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Healthcare Management Forum May 2020The use of pharmacogenetic information is becoming mainstream with insurance companies and others starting to pay for widescale implementation of this new technology...
The use of pharmacogenetic information is becoming mainstream with insurance companies and others starting to pay for widescale implementation of this new technology starting with patients who have anxiety and depression. It has been introduced in response to the unpredictability of medication, the high number of adverse drug events, and lack of drug effectiveness. Greater than one-third of patients are identified as having one or more pharmacogenetic variants. Each pharmacogenetic variant may affect the metabolism of several medications used in primary care, in addition to the antidepressant and anti-anxiolytic medications. Pharmacogenetic information is evolving with major international working groups providing continuous updates. It is challenging to incorporate this new information along with all the other variables needed to identify safe and effective drug options within a normal consultation. Medication decision support software is one solution that can help address this.
Topics: Cost-Benefit Analysis; Evidence-Based Medicine; Pharmacogenetics; Primary Health Care
PubMed: 32054324
DOI: 10.1177/0840470419901285 -
Human Molecular Genetics May 2018The field of pharmacogenomics is an area of great potential for near-term human health impacts from the big genomic data revolution. Pharmacogenomics research momentum... (Review)
Review
The field of pharmacogenomics is an area of great potential for near-term human health impacts from the big genomic data revolution. Pharmacogenomics research momentum is building with numerous hypotheses currently being investigated through the integration of molecular profiles of different cell lines and large genomic data sets containing information on cellular and human responses to therapies. Additionally, the results of previous pharmacogenetic research efforts have been formulated into clinical guidelines that are beginning to impact how healthcare is conducted on the level of the individual patient. This trend will only continue with the recent release of new datasets containing linked genotype and electronic medical record data. This review discusses key resources available for pharmacogenomics and pharmacogenetics research and highlights recent work within the field.
Topics: Big Data; Genomics; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 29635477
DOI: 10.1093/hmg/ddy116 -
BMC Health Services Research Oct 2021Pharmacogenetics targets genetic variations that influence drug response. It is relatively a new science that has not been vastly employed in most developing countries...
BACKGROUND
Pharmacogenetics targets genetic variations that influence drug response. It is relatively a new science that has not been vastly employed in most developing countries including Syria. Therefore we aimed at evaluating the depth of knowledge in pharmacogenetics and the attitude towards it amongst Syrian pharmacists and physicians.
METHODS
We carried out an internet-based questionnaire consisted of 26 questions, sent through specialized websites and private groups with a large number of pharmacists and physicians members. The survey was available online for a period of 1 month.
RESULTS
The total number of respondents was 154, mostly female pharmacists. Our statistical analysis showed a strong positive association between profession (in favour of pharmacists) and pharmacogenetics knowledge p = 0.049; however, no correlation with experience p = 0.811 was found. A significant difference was reported between the knowledge of pharmacists and physicians p = 0.001 concerning drugs that need pharmacogenetics testing before being prescribed. The majority of respondents had no information about applying genetic tests in Syria before prescribing medications nor did they possess the knowledge regarding drugs that show differential responses in patients according to their unique genotypes. In our study, the percentage knowledge assessment score was low in general (mean ± Standard deviation, SD) (46% ± 13.9%). The majority of the respondents agreed that pharmacists should provide counselling to patients on the subject of pharmacogenetics. Respondents' opinions varied concerning making pharmacogenetics learning a priority.
CONCLUSION
Lack of pharmacogenetics knowledge was found amongst respondents in general. Our findings raise concerns about the lack of awareness amongst physicians, which may hinder the implementation of this crucial field in Syria. We suggest an emphasis on the role of education, training, and conducting genotyping research on the Syrian population.
