See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/260790579

PHARMACOVIGILANCE: A PROTECTIVE TOOL FOR GLOBAL DRUG SAFETY

ANALYSIS

Article · January 2014

CITATIONS READS

2 600

2 authors:

Yogesh Kumar Paliwal Dr. Sidharth Mehan

Bharat Serums and Vaccines Ltd ISF College of Pharmacy
7 PUBLICATIONS   3 CITATIONS    85 PUBLICATIONS   265 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

NEURODEGENERATION View project

All content following this page was uploaded by Dr. Sidharth Mehan on 15 March 2014.

The user has requested enhancement of the downloaded file.

INTERNATIONAL JOURNAL OF RECENT ADVANCES IN PHARMACEUTICAL RESEARCH
JANUARY 2014; 4(1): 18-24
____________________________________________________________________________________________________________________________________________

PHARMACOVIGILANCE: A PROTECTIVE TOOL FOR

GLOBAL DRUG SAFETY ANALYSIS
YOGESH KUMAR PALIWAL*1, SIDHARTH MEHAN2

1DEPARTMENT OF PHARMACOVIGILANCE, APHETA INSTITUTE OF CLINICAL RESEARCH (NEW DELHI)

2DEPARTMENT OF PHARMACOLOGY, RAJENDRA INSTITUTE OF TECHNOLOGY & SCIENCES (SIRSA)

ABSTRACT
The safety concern of drug is now becoming the priority area in healthcare industry, drug regulatory
authorities and public community. The shocking thalidomide tragedy of 1960’s opened the eyes of drug
regulators as well as other concern body to establish a way to ensure drug safety, previously the issues was in
shadow. The drug safety issues were globalised, build up and systematized after the establishment of World
Health Organization (WHO) Programme for International Drug Monitoring in 1968. Indian Pharmacopoeia
Commission (IPC) will be adding 150 new Adverse Drug Reaction (ADR) monitoring centres across the
country by end of 2014 in order to further strengthen the Pharmacovigilance Programme of India (PvPI).
Around 48,000 ADR‘s have been reported under Pharmacovigilance program in India by July, 2013. In terms
of ADR reporting knowledge and attitudes of health professionals is strongly related. There are many factors
associated with under reporting of ADRs; categorized as personnel and professional characteristics of
healthcare professional and their knowledge and attitude to ADR reporting. Under-reporting can be
significantly improved by appropriate educational intervention. Pharmacovigilance is an emergent discipline
with a global focus and plenty of scope for innovation and it still required a long way to go ahead.

Keywords: Adverse Drug Reaction (ADR), World Health Organization (WHO), Uppsala Monitoring Centre
(UMC), Pharmacovigilance Programme of India (PvPI)

