Golden Helix Foundation

The Ubiquitous Pharmacogenomics consortium (www.upgx.eu) has recently completed and published the Preemptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions (PREPARE) study on the implementation of panel-based pharmacogenetic testing. PREPARE has provided interesting lessons for the design, execution, and interpretation of future clinical implementation studies. In this paper, we share our experience and lessons learned from the PREPARE study for future pharmacogenetic implementation studies. Issues addressed are the study population, intervention, endpoint, randomization, blinding, crossover, ethics, real-world changes during the study, and data analysis and reporting.

IntroductionNowadays, many relevant gene-drug associations have been discovered, but pharmacogenomics (PGx)-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health-care.ObjectivesTo address current challenges, this systematic review provides an update regarding previously published studies, which assessed the cost-effectiveness of pharmacogenomics testing for the prescription of antidepressants and antipsychotics.MethodsOur initial screening revealed 1159 articles, which was subsequently reduced to 32 articles, deducted by analysis of their abstract. Full-text analysis performed by all authors resulted in 18 papers that were further included in the analysis.ResultsOf the 18 studies evaluations, 16 studies (88.89%) drew conclusions in favor of PGx testing, of which 9 (50%) were cost-effective and 7 (38.9%) were less costly based on cost analysis. In brief, we found sufficient evidence on the cost-effectiveness of PGx in psychiatric disease care. More precisely, supportive evidence exists for CYP2D6 and CYP2C19 gene-drug associations and for combinatorial PGx panels, but evidence is limited for many other drug–gene combinations. Amongst the limitations of the field are the unclear explanation of perspective and cost inputs in many economic studies, as well as the underreporting of study design elements, which can influence significantly the economic evaluations.ConclusionsOverall, this systematic review highlights the need for additional research on economic evaluations of PGx implementation with an emphasis on psychiatric pharmacogenomics.

Pharmacogenomics has been recognized as a fundamental tool in the era of personalized medicine with up to 266 drug labels, approved by major regulatory bodies, currently containing pharmacogenomics information. Next-generation sequencing analysis assumes a critical role in personalized medicine, providing a comprehensive profile of an individual’s variome, particularly that of clinical relevance, comprising of pathogenic variants and pharmacogenomic biomarkers. Here, we propose a strategy to integrate next-generation sequencing into the current clinical pharmacogenomics workflow from deep resequencing to pharmacogenomics consultation, according to the existing guidelines and recommendations.