Abstract:
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Much has been written about methods for detecting gene-environment interaction in the framework of case-control studies, particularly with reference to the assumption of independence of genotype and exposure. In the context of a clinical trial, wherein one is examining gene-drug interactions with regard to outcomes, some of these techniques may be readily applied since these two factors are independent due to randomization. In the case of an active control trial, gene-drug interactions for genotype and exposure (new treatment vs. comparator) can be estimated. Also, the effect of the new treatment versus a putative placebo can be estimated using data from prior comparator vs. placebo-controlled trials. However, can one say anything about interactions of genotype and exposure (new treatment versus placebo)? Using independence of genotype and treatment and incorporating information on marginal effects (relative risks) of genotype and exposure from previous studies, such interaction can be estimated. Examples from the Genetics of Hypertension Associated Treatment, a large pharmacogenetics, ancillary study of a cardiovascular clinic trial, will be used to illustrate this method.
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