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The Pharmacogenomics Journal Oct 2017Pharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene-drug associations have been discovered, but PGx-guided treatment... (Review)
Review
Pharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene-drug associations have been discovered, but PGx-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health-care. We reviewed economic evaluations for PGx associations listed in the US Food and Drug Administration (FDA) Table of Pharmacogenomic Biomarkers in Drug Labeling. We determined the proportion of evaluations that found PGx-guided treatment to be cost-effective or dominant over the alternative strategies, and estimated the impact on this proportion of removing the cost of genetic testing. Of the 137 PGx associations in the FDA table, 44 economic evaluations, relating to 10 drugs, were identified. Of these evaluations, 57% drew conclusions in favour of PGx testing, of which 30% were cost-effective and 27% were dominant (cost-saving). If genetic information was freely available, 75% of economic evaluations would support PGx-guided treatment, of which 25% would be cost-effective and 50% would be dominant. Thus, PGx-guided treatment can be a cost-effective and even a cost-saving strategy. Having genetic information readily available in the clinical health record is a realistic future prospect, and would make more genetic tests economically worthwhile.
Topics: Cost-Benefit Analysis; Economics, Pharmaceutical; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; United States; United States Food and Drug Administration
PubMed: 28607506
DOI: 10.1038/tpj.2017.21 -
Pharmacogenomics Jun 2016Recent research highlighted the large extent of rare variants in pharmacogenes and, on this basis, it was estimated that rare variants account for 30-40% of the... (Review)
Review
Recent research highlighted the large extent of rare variants in pharmacogenes and, on this basis, it was estimated that rare variants account for 30-40% of the functional variability in pharmacogenes. It has been proposed that comprehensive next-generation sequencing (NGS)-based sequencing of pharmacogenes could soon be a cost-effective methodology for clinical routine genotyping. Yet, multiple challenges on technical, interpretative and ethical levels need to be overcome to enable the reasonable dissemination of comprehensive pharmacogenetic genotyping, that includes rare genetic variation, into clinical practice. We argue that current pre-emptive pharmacogenetic testing cannot be based on comprehensive approaches but needs to be restricted to validated variants. Rather, comprehensive strategies should only be used for retrospective analyses of patients exhibiting unanticipated drug responses. Thereby, subsequent to computational analyses and functional validations, emerging variants with confirmed functional relevance can be incorporated into candidate genotyping strategies, thus refining and enhancing future pre-emptive genetic testing.
Topics: Genotyping Techniques; High-Throughput Nucleotide Sequencing; Humans; Pharmacogenetics; Phenotype; Retrospective Studies
PubMed: 27248710
DOI: 10.2217/pgs-2016-0023 -
Advances in Pharmacology (San Diego,... 2018Currently, germline pharmacogenomics (PGx) is successfully implemented within certain specialties in clinical care. With the integration of PGx in pharmacotherapy... (Review)
Review
Currently, germline pharmacogenomics (PGx) is successfully implemented within certain specialties in clinical care. With the integration of PGx in pharmacotherapy multiple stakeholders are involved, which are identified in this chapter. Clinically relevant pharmacogenes with their related PGx test are discussed, along with diagnostic test criteria to guide clinicians and policy makers in PGx test selection. The chapter further reviews the similarities and the differences between the guidelines of the Dutch Pharmacogenetics Working Group and the Clinical Pharmacogenetics Implementation Consortium which both support healthcare professionals in understanding PGx test results and help guiding pharmacotherapy by providing evidence-based dosing recommendations. Finally, clinical studies which provide scientific evidence and information on cost-effectiveness supporting clinical implementation of PGx in clinical care are discussed along with the remaining barriers for adoption of PGx testing by healthcare professionals.
Topics: Clinical Medicine; Cost-Benefit Analysis; Humans; Patient Care; Pharmacogenetics; Practice Guidelines as Topic
PubMed: 29801576
DOI: 10.1016/bs.apha.2018.04.003 -
Clinical and Translational Science Jan 2021Interindividual variability in drug efficacy and toxicity is a major challenge in clinical practice. Variations in drug pharmacokinetics (PKs) and pharmacodynamics (PDs)... (Review)
Review
Interindividual variability in drug efficacy and toxicity is a major challenge in clinical practice. Variations in drug pharmacokinetics (PKs) and pharmacodynamics (PDs) can be, in part, explained by polymorphic variants in genes encoding drug metabolizing enzymes and transporters (absorption, distribution, metabolism, and excretion) or in genes encoding drug receptors. Pharmacogenomics (PGx) has allowed the identification of predictive biomarkers of drug PKs and PDs and the current knowledge of genome-disease and genome-drug interactions offers the opportunity to optimize tailored drug therapy. High-throughput PGx genotyping, from targeted to more comprehensive strategies, allows the identification of PK/PD genotypes to be developed as clinical predictive biomarkers. However, a biomarker needs a robust process of validation followed by clinical-grade assay development and must comply to stringent regulatory guidelines. We here discuss the methodological challenges and the emerging technological tools in PGx biomarker discovery and validation, at the crossroad among molecular genetics, bioinformatics, and clinical medicine.
Topics: Biomarkers, Pharmacological; Computational Biology; Drug Interactions; Feasibility Studies; Genome-Wide Association Study; Genotyping Techniques; High-Throughput Nucleotide Sequencing; Humans; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Translational Research, Biomedical; Validation Studies as Topic
PubMed: 33089968
DOI: 10.1111/cts.12869 -
Pharmacogenomics Nov 2022To assess knowledge and attitudes toward pharmacogenomics (PGx) of incoming doctoral pharmacy students, to evaluate the internal structure and reliability of the PGx...
