Epidemiological study design

Semere Gebremariam (PhD)

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 Learning objectives

After the end of this session, students will be expected to:

 List type of epidemiological study designs
 Discuss the difference between descriptive and analytical
studies
 Describe the purpose of descriptive studies and analytical
studies
 State strength and limitation of studies designs
 Understand selection of study design

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 A study design
 Specific plan or protocol for conducting the study
 Allows the investigator to translate the conceptual hypothesis
into an operational one.
 The research design of a study spells out the strategies that
researchers adopt to answer their questions and test their
hypotheses
Epidemiologic Study Designs
 • Descriptive studies

• Examine patterns of disease

• Analytical studies

• Studies of suspected causes of diseases

• Experimental studies

• Compare treatment modalities

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Study Design Details: Descriptive studies

 Descriptive studies
 Can help to give perspective to the burden of disease and
may assist in planning services.
 Examine patterns of disease

 Aims
 To measure the importance of, and monitor changes in,
diseases in a community
 To describe the frequency of different diseases within a
community
Study Design Details: Descriptive studies Methods

 Analyse morbidity or mortality statistics or data on health-related

variables looking for variations :
 Time: secular trends; cyclic changes; seasonal variation; epidemics
 Place: geographical; urban-rural; institution
 Person: age and sex; marital status; ethnicity; family; occupation and
socio-economic status
 2. Types of descriptive study designs

• Case report
• Case series
• Ecological
• Cross sectional
 2.1 Case report and case series

• Case reports describe the experience of a

single patient
• Case series describe the experience of a group
of patients with similar diagnosis
• Both document unusual occurrences
 Example of Case report
• In April 1983 it had not yet been shown that AIDS could be
transmitted by blood or blood products. An infant born with Rh
incompatibility; required blood products from 18 donors over 8
weeks and subsequently developed unusual recurrent infections
with opportunistic agents such as Candida.

• The infant's T cell count was low, suggesting AIDS. There was no
family history of immunodeficiency, but one of the blood donors
was found to have died of AIDS. This led the investigators to
hypothesize that AIDS could be transmitted by blood transfusion.
 Example of case series
• In 1974, Creech and Johnson reported a case series
of three men with angiosarcoma of the liver among
workers at a vinyl chloride plant.
• This number in such a small population during the
time period studied was clearly in excess of what
was expected
• this led to the formulation of the hypothesis that
occupational exposure to vinyl chloride caused
hepatic angiosarcoma.
• Later the same year, this hypothesis was
substantiated by data from two analytic studies
 Example 2 of case series
• In 1980 -1981 four previously healthy young men were diagnosed with Pneumocystis
carinii pneumonia, an unusual "opportunistic" infection that had only been seen in
immune compromised people with hereditary disorders or in people with immune
compromise due to chemotherapy. The medical histories didn't suggest any preexisting
immunodeficiency, but all four men had decreased immune responses and low T cell
counts.

• These unusual infections suggested the possibility of a previously unknown disease. It

was noted that all four men were sexually active homosexuals, and in the case series
which was published in the New England Journal of Medicine the authors speculated
that the immune dysfunction was due to a sexually transmitted infectious agent.

• This was an extraordinarily important case series (a detailed description of

characteristics of a series of people who all have the same disease) that suggested that
this new syndrome was associated with sexual activity in male homosexuals. Alerting
the medical establishment and proposing a hypothesis was an important milestone in
the AIDS epidemic.
 Strengths of Case Reports and Case Series

• They are relatively quick and inexpensive, often conducted

on available data
• They may recognize and describe new and emerging health
problems
• They may generate hypotheses based on similarities among
group
• They may give insights into disease mechanisms
 Limitations of Case Reports and
Case Series
• There is no comparison group.
• The temporal relationship between the
exposure and the health outcome is often
unclear, i.e., it is not always clear that the
exposure preceded the outcome
•
 2.2. Cross sectional surveys