UMC was joined by India from 1998, great

1.0. INTRODUCTION
Adverse Drug Reactions (ADRs) observation and
detection are the primary objectives of
pharmacovigiliance as these ADR are associated
with a significant morbidity and mortality. Between
3% and 11% of hospital admissions have been
attributed to adverse effects [1,2,3]. The Uppsala
Monitoring Centre (UMC, WHO), Sweden is
maintaining the international database of adverse
drug reaction reports received from several
national centers.
_________________________________________________
*Correspondence
Yogesh Kumar Paliwal
Add. H.No. 107/7, Paliwal Electronics,
Near Allahabad Bank, GOHANA,
Sonepat-131301, Haryana
E-mail: yogesh05paliwal@gmail.com
Mobile contact: 09818164970
____________________________________________________________________________________________________________________________________________
PALIWAL & MEHAN INT J RECENT ADV PHARM RES, 2014; 4(1): 18-24
ISSN: 2230-9306; WWW.IJRAPRONLINE.COM
achievements were made during this retro, but
much more still needs to be done in this field in
India [4]. ADR occurrence has been reported to
range from 5.9 to 22.3% of all emergency
department admissions in India. It has been
reported that deaths due to ADRs account for 1.8%
of total of deaths in India [5].
About, 90 medical colleges, laboratories
and hospitals across the country which registered
under the Pharmacovigilance Programme of India
(PvPI), playing a very crucial important role in
monitoring and signaling timely updates on the ADR
reports of the drugs running in the market.
However, Indian Pharmacopoeia Commission (IPC),
is now planning to streamline the growth of the
PvPI programme further by including all the
medical colleges across the country under its fold.
The commission aims to extend and attain its goal of
setting up 350 ADR centres across India by 2015,
making the pharmacovigilence programme of India
largest in the world. Nearly 48,000 adverse drug
18
INTERNATIONAL JOURNAL OF RECENT ADVANCES IN PHARMACEUTICAL RESEARCH
JANUARY 2014; 4(1): 18-24
____________________________________________________________________________________________________________________________________________
reactions have been reported under
Pharmacovigilance program in India till July, 2013
[6]. The value of pharmacovigilance is increasing
day by day and with recent high-profile drug
withdrawals was done from markets the regulatory
agencies, consumers and others because the
importance of pharmacovigilance increased and
people become more attentive about the advantage
and hazards of medicines [4]. The WHO, USFDA and
EMA have accepted the need to evaluate the
beneficial and harmful effects of drugs and to
frequently improve their use in order to provide
appropriate, safe and effective drug therapies
[7,8,9]. Spontaneous reporting is a passive system,
used to obtained details of ADEs.
ORIGIN AND DEFINITION
PHARMACOVIGILANCE [10]
In the starting, there was thalidomide tragedy. It
can be argued that the history of pharmacovigilance
goes back further but, for practical intention, the
story of modern pharmacovigilance begins there.
In 1957 there was little, if any, regulation of
medicines outside the USA (where thalidomide was
not marketed), and their testing and development
was almost entirely in the hands of pharmaceutical
companies. By 1960, thalidomide was marketed in
46 countries and unjustified claims of safety in
pregnancy were made and its use as a sedative was
targeted at pregnant women. The drug turned out to
be a teratogen, producing a number of birth defects
but particularly limb defects known as phocomelia
(Figure 1). Worldwide, about 10,000 fetuses were
affected, mostly in Germany where the drug was
first marketed.
In 1961 three cases associated with
thalidomide was reported in The Lancet, the
problem was finally accepted and the drug
withdrawn from sale. At the starting of the 1960s,
publication of potential adverse effects of drugs in
the medical literature was effectively the only way
for drawing attention to them. Thalidomide caused
a non-lethal but visible and scandalous adverse
effect, leading people to ask why so many damaged
babies had been born before anything had been
done? This query is central to preceding
developments. It is doubtful that we will ever be
proficient to predict and prevent all the harms
____________________________________________________________________________________________________________________________________________
PALIWAL & MEHAN INT J RECENT ADV PHARM RES, 2014; 4(1): 18-24
ISSN: 2230-9306; WWW.IJRAPRONLINE.COM
which may be caused by medicines but limiting the
damage to much lesser numbers is now achievable.
MAIN LESSONS FROM THALIDOMIDE
• The possible connection between marketing
claims and safety of medicines.
• The requirement of government law of medicines.
• The need for systems to identify the adverse drug
effects.
• The need for satisfactory testing of drugs or
medicines prior to marketing.
• Avoidance of needless use of medicines during
pregnancy.
• That some risks can be effectively and significantly
minimised.
OF The ramifications of the thalidomide
disaster were many fold but the key message for the
development of pharmacovigilance was that active
methods for detecting hazards are required. Within
a few years this had been taken onward with the
beginning of voluntary (or ‘spontaneous’) schemes
for analysis of suspected adverse drug reactions
(ADRs) which have stood the test of time as an early
warning system’.
PHARMACOVIGILANCE IN TERMS OF WHO
Pharmacovigilance has been defined by the WHO as
'The pharmacological science and activities relating
to the detection, assessment, understanding and
prevention of adverse effects or any other drug-
related problems' weather it is short term or long
term adverse effect of drug. This is a thought which
is appropriate to many aspects of present life but,
shockingly, its open use in relation to
pharmaceuticals is quite a recent development.
AIM AND OBJECTIVE OF PHARMACOVIGILANCE
ACCORDING TO NATIONAL
PHARMACOVIGILANCE POLICY [11,12]
Events such as the thalidomide tragedy highlight
the extreme importance of effective drug
monitoring systems for all medicines save the life of
19
INTERNATIONAL JOURNAL OF RECENT ADVANCES IN PHARMACEUTICAL RESEARCH
JANUARY 2014; 4(1): 18-24
____________________________________________________________________________________________________________________________________________

FIGURE 1. MANY CHILDREN IN THE 1960'S, AS PICTURED, WERE BORN WITH PHOCOMELIA AS A SIDE
EFFECT OF THE DRUG THALIDOMIDE, RESULTING IN THE SHORTENING OR ABSENCE OF LIMBS.

