A review on the design and reporting of studies on drug-gene interaction

Objective: Methodological standards for clinical pharmacogenetic studies should be developed to improve reporting of studies and facilitate their inclusion in systematic reviews. The essence of these studies lies within the concept of effect modification. Study Design and Setting: A narrative review discussing methodological issues in the design and reporting of pharmacogenetic studies. Results: Studying effect modification within a trial leads to the comparison of subgroups based on genotype. Differences in effect based on genotype should preferably be expressed in absolute terms (risk differences) to facilitate clinical decisions on treatment. Information on the distribution of potential effect modifiers or prognostic factors should be available to prevent a biased comparison of differences in effect between genotypes. The distribution of genotypes should also be presented and compared to Hardy-Weinberg equilibrium to check for selection bias. Additional points of interest include the possibility of selective nonavailability of biomaterial and the choice of a statistical model to study effect modification. Conclusion: Additional methodological issues should be taken into account when designing and reporting pharmacogenetic studies, to ensure high study quality. We present several important issues for future studies investigating drug-gene interactions that can serve as a basis for further discussion on methodology in pharmacogenetics. (c) 2005 Elsevier Inc. All rights reserved.