To assess knowledge and attitudes toward pharmacogenomics (PGx) of incoming doctoral pharmacy students, to evaluate the internal structure and reliability of the PGx survey and to identify variables associated with the different responses. A PGx survey based on the core pharmacist competencies in PGx was created. Of 83.2% analyzable responses, 91% believed PGx is a useful tool and relevant to future practice but over 70% stated they lack confidence in clinical PGx knowledge. This 38-item PGx survey included three factors showing high reliability. Prior genetic/PGx testing and unsatisfactory medication experiences were associated with a more positive attitude toward PGx. The majority of students have positive attitudes toward PGx, but lack knowledge in genetic concepts and clinical PGx.
Topics: Humans; Students, Pharmacy; Pharmacogenetics; Reproducibility of Results; Pharmacists; Attitude
PubMed: 36314296
DOI: 10.2217/pgs-2022-0094 -
Pharmacogenomics Jul 2021Several healthcare organizations across Minnesota have developed formal pharmacogenomic (PGx) clinical programs to increase drug safety and effectiveness. Healthcare... (Review)
Review
Several healthcare organizations across Minnesota have developed formal pharmacogenomic (PGx) clinical programs to increase drug safety and effectiveness. Healthcare professional and student education is strong and there are multiple opportunities in the state for learners to gain workforce skills and develop advanced competency in PGx. Implementation planning is occurring at several organizations and others have incorporated structured utilization of PGx into routine workflows. Laboratory-based and translational PGx research in Minnesota has driven important discoveries in several therapeutic areas. This article reviews the state of PGx activities in Minnesota including educational programs, research, national consortia involvement, technology, clinical implementation and utilization and reimbursement, and outlines the challenges and opportunities in equitable implementation of these advances.
Topics: Biomedical Research; Education, Pharmacy, Graduate; Health Personnel; Humans; Minnesota; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 34137665
DOI: 10.2217/pgs-2021-0058 -
Annual Review of Pharmacology and... Jan 2024The association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic... (Review)
Review
The association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic variants and drug efficacy or toxicity, we are able to optimize pharmacological therapy according to an individual's genotype. Pharmacogenomics research has historically suffered from bias and underrepresentation of people from certain ancestry groups and of the female sex. These biases can arise from factors such as drugs and indications studied, selection of study participants, and methods used to collect and analyze data. To examine the representation of biogeographical populations in pharmacogenomic data sets, we describe individuals involved in gene-drug response studies from PharmGKB, a leading repository of drug-gene annotations, and showcase, a gene that metabolizes approximately 25% of all prescribed drugs. We also show how the historical underrepresentation of females in clinical trials has led to significantly more adverse drug reactions in females than in males.
Topics: Male; Humans; Female; Sexism; Pharmacogenetics; Drug-Related Side Effects and Adverse Reactions
PubMed: 37450899
DOI: 10.1146/annurev-pharmtox-030823-111731 -
The AAPS Journal May 2016Biotherapeutics (BTs), one of the fastest growing classes of drug molecules, offer several advantages over the traditional small molecule pharmaceuticals because of... (Review)
Review
Biotherapeutics (BTs), one of the fastest growing classes of drug molecules, offer several advantages over the traditional small molecule pharmaceuticals because of their relatively high specificity, low off-target effects, and biocompatible metabolism, in addition to legal and logistic advantages. However, their clinical utility is limited, among other things, by their high immunogenic potential and/or variable therapeutic efficacy in different patient populations. Both of these issues, also commonly experienced with small molecule drugs, have been addressed effectively in a number of cases by the successful application of pharmacogenomic tools and approaches. In this introductory article of the special issue, we review the current state of application of pharmacogenomics to BTs and offer suggestions for further expansion of the field.
Topics: Animals; Biological Products; Biological Therapy; Biopharmaceutics; Humans; Pharmacogenetics; Recombinant Proteins
PubMed: 27007601
DOI: 10.1208/s12248-016-9903-4 -
Current Drug Metabolism 2020Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine... (Review)
Review
BACKGROUND
Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure. These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Pharmacogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment protocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice.
OBJECTIVE
The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant care.
METHODS
We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases.
RESULTS
TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce.
CONCLUSION
Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics.
Topics: Azathioprine; Genetic Markers; Humans; Inflammatory Bowel Diseases; Pediatrics; Pharmacogenetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 32124692
DOI: 10.2174/1389200221666200303113456 -
Pharmacogenomics Sep 2021Opioid misuse and mismanagement has been a public health crisis for several years. Pharmacogenomics (PGx) has been proposed as another tool to enhance opioid selection... (Review)
Review
Opioid misuse and mismanagement has been a public health crisis for several years. Pharmacogenomics (PGx) has been proposed as another tool to enhance opioid selection and optimization, with recent studies demonstrating successful implementation and outcomes. However, broad engagement with PGx for opioid management is presently limited. The purpose of this article is to highlight a series of barriers to PGx implementation within the specific context of opioid management. Areas of advancement needed for more robust pharmacogenomic engagement with opioids will be discussed, including clinical and economic research needs, education and training needs, policy and public health considerations, as well as legal and ethical issues. Continuing efforts to address these issues may help to further operationalize PGx toward improving opioid use.
Topics: Analgesics, Opioid; Humans; Opioid-Related Disorders; Pain; Pain Management; Pharmacogenetics; Practice Guidelines as Topic; Public Health Practice
PubMed: 34521258
DOI: 10.2217/pgs-2021-0044