This document discusses nested case-control studies, case-cohort studies, and case-crossover studies. It provides examples and discusses the advantages and disadvantages of each study design. Nested case-control studies select controls from within a prospective cohort study. Case-cohort studies select a random subcohort of controls from the entire cohort. Case-crossover studies use individuals as their own controls by comparing exposure during case periods to control periods.

1. Nested case control,
case cohort,
case cross over studies
Presented by-
Dr. Shefali Jain
(PG 1ST 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.

6. 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.

7. • 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.

8. • 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.

9. 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

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

11. 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

12. • 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.

15. 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.

16. • 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.

17. 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.

18. 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.

20. • 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).

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

22. DISADVANTAGE
• Recall bias.

23. REFERENCES
• Leon Gordis, Gordis Epidemiology, ELSEVIER
6th 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.

25. • 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

26. • 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