• Often called prevalence studies

• Exposure and disease status are assessed

simultaneously
• help in assessing the health status and health care
needs of a population
• Several countries conduct regular cross-sectional
surveys on representative samples of their population.
 Advantages of cross sectional studies:
• one-stop, one-time collection of data
• less expensive & easier to conduct
• provide much information useful for planning health
services and medical programs
• show distribution of conditions, disease, injury and
disability in groups and populations
• studies are based on a sample - do not rely on
individuals that present themselves for medical
treatment
 Disadvantages of cross-sectional studies
1) chicken or egg dilemma -which occurred first? the
exposure or the outcome ?
 2.3 Correlational (Ecological) studies
• Measures that represent characteristics of entire
population are used to describe disease in relation to
some factor of interest
• The units of analysis are populations or groups of
people rather than individuals
• Compare populations in different countries at the same
time or the same population of a country at different
times.
 Example of correlational study
• To describe patterns of mortality from CHD in 1960,
death rates from 44 states were correlated with
percapita cigarette sales.
• Death rates were highest in states with the most
cigarette sales
• This contributed to the formulation of the hypothesis
that cigarette smoking causes fatal CHD
• This has been substantiated in a large number of
subsequent analytic epidemiologic studies.
• The correlation coefficient (r) is the descriptive
measure of association.
 Cont’d…..example of correlational study
• Correlation coefficient quantifies the extent to
which there is linear relationship between
exposure and disease i.e whether for every unit of
change in level of exposure, the disease frequency
increases or decreases proportionately
• The value of r can vary between +1 and -1.
• correlation of zero indicates that the variables are
not related
• a correlation of 1 indicates that they are perfectly
related.
 Ecological Studies- Example
Age-adjusted annual coronary heart disease incidence per 100,000

35 Finland

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25 Sweden
2
Norway R = 0.53
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UK US Denmark
15
Netherlands
10 NZ Canada Austria

5 Australia France
Japan
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Average annual coffee consumption (kg/person)
1978-1982
 Strengths and Limitations of correlational studies

Strength
can be done quickly and inexpensively, often
using already available information
Limitation
1) Since the unit of analysis is a population or
group, the individual link between exposure
and effect cannot be made
 Cont’d…..Limitations of correlational studies
2) lack of ability to control for the effects of
potential confounding factors
3) correlational data represent average
exposure levels rather than actual individual
values.
This may lead to - Ecological fallacy- the
association observed between variables at
the group level does not necessarily
represent the association that exists at
individual level
 Analytic Studies

 Hypotheses generated from associations between diseases

and possible determinants in descriptive studies need to be
tested by analytic studies
 There are three types of analytic studies:
 Cross-sectional studies
 Cohort studies
 Case control studies
 Analytic Studies: Cross-sectional studies

 Aims
 To test hypotheses on disease causation by showing the degree
of correlation between possible determinants and disease
 To assist health service planning by measuring the burden of
disease in subgroups and identifying those in greatest need of
services
Cohort studies

 Group of persons with common characteristics

 Exposure or involvement in a defined population who
are followed or traced over a period of time
 Any designated group of persons who are followed or traced
over a period of time
Examples of cohort:
 Birth cohort
 Inception cohort
 Immigration cohort
 Treatment cohort
 Exposure cohort
Cohort studies
Basic elements of cohort studies

 “Disease free” or “without outcome” population at entry

 Selected by exposure status rather than outcome status
 Follow up is needed to determine the incidence of the outcome
 Compares incidence rates among exposed against non-exposed
groups
Data to be collected in cohort studies

 Data on the exposure of interest to the study hypotheses

 Data on the outcome of interest to the study hypotheses
 Characteristics of the cohort that might confound the
association under study

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What is exposure of interest?
 Exposure in usual sense
 E.g. Ingestion of contaminated food
 E.g. Droplets from someone with active pulmonary
tuberculosis
 Behaviors
 E.g. Sharing needles, drinking alcohol, fatty food eating
habit etc
 Treatment
 E.g. Intervention - education program

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What is outcome of interest?

 Disease
 E.g. Diabetes, TB,
 Event
 E.g. Injury from land mine
 Condition
 E.g. Blindness
 Death
 Others

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Sources of exposure and outcome information

 Pre-existing records
 Information supplied by the study subjects
 Direct physical examination or screening tests

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Possible outcomes in cohort studies

 No disease
 Disease
 Death from the computing risk
 Lost to follow up

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 Follow up period of cohort studies

 The follow-up is the most critical and demanding part of a cohort study

 Lost to follow-up should be kept to an absolute minimum (< 10-15%)

 Changes in the level of exposure to key risk factors, after the initial survey
and during the follow-up period, are a potentially important source of
random bias

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Follow up time in cohort studies
 The outcome has not occurred at the beginning of the study
 Length of follow-up time required is dependent on:
 the incidence rate of the outcome
 the size of the population at risk
 the latency period of the outcome

