D,
Pajak A, for the WHO MONICA Project. Analysis of the relationship between
total cholesterol, age, body mass index among males and females in the WHO
MONICA Project. Int J Obes 2004;28:1082-1090. [PubMed]
52. Barnett AG, Dobson AJ, for the WHO MONICA Project. Is the increase in
coronary events on Mondays an artifact? Epidemiology 2004;15:583-588.
[PubMed]
53. Mähönen M, McElduff P, Dobson AJ, Kuulasmaa K, Evans A, for the WHO
MONICA Project. Current smoking and the risk of nonfatal myocardial infarction
in the WHO MONICA Project populations. Tob Control 2004;13:244-250.
[PubMed]
54. Barnett AG, Dobson AJ, for the WHO MONICA Project. Estimating trends and
seasonality in coronary heart disease. Stat Med 2004;23:3505-3523. [PubMed]
55. Yarnell JWG, McCrum E, Rumley A, Patterson CC, Salomaa V, Lowe GDO,
Evans A, on behalf of the MONICA Optional Haemostasis Study Investigators.
Association of European population levels of thrombotic and inflammatory
factors with risk of coronary heart disease: the MONICA Optional Haemostasis
Study. Eur Heart J 2005;26:332-42. [PubMed]
56. Tolonen H, Keil U, Ferrario M, Evans A, for the WHO MONICA Project.
Prevalence, awareness and treatment of hypercholesterolaemia in 32 populations:
 results from the WHO MONICA Project. Int J Epidemiol 2005;34:181-192.
[PubMed]
57. Wolf HK, Kuulasmaa K, Tolonen H, Sans S, Molarius A, Eastwood BJ, for the
WHO MONICA Project. Effect of sampling frames on response rates in the WHO
MONICA risk factor surveys. Eur J Epidemiol 2005;20:293-299. [PubMed]
58. Tolonen H, Ferrario M, Kuulasmaa K, for the WHO MONICA Project.
Standardization of total cholesterol measurement in population surveys - pre-
analytic sources of variation and their effect on the prevalence of
hypercholesterolaemia. Eur J Cardiovasc Prev Rehabil 2005;12:257-267.
[PubMed]
59. Barnett AG, Dobson AJ, McElduff P, Kuulasmaa K, Salomaa V, Sans S, for the
WHO MONICA Project. Cold periods and coronary events: an analysis of
populations worldwide. J Epidemiol Community Health 2005;59:551-557.
[PubMed]
60. Tolonen H, Dobson A, Kulathinal S for the WHO MONICA Project. Effect on
trend estimates of the difference between survey respondents and non-
respondents: results from 27 populations in the WHO MONICA Project. Eur J
Epidemiol 2005;20:887-898. [PubMed]
61. Antikainen R, Moltchanov V, Chukwuma C, Kuulasmaa K, Marques-Vidal P,
Sans S, Wilhelmsen L, Tuomilehto J, for the WHO MONICA Project. Trends in
the prevalence, awareness, treatment and control of hypertension: the WHO
MONICA Project. Eur J Cardiovasc Prev Rehabil 2006;13:13-29. [PubMed]
62. Tolonen H, Dobson A, Kulathinal S, for the WHO MONICA Project. Assessing
the quality of risk factor survey data: lessons from the WHO MONICA Project.
Eur J Cardiovasc Prev Rehabil 2006;13:104-114. [PubMed]
63. Tunstall-Pedoe H, Connaghan J, Woodward M, Tolonen H, Kuulasmaa K. Pattern
of declining blood pressure across replicate population surveys of the WHO
MONICA project, mid-1980s to mid-1990s, and the role of medication. BMJ
2006;332:629-635. [PubMed]
64. Barnett A, Sans S, Salomaa V, Kuulasmaa K, Dobson A, for the WHO MONICA
Project. The effect of temperature on systolic blood pressure. Blood Press Monit
2007;12:195-203. [PubMed]
65. Wietlisbach V, Marques-Vidal P, Kuulasmaa K, Karvanen J, Paccaud F, for the
WHO MONICA Project. The relation of body mass index and abdominal
adiposity with dyslipidemia in 27 general populations of the WHO MONICA
Project. Nutr Metab Carbiovasc Dis. In press

Publications in the World Wide Web

1. WHO MONICA Project. MONICA Manual. (1998-1999). Available from
URL:http://www.ktl.fi/publications/monica/manual/index.htm, URN:NBN:fi-
fe19981146.
