The Return of Pharmacogenomic Variants in the MedSeq Project: Reporting Approach and Physician Response. J. B. Krier1,4, H. M. McLaughlin2,6, W. J. Lane2,5, D. Metterville6, I. Leshchiner3,4,6, J. L. Vassy3,4,7, C. MacRae3,5, M. S. Lebo2,5,6, D. Lautenbach4, R. C. Green3,4, H. L. Rehm2,5,6 1) Department of Pediatrics, Harvard Medical School, Boston, MA; 2) Department of Pathology, Harvard Medical School, Boston, MA; 3) Department of Medicine, Harvard Medical School, Boston, MA; 4) Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA; 5) Department of Pathology, Brigham and Women's Hospital, Boston, MA; 6) Laboratory for Molecular Medicine, Partners Center for Personalized Genetic Medicine, Cambridge, MA; 7) VA Boston Healthcare System, Boston, MA.
Background. The refinement of drug selection and dosage poses an exciting opportunity for the integration of genomic sequencing data into clinical medicine. However, few examples of pharmacogenomic (PGx) testing have been adopted clinically and no standards or best practices exist in utilizing whole genome sequencing (WGS) for PGx variant reporting. The MedSeq Project is a randomized clinical trial that seeks to develop tested approaches for the evaluation of individual genomes and to assess the impact of integrating WGS, including PGx variants, into medical practice in primary care and cardiology clinics. Methods. MedSeq participants randomized to WGS receive a General Genome Report (GGR). Consistent with the goal of the GGR to provide a concise summary of genomic data with potential clinical relevance, a set of PGx variants were selected for inclusion in the GGR based on the level of evidence supporting their associations with specific drug responses. Among the Class I and Class II PGx variants in the PharmGKB Clinical Annotation Levels of Evidence classification system, a short, final list of variants and associations were selected based on their relevance in primary care and cardiology: warfarin dosing, clopidogrel efficacy, metformin efficacy, digoxin dosing, and risk of simvastatin-associated myopathy. Additional PharmGKB Class I PGx variants are also available for validation and reporting if clinically indicated by concurrent medical therapy for any MedSeq participant. Results. The report of PGx variants includes brief summary statements accompanied by detailed interpretations that describe specific genotype, population frequencies, clinical implication and, where relevant, links to genotype-based dosing guidelines. Initial anecdotal data suggests that physicians have significant enthusiasm for receiving PGx variants, and we describe qualitative data from MedSeq primary care physicians and cardiologists on the perceived utility of the PGx variants. Additionally, we will present data from the disclosure of the PGx results to patients and early experiences on clinical decision-making impacted by PGx variant status. Conclusion. PGx variants are a key component of clinical WGS reports and of great interest to physicians, and PGx reporting must recognize clinicians desire for concise and consistent reporting formats while also providing sufficient supporting evidence and contextualization.
You may contact the first author (during and after the meeting) at