The Triangulation WIthin a STudy (TWIST) framework for causal inference within pharmacogenetic research.

ABSTRACT: In this paper we review the methodological underpinnings of the general pharmacogenetic approach for uncovering genetically-driven treatment effect heterogeneity. This typically utilises only individuals who are treated and relies on fairly strong baseline assumptions to estimate what we term the 'genetically moderated treatment effect' (GMTE). When these assumptions are seriously violated, we show that a robust but less efficient estimate of the GMTE that incorporates information on the population of untreated individuals can instead be used. In cases of partial violation, we clarify when Mendelian randomization and a modified confounder adjustment method can also yield consistent estimates for the GMTE. A decision framework is then described to decide when a particular estimation strateg

SUBMITTER: Bowden J 

PROVIDER: S-EPMC8452063 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature