Epidemiological Study

Designs

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 Classification of Epidemiologic study designs

Definition of design

• Design is an arrangement of conditions for the collection & analysis of

data that leads to the most accurate answer to the research question and
in the most economical way.

• Study design is a specific plan or protocol for conducting the study,

which allows the investigator to translate the conceptual hypothesis into
an operational one.

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 Descriptive Analytic

Study Designs
Case report Cohort study
RCT

Case series Case-Control

study
Descriptive
Epidemiology Case-Crossover
study

Cross-sectional
study

Ecologic study

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 Descriptive studies:
provide information related to person, place, and time,
answering the Who?, Where?, and When? questions.

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 Descriptive study designs
Purpose and characteristics of descriptive study
Designs: -

• Concerned with the distribution of diseases with respect to

time, place and person.
• They are useful for health managers to allocate resources.
• Important for hypothesis generation.
• Descriptive studies can use routinely collected information.
• They are less time consuming and less expensive.
• The most common study designs used by epidemiologists.
• Identify high risk populations for the health problem

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 Types of descriptive study designs

I. Case report/ case study:

• Simplest type of descriptive study

• Describes a single case of illness, often an unusual or distinctive case

– New diseases or health hazards

– New clinical manifestations or syndromes

– New modes of disease transmission

– New treatments
• consists of a careful, detailed report by one or more clinicians of the profile of a
single patient.
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•
Example: Case report in 1961

• A 40-year old pre-menopausal woman developed

pulmonary embolism 5 weeks after beginning to use
an oral contraceptive preparation to treat
endometriosis.
• What is unusual in this report? Pulmonary embolism is
common in older, postmenopausal women. The investigator
postulated that the drug may have been responsible for this
rare occurrence.

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• II. Case series:-
• A study of multiple occurrences of unusual cases that have similar
characteristics.
• Series of case reports with common elements such as;

– Similar clinical features

– Suspected common exposures

– Similar geographic area

• They can be valuable early evidence for associations between exposures and diseases
which can be studied in more detail later on.
– Early in an outbreak investigation a case series is often used as the first attempt at
finding a common link between cases. 9
• Example: Five young, previously healthy homosexual
men were diagnosed as having pneumocystis carinii
pneumonia at Los Angeles hospitals during a 6 month
period in 1980 to 1981.

• What is unusual in this case series? Until then this form of

pneumonia had been seen almost exclusively among older
men and women whose immune systems were suppressed.
• HIV/AIDS was the final investigation of these cases.

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 Strength and limitations of Case report and Case
series
Strength
• Very useful for hypothesis generation

Limitation
• Report is based on a single or few patients which can happen just by
coincidence

• Neither a case study nor a case series includes a comparison group.

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 III. Descriptive Cross sectional studies (survey)

• Descriptive cross-sectional studies: Examine the prevalence of disease

(or exposure) in a defined population at one point in time

• A study with individual-level variables that measures exposure and

disease at one point in time.

• This study design provides weak evidence of causal association

between exposure and outcome because the exposure may not have
preceded the disease.
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 Cross sectional studies

• Cross sectional studies also show the picture of social, environmental,

or other problems or events in a population.

• The point in time may be as short as few minutes or as long as two or

three months.
• The time frame of "point in time" is based on the speed of data collection.

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 Cross sectional.. cont…
• Cross sectional studies are useful for raising the question of the presence of an
association rather than for testing hypothesis.
• But for factors that remain unaltered over time such as sex, race, blood
group, cross sectional studies can provide evidence of a valid statistical
association.

• An example of a cross sectional study would be to see how many of a

particular group of people smoke and how many of that group have lung
cancer.
• What is the prevalence of diabetes in this community?
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 Advantages of cross sectional studies

• One-stop, one-time collection of data

• Less expensive & more convenient to conduct

• Provide much information useful for planning health services and medical
programs

• Show relative distribution of conditions, disease, injury and disability in

groups and populations

• Studies are based on a sample of a major population and do not rely on

individuals that present themselves for medical treatment.
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Disadvantages of cross sectional studies

• It is difficult to know which occurred first, the exposure or the outcome.

This is known as "chicken or egg dilemma". so this is a very weak design
for drawing conclusion about cause and Effect.

• It may not show strong cause-effect relationships if sample size is small.

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IV. Ecological Studies

• The unit of observation is a group or aggregation of people,

thus another term used is ‘aggregate’ studies.

