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A large-scale, collaborative study (PREPARE) has found that using a 12-gene pharmacogenetic (PGx) panel to preemptively screen all patients reduces adverse drug events significantly. The study also demonstrated feasibility of such testing, as it included 18 hospitals, nine community health centers, and 28 community pharmacies in seven European countries.

As the authors write, “Several studies, including randomized control trials, have shown that individualizing drug therapy on the basis of pharmacogenetic testing leads to improved patients outcomes for specific drug -gene combinations.”

The drugs with known variations that are worth testing for include abacavir (NEJM 2008), warfarin (NEJM 2013), and thiopurine treatment of inflammatory bowel disease (Gastroenterology 2015). However, there has been debate about its clinical utility.

Pharmacogenetics has been held back by such hurdles as, “The lack of standardized testing methods and data analytics, poorly informed payer perceptions, and misconceptions held by both the public and healthcare industry professionals give rise to many questions and ambiguities,” according to an Inside Precision Medicine report.

This study looked at a wide implementation of PGx screening in a general population.

As the authors point out, “Consortia such as the Dutch Pharmacogenetics Working Group (DPWG) and the Clinical Pharmacogenetics Implementation Consortium have created guidelines based on evidence from the literature, which include more than 100 gene-drug pairs.”

The PREPARE study was a cluster-randomized, crossover implementation study conducted in Austria, Greece, Italy, the Netherlands, Slovenia, Spain and the U.K. It evaluated the clinical utility of a pre-emptive genotyping strategy. The panel they used tested known actionable variants for all drugs present in the DPWG recommendations with the exceptions of abacavir, omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprozole, and drugs containing estrogen, for various reasons.

Notable, to help health care professionals and subjects prepare for pre-emptive testing, the team did a “systemic survey on current knowledge about pharmacogenomics,” they write. Further, participants were given education at a site-initiation visit.

Between March 7, 2017, and June 30, 2020, 41,696 patients were assessed for eligibility and 6,944 (51·4 % female, 48·6% male; 97·7% self-reported European, Mediterranean, or Middle Eastern ethnicity) were enrolled and assigned to receive genotype-guided drug treatment (n=3342) or standard care (n=3602).

Results were promising. In patients with an actionable test result for the index drug (n=1558), a clinically relevant adverse drug reaction occurred in 152 (21·0%) of 725 patients in the study group and 231 (27·7%) of 833 patients in the control group. For all patients, the incidence was 628 (21·5%) of 2923 patients in the study group and 934 (28·6%) of 3270 patients in the control group.

The authors conclude that: “To our knowledge this is the first study to show the feasibility and benefits of a pharmacogenetic-panel strategy across a diversity of European health-care systems organizations and settings.”

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