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 Types of cohort studies

 Cohort studies can be classified depending on the temporal

relationship between the initiation of the study and the
occurrence of the outcome of interest

 Prospective cohort studies

 Retrospective cohort studies

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Cohort study design

Classical (prospective)

1. measure exposure 2. measure outcome

Historical (retrospective)

1. Record of exposure 2. measure outcome

Steps in prospective cohort studies
1. Define the population at risk
2. Determine exposure status to a factor of interest
3. Make sure that study subjects are free of the disease of
interest at time of enrolment
4. Follow exposed and non-exposed forward in time to
ascertain whether they develop the outcome of interest
5. Compare the outcomes in the exposed and non-exposed
groups
6. Conclude whether the exposure to risk factor contributes for
the outcome of interest

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Retrospective cohort studies

 Both exposure and outcome status have occurred at the

beginning of the study
 Studies only prior outcomes and not future ones
 A historical cohort study depends upon the availability of data or
records that allow reconstruction of the exposure of cohorts to a
suspected risk factor and follow-up of their mortality or
morbidity over time

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Ascertainment of outcome of interest
 The aim of good case ascertainment is to ensure that the
process of finding cases, whether deaths, illness episodes, or
people with a characteristic, is as complete as possible using:
 Operational definition
 Standard definition
 Eligibility criteria
 Case definition
 Case finding
 Case ascertainment

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Strength of cohort studies:
 Particularly efficient when exposure is rare
 Can examine multiple effects of a single exposure
e.g. (smoking > lung cancer, COPD, larynx cancer)
 Minimize bias in outcome measurement if prospective
 Allows direct measurement of incidence (risk) and prognosis
(natural history)
 Can elucidate temporal relationship between exposure and
outcome of interest (if prospective )

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Limitation of cohort studies:

 Costly and time consuming if disease is rare and/or long

latency period (if prospective)
 Validity of the results can be seriously affected by loss to
follow up (if prospective)
 Relatively statistically inefficient unless disease is common
(need large sample size)
 If retrospective, requires availability of adequate records
 In-efficient for evaluation of rare diseases, unless attributable-
risk is high
 Exposure status may change during the course of study

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Case-Control Studies

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 Case-control studies

Direction of inquiry

Exposed
Cases
Non-exposed

Population

Exposed
Controls
Non-exposed

Time
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Steps of case-control studies
1. Define cases and controls
2. Identify group of cases
3. Identify group of controls
4. Review both groups for previous history of exposure to risk
factors under study
5. Measure frequency of exposure to risk factors occurrence in
both groups
6. Compare frequency of exposure to risk factors between cases
and controls
7. Conclude that previous history of exposure to risk factors
contributed for the cases more than controls or not
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 Applications of case-control studies

 It is good to do for rare diseases

 It may be possible to explore a wide range of potential
exposures to risk factors for a single disease

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What is case?
 Establish a clear operational definition or use standard definition of
disease (outcome) of interest in order to have a clear
understanding of exposure-disease association
 It is the outcome of interest under study
 It can be:
 A disease
 E.g. HIV status, malaria case
 A behavior
 E.g. Alcohol drinking habit, cigarette smoking
 Occurrence of an event
 E.g. migration
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 Selection of case …
 Define ‘disease’ and how it will be measured
 Selecting the source population of cases (homogeneous cases)
 Sources of cases are commonly:

 All persons with the disease in a population during a specific

time of period
 All persons with the disease seen at a particular facility (e.g. a
hospital) in a specific time period

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Sources of cases

Hospital-based:
 Easy and in-expensive to conduct
 It is prone for selection bias
Population-based:
 Avoids selection bias
 Allows the description of a disease in the entire population
and the direct computation of rates of disease in exposed
and non-exposed groups

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What is control?
 It is the comparison group (referent)
 It should be free of the disease (outcome of interest under
study)
 It should be as similar as the cases in all aspects except for the
disease of interest under study
 Controls must have the same opportunity of getting exposure to
risk factors as cases and should be subjected to the same
inclusion and exclusion criteria

 Practically, no one control group is optimal for all situations

comparable with cases

 It needs scientific, economic and practical considerations

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Sources of controls
1. Population-based controls
2. Hospital-based (health institution) controls
3. Specials controls: neighbourhood, friends, spouses or
relatives (siblings)
o Potential bias regarding ethnic backgrounds,
socioeconomic status and environmental exposures
E.g. If diet and smoking as exposure factor will
underestimate the effect of exposure to the occurrence
of disease

