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Circulation. Genomic and Precision... Aug 2018In genotype-based recall (GBR) studies, people (or their biological samples) who carry genotypes of special interest for a given hypothesis test are recalled from a... (Review)
Review
In genotype-based recall (GBR) studies, people (or their biological samples) who carry genotypes of special interest for a given hypothesis test are recalled from a larger cohort (or biobank) for more detailed investigations. There are several GBR study designs that offer a range of powerful options to elucidate (1) genotype-phenotype associations (by increasing the efficiency of genetic association studies, thereby allowing bespoke phenotyping in relatively small cohorts), (2) the effects of environmental exposures (within the Mendelian randomization framework), and (3) gene-treatment interactions (within the setting of GBR interventional trials). In this review, we overview the literature on GBR studies as applied to cardiometabolic health outcomes. We also review the GBR approaches used to date and outline new methods and study designs that might enhance the utility of GBR-focused studies. Specifically, we highlight how GBR methods have the potential to augment randomized controlled trials, providing an alternative application for the now increasingly accepted Mendelian randomization methods usually applied to large-scale population-based data sets. Further to this, we consider how functional and basic science approaches alongside GBR designs offer intellectually intriguing and potentially powerful ways to explore the implications of alterations to specific (and potentially druggable) biological pathways.
Topics: Biological Specimen Banks; Cardiovascular Diseases; Genetic Association Studies; Genotype; Heterozygote; Humans; Metabolic Diseases; Multifactorial Inheritance; Patient Selection; Pharmacogenomic Testing; Randomized Controlled Trials as Topic; Research Design
PubMed: 30354344
DOI: 10.1161/CIRCGEN.118.001947 -
The American Journal of Managed Care Jun 2015To describe the lifetime outcomes and economic implications of combinatorial pharmacogenomic (CPGx) testing versus treatment as usual (TAU) psychopharmacologic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To describe the lifetime outcomes and economic implications of combinatorial pharmacogenomic (CPGx) testing versus treatment as usual (TAU) psychopharmacologic medication selection for a representative major depressive disorder patient who has not responded to previous treatment(s).
STUDY DESIGN
Markov state-transition analysis based on clinical studies.
METHODS
Clinical validity and utility were based on published findings in prospective clinical studies of a commercially available CPGx test. Data for quality of life, direct costs, and indirect costs were extracted from meta-analyses of published literature on clinical studies and claims databases. Outcomes were assessed from a societal perspective, and included differences between the CPGx and the TAU strategies in quality-adjusted life-years (QALYs), cumulative direct and indirect costs, and cost per QALY gained.
RESULTS
CPGx improved the treatment response rate by 70% (1.7 times as high as that with TAU), increasing QALYs by 0.316 years. With these health benefits, CPGx is expected to save $3711 in direct medical costs per patient and $2553 in work productivity costs per patient over the lifetime. The cost-effectiveness of CPGx testing was robust over a wide range of variation in the input parameters, including the scenario when testing efficacy was set to its lower limit.
CONCLUSIONS
CPGx testing has been shown by prospective studies to modify treatment decisions for patients nonresponsive to previous treatment(s), with increased rates of treatment response. These effects are projected to increase quality-adjusted survival, and to save both direct and indirect costs to individual patients and society generally.
Topics: Antidepressive Agents; Cost-Benefit Analysis; Depressive Disorder, Major; Drug Resistance; Humans; Pharmacogenomic Testing; Quality-Adjusted Life Years
PubMed: 26247576
DOI: No ID Found -
Current Protocols Jul 2021Cardiovascular pharmacogenomics is the study and identification of genomic markers that are associated with variability in cardiovascular drug response, cardiovascular...
Cardiovascular pharmacogenomics is the study and identification of genomic markers that are associated with variability in cardiovascular drug response, cardiovascular drug-related outcomes, or cardiovascular drug-related adverse events. This overview presents an introduction and historical background to cardiovascular pharmacogenomics, and a protocol for designing a cardiovascular pharmacogenomics study. Important considerations are also included for constructing a cardiovascular pharmacogenomics phenotype, designing the replication or validation strategy, common statistical approaches, and how to put the results in context with the cardiovascular drug or cardiovascular disease under investigation. © 2021 Wiley Periodicals LLC. Basic Protocol: Designing a cardiovascular pharmacogenomics study.
Topics: Cardiovascular Agents; Cardiovascular Diseases; Humans; Pharmacogenetics; Pharmacogenomic Testing; Phenotype
PubMed: 34232575
DOI: 10.1002/cpz1.189 -
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 -
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 -
International Journal of Molecular... Oct 2021Pharmacogenomic studies in epilepsy are justified by the high prevalence rate of this disease and the high cost of its treatment, frequent drug resistance, different... (Review)
Review
Pharmacogenomic studies in epilepsy are justified by the high prevalence rate of this disease and the high cost of its treatment, frequent drug resistance, different response to the drug, the possibility of using reliable methods to assess the control of seizures and side effects of antiepileptic drugs. Candidate genes encode proteins involved in pharmacokinetic processes (drug transporters, metabolizing enzymes), pharmacodynamic processes (receptors, ion channels, enzymes, regulatory proteins, secondary messengers) and drug hypersensitivity (immune factors). This article provides an overview of the literature on the influence of genetic factors on treatment in epilepsy.
Topics: ATP Binding Cassette Transporter, Subfamily B; Animals; Drug Resistance; Epilepsy; Humans; Inactivation, Metabolic; Pharmacogenomic Testing; Pharmacogenomic Variants
PubMed: 34769124
DOI: 10.3390/ijms222111696 -
Clinical and Experimental Rheumatology 2021Rheumatology medications are often associated with adverse drug reactions (ADRs) or inadequate response (IR). Pharmacogenomics may be a solution, but there is limited...