PHARMACOVIGILANCE
AIM & SERVICES

RECEPTORS MAY BE
DOCTORS, REPORTING & DETECTION
PHARMACIST, OF ADVERSE EVENTS
NURSES AND
HEALTH CARE WORKERS

DATA COLLECTION, DATA

EVALUATORS MAY BE PROCESSING & EVALUATION
MEDICAL SPECIALIST,
CLINICAL
DECISION MAKING, SAFETY
PHARMACOLOGIST
REVIEW & APPROPRIATE
AND PHARMACIST
ACTION BY REGULATRY
BODIES

PREVENT MEDICINE RELATED

PROBLEMS & REDUCE
MORBIDITY AND MORTILITY

FIGURE 2. STRUCTURE OF PHARMACOVIGILANCE ACTIVITY

____________________________________________________________________________________________________________________________________________
PALIWAL & MEHAN INT J RECENT ADV PHARM RES, 2014; 4(1): 18-24
ISSN: 2230-9306; WWW.IJRAPRONLINE.COM 20
INTERNATIONAL JOURNAL OF RECENT ADVANCES IN PHARMACEUTICAL RESEARCH
JANUARY 2014; 4(1): 18-24
____________________________________________________________________________________________________________________________________________
human beings (Figure 2.). As we know once a
medicine comes to the market, it leaves the safe and
protected scientific environment of clinical trials
and is legally set free for consumption by the
general population group all over the world. After
entry of medicines in to market, most medicines will
only have been tested for short-term safety and
efficacy on a limited number of carefully selected
individuals. It is generally estimated that in some
cases as few as 500 subjects, and rarely more than
5000, will have received the product prior to its
release. Due to this reason therefore, it is necessary
that new and medically still evolving treatments
should be monitored for their effectiveness and
safety under real-life conditions post release [13].
THE PRINCIPAL AIMS OF PHARMACOVIGILANCE
PROGRAMMES ARE
- To add the awareness of importance, detriment,
efficiency and hazard of medicines in terms of
patients safety.
- To encourage edification, education and clinical
training in pharmacovigilance and effective
communication to health professionals and to the
community.
- To promote rational, effective (including cost-
effective) and safe use of drugs.
Now as we know that there are considerable social
and economic consequences of adverse drug
reactions along with the positive benefit/cost ratio of
implementing suitable risk management – so there is
a need to connect health-care professionals and the
public at large, in such a way that a well-structured
programme is build for effective monitoring for
adverse drug reactions [14]. The purpose of the
programme is to collate data, analyze it and use the
inferences to suggest informed regulatory
interventions, besides of communicating risks to
healthcare professionals and the community. The
National Pharmacovigilance Programme will have the
following milestones:
Short-term objectives to promote a culture of
notification
Medium-term objectives to appoint several
healthcare professionals and NGOs in the drug
monitoring and information distribution processes.
Long-term objectives to attain such operational
efficiencies that would make Indian National
____________________________________________________________________________________________________________________________________________
PALIWAL & MEHAN INT J RECENT ADV PHARM RES, 2014; 4(1): 18-24
ISSN: 2230-9306; WWW.IJRAPRONLINE.COM
Pharmacovigilance Programme a standard for global
drug monitoring endeavors.
ADVERSE EVENT
An adverse event have no casual relationship with
patient treatment but it is one of the medical
incidence with patient. So an adverse event (AE) can
be any serious or Unintentional indication of disease
which is temporally related with the use of a drug
[15,16 ]
ADVERSE DRUG REACTIONS
Definitions
Standard, internationally accepted definitions of side-
effect, ADR and adverse event may be summarized as
follows:
• A side-effect is an unintended effect of a medicine.
Normally it is undesirable but it could be beneficial
(e.g. an anxiolytic effect from a beta-blocker
prescribed for hypertension).
• An adverse drug reaction (ADR) is an unintended
and noxious effect that is attributable to a medicine
when it has been given within the normal range of
doses used in man.
• An adverse event (AE) is an undesirable occurrence
that occurs in the context of drug treatment but
which may or may not be causally related to a
medicine.
MAINLY TWO TYPES OF ADR ARE CONSIDERED
1. UNLISTED / UNEXPECTED ADVERSE DRUG
REACTION
An adverse reaction is the nature or harshness of
drug which is not reliable with the proper product
data which available at the time of the clinical trials
