Whole exome sequencing (WES) has the potential of identifying secondary findings that are predictive of poor pharmacotherapy outcomes. The purpose of this study was to investigate patients’ wishes regarding the reporting of secondary pharmacogenomic findings. WES results (n = 106 patients) were retrospectively reviewed to determine the number of patients electing to receive secondary pharmacogenomic results. Phenotypes were assigned based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The percent of patients with a predicted phenotype associated with a gene-based CPIC dosing recommendation was determined. Ninety-nine patients (93.4%) elected to receive secondary pharmacogenomic findings. For each gene–drug pair analyzed, the number of patients with an actionable phenotype ranged from two (2%) to 43 patients (43.4%). Combining all gene–drug pairs, 84 unique patients (84.8%) had an actionable phenotype. A prospective multidisciplinary practice model was developed for integrating secondary pharmacogenomic findings into clinical practice. Our model highlights a unique collaboration between physician-geneticists, pharmacists, and genetic counselors.
Bibliographical noteFunding Information:
We thank Dr. Vickie Zurcher and the Genetic Counselors from Cleveland Clinic's Center for Personalized Genetic Healthcare for their efforts to consent patients to clinical exome sequencing. J.K.H. and C.E. wrote the article; J.K.H. and C.E. designed the research; J.K.H., A.Sh., A.Sc., M.C., R.N., M.N., R.M., T.M., A.E., and C.E. performed the research; J.K.H., A.Sh., A.Sc., M.C., R.N., M.N., R.M., T.M., A.E., and C.E. analyzed the data. J.K.H. and C.E. made substantial contributions to conception, design, data interpretation, and drafting of the article. All authors contributed to data acquisition, critical revisions of the article, final approval of publication, and agreement to be accountable for all aspects of the work. Ethics approval and consent to participate: This study was approved by the Cleveland Clinic Institutional Review Board. This IRB Human Subjects Protection-approved study waived patient consent as this is a retrospective study exploring existing data with minimal risk to patients. Consent for publication: All information is deidentified. This IRB Human Subjects Protection-approved study waived patient consent as this is a retrospective study exploring existing data with minimal risk to patients. Availability of data and material: The data sets generated and/or analyzed during the current study are not publicly available due to the WES data being protected health information per HIPPA. A deidentified WES data set is available from the corresponding author on reasonable request.
© 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.