Barriers to clinical adoption of pharmacogenomic testing in psychiatry: a critical analysis.
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ABSTRACT:
SUBMITTER: Virelli CR
PROVIDER: S-EPMC8492820 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The clinical adoption of psychiatric pharmacogenomic testing has taken place rapidly over the past 7 years. Initially, drug-metabolizing enzyme genes, such as the cytochrome P450 2D6 gene (CYP2D6), were identified. Genotyping the highly variable cytochrome P450 2D6 gene now provides clinicians with the opportunity to identify both poor metabolizers and ultrarapid metabolizers of 2D6 substrate medications. Subsequently, genes influencing the pharmacodynamic response of medications have been made available for clinical practice. Among the earliest "target genes" was the serotonin transporter gene (SLC6A4) which has variants that have been shown to influence the clinical response of patients of European ancestry when they are treated with selective serotonin reuptake inhibitors. Genotyping of some of the serotonin receptor genes is also available to guide clinical practice. The quantification of the clinical utility of pharmacogenomic testing is evolving, and ethical considerations for testing have been established. Given the increasingly clear cost-effectiveness of genotyping, it has recently been predicted that pharmacogenomic testing will routinely be ordered to guide the selection and dosing of psychotropic medications.
| S-EPMC3181940 | biostudies-literature
Project description:Pharmacogenomics can enhance patient care by enabling treatments tailored to genetic make-up and lowering risk of serious adverse events. As of June 2019, there are 132 pharmacogenomic dosing guidelines for 99 drugs and pharmacogenomic information is included in 309 medication labels. Recently, the technology for identifying individual-specific genetic variants (genotyping) has become more accessible. Next generation sequencing (NGS) is a cost-effective option for genotyping patients at many pharmacogenomic loci simultaneously, and guidelines for implementation of these data are available from organizations such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG). NGS and related technologies are increasing knowledge in the research sphere, yet rates of genomic literacy remain low, resulting in a widening gap in knowledge translation to the patient. Multidisciplinary teams-including physicians, nurses, genetic counsellors, and pharmacists-will need to combine their expertise to deliver optimal pharmacogenomically-informed care.
| S-EPMC6789586 | biostudies-literature
Project description:Introduction:Pharmacogenomic tests relevant to neuropsychiatric medications have been clinically available for more than a decade, but the utility of regular testing is still unknown. Tests available include both pharmacokinetic and pharmacodynamic targets. The potential practice benefits vary with each target. Methods:A 10-year literature review was completed utilizing the PubMed database to identify articles relating to the specific pharmacogenomic targets discussed. Further article selection was based on author review for clinical utility. Results:The clinical dosing guidance available for neuropsychiatric medications such as selective serotonin reuptake inhibitors and tricyclic antidepressants with varying genotypes is useful and has strong evidence to support testing, but it is limited to mainly pharmacokinetic application. Pharmacodynamic targets are gaining additional evidence with increased research, and although the mechanisms behind the potential interactions are scientifically sound, the bridge to clinical practice application is still lacking. Discussion:Although the benefits of decreasing adverse reactions and improving response time are appealing, clinicians may not utilize pharmacogenomic testing in routine practice due to several barriers. Further clinical guidance and studies are needed to support testing for other neuropsychiatric medications and targets.
| S-EPMC6125117 | biostudies-literature
Project description:Clinical research in high-income countries is increasingly demonstrating the cost- effectiveness of clinical pharmacogenetic (PGx) testing in reducing the incidence of adverse drug reactions and improving overall patient care. Medications are prescribed based on an individual's genotype (pharmacogenes), which underlies a specific phenotypic drug response. The advent of cost-effective high-throughput genotyping techniques coupled with the existence of Clinical Pharmacogenetics Implementation Consortium (CPIC) dosing guidelines for pharmacogenetic "actionable variants" have increased the clinical applicability of PGx testing. The implementation of clinical PGx testing in sub-Saharan African (SSA) countries can significantly improve health care delivery, considering the high incidence of communicable diseases, the increasing incidence of non-communicable diseases, and the high degree of genetic diversity in these populations. However, the implementation of PGx testing has been sluggish in SSA, prompting this review, the aim of which is to document the existing barriers. These include under-resourced clinical care logistics, a paucity of pharmacogenetics clinical trials, scientific and technical barriers to genotyping pharmacogene variants, and socio-cultural as well as ethical issues regarding health-care stakeholders, among other barriers. Investing in large-scale SSA PGx research and governance, establishing biobanks/bio-databases coupled with clinical electronic health systems, and encouraging the uptake of PGx knowledge by health-care stakeholders, will ensure the successful implementation of pharmacogenetically guided treatment in SSA.