[17]. Company is needed help during investigators
brochure for an unapproved drug and brief summary
of drug data sheet for an official product.
2. LISTED / EXPECTED ADVERSE DRUG REACTION
The information about ADR and its nature or severity
and specificity of the drug is already recorded [18].
21
INTERNATIONAL JOURNAL OF RECENT ADVANCES IN PHARMACEUTICAL RESEARCH
JANUARY 2014; 4(1): 18-24
____________________________________________________________________________________________________________________________________________
ADVERSE DRUG REACTION REPORTING
When the adverse reaction to drugs is curious,
potentially serious or clinically significant at that
time all health care workers, including doctors,
pharmacists, nurses and other health experts are
requested to clarify it. It is necessary to report an
adverse drug reaction to the pharmacovigilance
program even if you do not have all the facts or you
are unsure that the medicine is definitely
responsible for causing the adverse reaction.
The success or failure of any
pharmacovigilance activity depends on the
reporting of suspected adverse reactions.
1. Spontaneous reporting system
2. Other useful methods of collecting safety data in
different countries
3. National pharmacovigilance centres
4. WHO Programme for International Drug
Monitoring
1. SPONTANEOUS REPORTING SYSTEM
Spontaneous reporting is a passive system, used to
obtained details of ADRs and these are voluntarily
submitted by health professionals and
pharmaceutical manufacturers to the national
regulatory authority. The basic primary reason of
spontaneous ADR reporting is to provide initial
warnings or ‘signals’ of previously unrecognized drug
toxicity. We can define Spontaneous ADR as a scheme
for gathering individual case reports of clinical
suspicions of ADRs operated for the primary purpose
of detecting unknown, potentially seriously harmful
effects of drugs. Caution should be exercised in
evaluating spontaneous reports, especially when
comparing drugs. The submission of reports are
made on a voluntary basis and information from
them is entered onto a database which is screened
regularly for signals. The data accompanying
spontaneous reports are often incomplete.
It is further noticed that the rate at which
cases are reported is dependent on many factors
including the time since launch, pharmacovigilance-
related regulatory activity, media attention, and the
indication for use of the drug. Although, spontaneous
reporting is a good method of reporting ADRs but this
system has few limitations like difficulty of
recognizing ADRs with uncontrolled nature of
reporting method. The data contained in the reports
____________________________________________________________________________________________________________________________________________
PALIWAL & MEHAN INT J RECENT ADV PHARM RES, 2014; 4(1): 18-24
ISSN: 2230-9306; WWW.IJRAPRONLINE.COM
is uncertain and we are not sure about inconsistent
reporting more frequent reporting for unusual
reactions and reactions for new drugs and serious
reactions [19]. To minimize the error in as noticed in
spontaneous method, the retrospective and
prospective surveillance methods are considered as
most effective method. The prospective system is
more advantageous than spontaneous and
retrospective as it provides high quality of
information regarding adverse event with its early
identification [20].
2. OTHER USEFUL METHODS OF COLLECTING
SAFETY DATA IN DIFFERENT COUNTRIES
The other useful pharmacoepidemiological methods
have been implicated for collecting safety data. The
prescription event monitoring (PEM), record linkage
and case-control studies are some of the useful
methods used for the same purpose [21].
3. NATIONAL PHARMACOVIGILANCE CENTRES
These pharmacovigilance centres are responsible for
all step to step method of ADRs reporting. The no. of
pharmacovigilance centres has been increased from
10 to 67 since its beginning from 1968. The
published books namely Meyler’s Side effects, AHFS
Drugs Information hand book, David Text book of
ADR etc. has been provided to all national centres for
making proper guideline for ADRs reporting. It is
well known that post marketing surveillance of
medicines is usually co-ordinated by these national
centres. The Uppsala Monitoring Centre (UMC)
located in Sweden is the field name for WHO
collaborating centre for International drug
monitoring. is in direct collaboration with the these
National Centres and is achieving a great deal in
collecting, assessing and communicating information
