1. Case Control and Cohort Studies Dr Leela Dept Of Community Medicine

2. Learning Objectives At the end of the sessions, you will be able to: – Define case control and cohort studies – Identify applications for case-control and cohort studies – Describe prospective and retrospective cohort studies – Enumerate pros and cons in using case control/cohort studies – Describe two-by-two table – Compute odds ratio and relative risk

3. Epidemiologic Design Strategies Descriptive studies – Populations Correlated studies – Individuals E.g. case-series, case reports, cross-sectional surveys Analytical studies – Observational studies Case-control studies- rare diseases Cohort studies- common diseases – Intervention studies Clinical trials

4. Aim of epidemiological studies To determine distribution of disease To examine determinants of a disease To judge whether a given exposure causes or prevents disease

5. Case-Control Study

6. Definition…. The case-control study is an analytic epidemiologic research design in which the study population consists of groups who either have (cases) or do not have a particular health problem or outcome (controls). The investigator looks back in time to measure exposure of the study subjects. The exposure is then compared among cases and controls to determine if the exposure could account for the health condition of the cases.

7. Case-control study- 3 Distinct Features Both exposure and outcome( disease) have occurred before the start of the study The study proceeds backwards from effect to cause It uses control or comparison group to support or refute an inference

8. Case-control study Study Population Cases Controls Exposed Non-exposed Exposed Non-exposed

9. Retrospective assessment of exposure ( cigarette smoking) +- ill Disease occurred Exposure occurred Study takes place + - +- ill exp Case-Control Study Selection based on disease status ( lung cancer) Real Time Now

10. Setting-up a case-control study Identify group of cases and controls Matching Question both groups for possible exposure Analysis and interpretation

11. Selection of cases Establish a strict diagnostic criteria or definition for the disease: Examples: – Type 1 diabetes in children: severe symptoms, very high BG, marked glycosuria, and ketonuria. – Type 2 diabetes: few if any symptoms, Slightly elevated BG, diagnosis “complicated”. – Infants with gross congenital anomalies

12. Selection of cases Population-based cases: include all subjects or a random sample of all subjects with the disease at a single point or during a given period of time in the defined population: Hospital-based cases: All patients in a hospital department at a given time

13. Selecting Controls-pop /hosp Free from disease but similar to the cases as possible. 1.General population controls: – registries, households, telephone sampling – costly and time consuming – recall bias – eventually high non-response rate

14. Advantages/Disadvantages of general population controls: Advantages  Because of selection process, investigator is usually assured that they come from the same base population as the cases.  Disadvantages  Time consuming, expensive, hard to contact and get cooperation; may remember exposures differently than cases

15. Selecting Controls Example: Study of cigarette smoking and myocardial infarction among women. Cases identified from admissions to hospital coronary care units. Controls drawn from other units surgical, orthopedic, and medical unit of same hospital, (non coronary) 2.Hospital controls: – Patients at the same hospital as the cases – Easy to identify – Less recall bias – Higher response rate

16. Other controls 3. Neighbourhood control; same locality or factory 4.Relatives: but not siblings

17. Advantages of hospital controls Same selection factors that led cases to hospital led controls to hospital Easily identifiable and accessible Accuracy of exposure recall comparable to that of cases since controls are also sick More willing to participate than population-based controls

18. Disadvantages of hospital controls Hospital based controls are ill They may not accurately represent the exposure history in the population that produced the cases Hospital catchment areas may be different for different diseases

19. Matching Matching: selection of controls similar to cases with regards to certain variables e.g age, sex, occupation, social status etc If not done could distort or confound the results

20. Confunding “It is associated with exposure and disease, distributed unequally in study and control. ExposureDisease Confounder

21. Example of confounders “Second, third and fourth child are more often affected by Downs’ syndrome.” Many childrenDowns’ Maternal age

22. Bias in Case-Control studies Selection bias: groups compared are different, outcome different, not representative of population cases and controls are identified not independently of the exposure Observation bias – Recall Bias: Cases are more likely to remember exposure than controls Information Bias: Interviewer bias

23. Prevention of Bias Prevention of selection Bias Same selection criteria High response-rate High rate of follow-up Prevention of information Bias Clear definitions Good measuring methods Blinding Standardised procedures Quality control

24. Analysis: Odds ratio Exposed Smoking Not exposed Non smokers Case L. cancer Control No cancer a c b d Estimation of disease risk associated with exposure % of exposure among cases = a/(a+c) % of exposure among controls = b/(b+d) OR = 1 – no association OR > 1 – there is an association OR < 1 – the factor is some way protective

25. Advantages and disadvantages of case- control studies Advantages – Suitable for rare diseases – Can explore several exposures – Low cost – Rapid – Can cope with long latency – Small sample size – No ethical problems Disadvantages – Cannot calculate the risk – Not suitable for rare exposures – Temporal relationship difficult to establish – Subject to bias Selection of controls Recall bias …

