1. Dept of Family & Community Medicine
Cohort Study Designs
Ahmed Mandil
Dept of Family & Community Medicine
College of Medicine
King Saud University

2. Headlines Definitions Observational studies Characteristics
Advantages, disadvantages, problems
Examples
Analysis
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Cohort Studies

3. Observation Methods Selected Units: individuals, groups
Study Populations: cross-sectional, longitudinal
Data collection timing: prospectively, retrospectively, combination
Data collection types: primary, secondary
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Cohort Studies

4. Study populations
Cross-sectional: where only ONE set of observations is collected for every unit in the study, at a certain point in time, disregarding the length of time of the study as a whole
Longitudinal: where TWO or MORE sets of observations are collected for every unit in the study, i.e. follow-up is involved in order to allow monitoring of a certain population (cohort) over a specified period of time. Such populations are AT RISK (disease-free) at the start of the study.
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Cohort Studies

5. Epidemiological Measures
Frequency measures: incidence; prevalence
Effect measures: risk ratio (relative risk); odds ratio
Impact measures: attributable fraction; prevented fraction
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Cohort Studies

6. Observational Designs
Exploratory: used when the state of knowledge about the phenomenon is poor: small scale; of limited duration.
Descriptive: used to formulate a certain hypothesis: small / large scale. Examples: case-studies; cross-sectional studies
Analytical: used to test hypotheses: small / large scale. Examples: case-control, cross-sectional, cohort.
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Cohort Studies

7. Cross-sectional Studies (I)
(a) Characteristics:
A study to detect point prevalence
A reference population from which a random sample of chosen
Allows for stratification
Suitable for relatively frequent conditions
We are looking for both the disease and exposure status simultaneously
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Cohort Studies

8. Cross-sectional Studies (II)
(b) Advantages:
Feasible, relatively easy to administer
Less time-consuming (compared to prospective cohort studies)
Less costly
Allows for studying several conditions /exposures at the same time
Useful for health planning
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Cohort Studies

9. Cross-sectional Studies (III)
(c) Disadvantages:
Does not establish the temporal sequence of events necessary to suggest causal inference (temporal ambiguity)
Cannot distinguish risk from prognostic factors
Insufficient for studying of rare diseases (e.g. cancers)
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Cohort Studies

10. Case-control studies (I)
(a) Characteristics:
Two distinct source populations
We know the disease status, looking for the exposure status
Ratio of case:controls chosen by the investigator, minimum is 1:1.
Usually cannot calculate frequency measures
We have to assume that the non-cases (control) group is representative of the same source population of cases, in order to make any causal inferences.
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Cohort Studies

11. Case-control studies (II)
(b) Advantages:
Least expensive (smaller number of subjects involved)
Least time-consuming (relatively quick results)
Suitable for study of rare diseases
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Cohort Studies

12. Case-control studies (III)
(c) Disadvantages:
Not suitable for rare exposures
Cannot calculate frequency measures
Liable to selection bias (controls are usually selected after occurrence of cases)
Liable to recall bias -> measurement error, especially with effect estimation.
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Cohort Studies

13. Cohort Studies (I) (a) Characteristics:
A “cohort” is a group of people, referred to as “disease-free population” or “population at risk”
A survey is first carried out to exclude prevalent cases from the cohort
A period of "follow-up“ is specified, for possible new cases' occurrence
We know the exposure status, looking for the disease status
Historical designs are preferred under occupational settings, for less frequent effects / exposures.
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Cohort Studies

14. Cohort Studies (II) Two types are recognized:
Prospective (longitudinal): forward in time follow-up study
Retrospective (historical): backward in time study (depends on records: medical / employment). This is the type preferred under occupational settings
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Cohort Studies

15. Cohort Studies (III) (b) Advantages:
No / little temporal ambiguity (suggests cause-effect relationship)
Calculation of incidence rates
Suitable for rare exposures
Factors associated with selection cannot influence disease status and hence the results.
Several outcomes can be studied, after follow-up starts.
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Cohort Studies

16. Cohort Studies (IV) ( c ) Disadvantages (of prospective): Expensive
Time-consuming
May be impractical
Loss to follow-up may affect sample-size
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Cohort Studies

17. IDEAL COHORT An ideal cohort should be: STABLE COOPERATIVE COMMITTED
WELL-INFORMED
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Cohort Studies

18. Examples of Study Cohorts
General population
Selected occupational groups, e.g. health professionals (physicians, nurses, lab technologists, etc), manufacturers of mercury batteries for vehicles; asbestos workers, miners, etc
Special population groups (doctors) or exposure groups (occupational groups) are taken for the study, as these are easily available and follow up will be easier.
But they may reduce the external validity (generalization) to a certain extent, as these groups may not represent the general population.
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Cohort Studies

