Oni‐Orisan, Akinyemi

Barriers to incorporating pharmacogenetics into routine clinical practice in the United States are well documented. Initial surveys by the Clinical Pharmacogenetics Implementation Consortium (CPIC) in 2009 and 2010 identified barriers across four key domains that have hindered the widespread adoption of clinical pharmacogenetic testing. These are presented verbatim as: (i) absence of a definition of the processes required to interpret genotype information and to translate genetic information into clinical actions; (ii) need for recommended drug/gene pairs to implement clinically now; (iii) clinician resistance to consider pharmacogenetic information at the bedside; and (iv) concerns about test costs and reimbursement. Over time, many of these challenges have been overcome, and clinical pharmacogenetic testing has subsequently reached broader implementation. Despite this progress, several barriers remain that block further adoption. This narrative review used authors' expertise and experience to identify and describe current barriers to pharmacogenetic implementation across seven domains in the United States: equity and inclusion; guidelines and supporting evidence; regulatory agency oversight; payer coverage and insurance; availability of quality pharmacogenetic tests; electronic health records; and provider and patient education. Within each domain, it revisits past successes and challenges and explores remaining barriers. We also propose solutions to address ongoing challenges across these domains, including further expansion of recommendations beyond pharmacogenetic‐specific guidelines, standards for designing clinical decision support tools, and broader pharmacogenetics education. Addressing these remaining obstacles directs work to enable broader adoption of clinical pharmacogenetic implementation to ultimately improve patient outcomes.

Abstract Pharmacogenomics (PGx) is focused on the relationship between an individual's genetic makeup and their response to medications, with the overarching aim of guiding prescribing decisions to improve drug efficacy and reduce adverse events. The PGx and genomic medicine communities have worked independently for over 2 decades, developing separate standards and terminology, making implementation of PGx across all areas of genomic medicine difficult. To address this issue, the Clinical Genome Resource (ClinGen) Pharmacogenomics Working Group (PGxWG) was established by the National Institutes of Health (NIH)-funded ClinGen to initially create frameworks for evaluating gene–drug response clinical validity and actionability aligned with the ClinGen frameworks for evaluating monogenic gene–disease relationships, and a framework for classifying germline PGx variants similar to the American College of Medical Genetics (ACMG) and Association of Molecular Pathology (AMP) system for interpretation of disease-causing variants. These frameworks will leverage decades of work from well-established PGx resources facilitating buy-in among PGx stakeholders. In this report, we describe the background and major activities of the ClinGen PGxWG, and how this initiative will facilitate the critical inclusion of PGx into the larger context of genomic medicine.

Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardiovascular pharmacogenetics is limited education on this field for current healthcare providers and students. The abundance of pharmacogenetic literature underscores its promise, but it can also be challenging to learn such a wealth of information. Moreover, current clinical recommendations for cardiovascular pharmacogenetics can be confusing because they are outdated, incomplete, or inconsistent. A myriad of misconceptions about the promise and feasibility of cardiovascular pharmacogenetics among healthcare providers also has halted clinical implementation. Therefore, the main goal of this tutorial is to provide introductory education on the use of cardiovascular pharmacogenetics in clinical practice. The target audience is any healthcare provider (or student) with patients that use or have indications for cardiovascular drugs. This tutorial is organized into the following 6 steps: (1) understand basic concepts in pharmacogenetics; (2) gain foundational knowledge of cardiovascular pharmacogenetics; (3) learn the different organizations that release cardiovascular pharmacogenetic guidelines and recommendations; (4) know the current cardiovascular drugs/drug classes to focus on clinically and the supporting evidence; (5) discuss an example patient case of cardiovascular pharmacogenetics; and (6) develop an appreciation for emerging areas in cardiovascular pharmacogenetics. Ultimately, improved education among healthcare providers on cardiovascular pharmacogenetics will lead to a greater understanding for its potential in improving outcomes for a leading cause of morbidity and mortality.