OBJECTIVES
Rheumatology medications are often associated with adverse drug reactions (ADRs) or inadequate response (IR). Pharmacogenomics may be a solution, but there is limited knowledge of its potential utility within rheumatology.
METHODS
We analysed medication changes and pharmacogenomically actionable prescriptions for all adult rheumatology outpatient encounters at our medical centre between 10/2012-12/2018. Three sources defined pharmacogenomic actionability: FDA labels, Clinical Pharmacogenetics Implementation Consortium guidelines, and our institutionally-deliverable pharmacogenomic clinical decision support (CDS) summaries. A subset of patients (validation cohort) had previously undergone broad, preemptive pharmacogenomic testing within other clinics but results were unavailable within rheumatology. We assessed the occurrence of specific pharmacogenomic ADRs/IRs in this group.
RESULTS
From 174,834 prescribing events, 6300/7761 patients (81%) had clinically actionable pharmacogenomic drug prescriptions (i.e. institutional CDS summaries would have been deployable if testing had been done). Using more conservative standards (pharmacogenomically actionable by ≥2 guidance bodies), 4158/7761 (54%) patient prescriptions could have been impacted. The greatest proportions of potentially impacted rheumatologic prescriptions were for tramadol (47%), allopurinol (21%), azathioprine (17%) and celecoxib (8%). Among our validation cohort (94 previously-genotyped patients), 29 (31%) patients had a pharmacogenomic genotype that would have cautioned possible ADRs/IRs for ≥1 medication. Four patients actually suffered ADRs/IRs that would have been predicted by preemptive genotyping.
CONCLUSIONS
Pharmacogenomic genotyping could inform prescribing for the majority of rheumatology patients and may prevent a subset of ADRs/IRs. These findings justify prospective evaluation of pharmacogenomic testing including assessment of cost-effectiveness in selected rheumatology populations to further understand impact on therapy-related toxicities and treatment outcomes.
Topics: Adult; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacogenetics; Pharmacogenomic Testing; Rheumatology
PubMed: 33506753
DOI: 10.55563/clinexprheumatol/e3hfts -
Pharmacogenomics Aug 2021The application of pharmacogenomics could meaningfully contribute toward medicines optimization within primary care. This review identified 13 studies describing eight... (Review)
Review
The application of pharmacogenomics could meaningfully contribute toward medicines optimization within primary care. This review identified 13 studies describing eight implementation models utilizing a multi-gene pharmacogenomic panel within a primary care or community setting. These were small feasibility studies (n <200). They demonstrated importance and feasibility of pre-test counseling, the role of the pharmacist, data integration into the electronic medical record and point-of-care clinical decision support systems (CDSS). Findings were considered alongside existing primary care prescribing practices and implementation frameworks to demonstrate how issues may be addressed by existing nationalized healthcare and primary care infrastructure. Development of point-of-care CDSS should be prioritized; establishing clinical leadership, education programs, defining practitioner roles and responsibilities and addressing commissioning issues will also be crucial.
Topics: Decision Support Systems, Clinical; Drug Prescriptions; Humans; Pharmacists; Pharmacogenetics; Pharmacogenomic Testing; Primary Health Care
PubMed: 34467776
DOI: 10.2217/pgs-2021-0032 -
Pharmacogenomics Jun 2019The appropriate use and integration of pharmacogenetic (PGx) testing will pivot on provider preparation and training. Pharmacists have been recognized as one of the key...
The appropriate use and integration of pharmacogenetic (PGx) testing will pivot on provider preparation and training. Pharmacists have been recognized as one of the key providers in the delivery of PGx testing and as such, professional organizations have recommended inclusion of PGx content in pharmacy curricula. We reviewed the curriculum of 132 US pharmacy schools for information about PGx courses. A total of 70 core curriculum courses were identified. 55 (42%) pharmacy schools included at least one PGx course as part of the core curriculum, and ten (8%) schools that offered a PGx course elective. While many pharmacy schools have responded to the accreditation standards to include PGx, less than half of the schools have developed a standalone course.
Topics: Curriculum; Education, Pharmacy; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Schools, Pharmacy; Students, Pharmacy; United States
PubMed: 31250728
DOI: 10.2217/pgs-2019-0024 -
Pharmacogenomics Feb 2022To evaluate the potential impact of preemptive multigene pharmacogenomic (PGx) testing on medication prescribing in real-world clinical settings. Prescription...
To evaluate the potential impact of preemptive multigene pharmacogenomic (PGx) testing on medication prescribing in real-world clinical settings. Prescription frequencies for 65 medications with actionable PGx recommendations were collected in 215 percutaneous coronary intervention (PCI) and 131 allogeneic hematopoietic cell transplant (allo-HCT) patients. A simulation projected the number of PGx-guided prescribing opportunities. In PCI and allo-HCT patients, respectively, 66.5 and 90.1% were prescribed at least one medication with actionable PGx prescribing recommendations. Simulations projected 26.5 and 41.2 total PGx-guided prescribing opportunities per 100 PCI and allo-HCT patients, respectively, if multigene PGx results were available. A multigene PGx testing strategy offers potential to optimize medication prescribing beyond clopidogrel and tacrolimus in PCI and allo-HCT patients.
Topics: Bone Marrow Transplantation; Clopidogrel; Drug Prescriptions; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Percutaneous Coronary Intervention; Pharmacogenomic Testing; Platelet Aggregation Inhibitors; Tacrolimus
PubMed: 35083934
DOI: 10.2217/pgs-2021-0125