from member countries national pharmacovigilance
programs in regards programs in regards to the
benefits, harm, effectiveness and risk drugs [22].
4.WHO PROGRAMME FOR INTERNATIONAL DRUG
MONITORING
The WHO’s international collaborative programme
on drug safety was originally set up in 1968 and their
monitoring centre is now based in Uppsala, Sweden.
WHO receives spontaneous ADR reports 4 times per
22
INTERNATIONAL JOURNAL OF RECENT ADVANCES IN PHARMACEUTICAL RESEARCH
JANUARY 2014; 4(1): 18-24
____________________________________________________________________________________________________________________________________________
years from 90 national schemes till 2013 which are
already in collaboration.
A specific database which is assessable to national
authorities and pharmaceutical companies is
considered as a international reference source to
enter data.
Data mining approach supported by clinical
assessment is used by WHO centres for further
analysis and this clinical assessment is further
provided by team of reviewer in order to identify
signals of new adverse drug reactions. Information is
exchanged between WHO and the national centres
electronically. The UMC also publishes periodic safety
newsletters and is responsible for managing the WHO
Drug Dictionary (a widely used international
standard) and the WHO Adverse Reaction
Terminology (WHOART). WHOART has now largely
been known as MedDRA. Council for the Organization
of Medical Sciences (CIOMS) is based in Geneva and
operates under the WHO supervision. It has served as
a medium for planning between regulators and
industry on a range of pharmacovigilance topics since
the late 1980s. Over the years, reports from CIOMS
working groups have been highly prominent in
determining legislation and guidelines around the
world. Till date there have been 8 recognized CIOMS
working groups – the topics and broad vision of each
group are mentioned below:
CIOMS I: International reporting of ADRs (1990)
CIOMS II: International reporting of periodic safety
update summaries (1992)
CIOMS III: Guidelines for preparing core clinical-safety
information on drugs (1995)
CIOMS IV: Benefit-risk balance for marketed drugs –
evaluating safety signals (1998)
CIOMS V: Current challenges in pharmacovigilance –
pragmatic approaches (2001)
CIOMS VI: Management of safety information from
clinical trials (2005)
CIOMS VII: The Development Safety Update Report
(DSUR) – harmonising the format and content for
periodic safety reporting during clinical trials (2006)
CIOMS VIII: Application of signal detection and
managment in pharmacovigilance.
PHARMACOVIGILANCE IN DIFFERENT
COUNTRIES/REGIONS
All countries have their own specified
pharmacovigilance system and there working pattern
follow WHO guideline.
____________________________________________________________________________________________________________________________________________
PALIWAL & MEHAN INT J RECENT ADV PHARM RES, 2014; 4(1): 18-24
ISSN: 2230-9306; WWW.IJRAPRONLINE.COM
PHARMACOVIGILANCE IN JAPAN
The Ministry of Health, Labour and Welfare (MHLW)
and Pharmaceuticals and Medical Devices Agency
(PMDA) regulate the pharmacovigilance in Japan
effectively.
PHARMACOVIGILANCE IN EUROPE
The pharmacovigilance system in Europe is working
under coordination and cumulative effect of
European Medicines Agency (EMA) and National
Competent Authorities (NCAs). The
pharmacovigilance system in Europe which is
known as EudraVigilance contains separate but
similar databases of human and veterinary
suspected serious adverse reactions.
PHARMACOVIGILANCE IN UNITED STATES
The pharmacovigilance in the U.S. has a multi-faceted
approach and include mainly three branches, the
FDA, the pharmaceutical manufacturers, and the
academic/non-profit organizations like RADAR and
public citizen.
PHARMACOVIGILANCE IN INDIA
First time, the National Pharmacovigilance Program
(NPP) was established in November, 2004, in New
Delhi and the performance of various Zonal, Regional
and Peripheral Centers was supervised by the
National Pharmacovigilance Advisory Committee
(NPAC) and this performed the functions of “Review
Committee” for this program to check operational
frequency of NPP. The pharmacovigilance in India
was started as per WHO recommendations made in
the document titled "Safety Monitoring of Medicinal
Products: Guidelines for Setting Up and Running a
Pharmacovigilance Centre". Pharmacovigilance
programmed is initiated thoroughly in India by the
Central Drugs Standard Control Organization
(CDSCO) under the kind guidance of Ministry of