• Reasons for using ecological studies:

–Individual-level data not available
–Relatively quick and cheap
–Variation in exposure small at individual level
–Ecological effect may be more important than biological
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Outcome measurement in Ecological Studies

Population-level data, for example:

• National CVD or CHD rates;

• Regional suicide rates;
• National prevalence of asthma;
• National cancer mortality rates;
• National congenital birth defect incidence.
Exposure measurement in Ecological Studies

Overall index, for example:

• Regional alcohol or tobacco consumption from tax data;
• National salt or sugar consumption from sales figures;
• Group socio-economic status from census;
• National pharmaceutical use from drug agencies.
Examples of Ecological Studies
• Coronary heart disease incidence and coffee consumption
(international comparison)

• Stroke mortality and vitamin C intake (inter-regional

comparison)

• Stroke mortality and tobacco expenditure (inter-regional

comparison)
The Ecological Fallacy
• An alternative explanation for a presumed geographical
correlation;

• The exposure-outcome relationship may be confounded (eg coffee-

CHD)

• Within each geographical unit (town, region, country), it may

not be the exposed people who experience the outcome (eg
suicide rate and provincial religion).
Analytical – Observational Study Designs

• Case control Vs Cohort Study Designs

Case-Control Studies

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 Case-Control Study

Exposure
Disease
? (Case)

? No disease
(Control)

Retrospective Nature

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Case-Control Study
• PAST PRESENT

• It is a type of an observational analytic study

• Compares one group among whom a problem is present with

another group where the problem is absent in order to find out
factors contributing to or protective to the problem

• Problem examples- malnutrition, lung cancer, contracting cholera,

neonatal death
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Application of Case-Control studies

• It is good to do for rare diseases or outcomes

• Better for diseases with long latency between exposure and outcome

• It may be possible to explore a wide range of potential exposures for

a single outcome

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Principles of the Case-Control Approach

• Persons with the disease are compared with controls free of disease,
for presence of the factor under investigation

• Cases are compared to controls with respect to exposure frequency

• May be viewed as an efficient sampling scheme from a conceptual

study base

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 Major Steps in case-control study

• Define and select cases

• Select controls

• Ascertain exposure

• Compare exposure in cases and controls

• proportions/odds ratios ....

• Test any differences for statistical significance

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Cases
♦ It is the outcome of interest

♦ It can be
– A disease
eg. HIV status, Malaria caseness

– A behavior
eg Alcohol drinking habit, Cigarette smoking

– Occurrence of an event
eg migration
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Selection of cases
• Define ‘disease’ and how it will be ascertained

• Selecting the source population

• 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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Control
• It is the comparison group

• It should be free of the disease of interest

• It should be as similar as the cases in all aspects

except for the disease of interest

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Presentation of results

• Descriptive characteristics of cases and controls

• Distribution of exposure of interest in cases and controls

• Odds ratios

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 Advantages of Case-control Studies

• Assesses well for rare diseases

• It can assess several exposures (determinants) of a single outcome

• It can be completed within short time (Rapid)

• It can be performed with very cheap or Low cost

• A small sample size may be Enough

• It can also be done from available data

• Not needing detailed ethical problem/ issues 33

 Disadvantages of Case-control Studies

• No direct calculation of rates and risks

• Temporal relationship exposure-disease difficult to establish

• Not suitable for rare exposures

• Problems with bias

• Selection of controls

• Recall
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Cohort study

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 Cohort study
• It is also called follow up, longitudinal, prospective study.

• The word cohort is used to designate a group of people who share a

common experience.
• a Birth cohort,
• a Cohort of smokers,
• a Cohort of MPH graduates in 2023, etc.

• It is an observational study that measures incidence of disease occurrence.

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 Cohort studies
• An investigator studies a group of exposed and unexposed
subjects and follows the study subjects over a period of time
and compares the incidence of developing disease of interest in
the two groups
PRESENT TIME FUTURE TIME
Diseased
Exposed
No disease

Diseased
Unexposed
No disease
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 Basic elements
• “Disease” free at entry

• Selected by exposure status rather than outcome

• Follow up is needed to determine the incidence of the

outcome in each exposure group
• For non communicable chronic diseases this may take years

• Compares incidence rates among exposed against unexposed

groups
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 Exposure status
• Study subjects should be disease free

• Define study subjects using inclusion and exclusion

criteria on the basis of exposure status
• Environmental factors: smoking, air pollution, pesticides

• Criteria can be specified by amount of exposure

• Eg. Cigarette Smocking (# of cigarette per day)

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Possible outcomes in a cohort study

• No disease

• Disease

• Lost to follow up

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Features of cohort study
1. It shows temporal sequence

Exposure Disease

2. Good to assess effect of rare exposures

3. Could assess multiple effects of a single exposure

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 Types of cohort studies

• Two forms of cohort study

• The major difference is on the basis of

• Initiation of study and the occurrence of disease.

• The two forms are similar, because selection of study

subjects is made on the basis of their exposure status.

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 Types of cohort studies
1. Classical (Prospective) cohort
• The exposure may or may not have occurred at the time when the study
begin, but the outcome has certainly not yet occurred.

2. Historical (Retrospective) Cohort

• Both the exposure and outcome have already occurred when the study
is initiated.

