Incorporating a patient's genotype into the clinical decision-making process is one approach to precision medicine. The University of Florida (UF) Health Precision Medicine Program is a ...pharmacist-led multidisciplinary effort that has led the clinical implementation of six gene-drug(s) pairs to date. This study focuses on the challenges encountered and lessons learned with implementing pharmacogenetic testing for three of these: CYP2D6-opioids, CYP2D6/CYP2C19-selective serotonin reuptake inhibitors, and CYP2C19-proton pump inhibitors within six pragmatic clinical trials at UF Health and partners.
We compared common measures collected within each of the pharmacogenetic implementations as well as solicited feedback from stakeholders to identify challenges, successes, and lessons learned.
We identified several challenges related to trial design and implementation, and learned valuable lessons. Most notably, case discussions are effective for prescriber education, prescribers need clear concise guidance on genotype-based actions, having genotype results available at the time of the patient-prescriber encounter helps optimize the ability to act on them, children prefer noninvasive sample collection, and study participants are willing to answer patient-reported outcomes questionnaires if they are not overly burdensome, among others.
The lessons learned from implementing three gene-drug pairs in ambulatory care settings will help shape future pharmacogenetic clinical trials and clinical implementations.
The value of utilizing a multigene pharmacogenetic panel to tailor pharmacotherapy is contingent on the prevalence of prescribed medications with an actionable pharmacogenetic association. The ...Clinical Pharmacogenetics Implementation Consortium (CPIC) has categorized over 35 gene‐drug pairs as “level A,” for which there is sufficiently strong evidence to recommend that genetic information be used to guide drug prescribing. The opportunity to use genetic information to tailor pharmacotherapy among adult patients was determined by elucidating the exposure to CPIC level A drugs among 11 Implementing Genomics In Practice Network (IGNITE)‐affiliated health systems across the US. Inpatient and/or outpatient electronic‐prescribing data were collected between January 1, 2011 and December 31, 2016 for patients ≥ 18 years of age who had at least one medical encounter that was eligible for drug prescribing in a calendar year. A median of ~ 7.2 million adult patients was available for assessment of drug prescribing per year. From 2011 to 2016, the annual estimated prevalence of exposure to at least one CPIC level A drug prescribed to unique patients ranged between 15,719 (95% confidence interval (CI): 15,658–15,781) in 2011 to 17,335 (CI: 17,283–17,386) in 2016 per 100,000 patients. The estimated annual exposure to at least 2 drugs was above 7,200 per 100,000 patients in most years of the study, reaching an apex of 7,660 (CI: 7,632–7,687) per 100,000 patients in 2014. An estimated 4,748 per 100,000 prescribing events were potentially eligible for a genotype‐guided intervention. Results from this study show that a significant portion of adults treated at medical institutions across the United States is exposed to medications for which genetic information, if available, should be used to guide prescribing.
The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for ...clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This article provides recommendations for a minimum panel of variant alleles (Tier 1) and an extended panel of variant alleles (Tier 2) that will aid clinical laboratories when designing assays for PGx testing. The Association for Molecular Pathology PGx Working Group considered the functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, as well as other technical considerations for PGx testing when developing these recommendations. The ultimate goal of this Working Group is to promote standardization of PGx gene/allele testing across clinical laboratories. This article focuses on clinical TPMT and NUDT15 PGx testing, which may be applied to all thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15)-related medications. These recommendations are not to be interpreted as prescriptive, but to provide a reference guide.
The authors aimed to assess outcomes with a pharmacogenetic (PGx)-informed, pharmacist-guided, personalized consult service for warfarin dosing.
This retrospective cohort study included patients ...admitted with thromboembolic events. Eligible subjects received either PGx-informed (n = 389) or historical non-PGx pharmacist-guided warfarin dosing (Hx; n = 308) before hospital discharge. The composite of admission with bleeding or thromboembolic events over 90 days after the discharge was compared between the PGx and Hx groups.
The rate ratio (95% CI) of the composite of bleeding or thromboembolic admissions for PGx versus Hx was 0.32 (0.12-0.82). The estimated hazard ratio was 0.43 (0.16-1.12).
A PGx-informed warfarin dosing service was associated with decreased bleeding and thromboembolic encounters.
