1. Epidemiologic Study Designs Nancy D. Barker, MS

2. Epidemiologic Study Design The plan of an empirical investigation to assess an E – D relationship. Exposure Alcohol consumption Raw hamburger Smoking Health Outcome Breast Cancer E. Coli Lung Cancer

3. Type of Epidemiologic Studies Experimental: Randomization to exposure Observational: No randomization

4. Experimental Studies The investigator through randomization allocates subjects to different categories of exposure. Randomization: An allocation procedure that assigns subjects into (one of the) exposure groups being compared so that each subject has the same probability of being in one group as in any other.

5. Randomization Tends to make demographic, behavioral, genetic, and other characteristics of the comparison groups similar except for their exposure status. If the study finds any difference in health outcome between the comparison groups, that difference can only be attributable to their difference in exposure status.

7. Experimental Studies Advantage: Randomization – unmeasured variables evenly distributed among exposure Potential for bias is low Disadvantage: Ethical concerns Cost Length of study Not good for rare D

8. Observational Studies Investigator observes the exposure and outcome status of each Most Epidemiologic studies are observational

9. Observational Studies Descriptive Studies Analytic Studies

10. Observational Studies Descriptive Studies To organize and summarize data according to time, place, and person. Why? Describe natural history of disease Extent of public health problem Identify populations at greatest risk Allocation of health care resources Suggest hypothesis about causation

11. Observational Studies Analytic Studies Used to quantify the association between an exposure (E) and a health outcome (D), and to test hypotheses about causal relationships. Provides a control group (baseline) Test hypotheses about determinants Causation

12. In any research field involving the conduct of scientific investigations and the analysis of data derived from such investigations to test etiologic hypotheses, the assessment of causality is a complicated issue. In particular, the ability to make causal inferences in the health sciences typically depends on synthesizing results from several studies, both epidemiologic and non-epidemiologic (e.g., laboratory or clinical findings).

13. Observational Studies Advantage: Natural Setting Addresses ethical concerns Disadvantage: No randomization – investigator can only account for variables measured.

14. Common Observational Study Designs Cohort Study Case-Control Study Cross-sectional Study

15. Design Options Directionality Timing

16. Directionality When the exposure variable is observed relative in time to when the health outcome is observed.

17. Forward Directionality

19. Backwards Directionality

21. Non-Directionality

22. Timing Timing concerns whether the health outcome of interest, and therefore all study events, has already occurred before the study actually began.

23. Retrospective

24. Prospective

25. Retrospective or Prospective

26. Cohort Study Directionality: Always forward Timing: Prospective or Retrospective

27. Cohort Study Synonyms: Follow-up study Longitudinal study Incidence study

28. Cohort Study Example Example: Prospective: Framingham Heart Study (ActivEpi) Retrospective: VDTs and spontaneous abortions (ActivEpi)

29. The Exposure Variable in Cohort Studies If E is common, sample from large population, then divide into E and not E. If E is rare, sample E from special population, then sample not E from external comparison group. Caution: Healthy worker effect.

30. Cohort Study Advantages –Forward directionality –Free of certain selection biases –Prospective cohort less prone to obtaining incorrect information –Can study several diseases –Useful for examining rare exposures –Retrospective cohort study is low-cost and quick, e.g., occupational studies

31. Cohort Study Disadvantages –Prospective cohort study is costly and time consuming –Loss of subjects from migration, lack of participation, withdrawal and death leads to bias –Statistically and practically inefficient for rare diseases with long latency –The exposed may be followed more closely than the unexposed

32. Example Measure of Effect Risk Ratio (Cumulative incidence – risk) Rate Ratio (Incidence density – rate)

33. Case-Control Study Directionality: Always backwards Timing: Always Retrospective

34. Case-Control Study Examples: Case-control studies of aspirin and Reye's syndrome (ActivEpi) Case-control study of animal food products and Creutzfeldt-Jakob disease (ActivEpi)

35. Case-Control Study Advantages: Cheaper, quicker Sufficient number of cases Smaller sample size A variety of exposures

36. Case-Control Study Disadvantages: Do not allow several diseases Risk of disease cannot be estimated directly Selection bias Information bias Not for rare exposures

37. Case-Control Study Selection of Controls Representative of the source population from which the cases derived Population-based controls -Cases and controls come from the same source population Hospital-based controls -Easily accessible, tend to be cooperative, and are inexpensive -Not usually representative of the source population and may represent an illness caused by the exposure

38. Case-Control Study Measure of Effect Odds Ratio

39. Cross-Sectional Study Directionality: Always Non-directional Timing: Always Retrospective

40. Cross-Sectional Study Advantages: Convenient and inexpensive Can consider several exposures and several diseases Can generate hypotheses Usually represents the general population

41. Cross-Sectional Study Disadvantages: Cannot establish whether the exposure preceded disease or disease influenced exposure Can identify only prevalent cases rather than incident cases Possible bias since only survivors are available for study May under-represent diseases with short duration

42. Cross-Sectional Study Example: Cross-Sectional Study of Smoking and Peripheral Vascular Disease (ActivEpi)

43. Cross-Sectional Study Measure of Effect Prevalence ratio (PR) Prevalence odds ratio (POR)

44. Hybrid Designs Combine the elements of at least two basic designs, or extend the strategy of one basic design through repetition. The Case-Cohort design The Nested Case-Control Study

45. Incomplete Designs Studies in which information is missing on one or more relevant factors. Ecologic Studies Proportional Studies

46. References ActivEpi Companion Textbook; Kleinbaum, Sullivan, Barker Principles of Epidemiology; CDC Self-Study Course Epidemiology in Medicine; Hennekens, Buring Statistics in Public Health: Quantitative Approaches to Public Health Problems; Stroup, Teutsch Case-Control Studies; Schlesselman