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Translational Psychiatry Oct 2021Pharmacogenomics (PGx) is the study of genetic influences on an individual's response to medications. Improvements in the quality and quantity of PGx research over the... (Review)
Review
Pharmacogenomics (PGx) is the study of genetic influences on an individual's response to medications. Improvements in the quality and quantity of PGx research over the past two decades have enabled the establishment of commercial markets for PGx tests. Nevertheless, PGx testing has yet to be adopted as a routine practice in clinical care. Accordingly, policy regulating the commercialization and reimbursement of PGx testing is in its infancy. Several papers have been published on the topic of challenges, or 'barriers' to clinical adoption of this healthcare innovation. However, many do not include recent evidence from randomized controlled trials, economic utility studies, and qualitative assessments of stakeholder opinions. The present paper revisits the most cited barriers to adoption of PGx testing: evidence for clinical utility, evidence for economic effectiveness, and stakeholder awareness. We consider these barriers in the context of reviewing PGx literature published over the past two decades and emphasize data from commercial PGx testing companies, since they have published the largest datasets. We conclude with a discussion of existing limitations to PGx testing and recommendations for progress.
Topics: Attitude; Pharmacogenetics; Pharmacogenomic Testing; Psychiatry
PubMed: 34615849
DOI: 10.1038/s41398-021-01600-7 -
Pharmacogenomics Jul 2023To understand how attitudes toward pharmacogenomic (PGx) testing among healthcare providers varies by specialty. Providers reported comfort ordering PGx testing and...
To understand how attitudes toward pharmacogenomic (PGx) testing among healthcare providers varies by specialty. Providers reported comfort ordering PGx testing and its perceived utility on web-based surveys before and after genetics education. Primary quantitative analyses compared primary care providers (PCPs) to specialty providers at both timepoints. PCPs were more likely than specialty care providers to rate PGx testing as useful at both timepoints. Education increased comfort ordering PGx tests, with larger improvements among PCPs than specialty providers. Over 90% of cardiology and internal medicine providers rated PGx testing as useful at pre- and post-education. PCPs overwhelmingly perceive PGx to be useful, and provider education is particularly effective for improving PCPs' confidence. Education for all specialties will be essential to ensure appropriate integration into routine practice.
Topics: Humans; Pharmacogenomic Testing; Attitude; Delivery of Health Care; Pharmacogenetics; Health Personnel
PubMed: 37458095
DOI: 10.2217/pgs-2023-0039 -
Clinical Chemistry and Laboratory... Jun 2017Pharmacogenomics has significantly added to our understanding of drug responses in clinical pharmacology, changing the paradigm of treatment decisions. Interrogations of... (Review)
Review
Pharmacogenomics has significantly added to our understanding of drug responses in clinical pharmacology, changing the paradigm of treatment decisions. Interrogations of both inherited and somatic variations for therapeutic purposes are increasingly being adopted in clinics, where quality control (QC) materials are required. However, for many pharmacogenomic tests, the acquisition of well-characterized QC materials is often difficult or impossible. In this review, several sources of appropriate QC materials for therapy-associated genetic testing are discussed. Among them, the novel methods for producing renewable controls that resemble patient samples are highlighted. Owing to technological complexity, more efforts are needed to develop proper controls for next-generation sequencing-based assay.
Topics: Genetic Testing; Humans; Mutation; Neoplasms; Pharmacogenomic Testing; Quality Control
PubMed: 27845879
DOI: 10.1515/cclm-2016-0755 -
Clinical Pharmacology and Therapeutics Dec 2022Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta-analyzed clinical trials for an association between the use of PGx-guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each trial was assessed for risk of bias and a random-effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx-guided antidepressant therapy (n = 2,395) were 1.41 (95% confidence interval (CI) = 1.15-1.74, P = 0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n = 2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13-1.88) and 1.26 (95% CI = 0.84-1.88), respectively. These results suggest that PGx-guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx-guided antidepressant therapy in the literature.