2. Mähönen M, Tolonen H, Kuulasmaa K, Tunstall-Pedoe H, Amouyel P, for the
WHO MONICA Project. Quality assessment of coronary event registration data
in the WHO MONICA Project. (January 1999). Available from
 URL:http://www.ktl.fi/publications/monica/coreqa/coreqa.htm, URN:NBN:fi-
fe19991072.
3. Moltchanov V, Kuulasmaa K, Torppa J, for the WHO MONICA Project. Quality
assessment of demographic data in the WHO MONICA Project. (April 1999).
Available from URL:http://www.ktl.fi/publications/monica/demoqa/demoqa.htm,
URN:NBN:fi-fe19991073.
4. Mähönen M, Cepaitis Z, Kuulasmaa K, for the WHO MONICA Project. Quality
assessment of acute coronary care data in the WHO MONICA Project. (February
1999). Available from
URL:http://www.ktl.fi/publications/monica/accqa/accqa.htm, URN:NBN:fi-
fe19991081.
5. Mähönen M, Tolonen H, Kuulasmaa K, for the WHO MONICA Project. Quality
assessment of stroke event registration data in the WHO MONICA Project.
(November 1998). Available from
URL:http://www.ktl.fi/publications/monica/strokeqa/strokeqa.htm, URN:NBN:fi-
fe19991080.
6. Kuulasmaa K, Tolonen H, Ferrario M, Ruokokoski E, for the WHO MONICA
Project. Age, date of examination and survey periods in the MONICA surveys.
(May 1998). Available from
URL:http://www.ktl.fi/publications/monica/age/ageqa.htm, URN:NBN:fi-
fe19991075.
7. Wolf HK, Kuulasmaa K, Tolonen H, Ruokokoski E, for the WHO MONICA
Project. Participation rates, quality of sampling frames and sampling fractions in
the MONICA Surveys. (September 1998). Available from
URL:http://www.ktl.fi/publications/monica/nonres/nonres.htm, URN:NBN:fi-
fe19991076.
8. Molarius A, Kuulasmaa K, Evans A, McCrum E, Tolonen H, for the WHO
MONICA Project. Quality assessment of data on smoking behaviour in the WHO
MONICA Project. (February 1999). Available from
URL:http://www.ktl.fi/publications/monica/smoking/qa30.htm, URN:NBN:fi-
fe19991077.
9. Kuulasmaa K, Hense H, Tolonen H, for theWHO MONICA Project. Quality
assessment of data on blood pressure in the WHO MONICA Project. (May 1998).
Available from URL:http://www.ktl.fi/publications/monica/bp/bpqa.htm,
URN:NBN:fi-fe19991082.
10. Ferrario M, Kuulasmaa K, Grafnetter D, Moltchanov V, for the WHO MONICA
Project. Quality assessment of total cholesterol measurements in the WHO
MONICA Project. (April 1999). Available from
URL:http://www.ktl.fi/publications/monica/tchol/tcholqa.htm, URN:NBN:fi-
fe19991083.
11. Marques-Vidal P, Ferrario M, Kuulasmaa K, Grafnetter D, Moltchanov V, for the
WHO MONICA Project. Quality assessment of data on HDL cholesterol in the
WHO MONICA Project. (June 1999). Available from
URL:http://www.ktl.fi/publications/monica/hdl/hdlqa.htm, URN:NBN:fi-
fe19991137.
12. Molarius A, Kuulasmaa K, Sans S, for the WHO MONICA Project. Quality
assessment of weight and height measurements in the WHO MONICA Project.
(May 1998). Available from
URL:http://www.ktl.fi/publications/monica/bmi/bmiqa20.htm, URN:NBN:fi-
fe19991079.
13. Molarius A, Sans S, Kuulasmaa K, for the WHO MONICA Project. Quality
assessment of data on waist and hip circumferences in the WHO MONICA
Project. (October 1998). Available from
URL:http://www.ktl.fi/publications/monica/waisthip/waisthipqa.htm,
URN:NBN:fi-fe19991091.
14. Molarius A, Kuulasmaa K, Moltchanov V, Ferrario M, for the WHO MONICA
Project. Quality assessment of data on marital status and educational achievement
in the WHO MONICA Project. (December 1998). Available from
URL:http://www.ktl.fi/publications/monica/educ/educqa.htm, URN:NBN:fi-
fe19991078.