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Hospital-based controls

Advantages:
 Minimize re-call bias
 Convenient
 Cooperative non-case patients (minimize non-response
bias)
Disadvantages:
 Control disease may be linked to exposure of interest
 Hospitalized controls differ from general population

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 Ratio of controls to cases
 A single control group is optimal in most of the times
 However, ratio of controls to cases may vary from 1:1
to 4:1
 Trade-off: cost versus power of the study
 Decision based on power calculation
 More than one control groups may be recommended
when the single control is not appropriate or has a
specific deficiency

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 Strengths of case-control studies

 To investigate rare disease (less than 10%)

 Suitable for the evaluation of diseases with long latency period
 Quick with time and in-expensive
 Relatively efficient with small sample size comparing with
cohort studies
 Little problem with attrition of study subjects
 Can examine multiple etiologic exposures for single outcome

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 Limitation of case-control studies
 In-efficient for rare exposures
 No calculation of rates and risks possible
 In some situations, the temporal relationship between
exposure and disease may be difficult to establish
 Temporal exposure–disease uncertainty
 Prone to selection and information bias
 Selection of controls difficult some times

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Interventional Studies

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Monitoring and Evaluation: Evaluation Designs
 Objectives of the Session

By the end of this session, participants will be able to:

 Understand the purpose, strengths, and shortcomings of
different study designs
 Distinguish between study designs that enable us to causally
link program activities to observed changes and study designs
that do not
 Link evaluation designs to the types of decisions that need to
be made
 The Basic Experimental Principle

 The intervention is the only difference between two groups

 This is achieved by random assignment
An Experimental Design
In this design:
 There are two groups, an experimental group and a control group
 Both have been randomly selected and both complete the pre-test
 Only the experimental group gets the intervention, then both groups
complete the post-test.

Experimental group O1 X O2
RA
Control group O3 O4

RA refers to random assignment

An Experimental Design-Cont’d
Steps
1. Identify people or groups
2. Pre-test everyone
3. Randomly assign some of the participants to either the
control group or the experimental group.
4. Deliver the intervention to the experimental group
– The control group may receive an alternative intervention
or nothing at all.
5. Post-test both groups with the same instrument under the
same conditions.
An Experimental Design-Example

• A Native non-profit wants to test the curriculum content of an HIV

education program they are developing for group settings. They
decide to do a formative evaluation on the curriculum using a true-
control-group design. They recruit support from a substance-abuse
provider in the community and ask to work with a group of clients
for about an hour. In a classroom setting, they ask everyone to
complete a knowledge, attitude, behavior, belief (KABB)on HIV and
risky behavior. They then randomly sort the group into either an
experimental or control group (e.g. everyone counts off, and all the
ones are in the control group and the twos are in the experimental
group). The group-level HIV-education program is delivered to the
experimental group. The control group gets free time or receives
information on an unrelated subject. Both groups are called back
together and asked to complete the post-test.
Factors that May Lead Us to Make Invalid Conclusions

 Dropout: There may be loss to follow-up.

 Instrumentation effects: Occur when a questionnaire is changed
between pre-test and post-test.
 Testing effects: Occur because study participants remember
questions that were asked of them at pre-test and perform
better at post-test because they are familiar with the questions.
 A Second Experimental Design
In this design:
 Experimental and control groups are formed;
 However, there is no pre-test
 Instead, the experimental group gets the intervention and then
both groups are measured at the end of the program

Experimental group X O2
RA
Control group O4
A Experimental Design: Example
• Health providers in a Native Nation want to find a method for
raising awareness about HIV and risky behaviors in the
adolescents in the community. They have identified two
programs that can be delivered in the classroom; however,
there is a considerable difference in the cost of the two
programs in terms of not only materials, but also staff time.
Before making a final recommendation, they decide to pilot
each program in a different school setting. Since the goals and
objectives of both programs were there, both groups receive
the same post-test at the conclusion of the program year.
Changes in the KABB of the students can be attributed to their
respective program.
A Non-Experimental Design
Time
Experimental group
O1 X O2

Only people who are participating in program get pre- and post-test.
Steps
1. Pre-test everyone in the program
2. Deliver the intervention
3. Post-test the same individuals

