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Trends in Pharmacological Sciences Oct 2022Recent advances in next-generation sequencing (NGS) have resulted in the identification of tens of thousands of rare pharmacogenetic variations with unknown functional... (Review)
Review
Recent advances in next-generation sequencing (NGS) have resulted in the identification of tens of thousands of rare pharmacogenetic variations with unknown functional effects. However, although such pharmacogenetic variations have been estimated to account for a considerable amount of the heritable variability in drug response and toxicity, accurate interpretation at the level of the individual patient remains challenging. We discuss emerging strategies and concepts to close this translational gap. We illustrate how massively parallel experimental assays, artificial intelligence (AI), and machine learning can synergize with population-scale biobank projects to facilitate the interpretation of NGS data to individualize clinical decision-making and personalized medicine.
Topics: Artificial Intelligence; High-Throughput Nucleotide Sequencing; Humans; Machine Learning; Pharmacogenetics; Precision Medicine
PubMed: 36008164
DOI: 10.1016/j.tips.2022.07.002 -
Clinical Pharmacology and Therapeutics Nov 2019
Topics: Databases, Genetic; Decision Support Systems, Clinical; Electronic Health Records; Humans; Leadership; Pharmacogenetics; Pharmacogenomic Variants; Precision Medicine
PubMed: 31498426
DOI: 10.1002/cpt.1600 -
Pharmacogenomics Apr 2022Global migration trends are accelerating population admixture. Increasing population diversity met with minority health disparities necessitates thoughtful training of... (Review)
Review
Global migration trends are accelerating population admixture. Increasing population diversity met with minority health disparities necessitates thoughtful training of health professional students. Health professional accreditation standards emphasize pharmacogenomics and clinical cultural competency (CCC); however, published studies focus on students' knowledge in pharmacogenomics alone. This report reviews considerations for integrating CCC into required pharmacogenomic education in pharmacy and other health disciplines. By coupling both topics during didactic training and active learning exercises repeated throughout the existing curriculum, students can become adept at these individualized patient care skills and retain their knowledge into their careers. Moving beyond race as a proxy for healthcare decision-making, the CCC of clinicians coupled with patients' genetic test results could empower clinicians to address health disparities and facilitate discussions about the role of race in clinical practice. Ultimately, an integrated approach of teaching pharmacogenomics and CCC could dismantle race-norming or race-based clinical practices.
Topics: Clinical Competence; Cultural Competency; Curriculum; Education, Pharmacy; Humans; Pharmacogenetics
PubMed: 35311348
DOI: 10.2217/pgs-2022-0009 -
Methods in Molecular Biology (Clifton,... 2022Genetic ancestry inference can be used to stratify patient cohorts and to model pharmacogenomic variation within and between populations. We provide a detailed guide to...
Genetic ancestry inference can be used to stratify patient cohorts and to model pharmacogenomic variation within and between populations. We provide a detailed guide to genetic ancestry inference using genome-wide genetic variant datasets, with an emphasis on two widely used techniques: principal components analysis (PCA) and ADMIXTURE analysis. PCA can be used for patient stratification and categorical ancestry inference, whereas ADMIXTURE is used to characterize genetic ancestry as a continuous variable. Visualization methods are critical for the interpretation of genetic ancestry inference methods, and we provide instructions for how the results of PCA and ADMIXTURE can be effectively visualized.
Topics: Genetic Techniques; Genetics, Population; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Population Groups; Principal Component Analysis
PubMed: 36068478
DOI: 10.1007/978-1-0716-2573-6_21 -
Pharmacogenomics Aug 2019The Nigerian population exhibits huge ethnic and genetic diversity, typical of African populations, which can be harnessed for improved drug-response and disease... (Review)
Review
The Nigerian population exhibits huge ethnic and genetic diversity, typical of African populations, which can be harnessed for improved drug-response and disease management. Existing data on genes relevant to drug response, so far generated for the population, indeed confirm the prevalence of some clinically significant pharmacogenes. These reports detail prevailing genetic alleles and metabolic phenotypes of vital drug metabolizing monooxygenases, transferases and drug transporters. While the utilization of existing pharmacogenomic data for healthcare delivery remains unpopular, several past and on-going studies suggest that a future shift toward genotype-stratified dosing of drugs and disease management in the population is imminent. This review discusses the present state of pharmacogenomics in Nigeria and the potential benefits of sustained research in this field for the population.
Topics: Alleles; Animals; Ethnicity; Genetic Variation; Genotype; Humans; Nigeria; Pharmacogenetics; Phenotype
PubMed: 31453771
DOI: 10.2217/pgs-2019-0046 -
Methods in Molecular Biology (Clifton,... 2022Precision medicine exemplifies the emergence of personalized treatment options which may benefit specific patient populations based upon their genetic makeup....
Precision medicine exemplifies the emergence of personalized treatment options which may benefit specific patient populations based upon their genetic makeup. Application of pharmacogenomics requires an understanding of how genetic variations impact pharmacokinetic and pharmacodynamic properties. This particular approach in pharmacotherapy is helpful because it can assist in and improve clinical decisions. Application of pharmacogenomics to cardiovascular pharmacotherapy provides for the ability of the medical provider to gain critical knowledge on a patient's response to various treatment options and risk of side effects.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacogenetics; Precision Medicine
PubMed: 36068466
DOI: 10.1007/978-1-0716-2573-6_9 -
Clinical Pharmacology and Therapeutics Apr 2023Clinical decision support (CDS) is often cited as an essential part of pharmacogenomics (PGx) implementations. A multitude of strategies are available; however, it is... (Review)
Review
Clinical decision support (CDS) is often cited as an essential part of pharmacogenomics (PGx) implementations. A multitude of strategies are available; however, it is unclear which strategies are effective and which metrics are used to quantify clinical utility. The objective of this scoping review was to aggregate previous studies into a cohesive depiction of the current state of PGx CDS implementations and identify areas for future research on PGx CDS. Articles were included if they (i) described electronic CDS tools for PGx and (ii) reported metrics related to PGx CDS. Twenty of 3,449 articles were included and provided data on PGx CDS metrics from 15 institutions, with 93% of programs located at academic medical centers. The most common tools in CDS implementations were interruptive post-test alerts. Metrics for clinical response and alert response ranged from 12-73% and 21-98%, respectively. Few data were found on changes in metrics over time and measures that drove the evolution of CDS systems. Relatively few data were available regarding support of optimal approaches for PGx CDS. Post-test alerts were the most widely studied approach, and their effectiveness varied greatly. Further research on the usability, effectiveness, and optimization of CDS tools is needed.
