CLIO Learning Modules
Study DesignSelectionSample SizeData Collection and AnalysisHuman Subjects

'Me too studies'
Target Population
Attributable Risk
Relative Risk
Data Sources
Study Time
Case Control
Nested Case-Control
Prospective Cohort
Retrospective Cohort
Randomized Clinical Trial
Nested Case Control

A nested case-control study is a type of case-control study that draws its cases and controls from a cohort population that has been followed for a period of time.


A nested-case control study depends on the pre-existence of a cohort that has been followed over time. This cohort, at its inception or during the course of follow-up, has had exposure information and/or biospecimens collected of interest to the investigator. The investigator identifies cases of disease that occurred in the cohort during the follow-up period. The investigator also identifies disease-free individuals within the cohort to serve as controls. Using previously collected data and obtaining additional measurements of exposures from available biospecimens, the investigator compares the exposure frequencies in cases and controls as in a non-nested case-control study.


To determine if H. pylori (HP) infection was associated with the development of gastric cancer, Parsonnet et al (N Engl J Med. 1991 Oct 17;325(16):1127-31) first identified a cohort of 128,992 persons who had been followed since the mid-1960’s. Of the original cohort, 189 patients developed gastric cancer. The investigators carried out a nested case-control study by selecting all of the 189 gastric cancer patients as cases and another 189 cancer-free individuals from the same cohort as controls. HP infection status was determined using serum obtained in the beginning of the follow-up. All total of 84% of the confirmed gastric cancer cases had been infected previously with HP, while only 61% of the controls had been infected; this indicated a positive association between HP infection and gastric cancer risk.


Nested case-control studies are carried out when it is either too costly or not feasible to perform additional biospecimen analyses on an entire cohort. Such data may be newly thought of, after the initial exposure measurements had been made, as was the case in the above example. These studies may have some important advantages over standard case-control studies. Nested studies 1) can utilize the exposure and confounder data originally collected before the onset of the disease, thus reducing potential recall bias and temporal ambiguity, and 2) include cases and controls drawn from the same cohort, decreasing the likelihood of selection bias. The nested case-control study is thus considered a strong observational study, comparable to its parent cohort study in the likelihood of an unbiased association between an exposure and an outcome. A concern, usually minor, is that the remaining nondiseased persons from whom the controls are selected when it is decided to do the nested study, may not be fully representative of the original cohort due to death or losses to follow-up.

Further reading

Fundamentals of epidemiology (Univ. of North Carolina, Chapel Hill)
Study Design

June 4, 2004 v0.20
Copyright © 2004 Stanford School of Medicine