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Pharmacogenomics May 2020
Topics: Drug Interactions; Evidence-Based Medicine; Humans; Off-Label Use; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomic Testing; Practice Guidelines as Topic; United States; United States Food and Drug Administration
PubMed: 32319356
DOI: 10.2217/pgs-2020-0017 -
British Journal of Clinical Pharmacology Oct 2022Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug... (Review)
Review
Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug safety, helping to improve drug efficacy or reduce the risk of toxicity. Despite its clinical relevance, the implementation of PGx testing in paediatric practice to date has been variable and limited. As with most paediatric pharmacological studies, there are well-recognised barriers to obtaining high-quality PGx evidence, particularly when patient numbers may be small, and off-label or unlicensed prescribing remains widespread. Furthermore, trials enrolling small numbers of children can rarely, in isolation, provide sufficient PGx evidence to change clinical practice, so extrapolation from larger PGx studies in adult patients, where scientifically sound, is essential. This review paper discusses the relevance of PGx to paediatrics and considers implementation strategies from a child health perspective. Examples are provided from Canada, the Netherlands and the UK, with consideration of the different healthcare systems and their distinct approaches to implementation, followed by future recommendations based on these cumulative experiences. Improving the evidence base demonstrating the clinical utility and cost-effectiveness of paediatric PGx testing will be critical to drive implementation forwards. International, interdisciplinary collaborations will enhance paediatric data collation, interpretation and evidence curation, while also supporting dedicated paediatric PGx educational initiatives. PGx consortia and paediatric clinical research networks will continue to play a central role in the streamlined development of effective PGx implementation strategies to help optimise paediatric pharmacotherapy.
Topics: Child; Cost-Benefit Analysis; Humans; Netherlands; Pediatrics; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 34907575
DOI: 10.1111/bcp.15181 -
Drug Metabolism and Pharmacokinetics Aug 2021Several barriers present challenges to implementing pharmacogenomics into practice. This review will provide an overview of the current pharmacogenomics practices and... (Review)
Review
Several barriers present challenges to implementing pharmacogenomics into practice. This review will provide an overview of the current pharmacogenomics practices and research in Thailand, address the challenges and lessons learned from delivering clinical pharmacogenomic services in Thailand, emphasize the pharmacogenomics implementation issues that must be overcome, and identify current pharmacogenomic initiatives and plans to facilitate clinical implementation of pharmacogenomics in Thailand. Ever since the pharmacogenomics research began in 2004 in Thailand, a multitude of pharmacogenomics variants associated with drug responses have been identified in the Thai population, such as HLA-B∗15:02 for carbamazepine and oxcarbazepine, HLA-B∗58:01 for allopurinol, HLA-B∗13:01 for dapsone and cotrimoxazole, CYP2B6 variants for efavirenz, CYP2C9∗3 for phenytoin and warfarin, CYP3A5∗3 for tacrolimus, and UGT1A1∗6 and UGT1A1∗28 for irinotecan, etc. The future of pharmacogenomics guided therapy in clinical settings across Thailand appears promising because of the availability of evidence of clinical validity of the pharmacogenomics testing and support for reimbursement of pharmacogenomics testing.
Topics: Humans; Pharmacogenetics; Precision Medicine; Research; Thailand
PubMed: 34098253
DOI: 10.1016/j.dmpk.2021.100399 -
Briefings in Bioinformatics Sep 2019Recent years have seen an increase in the availability of pharmacogenomic databases such as Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line... (Review)
Review
Recent years have seen an increase in the availability of pharmacogenomic databases such as Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) that provide genomic and functional characterization information for multiple cell lines. Studies have alluded to the fact that specific characterizations may be inconsistent between different databases. Analysis of the potential discrepancies in the different databases is highly significant, as these sources are frequently used to analyze and validate methodologies for personalized cancer therapies. In this article, we review the recent developments in investigating the correspondence between different pharmacogenomics databases and discuss the potential factors that require attention when incorporating these sources in any modeling analysis. Furthermore, we explored the consistency among these databases using copulas that can capture nonlinear dependencies between two sets of data.