Topics: Female; Health Knowledge, Attitudes, Practice; Humans; Male; Pharmacists; Pharmacogenetics; Physicians; Surveys and Questionnaires; Syria
PubMed: 34592972
DOI: 10.1186/s12913-021-07040-9 -
Clinical Pharmacokinetics Apr 2017Cancer treatment is becoming more and more individually based as a result of the large inter-individual differences that exist in treatment outcome and toxicity when... (Review)
Review
Cancer treatment is becoming more and more individually based as a result of the large inter-individual differences that exist in treatment outcome and toxicity when patients are treated using population-based drug doses. Polymorphisms in genes encoding drug-metabolizing enzymes and transporters can significantly influence uptake, metabolism, and elimination of anticancer drugs. As a result, the altered pharmacokinetics can greatly influence drug efficacy and toxicity. Pharmacogenetic screening and/or drug-specific phenotyping of cancer patients eligible for treatment with chemotherapeutic drugs, prior to the start of anticancer treatment, can identify patients with tumors that are likely to be responsive or resistant to the proposed drugs. Similarly, the identification of patients with an increased risk of developing toxicity would allow either dose adaptation or the application of other targeted therapies. This review focuses on the role of genetic polymorphisms significantly altering the pharmacokinetics of anticancer drugs. Polymorphisms in DPYD, TPMT, and UGT1A1 have been described that have a major impact on the pharmacokinetics of 5-fluorouracil, mercaptopurine, and irinotecan, respectively. For other drugs, however, the association of polymorphisms with pharmacokinetics is less clear. To date, the influence of genetic variations on the pharmacokinetics of the increasingly used monoclonal antibodies has hardly been investigated. Some studies indicate that genes encoding the Fcγ-receptor family are of interest, but more research is needed to establish if screening before the start of therapy is beneficial. Considering the profound impact of polymorphisms in drug transporters and drug-metabolizing enzymes on the pharmacokinetics of chemotherapeutic drugs and hence, their toxicity and efficacy, pharmacogenetic and pharmacokinetic profiling should become the standard of care.
Topics: Animals; Antineoplastic Agents; Cytochrome P-450 Enzyme System; Genetic Variation; Genotype; Glucuronosyltransferase; Humans; Neoplasms; Pharmacogenetics; Polymorphism, Single Nucleotide
PubMed: 27641154
DOI: 10.1007/s40262-016-0450-z -
Pharmacogenetics and Genomics Feb 2022Evaluations from pharmacogenetics implementation programs at major US medical centers have reported variability in the clinical adoption of pharmacogenetics across...
OBJECTIVES
Evaluations from pharmacogenetics implementation programs at major US medical centers have reported variability in the clinical adoption of pharmacogenetics across therapeutic areas. A potential cause for this variability may involve therapeutic area-specific differences in published pharmacogenetics recommendations to clinicians. To date, however, the potential for differences in clinical pharmacogenetics recommendations by therapeutic areas from prominent US guidance sources has not been assessed. Accordingly, our objective was to comprehensively compare essential elements from clinical pharmacogenetics recommendations contained within Clinical Pharmacogenetics Implementation Consortium guidelines, US Food and Drug Administration drug labels and clinical practice guidelines from US professional medical organizations across therapeutic areas.
METHODS
We analyzed clinical pharmacogenetics recommendation elements within Clinical Pharmacogenetics Implementation Consortium guidelines, US Food and Drug Administration drug labels and professional clinical practice guidelines through 05/24/19.
RESULTS
We identified 606 unique clinical pharmacogenetics recommendations, with the most recommendations involving oncology (217 recommendations), hematology (79), psychiatry (65), cardiovascular (43) and anesthetic (37) medications. Within our analyses, we observed considerable variability across therapeutic areas within the following essential pharmacogenetics recommendation elements: the recommended clinical management strategy; the relevant genetic biomarkers; the organizations providing pharmacogenetics recommendations; whether routine genetic screening was recommended; and the time since recommendations were published.
CONCLUSIONS
On the basis of our results, we infer that observed differences in clinical pharmacogenetics recommendations across therapeutic areas may result from specific factors associated with individual disease states, the associated genetic biomarkers, and the characteristics of the organizations providing recommendations.
Topics: Genetic Markers; Genetic Testing; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 34412102
DOI: 10.1097/FPC.0000000000000452 -
The Journal of Applied Laboratory... Jan 2024Pharmacogenetics or pharmacogenomics (PGx) is the study of the role of inherited or acquired sequence change in drug response. With the rapid evolution of molecular...
BACKGROUND
Pharmacogenetics or pharmacogenomics (PGx) is the study of the role of inherited or acquired sequence change in drug response. With the rapid evolution of molecular techniques, bioinformatic tools, and increased throughput of functional genomic studies, the discovery of PGx associations and clinical implementation of PGx test results have now moved beyond a handful variants in single pharmacogenes and multi-gene panels that interrogate a few pharmacogenes to whole-exome and whole-genome scales. Although some laboratories have adopted next-generation sequencing (NGS) as a testing platform for PGx and other molecular tests, most clinical laboratories that offer PGx tests still use targeted genotyping approaches.
CONTENT
This article discusses primarily the technical considerations for clinical laboratories to develop NGS-based PGx tests including whole-genome and whole-exome sequencing analyses and highlights the challenges and opportunities in test design, content selection, bioinformatic pipeline for PGx allele and diplotype assignment, rare variant classification, reporting, and briefly touches a few additional areas that are important for successful clinical implementation of PGx results.