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 Cont….
1. Prospective cohort
• Exposure status determined at present
Past Present Future
• Study groups followed up and disease
outcome will be ascertained in the Disease
Exposure
future outcome

2. Retrospective cohort
• Exposure determined in the past from
records
Disease
• Disease outcome ascertained at Exposure outcome
present
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Other classification
Open and closed cohort design

1. Closed (fixed) cohort

• Members of the cohort will be followed without adding
others.
• E.g 1000 children followed for 2 or 3 years

2. Open (Dynamic) cohort study

• Other than initially chosen study group, others could be
added or be lost.
• People at risk are measured using person-time (incidence
density)
• Data may be analyzed using ‘Time tables’ and Kaplan
Meir/ Cox regression. 45
Open (Dynamic) cohort study

Birth In-migrants

Death Out-migrants

E. g. Butajira Rural Health Program

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 Steps in a prospective cohort study
1. Define the population at risk (=cohort)

2. Determine exposure status to a factor of interest of all subjects in the cohort

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 the unexposed group with each
other
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Measures of association

• Calculate rate ratio (relative risk)

• Incidence risk (Cumulative incidence)
Denominator = # of individuals at risk at baseline

• Incidence (density) rate

 Denominator = ‘person time’

• Attributable risk (risk difference)

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 Measures of Association …
Relative Measure Ie
• Relative Risk (RR)
Rate ratio
Risk ratio Iue

Effect (impact) measures

• Absolute measures
Ie = incidence in exposed
• Risk difference (RD) Ie - Iue Iue= incidence in unexposed

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Summary
Strength
Is of particular value when the exposure is rare.

Can examine multiple effects of a single exposure.

Can elucidate temporal relationship between

exposure and disease.

Allows direct measurement of incidence of disease in

the exposed and non exposed.

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Summary
Limitations
Is inefficient for the evaluation of rare diseases,

Ifprospective, can be extremely expensive and

time consuming.

Ifretrospective, it requires the availability of

adequate records.

Validity of results can be seriously affected by

losses to follow up.

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Interventional
Study
design
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 Design and Temporal Direction
Past Start Future

Exposure Retrospective Disease

Exposure Prospective Disease

Cross-sectional
Disease & Exposure

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Experimental study
o It is a design that could bring high quality of a research
that resembles a controlled experiment done by basic
science, “Gold Standard”.

o It is similar to cohort study design that individuals are

enrolled on the basis of their exposure (natural exposure).

o Investigator assigns subjects to exposure and non-

exposure and makes follow up to measure for the
occurrence of a disease.

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Experimental studies

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Three major
types of interventional designs
1. Quasi-experimental design

2. Non-experimental design

3. Experimental design

• Major difference is on assignment of a true comparison group

• In experimental design, the comparison group is assigned

using scientifically proven randomization

• In Quasi-experimental design the comparison group are

selected conveniently or purposely 56
1. Quasi-experimental design
• A quasi-experimental design is one that looks like an
experimental design but lacks the key ingredient, the
“random assignment”.

• With respect to internal validity, they often appear to

be inferior to randomized experiments.

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2. Non-experimental
• In non-experimental study design, there is no proper comparison group

• The comparison group can be with the same people as before and after
intervention

• Only one arm exists.

Disadvantage
o x o
• Counterfactual:- Absence of timely and truly comparable participants
in a program
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 3. Experimental designs
Three types of designs
1. Therapeutic (Secondary prevention)
 Interventions made among patients
 Usually within health institutions
 (Clinical Trial)

2. Preventive (Primary prevention)

 Intervention performed among healthy people
 Individuals as study subjects (Field trial)
 Community (clusters) as study subjects (Community intervention)

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 Experimental study design (Clinical trial)

Direction of inquiry

Recover
Treatment
Patients Not recovering
with a
Population disease

Recover
Placebo
Not recovering

Manipulation
Time
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 Experimental study design (Field trial)

Direction of inquiry

Disease
Intervention
People No disease
with out a
Population disease

Disease
Non-intervention
No disease

Manipulation
Time
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 Experimental study (Community
intervention)
Direction of inquiry

Disease
Intervention
No disease
Community
Population with out a
disease
(cluster)
Disease
Non-intervention
No disease
Manipulation

Time
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 Problems in experimental studies
1. Ethical issues
• Humans are not experimental animals that could be manipulated

2. Feasibility
• Difficult to find sufficient sample size
• Even if found, only few complete the study

3. Cost
• It is more expensive than observational studies
• Cost of intervention element, cost of follow up (time, and expertise
assistance)

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Randomization
• It is a process of assigning study subjects into two or more
groups

• It is through random allocation of study subjects

• To randomly allocate study subjects, sampling frame is

needed

• A lot of statistical software may be used to allocate study

subjects [excel, spss, epi-info, random tables etc]

• If two groups, half would be to treatment and others would be

to non-treatment 64
Randomization
 Introduction of bias due to selection could be
avoided

 Investigators could be confident for any difference

 Study subjects could be comparable with all

variables except the intervention

 Known and unknown confounding variables could be

equally distributed between the two groups, thus their
effect could not be observed

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Blinding
• Even after randomization, it is possible that
experimental subjects may be treated differently than
controls

• To combat this, “blinding” (also called masking) is

often used

• Blinding means that the subject, investigator, or both

(double-blind) do not know to what group a study
subject is assigned to

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Levels of Blinding
• Blinding patients (single blinding)

• Blinding patients and treatment team (double

blinding)

• Blinding patients, treatment team and those

performing trial analysis (triple blinding)

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