1. 1 Chapter 8 Case-Control Studies

2. 2 Chapter Outline 8.1 Introduction 8.2 Identification of cases and controls 8.3 Obtaining information on exposure 8.4 Data analysis 8.5 Statistical justifications …

3. 3 Case-Control Studies Identify cases in a source population Select at random non-cases from the same source population Compare exposure histories in cases & controls Population Cases Sample non-cases Exposure histories Odds Ratio Note: case-control samples do not permit the calculatino of incidence or prevalence!

4. 4 Case-Control 2-by-2 Table CasesControls ExposedA1A1 B1B1 NonexposedA0A0 B0B0 M1M1 M2M2 cross-tabulate exposure & disease status If done properly, the OR from the case control sample is stochastically equivalent to the rate ratio in the underlying source population

5. 5 Illustrative Example 8.2 Source populationSource population: A Seattle area HMO confirmed prostate cancer cases175 histologically confirmed prostate cancer cases selected at random from source population controls258 similarly aged men selected at random from source population (controls) ExposureExposure: prior vasectomy D+D- E+6193 E−E−114165 175258  about equal risk of prostate cancer in vasectomized and non-vasectomized men (“no association”)

6. 6 ORs Interpretation of case-control ORs Case-control OR is stochastically equivalent to an RR Multiple justifications are provided in §8.5 One such justification is shown on the next slide

7. 7 Case-Control Odds Ratio = Rate Ratio in Underlying Cohort (Incidence Density Sampling) The 2-by-2 table should be viewed as a sample from a conceptual prospective cohort Consider following a cohort: as a case occurs, select at random one or more controls

8. 8 Identifying Cases Types of cases –Incident cases (preferred) –Incident cases  onset of disease during study interval (preferred) –Prevalent cases –Prevalent cases  onset of disease before or during study interval Sources of cases –Population surveillance –Hospitals and clinics –Death certificates –Administrative health records –Pharmacy records Accurate ascertainment of cases = essential!

9. 9 Selection of Controls objective the relative frequency of exposure in the source populationThe objective of the control series is to reflect the relative frequency of exposure in the source population (B 1 /B 0 ≈ T 1 /T 0 )  controls represent a random sample of the source population If using hospital-based cases → random sample of hospital’s catchment area Sources of controls in practice –Population-based sample –Hospitals / clinics –“Friend controls” –Nested in a cohort

10. 10 Number of Controls per Case Maximum efficiency with 1 control per case (1:1) To increase statistical power when the number of cases is limited, select up to 4 controls per case (4:1)

11. 11 Sources of Exposure Information Interview Medical records Birth & death certificates Employment records Environmental records Biological specimens

12. 12 Good Information

13. 13 Data Analysis Covered –Dichotomous exposure –Multiple levels of exposure Not covered –Matched pairs –Matched tuples

14. 14 Multiple Levels of Exposure Exposure Level CasesControls 0 A0A0 B0B0 1 A1A1 B1B1 i K AkAk BkBk M1M1 M0M0

15. 15 Multiple Levels of Exposure Alcohol gm/day Esoph CA+ Esoph CA- 0-39 [0] 29386 40-79 [1] 75280 80-119 [2] 5187 120+ [3] 4522 200775

16. 16 Matched-Pairs Pair member Case E+Case E− Control E+tu Control E−vw

17. 17 Example 8.4: Toxic Shock Syndrome (TSS) and Tampon Use Case E+Case E− Control E+331 Control E−91 44 TSS cases & 44 friend controls Exposure = Continual tampon use

18. 18 Baldness and acute MI (a)Calculate the odds ratios associated with each level of baldness. (b)Based on your understanding of the properties of confounding, list 3 potential confounders that you should consider during further analysis. (c)The information on baldness status was self-reported type of issues does this raise?

19. 19 Colon Polyps and Fruit/Veg Consumption (a)Why do you suppose the study matched on these factors? (b)Show these data in the form of a matched pair cross-tabulation. (c)How many people in total were studied? How many cases? How many exposed cases did the study identify. (d)Calculate the odds ratios associated with low fruit/veg consumption. Interpret your results. (e)A separate validation study completed by the investigators showed that the correlation between self-reported fruit/veg consumption and information in historical food diaries was.56 (moderate correlation). How does this influence your interpretation. A case-control study used matched pairs to study the relationship between colon polyps and fruit/veggie consumption. Controls were matched to cases on several factors, including clinic, family history of colon polyps, age, race, and sex. There were 45 pairs in which the case but not the control reported low fruit/veg consumption. There were 24 pairs in which the control but not the case reported low fruit/veggie consumption. There were 25 pairs in which both the case and control reported high fruit/veg consumption, and there were 32 pairs in which both the case and control reported low fruit/veg consumption.