SUMMARY
The accelerated speed of technology development associated with continuous cost reduction and enhanced ability to interrogate complex genome regions makes it inevitable for most, if not all, clinical laboratories to transition PGx testing to an NGS-based platform in the near future. It is important for laboratories and relevant professional societies to recognize both the potential and limitations of NGS-based PGx profiling, and to work together to develop a standard and consistent practice to maximize the variant or allele detection rate and utility of PGx testing.
Topics: Humans; Pharmacogenetics; Alleles; Computational Biology; High-Throughput Nucleotide Sequencing
PubMed: 38167765
DOI: 10.1093/jalm/jfad097 -
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 -
Pharmaceutical Research Aug 2017While recent discoveries have paved the way for the use of genotype-guided prescribing in some clinical environments, significant debate persists among clinicians and... (Review)
Review
While recent discoveries have paved the way for the use of genotype-guided prescribing in some clinical environments, significant debate persists among clinicians and researchers about the optimal approach to pharmacogenetic testing in clinical practice. One crucial factor in this debate surrounds the timing and methodology of genotyping, specifically whether genotyping should be performed reactively for targeted genes when a single drug is prescribed, or preemptively using a panel-based approach prior to drug prescribing. While early clinical models that employed a preemptive approach were largely developed in academic health centers through multidisciplinary efforts, increasing examples of pharmacogenetic testing are emerging in community-based and primary care practice environments. However, educational and practice-based resources for these clinicians remain largely nonexistent. As such, there is a need for the health care system to shift its focus from debating about preemptive genotyping to developing and disseminating needed resources to equip frontline clinicians for clinical implementation of pharmacogenetics. Providing tools and guidance to support these emerging models of care will be essential to support the thoughtful, evidence-based use of pharmacogenetic information in diverse clinical practice environments. Specifically, the creation of efficient and accurate point-of-care resources, practice-based tools, and clinical models is needed, along with identification and dissemination of sustainable avenues for pharmacogenetic test reimbursement.
Topics: Dose-Response Relationship, Drug; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 28466392
DOI: 10.1007/s11095-017-2163-x -
American Journal of Health-system... Dec 2016Both regulatory science and clinical practice rely on best available scientific data to guide decision-making. However, changes in clinical practice may be driven by... (Review)
Review
PURPOSE
Both regulatory science and clinical practice rely on best available scientific data to guide decision-making. However, changes in clinical practice may be driven by numerous other factors such as cost. In this review, we reexamine noteworthy examples where pharmacogenetic testing information was added to drug labeling to explore how the available evidence, potential public health impact, and predictive utility of each pharmacogenetic biomarker impacts clinical uptake.
SUMMARY
Advances in the field of pharmacogenetics have led to new discoveries about the genetic basis for variability in drug response. The Food and Drug Administration recognizes the value of pharmacogenetic testing strategies and has been proactive about incorporating pharmacogenetic information into the labeling of both new drugs and drugs already on the market. Although some examples have readily translated to routine clinical practice, clinical uptake of genetic testing for many drugs has been limited.
CONCLUSION
Both regulatory science and clinical practice rely on data-driven approaches to guide decision making; however, additional factors are also important in clinical practice that do not impact regulatory decision making, and these considerations may result in heterogeneity in clinical uptake of pharmacogenetic testing.
Topics: Clinical Decision-Making; Genetic Testing; Humans; Pharmacogenetics; Pharmacogenomic Testing; United States; United States Food and Drug Administration
PubMed: 27864207
DOI: 10.2146/ajhp160476 -
Blood Reviews Jul 2015Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults accounting for no more than 20% of all cases of acute leukemia. By contrast with the pediatric... (Review)
Review
Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults accounting for no more than 20% of all cases of acute leukemia. By contrast with the pediatric population, in whom significant improvements in long term survival and even cure have been achieved over the last 30years, adult ALL remains a significant challenge. Overall survival in this group remains a relatively poor 20-40%. Modern research has focused on improved pharmacokinetics, novel pharmacogenetics and personalized principles to optimize the efficacy of the treatment while reducing toxicity. Here we review the pharmacogenetics of medications used in the management of patients with ALL, including l-asparaginase, glucocorticoids, 6-mercaptopurine, methotrexate, vincristine and tyrosine kinase inhibitors. Incorporating recent pharmacogenetic data, mainly from pediatric ALL, will provide novel perspective of predicting response and toxicity in both pediatric and adult ALL therapies.
Topics: Female; Humans; Male; Pharmacogenetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 25614322
DOI: 10.1016/j.blre.2015.01.001