-
Clinical and Translational Science Mar 2024Pharmacogenomics has the potential to inform drug dosing and selection, reduce adverse events, and improve medication efficacy; however, provider knowledge of...
Pharmacogenomics has the potential to inform drug dosing and selection, reduce adverse events, and improve medication efficacy; however, provider knowledge of pharmacogenomic testing varies across provider types and specialties. Given that many actionable pharmacogenomic genes are implicated in cardiovascular medication response variability, this study aimed to evaluate cardiology providers' knowledge and attitudes on implementing clinical pharmacogenomic testing. Sixty-one providers responded to an online survey, including pharmacists (46%), physicians (31%), genetic counselors (15%), and nurses (8%). Most respondents (94%) reported previous genetics education; however, only 52% felt their genetics education prepared them to order a clinical pharmacogenomic test. In addition, most respondents (66%) were familiar with pharmacogenomics, with genetic counselors being most likely to be familiar (p < 0.001). Only 15% of respondents had previously ordered a clinical pharmacogenomic test and a total of 36% indicated they are likely to order a pharmacogenomic test in the future; however, the vast majority of respondents (89%) were interested in pharmacogenomic testing being incorporated into diagnostic cardiovascular genetic tests. Moreover, 84% of providers preferred pharmacogenomic panel testing compared to 16% who preferred single gene testing. Half of the providers reported being comfortable discussing pharmacogenomic results with their patients, but the majority (60%) expressed discomfort with the logistics of test ordering. Reported barriers to implementation included uncertainty about the clinical utility and difficulty choosing an appropriate test. Taken together, cardiology providers have moderate familiarity with pharmacogenomics and limited experience with test ordering; however, they are interested in incorporating pharmacogenomics into diagnostic genetic tests and ordering pharmacogenomic panels.
Topics: Humans; Pharmacogenomic Testing; Cardiovascular System; Genetic Testing; Pharmacists; Pharmacogenetics
PubMed: 38421234
DOI: 10.1111/cts.13737 -
Romanian Journal of Internal Medicine =... Jun 2020Pharmacogenomics describes the link between the genetic code and variations in drug response or adverse effects. It is rapidly gaining in both interest and... (Review)
Review
Pharmacogenomics describes the link between the genetic code and variations in drug response or adverse effects. It is rapidly gaining in both interest and accessibility. The knowledge of the gene-drug pairing for a wide range of medications will allow the clinician to select drugs with the best efficacy, appropriate dose and lowest likelihood of serious side effects. In order to apply this knowledge, practitioners need to be familiar with the basic principles of pharmacodynamics and pharmacokinetics and how these relate to drug response. Once these are understood, so can be the genetic variations that lead to different phenotypes. Our review explains these concepts and uses examples of commonly prescribed medications and their gene pairings. At the present time, the Food and Drug Administration (FDA) guidelines remain sparse in regards to pharmacogenomic testing but, despite this, direct-to-consumer testing is widely available. In this context, we detail how to interpret a pharmacogenomic report, we review the indications for testing, as well as its limitations. This information is a step ahead towards invidualized medicine, in the hope that tailoring medications and doses to an individual's genetic make-up will predict a safe and effective response.
Topics: Cytochrome P-450 Enzyme System; HLA Antigens; Humans; Liver-Specific Organic Anion Transporter 1; Methyltransferases; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Practice Guidelines as Topic
PubMed: 32074077
DOI: 10.2478/rjim-2020-0001 -
Clinical Pharmacokinetics Nov 2023Side effects of irinotecan treatment can be dose limiting and may impair quality of life. In this study, we investigated the correlation between single nucleotide...
BACKGROUND AND OBJECTIVE
Side effects of irinotecan treatment can be dose limiting and may impair quality of life. In this study, we investigated the correlation between single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in the irinotecan metabolism and transport, outside UGT1A1, and irinotecan-related toxicity. We focused on carboxylesterases, which are involved in formation of the active metabolite SN-38 and on drug transporters.
METHODS
Patients who provided written informed consent at the Erasmus Medical Center Cancer Institute to the Code Geno study (local protocol: MEC02-1002) or the IRI28-study (NTR-6612) were enrolled in the study and were genotyped for 15 SNPs in the genes CES1, CES2, SLCO1B1, ABCB1, ABCC2, and ABCG2.
RESULTS
From 299 evaluable patients, 86 patients (28.8%) developed severe irinotecan-related toxicity. A significantly higher risk of toxicity was seen in ABCG2 c.421C>A variant allele carriers (P = 0.030, OR 1.88, 95% CI 1.06-3.34). Higher age was associated with all grade diarrhea (P = 0.041, OR 1.03, 95% CI 1.00-1.06). In addition, CES1 c.1165-41C>T and CES1 n.95346T>C variant allele carriers had a lower risk of all-grade thrombocytopenia (P = 0.024, OR 0.42, 95% CI 0.20-0.90 and P = 0.018, OR 0.23, 95% CI 0.08-0.79, respectively).
