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Pharmacogenomic Testing: Clinical Evidence and Implementation Challenges.

ABSTRACT: Pharmacogenomics can enhance patient care by enabling treatments tailored to genetic make-up and lowering risk of serious adverse events. As of June 2019, there are 132 pharmacogenomic dosing guidelines for 99 drugs and pharmacogenomic information is included in 309 medication labels. Recently, the technology for identifying individual-specific genetic variants (genotyping) has become more accessible. Next generation sequencing (NGS) is a cost-effective option for genotyping patients at many pharmacogenomic loci simultaneously, and guidelines for implementation of these data are available from organizations such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG). NGS and related technologies are increasing knowledge in the research sphere, yet rates of genomic literacy remain low, resulting in a widening gap in knowledge translation to the patient. Multidisciplinary teams-including physicians, nurses, genetic counsellors, and pharmacists-will need to combine their expertise to deliver optimal pharmacogenomically-informed care.

SUBMITTER: Hippman C

PROVIDER: S-EPMC6789586 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Pharmacogenomic Testing: Clinical Evidence and Implementation Challenges.

Hippman Catriona C Nislow Corey C

Journal of personalized medicine 20190807 3

Pharmacogenomics can enhance patient care by enabling treatments tailored to genetic make-up and lowering risk of serious adverse events. As of June 2019, there are 132 pharmacogenomic dosing guidelines for 99 drugs and pharmacogenomic information is included in 309 medication labels. Recently, the technology for identifying individual-specific genetic variants (genotyping) has become more accessible. Next generation sequencing (NGS) is a cost-effective option for genotyping patients at many pha ...[more]

PMID: 31394823

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Project description:Pharmacogenomics seeks to improve prescribing by reducing drug inefficacy/toxicity. However, views of patients during pharmacogenomic-guided care are largely unknown. We sought to understand the attitudes and perceptions of patients in an institutional implementation project and hypothesized that views would differ on the basis of experience with pharmacogenomic-guided care.Two focus groups were conducted - one group included patients who had previously been subjected to broad pharmacogenomic genotyping with results available to physicians (pharmacogenomic group), whereas the other had not been offered genotyping (traditional care). Five domains were explored: (i) experiences with medications/side effects, (ii) understanding of pharmacogenomics, (iii) impact of pharmacogenomics on relationships with healthcare professionals, (iv) scenarios involving pharmacogenomic-guided prescribing, and (v) responses to pharmacogenomic education materials.Nine pharmacogenomic and 13 traditional care participants were included. Participants in both groups agreed that pharmacogenomics could inform prescribing and help identify problem prescriptions, but expressed concerns over insurance coverage and employment discrimination. Both groups diverged on who should be permitted to access pharmacogenomic results, with some preferring access only for providers with a longstanding relationship, whereas others argued for open access. Notably, traditional care participants showed greater skepticism about how results might be used. Case scenarios and tested educational materials elicited strong desires on the part of patients for physicians to engage participants when considering pharmacogenomic-based prescribing and to utilize shared decision-making.Participants experiencing pharmacogenomic-guided care were more receptive toward pharmacogenomic information being used than traditional care participants. As key stakeholders in implementation, addressing patients' concerns will be important to successfully facilitate clinical dissemination.

Project description:ImportancePharmacogenomic (PGx) testing provides preemptive pharmacotherapeutic guidance regarding the lack of therapeutic benefit or adverse drug reactions of PGx targeted drugs. Pharmacogenomic information is of particular value among children with complex medical conditions who receive multiple medications and are at higher risk of developing adverse drug reactions.ObjectivesTo assess the implementation outcomes of a PGx testing program comprising both a point-of-care model that examined targeted drugs and a preemptive model informed by whole-genome sequencing that evaluated a broad range of drugs for potential therapy among children in a pediatric tertiary care setting.Design, setting, and participantsThis cohort study was conducted at The Hospital for Sick Children in Toronto, Ontario, from January 2017 to September 2020. Pharmacogenomic analyses were performed among 172 children who were categorized into 2 groups: a point-of-care cohort and a preemptive cohort. The point-of-care cohort comprised 57 patients referred to the consultation clinic for planned therapy with PGx targeted drugs and/or for adverse drug reactions, including lack of therapeutic benefit, after the receipt of current or past medications. The preemptive cohort comprised 115 patients who received exploratory whole-genome sequencing-guided PGx testing for their heart conditions from the cardiac genome clinic at the Ted Rogers Centre for Heart Research.ExposuresPatients received PGx analysis of whole-genome sequencing data and/or multiplex genotyping of 6 pharmacogenes (CYP2C19, CYP2C9, CYP2D6, CYP3A5, VKORC1, and TPMT) that have established PGx clinical guidelines.Main outcomes and measuresThe number of patients for whom PGx test results warranted deviation from standard dosing regimens.ResultsA total of 172 children (mean [SD] age, 8.5 [5.6] years; 108 boys [62.8%]) were enrolled in the study. In the point-of-care cohort, a median of 2 target genes (range, 1-5 genes) were investigated per individual, with CYP2C19 being the most frequently examined; genotypes in 21 of 57 children (36.8%) were incompatible with standard treatment regimens. As expected from population allelic frequencies, among the 115 children in the whole-genome sequencing-guided preemptive cohort, 92 children (80.0%) were recommended to receive nonstandard treatment regimens for potential drug therapies based on their 6-gene pharmacogenetic profile.Conclusions and relevanceIn this cohort study, among both the point-of-care and preemptive cohorts, the multiplex PGx testing program provided dosing recommendations that deviated from standard regimens at an overall rate that was similar to the population frequencies of relevant variants.

Project description: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.

Dataset Information

Pharmacogenomic Testing: Clinical Evidence and Implementation Challenges.

Publications

Pharmacogenomic Testing: Clinical Evidence and Implementation Challenges.

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