Mroz Pawel, Michel Stephen, Allen Josiah D, Meyer Tim, McGonagle Erin J, Carpentier Rachel, Vecchia Alexandra, Schlichte Allyson, Bishop Jeffrey R, Dunnenberger Henry M, Yohe Sophia, Thyagarajan Bharat, Jacobson Pamala A, Johnson Steven G
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, United States.
Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, MN, United States.
Front Genet. 2021 Oct 20;12:712602. doi: 10.3389/fgene.2021.712602. eCollection 2021.
Pharmacogenomics (PGx) studies how a person's genes affect the response to medications and is quickly becoming a significant part of precision medicine. The clinical application of PGx principles has consistently been cited as a major opportunity for improving therapeutic outcomes. Several recent studies have demonstrated that most individuals (> 90%) harbor PGx variants that would be clinically actionable if prescribed a medication relevant to that gene. In multiple well-conducted studies, the results of PGx testing have been shown to guide therapy choice and dosing modifications which improve treatment efficacy and reduce the incidence of adverse drug reactions (ADRs). Although the value of PGx testing is evident, its successful implementation in a clinical setting presents a number of challenges to molecular diagnostic laboratories, healthcare systems, providers and patients. Different molecular methods can be applied to identify PGx variants and the design of the assay is therefore extremely important. Once the genotyping results are available the biggest technical challenge lies in turning this complex genetic information into phenotypes and actionable recommendations that a busy clinician can effectively utilize to provide better medical care, in a cost-effective, efficient and reliable manner. In this paper we describe a successful and highly collaborative implementation of the PGx testing program at the University of Minnesota and MHealth Fairview Molecular Diagnostic Laboratory and selected Pharmacies and Clinics. We offer detailed descriptions of the necessary components of the pharmacogenomic testing implementation, the development and technical validation of the in-house SNP based multiplex PCR based assay targeting 20 genes and 48 SNPs as well as a separate CYP2D6 copy number assay along with the process of PGx report design, results of the provider and pharmacists usability studies, and the development of the software tool for genotype-phenotype translation and gene-phenotype-drug CPIC-based recommendations. Finally, we outline the process of developing the clinical workflow that connects the providers with the PGx experts within the Molecular Diagnostic Laboratory and the Pharmacy.
药物基因组学（PGx）研究个体基因如何影响药物反应，并且正迅速成为精准医学的重要组成部分。PGx原则的临床应用一直被视为改善治疗效果的重大机遇。最近的几项研究表明，大多数个体（>90%）携带PGx变异，如果开具与该基因相关的药物，这些变异在临床上是可采取行动的。在多项精心开展的研究中，PGx检测结果已被证明可指导治疗选择和剂量调整，从而提高治疗效果并降低药物不良反应（ADR）的发生率。尽管PGx检测的价值显而易见，但其在临床环境中的成功实施给分子诊断实验室、医疗系统、医疗服务提供者和患者带来了诸多挑战。可以应用不同的分子方法来识别PGx变异，因此检测方法的设计极为重要。一旦获得基因分型结果，最大的技术挑战在于将这种复杂的遗传信息转化为表型以及可操作的建议，忙碌的临床医生能够以经济高效且可靠的方式有效利用这些建议来提供更好的医疗服务。在本文中，我们描述了明尼苏达大学、MHealth Fairview分子诊断实验室以及选定的药房和诊所成功且高度协作实施PGx检测项目的情况。我们详细介绍了药物基因组学检测实施的必要组成部分、针对20个基因和48个单核苷酸多态性（SNP）的基于SNP的内部多重聚合酶链反应（PCR）检测方法以及单独的CYP2D6拷贝数检测方法的开发和技术验证，以及PGx报告设计过程、医疗服务提供者和药剂师可用性研究结果，还有用于基因型 - 表型转化以及基于CPIC的基因 - 表型 - 药物建议的软件工具的开发。最后，我们概述了开发将医疗服务提供者与分子诊断实验室和药房内的PGx专家联系起来的临床工作流程的过程。