• This design does not provide any information about what kinds of results
might have occurred without the program and is the weakest in terms of
scientific rigor
 Another Factor that May Lead to Invalid Conclusions

 History effects: These occur when extraneous events (events that

occur outside the study) influence study-measured outcomes.
Example of history effects:
 A mass media campaign has been initiated to increase condom use.
However, a major sports figure in the country admits that he/she
has AIDS and warns people on national television to avoid
unprotected sex. The pre-test-post-test non-experimental design
does not permit us to determine if the changes observed are due to
the intervention. In other words, is the difference between O1 and
O2 in the previous slide due to the mass media campaign or due to
the effect of the sports figures public acceptance of being HIV
positive? It is worth noting that, in the experimental design, the
control group will pick up effects due to extraneous events.
 A Second Non-Experimental Design

Time

Experimental groupO1 O2 O3 X O4 O5 O6

 This is called a time-series design.

 It is stronger than a pre-test post-test only design
 because it has the advantage of multiple measures before and
after the program intervention.
 A Second Non-Experimental Design-Steps
Steps
1. Select a program-outcome measure that can be used
repeatedly.
2. Decide who will be in the experimental group
– Will it be the same group of people measured many times, or
– will it be successive groups of different people?
3. Collect at least three measurements prior to the intervention
that were made at regular intervals.
4. Check the implementation of the intervention.
5. Continue to collect measurements, at least through the
duration of the program.
 A Quasi-Experimental Design

Time

Experimental group O1 X O2
---------------------------------
Comparison group O3 O4

 Useful for program evaluation

 Stronger than a non-experimental design
 Instead of a control group (which is created by random assignment),
this design has a comparison group
 A comparison group is selected if its observed characteristics are
similar to the observed characteristics of the experimental group
 The dotted line indicates the separation of two groups that have not
been randomly assigned to experimental and control conditions.
A Quasi-Experimental Design: Steps

1. Identify people who will be getting the program

2. Identify people who are not getting the program, but are
other ways very similar.
3. Pre-test both groups.
4. Deliver the intervention to the experimental group
– The control group may receive an alternative intervention or nothing
at all.
5. Post-test both groups.
Example:

• A nurse working with women in an OB/GYN clinic wanted to see if her HIV-
education programs were increasing awareness among pregnant women
and new mothers.
• She asked a colleague working with women at another OB/GYN clinic to
help her. Women in their second trimester of pregnancy in both clinics were
asked to complete a pre-test. Visits by women in the experimental clinic
also included regular HIV-education messages, delivered during their
routine clinic visits.

• At the post-partum visit, six weeks after the birth of their child, participants
at both clinics completed the post-test. If the intervention proved
successful, the information could be used to train other nurses to deliver
prevention messages during the regular course of their work.
 Threat to Validity

 Selection effects: Occur when people selected for a comparison

group differ from the experimental group

 Example of selection effects:

 A training of all health providers is conducted among all providers of District
A in a country. An adjacent district, District B, which is thought to be similar
in terms of clinic facilities serves as a comparison district. However, when
data is collected during the study, the researchers find that the providers in
District A have, on average, been in service for longer than providers in
District B and have been exposed to more trainings during the period of
their employment.
Summary Features of Different Study Designs

True experiment Quasi-experiment Non-experimental

Control group Comparison group --

Strongest design Weaker than Weakest design

experimental design

Most expensive Moderately expensive Least expensive

Summary Features of Different Study Designs-Cont’d.

I. Non-experimental (One-Group, Post-Only)

Implement Program Assess Target Group After Program

II. Non-experimental (One-Group, Pre- and Post-Program)

Assess Target Assess Target Group After

Group Before Implement Program
Program
Program
 Summary Features of Different Study Designs-ctd

III. Experimental (Pre- and Post-Program with Control Group)

Target Assess Implement Assess

Randomly Assign Group A Program With Target
Target
People From The Target Group A Group A
Group A
Same Target
Population To
Group A
Assess Assess
Or Control
Target Control
Group B
Group B Group A Group B
Summary Features of Different Study Designs

IV. Quasi-Experimental (Pre- and Post-Program with Non-

Randomized Comparison Group)

Assess Targer Group Assess Target Group

Before Program Implement Program After Program

Assess Comparison Assess Comparison

Group Before Group After
Program Program
 When an experimental studies warranted ?
 The research questions cannot be answered by
observational studies

 Existing knowledge is not sufficient to determine clinical or

public health practices and policies

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Thank You !

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