Topics: Humans; Pharmacogenetics; Electronic Health Records; Decision Support Systems, Clinical; Medical Order Entry Systems; Software
PubMed: 35838358
DOI: 10.1002/cpt.2711 -
Biomedicine & Pharmacotherapy =... Jun 2022Mendelian randomization (MR) is an epidemiological method that uses genetic variants to proxy an exposure predicting its causal association with an outcome. It occupies... (Review)
Review
Mendelian randomization (MR) is an epidemiological method that uses genetic variants to proxy an exposure predicting its causal association with an outcome. It occupies a valuable niche between observational studies and randomized trials. MR applications expanded lately, facilitated by the availability of big data, to include disease risk causation prediction, supporting evidence of prior observational data, identifying new drug targets, and drug repurposing. Concurrently, the last decade witnessed the growth of pharmacogenomics (PGx) research as a cornerstone in precision medicine. PGx research, conducted at discovery and implementation levels, resulted in validated PGx biomarkers and tests. Despite many clinically relevant PGx associations that could be translated into clinical applications, worldwide implementation is lagging far behind. The current review examines the intersection zones between MR and PGx research. MR can provide supporting evidence that allows generalizing PGx findings supporting its implementation. Interchangeability, PGx research can fuel MR studies with libraries of genetic variants of validated biological relevance. Furthermore, PGx and MR exhibit a synergistic relationship in drug discovery that can accelerate identifying new targets and repurposing old drugs. Interdisciplinary research applied by PGx researchers, epidemiologists with MR experience, and data scientists' collaborations can unlock unforeseen opportunities in accelerating precision medicine acquisition.
Topics: Drug Discovery; Mendelian Randomization Analysis; Pharmacogenetics; Precision Medicine
PubMed: 35429744
DOI: 10.1016/j.biopha.2022.112952 -
British Journal of Clinical Pharmacology Sep 2023Pharmacogenomic testing has the potential to target medicines more effectively towards those who will benefit and avoid use in individuals at risk of harm. Health... (Review)
Review
AIMS
Pharmacogenomic testing has the potential to target medicines more effectively towards those who will benefit and avoid use in individuals at risk of harm. Health economies are actively considering how pharmacogenomic tests can be integrated into health care systems to improve use of medicines. However, one of the barriers to effective implementation is evaluation of the evidence including clinical usefulness, cost-effectiveness, and operational requirements. We sought to develop a framework that could aid the implementation of pharmacogenomic testing. We take the view from the National Health Service (NHS) in England.
METHODS
We used a literature review using EMBASE and Medline databases to identify prospective studies of pharmacogenomic testing, focusing on clinical outcomes and implementation of pharmacogenomics. Using this search, we identified key themes relating to the implementation of pharmacogenomic tests. We used a clinical advisory group with expertise in pharmacology, pharmacogenomics, formulary evaluation, and policy implementation to review data from our literature review and the interpretation of these data. With the clinical advisory group, we prioritized themes and developed a framework to evaluate proposals to implement pharmacogenomics tests.
RESULTS
Themes that emerged from review of the literature and subsequent discussion were distilled into a 10-point checklist that is proposed as a tool to aid evidence-based implementation of pharmacogenomic testing into routine clinical care within the NHS.
CONCLUSION
Our 10-point checklist outlines a standardized approach that could be used to evaluate proposals to implement pharmacogenomic tests. We propose a national approach, taking the view of the NHS in England. Using this approach could centralize commissioning of appropriate pharmacogenomic tests, reduce inequity and duplication using regional approaches, and provide a robust and evidence-based framework for adoption. Such an approach could also be applied to other health systems.
Topics: Humans; Pharmacogenetics; State Medicine; Pharmacogenomic Testing; Prospective Studies; England
PubMed: 37313748
DOI: 10.1111/bcp.15820 -
Pharmacogenomics Feb 2021Pharmacogenetics represents a major driver of precision medicine, promising individualized drug selection and dosing. Traditionally, pharmacogenetic profiling has been... (Review)
Review
Pharmacogenetics represents a major driver of precision medicine, promising individualized drug selection and dosing. Traditionally, pharmacogenetic profiling has been performed using targeted genotyping that focuses on common/known variants. Recently, whole-genome sequencing (WGS) is emerging as a more comprehensive short-read next-generation sequencing approach, enabling both gene diagnostics and pharmacogenetic profiling, including rare/novel variants, in a single assay. Using the example of the pharmacogene , we demonstrate the potential of WGS-based pharmacogenetic profiling as well as emphasize the limitations of short-read next-generation sequencing. In the near future, we envision a shift toward long-read sequencing as the predominant method for gene diagnostics and pharmacogenetic profiling, providing unprecedented data quality and improving patient care.
Topics: Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Whole Genome Sequencing
PubMed: 33517770
DOI: 10.2217/pgs-2020-0155