Topics: Antineoplastic Agents; Cell Line, Tumor; Databases, Genetic; Humans; Neoplasms; Pharmacogenetics
PubMed: 31846027
DOI: 10.1093/bib/bby046 -
Clinical Pharmacology and Therapeutics Jan 2020Pharmacogenomics (PGx) decision support and return of results is an active area of precision medicine. One challenge of implementing PGx is extracting genomic variants...
Pharmacogenomics (PGx) decision support and return of results is an active area of precision medicine. One challenge of implementing PGx is extracting genomic variants and assigning haplotypes in order to apply prescribing recommendations and information from the Clinical Pharmacogenetics Implementation Consortium (CPIC), the US Food and Drug Administration (FDA), the Pharmacogenomics Knowledgebase (PharmGKB), etc. Pharmacogenomics Clinical Annotation Tool (PharmCAT) (i) extracts variants specified in guidelines from a genetic data set derived from sequencing or genotyping technologies, (ii) infers haplotypes and diplotypes, and (iii) generates a report containing genotype/diplotype-based annotations and guideline recommendations. We describe PharmCAT and a pilot validation project comparing results for 1000 Genomes Project sequences of Coriell samples with corresponding Genetic Testing Reference Materials Coordination Program (GeT-RM) sample characterization. PharmCAT was highly concordant with the GeT-RM data. PharmCAT is available in GitHub to evaluate, test, and report results back to the community. As precision medicine becomes more prevalent, our ability to consistently, accurately, and clearly define and report PGx annotations and prescribing recommendations is critical.
Topics: Decision Support Techniques; Genomics; Genotype; Genotyping Techniques; Humans; Pharmacogenetics; Pilot Projects; Precision Medicine
PubMed: 31306493
DOI: 10.1002/cpt.1568 -
Annual Review of Pharmacology and... Jan 2024Interindividual variability in genes encoding drug-metabolizing enzymes, transporters, receptors, and human leukocyte antigens has a major impact on a patient's response... (Review)
Review
Interindividual variability in genes encoding drug-metabolizing enzymes, transporters, receptors, and human leukocyte antigens has a major impact on a patient's response to drugs with regard to efficacy and safety. Enabled by both technological and conceptual advances, the field of pharmacogenomics is developing rapidly. Major progress in omics profiling methods has enabled novel genotypic and phenotypic characterization of patients and biobanks. These developments are paralleled by advances in machine learning, which have allowed us to parse the immense wealth of data and establish novel genetic markers and polygenic models for drug selection and dosing. Pharmacogenomics has recently become more widespread in clinical practice to personalize treatment and to develop new drugs tailored to specific patient populations. In this review, we provide an overview of the latest developments in the field and discuss the way forward, including how to address the missing heritability, develop novel polygenic models, and further improve the clinical implementation of pharmacogenomics.
Topics: Humans; Pharmacogenetics; Membrane Transport Proteins; Technology
PubMed: 37506333
DOI: 10.1146/annurev-pharmtox-051921-091209 -
The Journal of Applied Laboratory... Jan 2024
Topics: Humans; Pharmacogenetics; Genotype; Precision Medicine
PubMed: 38167767
DOI: 10.1093/jalm/jfad064 -
Cardiovascular Drugs and Therapy Jun 2021Pharmacogenomics has a burgeoning role in cardiovascular medicine, from warfarin dosing to antiplatelet choice, with recent developments in sequencing bringing the... (Review)
Review
Pharmacogenomics has a burgeoning role in cardiovascular medicine, from warfarin dosing to antiplatelet choice, with recent developments in sequencing bringing the promise of personalised medicine ever closer to the bedside. Further scientific evidence, real-world clinical trials, and economic modelling are needed to fully realise this potential. Additionally, tools such as polygenic risk scores, and results from Mendelian randomisation analyses, are only in the early stages of clinical translation and merit further investigation. Genetically targeted rational drug design has a strong evidence base and, due to the nature of genetic data, academia, direct-to-consumer companies, healthcare systems, and industry may meet in an unprecedented manner. Data sharing navigation may prove problematic. The present manuscript addresses these issues and concludes a need for further guidance to be provided to prescribers by professional bodies to aid in the consideration of such complexities and guide translation of scientific knowledge to personalised clinical action, thereby striving to improve patient care. Additionally, technologic infrastructure equipped to handle such large complex data must be adapted to pharmacogenomics and made user friendly for prescribers and patients alike.