15. Molarius A, Tuomilehto J, Kuulasmaa K, for the WHO MONICA Project.
Quality assessment of data on hypertension control in the WHO MONICA
Project. (October 1998). Available from
URL:http://www.ktl.fi/publications/monica/hyperten/hbpdrug.htm, URN:NBN:fi-
fe19991084.
16. Tolonen H, Ferrario M, Minoja M, for the WHO MONICA Project. Quality
assessment of data on awareness and treatment of high cholesterol in the WHO
MONICA Project. (June 1999). Available from
URL:http://www.ktl.fi/publications/monica/hich/hchdrug.htm, URN:NBN:fi-
fe19991130.
17. Tolonen H, Kuulasmaa K, for the WHO MONICA Project. Quality assessment of
data on use of aspirin in the WHO MONICA Project. (June 1999). Available from
URL:http://www.ktl.fi/publications/monica/aspirin/aspirinqa.htm, URN:NBN:fi-
fe19991129.
18. Lundberg V, Tolonen H, Kuulasmaa K, for the WHO MONICA Project. Quality
assessment of data on menopausal status and hormones in the WHO MONICA
Project. (June 1999). Available from
URL:http://www.ktl.fi/publications/monica/womenqa/womenqa.htm,
URN:NBN:fi-fe19991131.
19. Molarius A, Seidell JC, Sans S, Tuomilehto J, Kuulasmaa K, for the WHO
MONICA Project. Varying sensitivity of waist action levels to identify subjects
with overweight or obesity in 19 populations of the WHO MONICA Project -
tables and figures for waist action level 1. (December 1999). Available from
URL:http://www.ktl.fi/publications/monica/waction/waction.htm, URN:NBN:fi-
fe19991138.
20. Kuulasmaa K, Dobson A, Tunstall-Pedoe H, Fortmann S, Sans S, Tolonen H,
Evans A, Ferrario M, Tuomilehto J, for the WHO MONICA Project. Estimation
of contribution of changes in classical risk factors to trends in coronary-event
rates across the WHO MONICA Project populations: methodological appendix to
a paper published in the Lancet. (February 2000). Available from
 URL:http://www.ktl.fi/publications/monica/earwig/appendix.htm, URN:NBN:fi-
fe19991356.
21. Vanuzzo D, Pilotto L, Pilotto L, Mähönen M, Hobbs M, for the WHO MONICA
Project. Pharmacological treatment during AMI and in secondary prevention: the
scientific evidence. (February 2000). Available from
URL:http://www.ktl.fi/publications/monica/carpfish/appenda/evidence.htm,
URN:NBN:fi-fe976567.
22. Hobbs M, Mähönen M, Jamrozik K, for the WHO MONICA Project.
Constructing an evidence-based treatment score for relating changes in treatment
to changes in mortality, coronary events and case fatality in the WHO MONICA
Project. (February 2000). Available from
URL:http://www.ktl.fi/publications/monica/carpfish/appendb/wts.htm,
URN:NBN:fi-fe976568.
23. Tunstall-Pedoe H, Mähönen M, Cepaitis Z, Kuulasmaa K, Vanuzzo D, Hobbs M,
Keil U, for the WHO MONICA Project. Derivation of an acute coronary care
quality score for the WHO MONICA Project. (February 2000). Available from
URL:http://www.ktl.fi/publications/monica/carpfish/appendc/accqscore.htm,
URN:NBN:fi-fe976569.
24. Mähönen M, Tunstall-Pedoe H, Rajakangas A-M, Cepaitis Z, Kuulasmaa K,
Dobson A, Keil U, for the WHO MONICA Project. Definitions of case fatality for
coronary events in the WHO MONICA Project. (February 2000). Available from
URL:http://www.ktl.fi/publications/monica/carpfish/appendd/cfdef.htm,
URN:NBN:fi-fe976570.
25. Mähönen M, Tolonen H, Kuulasmaa K, for the WHO MONICA Project.
MONICA Coronary event registration data book 1980-1995. (October 2000).
Available from URL:http://www.ktl.fi/publications/monica/coredb/coredb.htm
URN:NBN:fi-fe20001204.