Health & Family Welfare and Government of India.
The National Pharmacovigilance Centre shall
coordinate the program at CDSCO. It was finally
accepted that the National Centre will operate under
the supervision of the National Pharmacovigilance
Advisory Committee to recommend procedures and
guidelines for regulatory service [23].
23
 INTERNATIONAL JOURNAL OF RECENT ADVANCES IN PHARMACEUTICAL RESEARCH
JANUARY 2014; 4(1): 18-24
____________________________________________________________________________________________________________________________________________
CONCLUSION
Pharmacovigilance is an emergent discipline with a
global focus and plenty of scope for innovation. It is
the final but vital stage of drug development: there is
a need for a medicine to be shown to be acceptably
safe in practice. I have tried to exemplify what
pharmacovigilance is and how it has progressed over
a period of nearly half a century. Despite that
progress, no one should doubt that there is a long
way to go yet.
REFERENCE
1. Lazarou J, Pomeranz BH, Corey PN. Incidence of
adverse drug reactions in hospitalized patients-a
meta-analysis of prospective studies. JAMA 1998;
279: 1200-5.
2. Classen DC, Pestotnik SL, Evans RS et al. Adverse
drug events in hospitalized patients. JAMA 1997;
277 (4):301-6.
3. Pirmohamed M, James S, Meakin S, et al. Adverse
drug reactions as cause of admission to hospital:
prospective analysis of 18 820 patients. Br Med J.
2004; 329(7456):15
4.The Uppsala monitoring system, WHO
Collaborating Centre for International Drug
Monitoring World Health Organization.2002; 28-
34.
5, Amrita P, Singh SP. Status of spontaneous
reporting of adverse drug reaction by physicians
in Delhi. J Pharm Pract.2011; 4, 29-36.
6. Suja Nair Shirodkar,. IPC to add another 150 ADR
centres by 2014 end to strengthen PvPI
programme.
(www.pharmabiz.com/NewsDetails.aspx?aid=76
285&sid=1), Mumbai , Thursday, July 04, 2013,
08:00 Hrs [IST]
7. World Health Organization. The safety of
medicines in public health programmes:
Pharmacovigilance an essential tool (WHO Press,
World Health Organization, Geneva, Switzerland,
2006.
8. Pearson KC, Kennedy DL. Adverse drug reaction
and Food and Drug Administration. J Pharm
Pract. 1989; 2, 209-213.
9.Directive 2001/83/EC of the European Parliament
and of the Council of 6 November 2001 on the
Community Code Relating to medicinal products
____________________________________________________________________________________________________________________________________________
PALIWAL & MEHAN INT J RECENT ADV PHARM RES, 2014; 4(1): 18-24
ISSN: 2230-9306; WWW.IJRAPRONLINE.COM
View publication stats
for human use. Official Journal L 311, November
2004; 28, 67-128.
10. Bara Fintel, Athena T. Samaras, Edson Carias :
The thalidomide tragedy : Lesson for drug safety
and regulation, Helix magazine, July 28, 2009
11.http://en.wikipedia.org/wiki/Pharmacovigilance
2011.
12. WHO, Safety of medicines in public health
programmes : pharmacovigilance an essential
tool,WHO,2006. Department of CDSCO, Ministry
of Health and Family Welfare, Government of
India: Protocol for National pharmacovigilance
program, November 2004.
13. WHO, Pharmacovigilance: ensuring the safe use
of medicines, Geneva: WHO 2004.
14.Janaki.R.Torvi, Rajesh Hunashal,
Pharmacovigliance, International Journal of
Pharma and Bio Sciences, 2011; 2(4), 95-103.
15. Joerg H. Basic Principles of Pharmacovigilance
and Data Sources.
16. Sachdev Y. Pharmacovigilance: Safety Matters,
Indian Pharmacology. February 2008; 40.
17. Sachdev Y. Pharmacovigilance: Safety Matters,
Indian Pharmacology. February 2008; 40.
18. Sachdev Y. Pharmacovigilance: Safety Matters,
Indian Pharmacology. February 2008; 40.
19. Biriell C, Edwards R. Reasons for reporting
adverse drug reactions – some thoughts based
on an international review. Pharmacoepidemiol
Drug Saf 1997; 6, 21–26.
20. Smith CC, Bennett PM, Pearce HM, Harrison PI,
Reynolds DIM, Aronson JK et al. Adverse drug
reactions in a hospital general medicine unit
meriting notification to the Committee on Safety
of Medicines. Br J Clin Pharmacol. 1996; 42,
423-429.
21. Heeley E, Wilton LV, Shakir SA. Automated signal
generation in prescription-event monitoring.
Drug Safety 2002; 25, 423–432.
22. WHO, Safety of medicines in public health
programmes: pharmacovigilance an essential
tool,WHO,2006. Department of CDSCO, Ministry
of Health and Family Welfare, Government of
India: Protocol for National pharmacovigilance
program, 2004.
23. World Health Organization. Pharmacovigilance:
Ensuring the safe use of medicines. October,
2004.
24