Is supporting evidence from a randomized controlled trial (RCT) always necessary when implementing pharmacogenomics in the clinic? In an opinion piece authored by members of the PharmGKB team and published in Clinical Pharmacology and Therapeutics, we argue that an overreliance on evidence from RCTs is not beneficial to pharmacogenomic implementation.
An insistence that RCT evidence is made available prior to implementation assumes that RCTs will eventually be carried out for every actionable gene-drug pair. This is an unrealistic assumption, especially in the case of generic drugs. We also question why other factors which can influence drug clearance in a patient, such as hepatic or renal impairment, are easily incorporated into clinical care without RCT evidence while pharmacogenomics is held, seemingly arbitrarily, to a different standard.
There are also significant issues with pharmacogenomic RCTs, in terms of cohort diversity, adequate allele representation and statistical power; all of which can have serious, even fatal, consequences for patients. Furthermore, a reliance on evidence from RCTs overlooks the substantial evidence base from other studies, much of which is curated in PharmGKB. Evidence from non-RCT studies already informs clinical guidelines from international consortia, including CPIC and the DPWG.