In the nested case-control study, cases of a disease that occur in a defined cohort are identified and, for each, a specified number of matched controls is selected from among those in the cohort who have not developed the disease by the time of disease occurrence in the case. For many research questions, the nested case-control design potentially offers impressive reductions in costs and efforts of data collection and analysis compared with the full cohort approach, with relatively minor loss in statistical efficiency. The nested case-control design is particularly advantageous for studies of biologic precursors of disease. To advance its prevention research agenda, NIH might be encouraged to maintain a registry of new and existing cohorts, with an inventory of data collected for each; to foster the development of specimen banks; and to serve as a clearinghouse for information about optimal storage conditions for various types of specimens.

Compared with case-control studies, nested case-control studies can reduce ‘recall bias‘ and temporal ambiguity, and compared with cohort studies can reduce cost and save time.

The drawback of nested case-control studies is non-diseased persons from whom the controls are selected may not be fully representative of the original cohort, due to death or failure to follow-up cases.