CONCLUSION
Our study indicates that ABCG2 and CES1 SNPs might be used as predictive markers for irinotecan-induced toxicity.
Topics: Humans; Irinotecan; Camptothecin; Pharmacogenomic Testing; Quality of Life; Genotype; Glucuronosyltransferase; Antineoplastic Agents, Phytogenic; Liver-Specific Organic Anion Transporter 1
PubMed: 37715926
DOI: 10.1007/s40262-023-01279-7 -
Pharmacogenomic testing for antidepressant treatment selection: lessons learned and roadmap forward.Neuropsychopharmacology : Official... Jan 2024Pharmacogenomic technology is a developing field with enthusiastic interest and broad application potential. Three large, controlled studies have been published... (Review)
Review
Pharmacogenomic technology is a developing field with enthusiastic interest and broad application potential. Three large, controlled studies have been published exploring the benefit of pharmacogenomically guided antidepressant treatment selection. Though all three studies did not show significant benefit of using this technology, these studies laid the foundation for further research that should address the limitations of this previous research and currently available commercial platforms. Future research needs to include large scale pharmacogenomic trials with GWAS analytics across diverse groups with attention to cost-effectiveness models, particularly for cases of treatment resistance and polypharmacy. The application of results from these large scale pharmacogenomic trials must also include exploring optimal EHR user interface design.
Topics: Pharmacogenomic Testing; Pharmacogenetics; Antidepressive Agents; Research Design
PubMed: 37550439
DOI: 10.1038/s41386-023-01667-4 -
Pharmacogenomics Jul 2019Several high-profile examples of adverse outcomes from medications used in the perioperative setting are well known (e.g., malignant hyperthermia, prolonged apnea,... (Review)
Review
Several high-profile examples of adverse outcomes from medications used in the perioperative setting are well known (e.g., malignant hyperthermia, prolonged apnea, respiratory depression, inadequate analgesia), leading to an increased understanding of genetic susceptibilities underlying these risks. Pharmacogenomic information is increasingly being utilized in certain areas of medicine. Despite this, routine preoperative genetic screening to inform medication risk is not yet standard practice. In this review, we assess the current readiness of pharmacogenomic information for clinical consideration for several common perioperative medications, including description of key pharmacogenes, pharmacokinetic implications and potential clinical outcomes. The goal is to highlight medications for which emerging or considerable pharmacogenomic information exists and identify areas for future potential research.
Topics: Drug-Related Side Effects and Adverse Reactions; Genetic Predisposition to Disease; Genetic Testing; Humans; Perioperative Care; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 31411557
DOI: 10.2217/pgs-2019-0040 -
The Journal of Molecular Diagnostics :... Mar 2022Clinical laboratories offering genome sequencing have the opportunity to return pharmacogenomic findings to patients, providing the added benefit of preemptive testing...
Clinical laboratories offering genome sequencing have the opportunity to return pharmacogenomic findings to patients, providing the added benefit of preemptive testing that could help inform medication selection or dosing throughout the lifespan. Implementation of pharmacogenomic reporting must address several challenges, including inherent limitations in short-read genome sequencing methods, gene and variant selection, standardization of genotype and phenotype nomenclature, and choice of guidelines and drugs to report. An automated pipeline, lmPGX, was developed as an end-to-end solution that produces two versions of a pharmacogenomic report, presenting either Clinical Pharmacogenetics Implementation Consortium or US Food and Drug Administration guidelines for 12 genes. The pipeline was validated for performance using reference samples and pharmacogenetic data from the Genetic Testing Reference Materials Coordination Program. To determine performance and limitations, lmPGX was compared with three additional publicly available pharmacogenomic pipelines. The lmPGX pipeline offers clinical laboratories an opportunity for seamless integration of pharmacogenomic results with genome reporting.
