Imputing gene-treatment interactions when the genotype distribution is unknown using case-only and putative placebo analyses - A new method for the Genetics of Hypertension Associated Treatment (GenHAT) study

Barry R. Davis, Charles E. Ford, Eric Boerwinkle, Donna Arnett, John Eckeldt, Henry Black

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

There is a sizeable literature on 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 gene-drug interactions with regard to outcomes are examined, these methods may be readily applied, as gene and drug are independent by randomization. In an active-controlled trial (experimental treatment vs standard) that has collected genotype information, gene-drug interactions can be estimated. In addition, the effect of the experimental treatment vs placebo can be imputed by using data from a historical placebo-controlled trial (standard vs placebo) if either (a) genotype information is available from the historical trial or (b) assumptions are made about the prevalence of genotype and the odds ratios of genotype and disease in the historical trial using information from other studies. Motivation for these procedures is provided by the Genetics of Hypertension Associated Treatment, a large pharmacogenetics, ancillary study of a hypertension clinical trial, and examples from published hypertension trials will be used to illustrate the methods.

Original languageEnglish
Pages (from-to)2413-2427
Number of pages15
JournalStatistics in Medicine
Volume23
Issue number15
DOIs
StatePublished - Aug 15 2004

Keywords

  • Active control
  • Clinical trial
  • Imputation
  • Interaction
  • Pharmacogenetics
  • Subgroups

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability

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