26. When is it desirable to conduct a case-control study? When exposure data are expensive or difficult to obtain - Ex: Pesticide study When disease has long induction and latent period - Ex: Cancer, cardiovascular disease When the disease is rare –Ex: Studying risk factors for birth defects When little is known about the disease –Ex. Early studies of AIDS When underlying population is dynamic –Ex: Studying breast cancer

27. 2 minutes - Questions

28. Cohort Studies

29. What is a cohort? Cohort: Latin word for one of the 10 divisions of a Roman legion A group of individuals – Sharing same experience – Followed-up for a specified period of time Examples – Birth cohort – Occupational cohort chemical plant workers – A Rapid Response Team

30. COHORT STUDIES Cohort Study Key Point:  Presence or absence of risk factor is determined before outcome occurs. Basic Idea:Basic Idea: See if those with the risk factor develop more disease than those without the risk factorSee if those with the risk factor develop more disease than those without the risk factor

31. Cohort Study design  The best we can do is compare populations that are similar (not identical) in everything except the risk factor.  If we see increased disease only in the group with the risk factor, we can suspect that the risk factor caused the disease.

32. Elements of Cohort study Selection of study subjects Obtaining data on exposure Selection of comparison groups Follow up Analysis

33. Selection of Study subjects Sample of the general population: – Geographically area, special age groups, birth cohorts (Framingham Study) A group that is easy to identify – Nurses health study, college students, Special population (often occupational epidemiology): – Rare and special exposure – Permits the evaluation of rare outcomes

34. Obtaining data on exposure Interviews Questionnaires Review of records Medical examination or special tests Environmental surveys

35. Selection of the Comparison Population Internal Control Group – Exposed and non-exposed in the same Study population (Framingham study, Nurses health study) Minimise the differences between exposed and non- exposed External Control Group – Chosen in another group, another cohort (Occupational epidemiology: Asbestosis vs. cotton workers) The General Population

36. Follow Up Periodic medical examination Reviewing physician and hospital records Routine surveillance Mailed questionnaires, telephone calls, periodic home visits

37. 30 a 70 b 70 b 3 c 3 c 57 d 57 d smokingsmoking (+) (-) (+)(-) Disease = Lung cancer a + b 100 c + d 60 Risk =a/(a+b) =0.3 Risk =c/(c+d) = 0.05 Rel. risk= Analysis: Relative risk Incidence rate & Relative riska a + b c c + d 0.3/0.05 = 0.3/0.05 =6

38. COHORT STUDIES- Types Prospective Cohort: Outcomes have not yet occurred as study begins Eg Congenital anomalies Retrospective cohort: Outcomes have already occurred as the study begins. Eg Lung Cancer Combination of prospective and retrospective Eg radiation therapy for ankylosing spondilitis- outcome death due to leukemia or aplastic anemia, than prospective cohort

39. Cohort studies Retrospective – Exposure Disease Yes ? No ? Prospective – Exposure Disease Yes ? No ?

40. Exposure occurrence Study startsDisease occurrence Doll: Smoking & lung cancer, Framingham heart study Prospective Cohort Study Time + - +- ill exp + - Prospective assessment of exposure and disease Selection of population

41. Retrospective cohort study Study takes place Disease occurrence Exposure occurrence Retrospective assessment of exposure and disease Selection based on population + - +- ill exp Real Time Now

42. Prospective vs. retrospective Cohort Studies Prospective Cohort Studies – Time consuming, expensive – More valid information on exposure – Measurements on potential confounders Retrospective Cohort Studies – Quick, cheap – Appropriate to examine outcome with long latency periods – Admission to exposure data – Difficult to obtain information of exposure(recall) – Risk of confounding

43. Advantages and disadvantages of cohort studies Advantages – Can study rare exposures – Can measure incidence and risks – Several outcomes calculated – Direct estimate of relative risk – Less subject to selection bias Disadvantages – Requires a large sample size – Long period – Lost to follow-up – Ethical considerations- obliged to intervene to reduce or eliminate risk factor – Expensive

44. Strengths in Cohort vs. Case-control? Cohort study Rare exposure Examine multiple effects of a single exposure Minimizes bias in the in exposure determination Direct measurements of incidence of the disease Case-control study Quick, inexpensive Well-suited to the evaluation of diseases with long latency period Rare diseases Examine multiple etiologic factors for a single disease

45. Cohort studies are better but harder to carry out and provide true measure of risk Case-control studies are rapid and easy to carry out, but only provide estimates of risks Prefer cohort to case-control when feasible In field epidemiology, case-control studies are more frequently used when resources limited Conclusions