Topics: Adult; Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Pharmacogenomic Testing; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 36111494
DOI: 10.1002/cpt.2748 -
Ontario Health Technology Assessment... 2017A large proportion of the Ontario population lives with a diagnosed mental illness. Nearly 5% of Ontarians have major depressive disorder, and another 5% have another... (Review)
Review
BACKGROUND
A large proportion of the Ontario population lives with a diagnosed mental illness. Nearly 5% of Ontarians have major depressive disorder, and another 5% have another type of depressive disorder, bipolar disorder, schizophrenia, anxiety, or some other disorder not otherwise specified. Medications are commonly used to treat mental illness, but choosing the right medication for each patient is challenging, and more than 40% of patients discontinue their medication within 90 days because of adverse effects or lack of response. The Assurex GeneSight Psychotropic test is a pharmacogenomic panel that provides clinicians with a report to guide medication selection that is unique to each patient based on their individual genetic profile. However, it is uncertain whether guided treatment using GeneSight is effective compared with unguided treatment (usual care).
METHODS
We performed a systematic review to identify English-language studies published before February 22, 2016, that compared GeneSight-guided care and usual care among people with mood disorders, anxiety, or schizophrenia. Primary outcomes of interest were prevention of suicide, remission of depression symptoms, response to depression therapy, depression score, and quality of life. Secondary outcomes of interest were impact on therapeutic decisions and patient and clinician satisfaction. Risk of bias was evaluated, and the quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group criteria.
RESULTS
Four studies met the inclusion criteria. These studies used a version of GeneSight that included the , and genes; one of the studies also included . Patients who received the GeneSight test to guide psychotropic medication selection had improved response to depression treatment, greater improvements in measures of depression, and greater patient and clinician satisfaction compared with patients who received treatment as usual. We observed no differences in rates of complete remission from depression. The findings were based on GRADE assessment of low to very low quality evidence, and the body of evidence had several limitations: the included studies used an older version of GeneSight and were limited to a population with major depression, so results may not be generalizable to other versions of the test or different populations such as patients with anxiety or schizophrenia.
CONCLUSIONS
There is uncertainty about the use of GeneSight Psychotropic pharmacogenomic genetic panel to guide medication selection. It was associated with improvements in some patient outcomes, but not others. As well, our confidence in these findings is low because of limitations in the body of evidence.
Topics: Clinical Trials as Topic; Depressive Disorder, Major; Drug Administration Schedule; Genotype; Humans; Pharmacogenomic Testing; Psychotropic Drugs; Quality of Life; Treatment Outcome
PubMed: 28515818
DOI: No ID Found -
Genes Jun 2020Pharmacogenomics is one of the emerging approaches to precision medicine, tailoring drug selection and dosing to the patient's genetic features. In recent years, several...
Pharmacogenomics is one of the emerging approaches to precision medicine, tailoring drug selection and dosing to the patient's genetic features. In recent years, several pharmacogenetic guidelines have been published by international scientific consortia, but the uptake in clinical practice is still poor. Many coordinated international efforts are ongoing in order to overcome the existing barriers to pharmacogenomic implementation. On the other hand, existing validated pharmacogenomic markers can explain only a minor part of the observed clinical variability in the therapeutic outcome. New investigational approaches are warranted, including the study of the pharmacogenomic role of the immune system genetics and of previously neglected rare genetic variants, reported to account for a large part of the inter-individual variability in drug metabolism. In this Special Issue, we collected a series of articles covering many aspects of pharmacogenomics. These include clinical implementation of pharmacogenomics in clinical practice, development of tools or infrastractures to support this process, research of new pharmacogenomics markers to increase drug efficacy and safety, and the impact of rare genetic variants in pharmacogenomics.