Topics: Genetic Testing; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Phenotype
PubMed: 35041930
DOI: 10.1016/j.jmoldx.2021.12.001 -
Genes Oct 2020Digital health (DH) is the use of digital technologies and data analytics to understand health-related behaviors and enhance personalized clinical care. DH is... (Review)
Review
Digital health (DH) is the use of digital technologies and data analytics to understand health-related behaviors and enhance personalized clinical care. DH is increasingly being used in clinical trials, and an important field that could potentially benefit from incorporating DH into trial design is pharmacogenetics. Prospective pharmacogenetic trials typically compare a standard care arm to a pharmacogenetic-guided therapeutic arm. These trials often require large sample sizes, are challenging to recruit into, lack patient diversity, and can have complicated workflows to deliver therapeutic interventions to both investigators and patients. Importantly, the use of DH technologies could mitigate these challenges and improve pharmacogenetic trial design and operation. Some DH use cases include (1) automatic electronic health record-based patient screening and recruitment; (2) interactive websites for participant engagement; (3) home- and tele-health visits for patient convenience (e.g., samples for lab tests, physical exams, medication administration); (4) healthcare apps to collect patient-reported outcomes, adverse events and concomitant medications, and to deliver therapeutic information to patients; and (5) wearable devices to collect vital signs, electrocardiograms, sleep quality, and other discrete clinical variables. Given that pharmacogenetic trials are inherently challenging to conduct, future pharmacogenetic utility studies should consider implementing DH technologies and trial methodologies into their design and operation.
Topics: Computational Biology; Humans; Medical Informatics; Pattern Recognition, Automated; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Telemedicine; Wearable Electronic Devices
PubMed: 33114567
DOI: 10.3390/genes11111261 -
Journal of Personalized Medicine Nov 2022PGx testing requires a complex set of activities undertaken by practitioners and patients, resulting in varying implementation success. This systematic review aimed... (Review)
Review
PGx testing requires a complex set of activities undertaken by practitioners and patients, resulting in varying implementation success. This systematic review aimed (PROSPERO: CRD42019150940) to identify barriers and enablers to practitioners and patients implementing pharmacogenomic testing. We followed PRISMA guidelines to conduct and report this review. Medline, EMBASE, CINAHL, PsycINFO, and PubMed Central were systematically searched from inception to June 2022. The theoretical domain framework (TDF) guided the organisation and reporting of barriers or enablers relating to pharmacogenomic testing activities. From the twenty-five eligible reports, eleven activities were described relating to four implementation stages: ordering, facilitating, interpreting, and applying pharmacogenomic testing. Four themes were identified across the implementation stages: IT infrastructure, effort, rewards, and unknown territory. Barriers were most consistently mapped to TDF domains: memory, attention and decision-making processes, environmental context and resources, and belief about consequences.
PubMed: 36579514
DOI: 10.3390/jpm12111821 -
Genetics in Medicine : Official Journal... Apr 2022Pharmacogenomic testing interrogates germline sequence variants implicated in interindividual drug response variability to infer a drug response phenotype and to guide...
Pharmacogenomic testing interrogates germline sequence variants implicated in interindividual drug response variability to infer a drug response phenotype and to guide medication management for certain drugs. Specifically, discrete aspects of pharmacokinetics, such as drug metabolism, and pharmacodynamics, as well as drug sensitivity, can be predicted by genes that code for proteins involved in these pathways. Pharmacogenomics is unique and differs from inherited disease genetics because the drug response phenotype can be drug-dependent and is often unrecognized until an unexpected drug reaction occurs or a patient fails to respond to a medication. Genes and variants with sufficiently high levels of evidence and consensus may be included in a clinical pharmacogenomic test; however, result interpretation and phenotype prediction can be challenging for some genes and medications. This document provides a resource for laboratories to develop and implement clinical pharmacogenomic testing by summarizing publicly available resources and detailing best practices for pharmacogenomic nomenclature, testing, result interpretation, and reporting.
Topics: Genetics, Medical; Genomics; Humans; Pharmacogenetics; Pharmacogenomic Testing; Phenotype; United States
PubMed: 35177334
DOI: 10.1016/j.gim.2021.12.009 -
Frontiers in Pharmacology 2021Pharmacogenomics is becoming an important part of clinical practice and it is considered one of the basic pillars of personalised medicine. However, the rate of...
Pharmacogenomics is becoming an important part of clinical practice and it is considered one of the basic pillars of personalised medicine. However, the rate of pharmacogenomics adoption is still low in many healthcare systems, especially in low- or middle-income countries. The low level of awareness of healthcare specialists could be a potential reason due to which pharmacogenomics application is still in a premature stage but there are several other barriers that impede the aforementioned process, including the lack of the proper promotion of pharmacogenomic testing among interested stakeholders, such as healthcare professionals and biomedical scientists. In this study, we outline the available marketing theories and innovation that are applied to personalized medicine interventions that would catalyze the adoption of pharmacogenomic testing services in clinical practice. We also present the current ethical and legal framework about genomic data and propose ways to tackle the main concerns mentioned in the literature and to improve the marketing perspective of PGx.
PubMed: 34603034
DOI: 10.3389/fphar.2021.724311