19. Sources of Cohorts Population groups
Occupational settings (employment, medical records)
Hospital registers (medical records)
Death certificates
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Cohort Studies

20. Follow-up Techniques
PERIODICAL MEDICAL EXAMINATIONS AND MAILED QUESTIONNAIRES
DIRECT PERSONAL INTERVIEWS OR EXAMINATIONS
VIDEOCONFERENCE, NEIGHBORS, FRIENDS AND RELATIVES
LOST PERSONS CAN BE TRACED THROUGH THE LETTERS, FROM THEIR RELATIVES AND FRIENDS
MIGRATED COHORT SUBJECTS CAN ALSO BE TRACED THROUGH TRAVEL AND IMMIGRATION AUTHORITIES
DEAD PERSONS - LOCAL OR REGIONAL MORTALITY REGISTERS
OR DEATH CERTIFICATES
GOOD FOLLOW-UP INCREASES THE INTERNAL VALIDITY OF THE STUDY AS IT MINIMIZES ATTRITION.
FOLLOW-UP TECHNIQUES AND THEIR DURATION OF APPLICATION SHOULD BE SIMILAR TO BOTH THE COHORTS
Cohort subjects can be followed in several ways either through direct personal interviews or examinations or indirectly through mailed questionnaires, videoconference, neighbors, friends and relatives etc. Lost persons can be traced through the letters, from their relatives and friends.
Attrition should be restricted to minimum possible extent. Migrated cohort subjects can also be traced through travel and immigration authorities. Information about the dead persons regarding the cause of death can be obtained either from local or regional mortality registers or death certificates.
Follow-up through the periodical medical examinations and mailed questionnaires is usually practiced. Follow-up techniques and their duration of application should be similar to both the cohorts. Good follow-up increases the internal validity of the study as it minimizes attrition.
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Cohort Studies

21. Problems during Follow-up
FOLLOW-UP OF A LARGE GROUP
LIMITED RESOURCES
TIME SCARCITY
PAUCITY OF TRAINED PERSONNEL
ATTRITION, LOSS ON FOLLOW UP
ETHICAL CONCERNS
Diseases with high incidence, we choose for this study and the study needs large group of people. The follow-up of large group (usual in cohort study) over a longer period of time is difficult.
Several problems, like resource crunch, time scarcity, paucity of trained personnel can occur or even the investigator may die. Hence, unless these requirements are adequately met, the cohort study should not be chosen.
Moreover, the attrition, loss on follow up (due to deaths, change in addresses, non-cooperation and withdrawal) is another major draw back with this design. If this loss on follow-up is significant, the internal validity suffers.
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Cohort Studies

22. Attrition Reduction OBTAINING THE INFORMED CONSENT
RECORDING COMMITMENT TO CONTINUE AND COOPERATE IN THE STUDY
TRACING LOST SUBJECTS, TRYING TO INCLUDE THEM IN THE STUDY
CONSIDERING INFORMATION OF LOST PERSONS AT THE TIME OF ANALYSIS
KEEPING NON-RESPONSE AT A LOW LEVEL TO IMPROVE THE VALIDITY
To minimize loss, not only taking the informed consent but also enlisting the commitment to continue and cooperate in the study is to be given maximum consideration at the commencement of study itself. If lost during follow up, every effort must be made to trace and include them.
The information of the lost persons either from registers (e.g. death registers) or from the neighbors and relatives is also to be considered at the time of analysis.
It is always tried to keep the non-response at a low level to improve the validity.
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Cohort Studies

23. Examples of Cohort Studies
POPULATION-BASED
CARDIOVASCULAR
CHILD HEALTH
SPECIAL EXPOSURES
NON-POPULATION BASED
OCCUPATIONAL – for convenience
OCCUPATIONAL – to study the occupation
HEALTH CARE SETTINGS
VETERANS
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Cohort Studies

24. CARDIOVASCULAR DISEASE
USA: Framingham, MA; Tecumseh, MI; Evans county, GA; Muscatine, IA; Bogalusa, LA (children)
WHO MONICA (multi-center)
North Karelia, Norway
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Cohort Studies

25. Framingham Study (1951 – present time)
1ST Step: Selection of cohorts
Initially, 5209 subjects were enrolled into the study
Currently, thousands of people are followed up, both for cardiovascular risk factors (e.g. high serum cholesterol, smoking, hypertension, BMI, etc) and possible outcomes
PROSPECTIVE STUDY
Conducted at Framingham town, Messachusets, to find out the association between the coronary artery disease and the risk factors like high serum cholesterol, hypertension, smoking etc.
Framingham town was selected as it is compact, economically stable, more cooperative and represents U.S. population to a larger extent. (though sample is only 68%)
In 1948, a Cardiovascular demonstration programme was carried out in Framingham town. Later, in the year 1951, it was converted into a cohort study.
The volunteers who have attended for initial demonstration programme were also included in the study.
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Cohort Studies

