Cohort and case-control designs

1. Summer Course:Introduction to Epidemiology August 28, 1045-1215 Cohort and case-control designs Dr. N. Birkett, Department of Epidemiology & Community Medicine, University of Ottawa

2. Session Overview • Review basic features of these two designs • Discuss advantages and disadvantages • Key methodological features in implementation of the designs.

3. General (1) • Our main focus is on etiology and studies of relationships • External validity is not big issue • A much bigger issue for cross-sectional studies • A big issue for health care delivery, etc. • Methods of Data Collection • Structured vs. unstructured interviews • Qualitative vs. quantitative methods • Personal interview • Mail & telephone surveys

4. Cohort (1) • Key feature is that subjects are followed from before they became ill until they get the outcome • Two main methods of subject selection • Separate exposed and unexposed groups • Select a group of people with the exposure of interest and • Select a group of people without the exposure of interest • Select a group of people with a range of exposure experiences • Follow all subjects up to determine if they develop new cases of the outcome. • Compare the incidence of the outcome in each group.

7. Prospective Concurrent Historical Retrospective Mixed Historical Ambidirectional

8. Advantages of Cohort Studies • Demonstrate clear temporal relationship • Allow direct calculation of incidence rates and risks • Allow multiple outcomes to be studied in one project • Allow multiple exposures to be studied in one project. • Provides some indication of disease latency or the incubation period (sometimes) • Suitable for studying rare exposures • Reduced potential for bias • Eliminates recall bias • Controls exposure misclassification.

9. Disadvantages of Cohort studies • Often require large sample sizes and long follow-up times. • High cost and complexity. • Bias due to loss to follow-up • How to handle changes in exposure status during follow-up • Also a problem in case-control studies but usually ignored. • Lack of available information for creation of exposure history in historical cohort studies. • Outcome assessment misclassification/bias if staff not blinded to exposure status • Advances in technology or medical knowledge can invalidate the outcome assessment, or even the whole study hypothesis.

10. Key Design Points for Cohort Studies • Selecting the cohort • Determining exposure status • Determining outcome status • Healthy worker effect • Studies of prognosis require Inception Cohort.

11. Cohorts: Selecting the Cohort (1) • Subjects must be: • Free of outcome at time of entry; • At risk of developing the study outcome • General population • Members of specific groups (e.g. unions, schools, professional organisations) • Special exposed groups (environmental)

12. Cohorts: Selecting the Cohort (2) • Internal vs. External comparison group • Internal uses people within the cohort • Is generally the best option. • External goes outside the cohort. • External group can be hard to find due to problems in lack of comparability • General population may be a poor choice: • Will include people with exposure

13. Cohorts: Determining Exposure Status • Need to consider change in exposure over time. • Interviews • Self-completed questionnaires • Body specimens (e.g. blood, hair, toenail clippings) • Biomarkers (molecular epidemiology) • Administrative records • Company records • Birth records • Hospital/MD records • environmental monitoring data. • Physical Examination • Environmental tests • Job descriptions • Job exposure matrix

14. Cohorts: Determining Outcome Status • Self-report • validity • completeness • Administrative records • Vital statistics • Registries • Medical records • Physical examination • Biological samples

15. Cohorts: Ontario Health Study • e-mail and web sites to collect basic information of everyone • goal is to recruit all people living in Ontario • Sub-set approached for a more detailed interview • Sub-sub-set approached for physical examination, blood samples, MRI’s, etc. • Has over 200,000 registrants • Target is 1,000,000+

16. Case-control (1) • Key feature is that subjects are selected after they have developed the outcome of interest. • Interviews are done after the fact • Limits the potential for some measures in etiologically relevant time periods • biomarkers • psychological state • Subject to biases • Need a comparison group (control group or reference group) • Choosing a suitable group is a major challenge. • Can not compute incidence in case-control study.

18. Advantages of case-control studies • Relatively quick and cheap • not always • depends on the design used • Appropriate for studying rare outcomes. • Require a smaller number of subjects than cohort study • assuming you can find enough cases • Allows study of multiple potential exposure factors in the same study

19. Disadvantages of case-control studies • Can only study one outcome per study • Cannot determine incidence directly • Except in special circumstances. • Not appropriate for studying rare exposures. • Higher risk of biases in exposure estimation, etc. • Selection of appropriate comparison group can be hard. • They have a bad reputation • Complex design and methodological features • Finding controls is getting harder than finding cases

20. Key Design Points: Case-control Studies • Selecting the cases • Selecting the controls • Determining exposure status • Sample size and power.

21. Case control studies: Selecting the Cases (1) • Need a clear case definition (eligibility criteria) • How to find cases? • Hospital-based vs. population-based. • Population based in better but can be hard to find all cases in a pre-defined population. • Population-based registry can be useful.

22. Case control studies: Selecting the Cases (2) • Retrospective vs. prospective case identification • retrospective is faster • prospective is better • changes in diagnostic approaches, referral patterns, etc. can be a problem with retro. method • Incident vs. prevalent cases • Incident cases are MUCH better

23. Case control studies: Selecting Controls (1) Without controls, there can be no case-control studies but with the wrong controls, there can only be regrettable case-control studies.Oleckno • This is the biggest challenge is designing a case-control study!! • Should represent the source population which gave rise to the cases. • In a hospital case-control study, do not select as a control group people with diagnoses which are known to be related to the exposure. • Just finding candidate controls is becoming a big challenge • privacy laws • lack of public interest in research

24. Case control studies: Selecting Controls (2) • Some key questions about control groups • Do the controls come from the same source population as the cases? • Are the controls similar to the cases with respect to potentially confounding factors? (matching; stratified analysis) • Have any restrictions or exclusions been applied to both cases and controls? • Are hospital controls taken from groups which are not associated with the exposure of interest? • Have the controls been selected from the same time period as the cases?

25. Case control studies: Determining Exposure Status • Determine the etiologically relevant time period. • Can we measure exposure at that time? • Interviewer bias • Use the same method in cases and controls. • blinding • Recall Bias • Hard to prevent/control • Blind subjects to objectives • Include ‘lie detection’ questions • Use validated questionnaires • Use alternative sources of exposure information • records • biomarkers

26. Case control studies: Sample Size and Power • May need large sample size, especially if studying interactions • Multiple controls per case • Useful mainly when controls are more available than cases or are cheaper to study • 4 controls per case is the largest ratio usually used. • In ‘nested case-control studies in pharmacoepidemiology, can use up to 10 or 20 controls per case

28. Summary • Both cohort and case-control studies have strengths and weaknesses • Case-control studies are harder to design well. • Cohort studies are generally preferred but take also much longer to complete and are much more expensive.