Accuracy of warfarin dose prediction algorithms may be improved by including data from diverse populations in genetic studies of dose variability. Here, we surveyed single nucleotide polymorphisms in ...vitamin K‐related genetic pathways for association with warfarin dose requirements in two admixed Latino populations in standard‐principal component adjusted and contemporary‐local ancestry adjusted regression models. A total of five variants from vitamin K‐related genes/pathways were associated with warfarin dose in both cohorts (P < 0.0125) in standard models. Local ancestry‐adjusted analysis unveiled 35 associated variants with absolute effects ranging from β = 9.04 ( ±2.23) to 39.18 ( ±10.89) per ancestral allele in the discovery cohort and β = 6.47 (± 2.02) to 17.82 (± 6.83) in the replication cohort. Importantly, we demonstrate the technical validity of the Tractor model in cohorts with admixed ancestry from three founder populations and bring attention to the technical hurdles obstructing the inclusion of diverse, especially admixed, populations in pharmacogenomic research.
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.
The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for ...clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations for a minimum panel of variant alleles (tier 1) and an extended panel of variant alleles (tier 2) that will aid clinical laboratories when designing assays for PGx testing. The Association for Molecular Pathology PGx Working Group considered functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. The goal of this Working Group is to promote standardization of PGx gene/allele testing across clinical laboratories. This document will focus on clinical CYP3A4 and CYP3A5 PGx testing that may be applied to all CYP3A4- and CYP3A5-related medications. These recommendations are not to be interpreted as prescriptive but to provide a reference guide.
Objectives
To examine the knowledge, attitudes, and interest of an inner‐city population toward pharmacogenetic testing, with the primary objective of identifying facilitators and barriers toward ...pharmacogenetic testing; and secondary objectives of determining predictors of patient interest in pharmacogenetic testing and how much patients would pay for the test.
Methods
Patients were recruited from an Antithrombosis Clinic from March to April 2014. A cross‐sectional 19‐question survey was administered in person to determine patients' knowledge and awareness of pharmacogenetic testing and collect demographic information. After explaining pharmacogenetics, patients ranked their interest toward the test and answered open‐ended questions that elicited facilitators and barriers toward pharmacogenetic testing and elucidated how much patients would pay for testing.
Results
A total of 120 patients (mean age 55.0 ± 14.0 years, 39.2% male, 69.2% African American) were surveyed. Facilitators included providing further information about pharmacogenetic testing; elaborating on benefits of testing to predict treatment efficacy; patients' trust in their providers to make correct genotype‐guided prescribing decisions; and insurance coverage and test affordability. Barriers to testing included concerns about the negative consequences associated with test results; burden of the testing process; perceived lack of utility among elderly and those whose medications were working; privacy issues; and concerns regarding insurance coverage and test affordability. Women had 4.2 times higher adjusted odds of being interested in pharmacogenetic testing. Almost half (44.4%) of the patients with high interest in the test were willing to pay $20 or more, whereas 76.2% of patients with low interest wanted testing at no cost.
Conclusion
This study identified facilitators, such as providing additional pharmacogenetic test information, and barriers, such as perceived negative impact of the results and test utility, as issues to address when engaging an urban, largely minority population in pharmacogenetic testing. Female sex was a predictor of interest toward pharmacogenetic testing. These facilitators and barriers should be taken into consideration as pharmacogenetic testing gains widespread utility among inner‐city populations.
Swen et al.1 examine the utility of multi-gene pharmacogenetic testing in a large multi-national cohort. They show fewer adverse drug reactions among patients receiving testing and prescribing ...recommendations based on genotype results compared with those receiving usual care.
Swen et al.1 examine the utility of multi-gene pharmacogenetic testing in a large multi-national cohort. They show fewer adverse drug reactions among patients receiving testing and prescribing recommendations based on genotype results compared with those receiving usual care.
There have been significant advancements in precision medicine and approaches to medication selection based on pharmacogenetic results. With the availability of direct‐to‐consumer genetic testing and ...growing awareness of genetic interindividual variability, patient demand for more precise, individually tailored drug regimens is increasing. The University of Florida (UF) Health Precision Medicine Program (PMP) was established in 2011 to improve integration of genomic data into clinical practice. In the ensuing years, the UF Health PMP has successfully implemented several single‐gene tests to optimize the precision of medication prescribing across a variety of clinical settings. Most recently, the UF Health PMP launched a custom‐designed pharmacogenetic panel, including pharmacogenes relevant to supportive care medications commonly prescribed to patients undergoing chemotherapy treatment, referred to as “GatorPGx.” This tutorial provides guidance and information to institutions on how to transition from the implementation of single‐gene pharmacogenetic testing to a preemptive panel‐based testing approach. Here, we demonstrate application of the preemptive panel in the setting of an adult solid tumor oncology clinic. Importantly, the information included herein can be applied to other clinical practice settings.
PDF