26. CHILD HEALTH National Birthday Trust Studies
National Birthday Trust Studies
One week of births in England and Wales in 1946, 1958, 1970, etc
Project on Premature Infants
All births < 1,500 g or < 32 weeks in a specific nation
The National Children Study
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Cohort Studies

27. SPECIAL EXPOSURES
Atomic Bomb Casualty Commission (ABCC): Hiroshima and Nagasaki survivors (effects of radiation)
Dutch famine survivors (effects of starvation)
Seveso (effects of dioxin exposure)
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28. OCCUPATION-BASED COHORTS, CONVENIENT FOLLOW-UP
British Doctors Study (Doll – smoking)
Nurses Study (Speizer, Willett – many issues)
London civil servants (Marmot - SES)
Taiwanese civil servants (Beasley – liver cancer)
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Cohort Studies

29. OCCUPATION BASED, TO STUDY EXPOSURES
  Benzene-workers (leukemia)
Coke-oven workers (lung cancer)
Asbestos workers (lung cancer)
Radium dial painters (oral cancer)
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Cohort Studies

30. SAMPLING FROM HEALTH CARE SETTINGS
National Collaborative Perinatal Project:
Almost all pregnancies at 12 medical centers – N about 50,000. (causes of CP)
Child Health and Development Studies:
Kaiser-Permanente births (many issues)
Patients treated with radiation for polycythemia or ankylosing spondylitis (radiation and cancer)
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Cohort Studies

31. VETERANS Mustard-gas poisoning from WW I (lung disease)
Vietnam Veterans (post-traumatic stress disorder, agent orange effects)
Gulf War Veterans (Gulf war syndrome)
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32. 2x2 Table Disease No Disease Exposed a = Exposed Cases
b = Exposed Non-Cases
Total exposed (a + b)
Not Exposed
c = Non-Exposed Cases
d = Non-Exposed Non-Cases
Total non-exposed
(c + d)
Total Cases
Total Non-Cases
n =
a + b + c + d
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Cohort Studies

33. INCIDENCE RATES
INCIDENCE AMONG THE EXPOSED (NEW CASES AMONG THE SMOKERS) = (A/ A+B)
INCIDENCE AMONG THE NON-EXPOSED (NEW CASES AMONG THE NON-SMOKERS) = (C/ C+D )
FOR SHORT PERIOD STUDIES:-
Incidence rate (number of new cases / population at risk)
Instantaneous incidence rate (new cases per unit time relative to disease-free population at risk at time t.)
FOR LONGER STUDIES:-
Cumulative incidence (disease risk during a specific interval/length of that interval)
Cumulative incidence rate (summing the products of incidence rate and interval length over a series of intervals)
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34. Risk Calculations Relative Risk or Risk Ratio (RR)
(RR) = [A / (A+B)] / [C / C +D)] (incidence in the exposed (smokers) / incidence in the non-exposed (non-smokers)
Attributable risk (AR = excess risk/ incidence among the exposed (AETIOLOGICAL FRACTION)
Population attributable risk (PAR) = incidence in the total population minus incidence among the non-exposed.
Standardized morbidity rate (number of the cases observed /number of cases expected/
from the standard rates as applied to the age/time specific person-years of observation )
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Cohort Studies

35. RR Interpretations
Unity: exposure has no effect on outcome in the studied population (cohort)
More than 1: exposed have a higher risk of developing the outcome, compared to the unexposed
Less than 1: either no relationship, or a “protective” one exists (e.g. effect of interventions, immunization, health education, management, etc)
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Cohort Studies

36. Frequency & Effect Measures
Design
Frequency
Effect
Calculation
Cross-sectional
Prevalence
Odds Ratio
ad / bc
Case-control
Neone
Cohort
Incidence
Risk Ratio
Ie [a / a + b] /
Iue [c /c + d]
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37. Choice of study design Status of existent knowledge
Occurrence of disease
Duration of latent period
Nature and availability of information
Available resources
Time constraints
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38. References
Last JM. A dictionary of epidemiology. 5th edition. New York, Oxford, Toronto: Oxford University Press,
Gordis L. Epidemiology. Third edition. Philadelphia, London, New York, Sydney: W.B. Saunders, 2004.
Beaglehole R, Bonita R, Kjellstrom T. 2nd edition. Basic epidemiology. Geneva: WHO, 2006.
Friis RH, Sellers TA. Epidemiology for public health practice. Gaithersburg, MD: Aspen Publishers, 1999.
Kelsey JL, Thompson WD, Evans AL. Methods in observational epidemiology. New York: Oxford University Press, 1986.
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39. Thank you for your kind attention
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