1. Case Control Study Manish Chaudhary BPH, MPH manish264@gmail.com

2. Introduction 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.

3. Hallmark of the case-control study is that it begins with people with the disease (cases) and compares them to people without the disease (controls). Also called:- Case-Referent, Case-Compeer, Retrospective Study Determines the strength of the association between each predictor variable and the presence or absence of disease. Introduction Contd…..

4. Three Distinct Features A)both exposure and outcome have occurred before the start of the study. B)The study proceeds backwards from effect to cause and C)It uses a control or comparison group to support or refute an inference Characteristics

5. Steps of Case Control Study 1.Selection of Cases and Controls 2.Matching 3.Measure of Exposure 4.Analysis and Interpretation

6. A] Definition of Case:- i)Diagnostic Criteria: Must be specified before the study is undertaken. ii)Eligibility Criteria: Incident cases are eligible than prevalent cases. B] Sources of Cases:- i)Hospital patients, patients in physicians practices, or clinic patients. ii)General Population 1. Selection of Cases

7. Controls must be similar to the cases as possible, except for the absence of the disease under study. Sources of Controls:- Should come from population at risk of disease. Population of defined area Hospital patients Neighbors Friends Siblings, spouses or other relatives 1. Selection of Controls

8. Qualities of Control Comparability is more important than representativeness in the selection of controls The control must be at risk of getting the disease. Controls should emerge from the same study base, except that they are not cases. For example, if cases are selected exclusively from hospitalized patients, controls must also be selected from hospitalized patients. Obtain power by matching more than one (generally < 4) control per case.

9. The usual case control ratio is 1:1. Increasing the ratio of controls to cases increases the precision and efficiency of the analysis but it also increases the cost to undertake the study. Therefore, 1:4 ratio of case and control is suitable.

10. Selection of Case and Control Total Population Control Cases

12. Process of selecting controls so that they are similar to cases on certain specific characteristics such as sex, age, occupation, body mass index, smoking status and marital status etc. The cases and control should be comparable with confounding factors. Methods of matching- group matching, pairing 2. Matching

13. Potential problems of matching It will be difficult to find controls if too many variables are selected for matching. Variables used for matching can not be studied as exposures or confounders. Matching Contd……

14. 3. Measurement of Exposure Information about exposure may be obtained by interviews, by questionnaires or by studying past records of cases such as hospitals records, employment records etc. Information should be obtained in precisely the same manner for cases and controls.

15. 4. Analysis Estimation of disease risk associated with exposure (Odds Ratio):- The ratio of the ratio of exposure in Cases compared to the ratio of exposure in Control. Measures the strength of the association between risk factor and outcome. Cases Controls Exposed a b Unexposed c d OR = ad/bc

16. Example of Case Control Study We have sampled 40 Lung Cancer patients admitted in BPKIHS Hospital and 50 controls without Lung Cancer and ask about their smoking habit in the past. Smoker Non-smoker Cases 15 (a) 25 (b) Control 5 (c) 45 (d) 50 40

17. Odds Ratio (OR) = ad/bc = 5.4 Interpretation:- Smokers showed the risk of having lung cancer 5.4 times that of non smokers.

18. Bias in Case Control Study Bias is the Systematic error in the determination of the association between the exposure and disease 1.Bias due to Confounding 2.Memory or Recall Bias 3.Selection Bias 4.Berkesonian Bias: Arises due to different rates of admission to hospitals for people with different diseases (i.e. hospital cases and control) 5.Interviewer’s Bias

19. Important Discoveries by Case Control Study 1950's: Cigarette smoking and lung cancer 1970's Diethyl stilbestrol and vaginal adenocarcinoma Post-menopausal estrogens and endometrial cancer 1980's Aspirin and Reyes syndrome Tampon use and toxic shock syndrome L-tryptophan and eosinophilia-myalgia syndrome AIDS and sexual practices

20. Advantages Quick and inexpensive. Suitable to investigate rare diseases. Well suited to the evaluation of outcomes with long latent periods. It can examine multiple etiologic factors for a single disease. No attrition problem because it doesn't require follow up. Ethical problems are minimal.

21. DISADVANTAGES Cannot measure; Incidence, Prevalence and Relative Risk Can only study one outcome Limitations in recall and recall bias Problem of selection of appropriate control groups If disease is relatively common (> 5 to 10%), OR may not be reliable estimate of RR Other possible effects of exposure can not be studied

22. Summary Imagine a source population – Consists of exposed and unexposed people – Gives rise to cases Control group is a sample from this source population – Independent of exposure status – Same distribution of exposed persons (person- time) as in source population Determine exposure status of cases and controls Calculate odds ratio