26. Mähönen M, Tolonen H, Kuulasmaa K, for the WHO MONICA Project.
MONICA stroke event registration data book 1982-1995. (October 2000).
Available from URL:http://www.ktl.fi/publications/monica/strokedb/strokedb.htm,
URN:NBN:fi-fe20001205.
27. Tolonen H, Kuulasmaa K, Ruokokoski E, for the WHO MONICA Project.
MONICA population survey data book. (October 2000). Available from
URL:http://www.ktl.fi/publications/monica/surveydb/title.htm, URN:NBN:fi-
fe20001206.
28. Mähönen M, Asplund K, Tolonen H, Kuulasmaa K, for the WHO MONICA
Project. Stroke event trend quality score for the WHO MONICA Project.
(November 2001). Available from
URL:http://www.ktl.fi/publications/monica/strokescore/score.htm, URN:NBN:fi-
fe20011554.
29. Mähönen M, Cepaitis Z, Kuulasmaa K, for the WHO MONICA Project.
MONICA acute coronary care data book 1981-1995. (December 2001). Available
from URL:http://www.ktl.fi/publications/monica/accdb/accdb.htm, URN:NBN:fi-
fe20011304.
30. Tolonen H, Kuulasmaa K, Asplund K, Mähönen M, for the WHO MONICA
Project. Do trends in population levels of blood pressure and other cardiovascular
 risk factors explain trends in stroke event rates? - methodological appendix to a
paper published in Stroke. (August 2002). Available from
URL:http://www.ktl.fi/publications/monica/stroke_h1/appendix.htm,
URN:NBN:fi-fe20021258.
31. Barnett AG, Dobson AJ, for the WHO MONICA Project. Cold periods and
coronary events: method appendix to a paper published in Journal of
Epidemiology and Community Health (October 2004). Available from
URL:http://www.ktl.fi/publications/monica/chd_temperature/appendix.html,
URN:NBN:fi-fe20041397.
32. Barnett AG, for the WHO MONICA Project. Estimated trends and seasonal
components for the WHO MONICA Project data: appendix to a paper published
in Statistics in Medicine (November 2004). Available from
URL:http://www.ktl.fi/publications/monica/chd_seasonal/appendix.htm,
URN:NBN:fi-fe20041349.

Reviews and editorials

1. Pisa Z. The Monica Project for Cardiovasular Disease. World Health Forum
1982;3:336-7.
2. Tunstall-Pedoe H. Monitoring trends in cardiovascular diseases and risk factors:
The WHO MONICA Project. WHO Chronicle 1985;39:3-5. [PubMed]
3. Tunstall-Pedoe H, Beaglehole R, Böthig S, Keil U, Tuomilehto J. Editorial. Acta
Med Scan 1988;(Suppl.728):7-9.
4. Martin I, Gyarfas I. WHO MONICA Project: 1990 Midterm Review. CVD
Epidemiology Newsletter 1990; Number 46:1-4.
5. WHO MONICA project: 1990 mid-term review. WHO Bulletin 1990;68: 799-
800.
6. Gyarfas I, Martin I, Watson M-J. The WHO MONICA Project. Heartbeat
1990;Number 3,September.
7. Gutzwiller F, Gyarfas I, Richard JL, Sans S, Tunstall-Pedoe H, Tuomilehto J,
Ducimetiere P (R.E.S.P). Editorial in Rev Epidém et Santé Publ 1990;38:389-390.
8. Sans S. Community surveillance for coronary heart disease: The WHO MONICA
Project. Can J Cardiol 1993;9: (Suppl. D May):23D-24D.
9. Sans S. Risk factor prevalence from the WHO MONICA Project. Can J Cardiol
1993;9: (Suppl. D May):85D-86D.
10. Bonita R. The MONICA Project comes of age. Editorial in BMJ 1994;309:684.
[PubMed]
11. Bonita R, Beaglehole R. Monitoring stroke. An international challenge. Editorial
in Stroke 1995;26:541-2. [PubMed]
12. Tunstall-Pedoe H. Myocardial infarction and coronary deaths in the World Health
Organization MONICA Project. Heartbeat 1994;Number 3, November.
13. Tunstall-Pedoe H. Did MONICA really say that? BMJ 1998;317:1023. [PubMed]

MONICA homepage
Page last updated on 2011-10-07 by Kari Kuulasmaa (firstname.lastname@thl.fi)