Mendelian randomization: a novel approach for the prediction of adverse drug events and drug repurposing opportunities

TLDR

Identification of unintended drug effects, such as repurposing opportunities and adverse drug events, maximizes drug benefit and protects patient health, yet current observational methods are biased by confounding by indication, reverse causality, and missing data. The authors propose Mendelian randomization as a novel approach to predict unintended drug effects, advocating triangulation with other methods to strengthen causal inference. MR can be applied before or after drug approval, preventing harmful exposure in trials and beyond, and its evidence can be triangulated with other approaches to enhance causal inference. MR mitigates limitations of existing methods and holds promise as a pharmacovigilance and drug repurposing tool that could prevent adverse drug events and uncover new indications for existing drugs.

Abstract

Identification of unintended drug effects, specifically drug repurposing opportunities and adverse drug events, maximizes the benefit of a drug and protects the health of patients. However, current observational research methods are subject to several biases. These include confounding by indication, reverse causality and missing data. We propose that Mendelian randomization (MR) offers a novel approach for the prediction of unintended drug effects. In particular, we advocate the synthesis of evidence from this method and other approaches, in the spirit of triangulation, to improve causal inferences concerning drug effects. MR addresses some of the limitations associated with the existing methods in this field. Furthermore, it can be applied either before or after approval of the drug, and could therefore prevent the potentially harmful exposure of patients in clinical trials and beyond. The potential of MR as a pharmacovigilance and drug repurposing tool is yet to be realized, and could both help prevent adverse drug events and identify novel indications for existing drugs in the future.