Topics: Bioethics; Cardiovascular Diseases; Cost-Benefit Analysis; Drug Discovery; Humans; Mendelian Randomization Analysis; Pharmacogenetics; Precision Medicine; Risk Assessment; Translational Research, Biomedical
PubMed: 33528719
DOI: 10.1007/s10557-021-07149-3 -
Clinical Pharmacology and Therapeutics Sep 2021Pharmacogenetics (PGx) association studies are used to discover, replicate, and validate the association between an inherited genotype and a treatment outcome. The... (Review)
Review
Pharmacogenetics (PGx) association studies are used to discover, replicate, and validate the association between an inherited genotype and a treatment outcome. The objective of this tutorial is to provide trainees and novice PGx researchers with an overview of the major decisions that need to be made when designing and conducting a PGx association study. The first critical decision is to determine whether the objective of the study is discovery, replication, or validation. Next, the researcher must identify a patient cohort that has all of the data necessary to conduct the intended analysis. Then, the investigator must select and define the treatment outcome, or phenotype, that will be analyzed. Next, the investigator must determine what genotyping approach and genetic data will be included in the analysis. Finally, the association between the genotype and phenotype is tested using some statistical analysis methodology. This tutorial is divided into five sections; each section describes commonly used approaches and provides suggestions and resources for designing and conducting a PGx association study. Successful PGx association studies are necessary to discover and validate associations between inherited genetic variation and treatment outcomes, which enable clinical translation to improve efficacy and reduce toxicity of treatment.
Topics: Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Phenotype; Prospective Studies; Retrospective Studies
PubMed: 33880756
DOI: 10.1002/cpt.2270 -
Clinical Therapeutics Feb 2023A nonoptimized medication therapy (NOMT) event is an iatrogenic hazard or incident associated with medications and is a leading cause of death, serious injury, and... (Review)
Review
A nonoptimized medication therapy (NOMT) event is an iatrogenic hazard or incident associated with medications and is a leading cause of death, serious injury, and illness. NOMT events are often related to multidrug interactions in patients with polypharmacy. In these patients, NOMT events can be avoided by using advanced clinical decision support systems and clinical interventions such as separating the time of administration of certain drugs during the day. At the individual level, medication reconciliation is a first logical step for reducing adverse side effects. Then, intersubject variability in drug response should be considered to optimize patient drug regimens. Furthermore, patient pharmacogenomic status information can help ensure appropriateness of drug therapy. However, in patients with polypharmacy, such information is most valuable when combined with phenoconversion probability. At a population level, the virtual addition of drugs to various drug regimens and the use of a medication risk score can help predict the risk of NOMT events. This review outlines some of the mechanisms behind multidrug interactions and their association with drug safety and NOMTs, polypharmacy and its impact on patient outcomes, the value of pharmacogenomics, and an assessment of simulation studies and the virtual addition of drugs to a drug regimen using real-world data.
Topics: Humans; Drug-Related Side Effects and Adverse Reactions; Polypharmacy; Risk Factors; Pharmacogenetics; Decision Support Systems, Clinical; Drug Interactions
PubMed: 36682993
DOI: 10.1016/j.clinthera.2022.12.012