The multitime case-control design for time-varying exposures.
BACKGROUND
The conventional approach to improve precision of the odds ratio in a case-control study is to increase the number of controls per case. With time-varying exposures, an alternative is to increase the number of observations per control.


METHODS
We present the multitime case-control design, which uses multiple control person-moments of exposure within each control subject. The point and variance estimators of the odds ratio are corrected for within-subject correlation. We illustrate this approach using case-control data from studies of the effects of respiratory medications.


RESULTS
Simulations show that, with uncorrelated exposures, it is possible to reduce the variance of the odds ratio by around 30% by increasing the number of control person-moments per subject. With correlated exposures, an accurate variance can be obtained by correcting for within-subject correlation. The corrected variance increases with increasing correlation, depending on the number of control person-moments. The first illustration shows that the rate ratio (RR) of cardiac death associated with β-agonist use, not estimable with 1 control per case (30 cases) and 1 control person-moment, was 4.2 (95% confidence interval = 0.4-49) with 12 control person-moments. The second example finds a rate ratio of acute myocardial infarction associated with antibiotics of 2.00 (1.16-3.44) with 1 control per case, which improves in precision with 10 control subjects per case (RR = 2.13 [1.48-3.05]) but also with 1 control per case and 10 control person-moments per control subject (1.99 [1.36-2.90]).


CONCLUSIONS
When dealing with time-varying exposures, the multitime case-control design can increase the efficiency of conventional case-control studies without additional control subjects.
Suissa
Samy
S
Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada. samy.suissa@mcgill.ca
Dell'Aniello
Sophie
S
Martinez
Carlos
C
D016022:Case-Control Studies; D016757:Death, Sudden, Cardiac; D006801:Humans; D008962:Models, Theoretical; D009203:Myocardial Infarction / Q000401:mortality / Q000503:physiopathology; D016017:Odds Ratio; D012107:Research Design