-
Pharmacogenomics Jan 2022Pharmacogenomic testing can indicate which drugs may have limited therapeutic action or lead to adverse effects, hence guiding rational and safe prescribing. However,... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic testing can indicate which drugs may have limited therapeutic action or lead to adverse effects, hence guiding rational and safe prescribing. However, in the UK and other countries, there are still significant barriers to implementation of testing in primary care. This systematic review presents the barriers and enablers to the implementation of pharmacogenomics in primary care setting. MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched through to July 2020 for studies that reported primary qualitative data of primary care professionals and patient views. Following screening, data extraction and quality assessment, data synthesis was undertaken using meta-aggregation based on the theoretical domain's framework (TDF). Confidence in the synthesized findings relating to credibility and dependability was established using CONQual. Eligible papers were categorized into six TDF domains - knowledge; social and professional roles; behavioral regulation; beliefs and consequences; environmental context and resources; and social influences. From 1669 citations, eighteen eligible studies were identified across seven countries, with a sample size of 504 participants including both primary care professionals and patients. From the data, 15 synthesized statements, all with moderate CONQual rating emerged. These categories range from knowledge, awareness among Primary Care Physicians and patients, professional relationships, negative impact of PGx, belief that PGx can reduce adverse drug reactions, clinical evidence, cost-effectiveness, informatics, reporting issues and social issues. Through use of TDF, fifteen synthesized statements provide policymakers with valuable recommendations for the implementation of pharmacogenomics in primary care. In preparation, policymakers need to consider the introduction of effective educational strategies for both PCPs and patients to raise knowledge, awareness, and engagement. The actual introduction of PGx will require reorganization with decision support tools to aid use of PGx in primary care, with a clear delegation of roles and responsibilities between general professionals and pharmacists supplemented by a local pool of experts. Furthermore, policy makers need to address the cost effectiveness of pharmacogenomics and having appropriate infrastructure supporting testing and interpretation including informatic solutions for utilizing pharmacogenomic results.
Topics: Health Services Accessibility; Humans; Pharmacogenomic Testing; Primary Health Care
PubMed: 34911350
DOI: 10.2217/pgs-2021-0131 -
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 -
Revista Brasileira de Psiquiatria (Sao... Apr 2020
Topics: Antidepressive Agents; Decision Support Techniques; Depressive Disorder; Humans; Pharmacogenomic Testing; Practice Guidelines as Topic; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 32187320
DOI: 10.1590/1516-4446-2019-0799 -
Medecine Sciences : M/S Dec 2019Therapeutic antibodies have been increasingly used for the treatment of various diseases, including cancers and chronic inflammatory diseases. The pharmacokinetic... (Review)
Review
Therapeutic antibodies have been increasingly used for the treatment of various diseases, including cancers and chronic inflammatory diseases. The pharmacokinetic interindividual variability of mAbs is large and influences, at least in part, the clinical response to antibody treatment. This variability is explained by a number of individual sources of variability, which are reviewed here. Some of them are major because they are frequently reported to greatly influence the interindividual variability; notably, increased body size, the presence of anti-drug antibodies, and high antigen mass are associated with decreased antibody concentrations. Other individual sources of variability are of less critical importance. They include sex, age, co-treatments, or genetic polymorphisms of IgG Fc receptors (FcgRs). The interindividual variability of antibody pharmacokinetics should be soundly described in order to design optimal dosing strategy.
Topics: Age Factors; Antibodies, Monoclonal; Biomarkers, Pharmacological; Comorbidity; Dose-Response Relationship, Immunologic; Female; Humans; Individuality; Male; Pharmacogenomic Testing; Polymorphism, Genetic; Precision Medicine; Sex Factors
PubMed: 31903927
DOI: 10.1051/medsci/2019210 -
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 -
Canadian Journal of Psychiatry. Revue... Jun 2023With increasing evidence for the clinical utility of pharmacogenomic (PGx) testing for depression, there is a growing need to consider issues related to the clinical...
OBJECTIVES
With increasing evidence for the clinical utility of pharmacogenomic (PGx) testing for depression, there is a growing need to consider issues related to the clinical implementation of this testing. The perspectives of key stakeholders (both people with lived experience [PWLE] and providers) are critical, but not frequently explored. The purpose of this study was to understand how PWLE and healthcare providers/policy experts (P/HCPs) perceive PGx testing for depression, to inform the consideration of clinical implementation within the healthcare system in British Columbia (BC), Canada.
METHODS
We recruited two cohorts of participants to complete individual 1-h, semi-structured interviews: (a) PWLE, recruited from patient and research engagement networks and organizations and (b) P/HCPs, recruited via targeted invitation. Interviews were audiotaped, transcribed verbatim, de-identified, and analysed using interpretive description.
RESULTS
Seventeen interviews were completed with PWLE (7 with experience of PGx testing for depression; 10 without); 15 interviews were completed with P/HCPs (family physicians, psychiatrists, nurses, pharmacists, genetic counsellors, medical geneticists, lab technologists, program directors, and insurers). Visual models of PWLE's and P/HCP's perceptions of and attitudes towards PGx testing were developed separately, but both were heavily influenced by participants' prior professional and/or personal experiences with depression and/or PGx testing. Both groups expressed a need for evidence and numerous considerations for the implementation of PGx testing in BC, including the requirement for conclusive economic analyses, patient and provider education, technological and clinical support, local testing facilities, and measures to ensure equitable access to testing.
CONCLUSIONS
While hopeful about the potential for therapeutic benefit from PGx testing, PWLE and P/HCPs see the need for robust evidence of utility, and BC-wide infrastructure and policies to ensure equitable and effective access to PGx testing. Further research into the accessibility, effectiveness, and cost-effectiveness of various implementation strategies is needed to inform PGx testing use in BC.
Topics: Humans; Pharmacogenomic Testing; Depressive Disorder, Major; Depression; Pharmacogenetics; British Columbia
PubMed: 36437757
DOI: 10.1177/07067437221140383 -
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