Topics: Biomarkers; Humans; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine
PubMed: 32580376
DOI: 10.3390/genes11060679 -
Journal of Medical Genetics Jan 2023Population databases could help patients with cancer and providers better understand current pharmacogenomic prescribing and testing practices. This retrospective... (Observational Study)
Observational Study
Population databases could help patients with cancer and providers better understand current pharmacogenomic prescribing and testing practices. This retrospective observational study analysed patients with cancer, drugs with pharmacogenomic evidence and related genetic testing in the National Institutes of Health database. Most patients with cancer (19 633 (88.3%) vs 2590 (11.7%)) received ≥1 drug and 36 (0.2%) received genetic testing, with a significant association between receiving ≥1 drug and age group (p<0.001), but not sex (p=0.612), race (p=0.232) or ethnicity (p=0.971). Drugs with pharmacogenomic evidence-but not genetic testing-were common for patients with cancer, reflecting key gaps preventing precision medicine from becoming standard of care.
Topics: Humans; Precision Medicine; Pharmacogenomic Testing; Population Health; Pharmacogenetics; Neoplasms
PubMed: 34872990
DOI: 10.1136/jmedgenet-2021-108112 -
Journal of the American Pharmacists... 2023Pharmacogenetic (PGx) testing is an evidence-based approach to finding effective medication therapies. While community pharmacists are ideally situated to provide PGx... (Review)
Review
BACKGROUND
Pharmacogenetic (PGx) testing is an evidence-based approach to finding effective medication therapies. While community pharmacists are ideally situated to provide PGx testing, the extent of its implementation is limited within community pharmacies.
OBJECTIVE
This study aimed to explore trends in the international peer-reviewed primary literature on community pharmacists' implementation of PGx and map the main findings on the Theoretical Domains Framework (TDF).
METHODS
A literature search and 2-step screening were conducted per PRISMA Extension for Scoping Reviews. Inclusion criteria were English language, community pharmacy setting, full papers, and empirical research. Data were collated in a data extraction form. The main findings were deductively mapped on the TDF with a content analysis approach.
RESULTS
Of 1176 identified documents screened, 39 were included in this scoping review. Four groups of research were identified: pre-implementation surveys (interviews, and focus groups [56%, n = 22]); PGx implementation (single cohort to assess feasibility [38%, n = 15]); PGx implementation (controlled study to assess feasibility [n = 1, 2.5%]); and efficacy of PGx (2.5%, n = 1). Most studies throughout the 4 groups sought pharmacists' perceptions (46%, n = 18) and used the quantitative paradigm (77%, n = 30). TDF mapping documented positive beliefs about the benefits of PGx testing as a part of the pharmacists' role. Barriers to PGx use included pharmacists' awareness of knowledge gaps, low confidence in interpreting and communicating PGx results, concerns about cost, privacy, and integration into pharmacy workflow.
CONCLUSION
Research addressing PGx implementation within the community pharmacy evolved from assessing individuals' perceptions of PGx to determining the feasibility of PGx testing in pharmacies and evaluating the impact of PGx testing on patient outcomes in depression. Mapping the main findings on the TDF facilitates the development of multidimensional interventions, potentially targeting patients, pharmacists, and health policy.
Topics: Humans; Community Pharmacy Services; Pharmacies; Pharmacists; Pharmacogenetics; Pharmacogenomic Testing; Surveys and Questionnaires
PubMed: 36371398
DOI: 10.1016/j.japh.2022.09.019 -
Pharmacotherapy Sep 2017Advancing the use of biomarkers and pharmacogenomics has been a key priority area for the U.S. Food and Drug Administration (FDA). The FDA offers prescribing... (Review)
Review
Advancing the use of biomarkers and pharmacogenomics has been a key priority area for the U.S. Food and Drug Administration (FDA). The FDA offers prescribing recommendations to manage ~100 gene-drug interactions, and multiple institutions around the United States and abroad have incorporated genomic testing into patient care. However, the penetration of pharmacogenomic testing remains incomplete. In this perspective, we summarize the evidence streams to support the clinical utility of pharmacogenomic testing and its transition into clinical practice.
Topics: Clinical Trials as Topic; Humans; Pharmacogenetics; Pharmacogenomic Testing; United States; United States Food and Drug Administration
PubMed: 28605049
DOI: 10.1002/phar.1971 -
JAMA Jul 2022
Topics: Antidepressive Agents; Depression; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 35819435
DOI: 10.1001/jama.2022.10018