Nested case control,

Department of Community Medicine, BMC, Sagar

1. Nested case control, case cohort, case cross over studies Presented by- Dr. Shefali Jain (PG 1 ST Year) Guided by- Dr. Rohit Trivedi Dr. Bhupendra Rohit

2. Nested Case Control Nested case-control studies are not very different from classic case-control studies. They have a special name because of the way they are conducted. A nested case-control study is a case-control study situated within a prospective cohort study.

3. The prospective cohort study generates cases and potential controls for the nested case-control study. This provides a well-defined source population from which cases and controls both arise. Whenever a case occurs, a control can be selected from among the cohort members who do not have the disease at that point in time, providing a firm procedure for control selection.

4. Risk set sampling of controls allows estimation of the incidence rate ratio. By assessing exposure in the case group and in a sample of the non case group (controls), the nested case-control approach applies the familiar efficiency of the case-control design. It is often more efficient to properly select a subset of eligible cases rather than the whole group of all eligible cases.

5. Example of Nested Case Control Study • A nested case control study examined the relationship between serum organochlorides and breast cancer. • Study subject were drawn from a cohort of over 57,000 female members of Kaiser Permanente Medical Care Program who went multiphasic examination in late 1960s, at that time blood samples were collected and stored.

6. The cohort was followed upto 1990. 150 women who developed breast cancer during the follow up period were then randomly selected and individually matched to 150 women in the cohort who had remained free of breast cancer.

7. • Using the blood samples stored at baseline , serum levels were compared between cases and controls. • This approach resulted in considerably less cost and effort in processing of laboratory specimens.

8. Advantages • Efficient – not all members of parent cohort require diagnostic testing • Flexible • Reduces selection bias – cases and controls sampled from same population • Reduces information bias – risk factor exposure can be assessed with investigator blind to case status

9. Disadvantages • Reduces power of the study as sample size is decreased.

10. Case Cohort Study - In a case-cohort study, cases are defined as those participants of the cohort who developed the disease of interest, but controls are identified before the cases develop. - This means that controls are randomly chosen from all cohort participants regardless of whether they have the disease of interest or not, and that baseline data can be collected early in the study

11. Case-cohort study designs were proposed as an alternative to the nested case-control study design. Case-cohort study requires only the selection of a random sample, named a subcohort , and all cases.

12. ADVANTAGE We can study different diseases (different sets of cases) in the same case-cohort study using the same cohort for controls. In this design, in contrast to the nested case-control design, cases and controls are not matched on calendar time and length of follow-up ; instead, exposure is characterized for the subcohort .

13. In summary, nested case-control and case-cohort designs are efficient in terms of cost and can be used to evaluate the relationship between the exposure and diseases. Compared to a nested case-control design, the case-cohort design is more efficient and allows an investigator to study several disease outcomes by using the same random sample.

14. Case-crossover studies The case-crossover study design is especially appropriate where individual exposures are intermittent, wherein the disease occurs abruptly and the incubation period for detection and the induction period are short. Individuals serve as their own control.

15. Case-crossover studies The case-crossover design is primarily used for studying the etiology of acute outcomes such as myocardial infarctions or deaths from acute events in situations where the suspected exposure is transient and its effect occurs over a short time.

16. Design and findings of a hypothetical 4-month case-crossover study of air pollution and myocardial infarction(MI). A , Times of development of MI cases . B, Periods of high air pollution (shown by the colored bands). C, Defining at-risk periods (red brackets ). D, Defining control periods (blue brackets).

17. Advantage This design eliminates the additional cost that would be associated with identifying and interviewing a separate control population.

18. DISADVANTAGE Recall bias.

19. REFERENCES Leon Gordis , Gordis Epidemiology, ELSEVIER 6 th Edition, 2019 Langholz , B. and Thomas, D. (1990). Nested case-control and case-cohort methods of sampling from a cohort: A critical comparison. American Journal of Epidemiology , 131:169-76.

20. Example: Suppose have 200 cardiac events. Want to measure the association between cardiac events and particulate matter in the air • Case period – designated as 24 hours preceding cardiac event • Control period – designated as 1 week prior to the case period • Particulate matter may be classified as high vs low

21. • Based on table below– Among cardiac patients: – 60 experienced high particulate matter during the case and control periods – 40 experienced high-particulate matter during the case period but not low control period – 20 experienced low particulate matter during the case period but high-particulate during the control period – 80 experienced low-particulate matter during both the case and control periods Control (High) Control(low) Case-high 60 40 Case-low 20 80