| S-EPMC7560181 | biostudies-literature
Project description:ObjectivesImplementing new programs to support precision medicine in clinical settings is a complex endeavor. We describe challenges and potential solutions based on the Indiana GENomics Implementation: an Opportunity for the Underserved (INGenious) program at Eskenazi Health-one of six sites supported by the Implementing GeNomics In pracTicE network grant of the National Institutes of Health/National Human Genome Research Institute. INGenious is an implementation of a panel of genomic tests.MethodsWe conducted a descriptive case study of the implementation of this pharmacogenomics program, which has a wide scope (14 genes, 27 medications) and a diverse population (patients who often have multiple chronic illnesses, in a large urban safety-net hospital and its outpatient clinics).ChallengesWe placed the clinical pharmacogenomics implementation challenges into six categories: patient education and engagement in care decision making; clinician education and changes in standards of care; integration of technology into electronic health record systems; translational and implementation sciences in real-world clinical environments; regulatory and reimbursement considerations, and challenges in measuring outcomes. A cross-cutting theme was the need for careful attention to workflow. Our clinical setting, a safety-net health care system, presented some distinctive challenges. Patients often had multiple chronic illnesses and sometimes were taking more than one pharmacogenomics-relevant medication. Reaching patients for recruitment or follow-up was another challenge.ConclusionsNew, large-scale endeavors in health care are challenging. A description of the challenges that we encountered and the approaches that we adopted to address them may provide insights for those who implement and study innovations in other health care systems.
| S-EPMC7543044 | biostudies-literature
Project description:Pharmacogenomic testing may have clinical value in the treatment of patients with gastrointestinal malignancies such as colorectal and pancreatic cancer. These types of cancer are often treated with combination chemotherapy regimens. These regimens can lead to severe adverse effects in patients with diminished drug tolerability potentially due to certain genetic variants in the enzymes involved in the metabolism of the chemotherapies. Genetic variants resulting in decreased enzymatic activity of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and dihydropyrimidine dehydrogenase (DPD) are known to increase irinotecan and 5-fluorouracil-related toxicity, respectively. We report a case of a patient with pancreatic adenocarcinoma who was found to be not only homozygous for the UGT1A1?28 allele, but also heterozygous for a DPYD variant through pharmacogenomic testing. Potentially severe adverse effects were prevented in this patient's case by implementing preemptive dose reductions. On the basis of the significant implications of chemotherapy-related toxicity in this and other similar cases, we report on the clinical value of integrating pharmacogenomic testing into clinical practice to allow for preemptive and/or point-of-care dose reductions in patients potentially at risk for increased toxicity. This is even more important in an era where combinatorial triplet chemotherapies are increasingly being used.
| S-EPMC6249237 | biostudies-literature
Project description:AIMS:To investigate the longitudinal exposure of English primary care patients to pharmacogenomic drugs to inform design of pre-emptive testing. METHODS:Sixty-three drugs were identified with dosing guidelines based on variants of 19 pharmacogenes in the Pharmacogenomics Knowledgebase on 01 September 2018. Prescribing of these pharmacogenomic drugs between 1993 and 2017 was summarised for a sample of 648 141 English patients aged 50-99 years on 01 January 2013, registered with Clinical Practice Research Datalink practices during 2011-12. Exposure of patients to pharmacogenomic drugs retrospectively (2, 10, 20 y) and prospectively (5 y) was described. RESULTS:During 2011-12, 58% of patients were prescribed at least 1 pharmacogenomic drug, increasing to 80% over the previous 20 years. Multiple exposure was common, with 47% patients prescribed ?2 pharmacogenomic drugs and 7% prescribed ?5 pharmacogenomic drugs over the next 5 years. The likelihood of exposure to pharmacogenomic drugs increased with age, with 89% patients ?70 years prescribed at least 1 pharmacogenomic drug over the previous 20 years. Even among those aged 50-59 years, 71% were prescribed at least 1 pharmacogenomic drug over the previous 20 years. The pharmacogenomic drugs prescribed to the most patients were for pain relief, gastroprotection, psychiatric and cardiovascular conditions. Three pharmacogenes (CYP2D6, CYP2C19 and SLCO1B1) accounted for >95% pharmacogenomic drugs prescribed. CONCLUSIONS:In primary care patients, exposure to pharmacogenomic drugs is extremely common, multiplicitous and has commenced by relatively early adulthood. A small number of pharmacogenes account for the majority of drugs prescribed. These findings could inform design of pre-emptive pharmacogenomic testing for implementation in primary care.
| S-EPMC6955399 | biostudies-literature
Project description: Not available
| S-EPMC11204763 | biostudies-literature
Project description:BackgroundConventional clinical trials are essential for generating high-quality evidence by measuring the efficacy of interventions in rigorously controlled clinical environments. However, their execution can be expensive and time-consuming. In addition, clinical trials face several logistical challenges regarding the identification, recruitment, and retention of participants; consistent data collection during trials; and adequate patient follow-up. This might lead to inefficient resource utilization. In order to partially address the current problems with conventional clinical trials, there exists the need for innovations. One such innovation is the virtual clinical trial (VCT). VCTs allow for the collection and integration of diverse data from multiple information sources, such as electronic health records, clinical and demographic data, patient-reported outcomes, anthropometric and activity measurements, and data collected by digital biomarkers or (small) samples that participants can collect themselves. Although VCTs have the potential to provide substantial value to clinical research and patients because they can lower clinical trial costs, increase the volume of data collected from patients' daily environment, and reduce the burden of patient participation, so far VCT adoption is not commonplace.ObjectiveThis paper aims to better understand the barriers and facilitators to VCT adoption by determining the factors that influence individuals' considerations regarding VCTs from the perspective of various stakeholders.MethodsBased on online semistructured interviews, a qualitative study was conducted with pharmaceutical companies, food and health organizations, and an applied research organization in Europe. Data were thematically analyzed using Rogers' diffusion of innovation theory.ResultsA total of 16 individuals with interest and experience in VCTs were interviewed, including persons from pharmaceutical companies (n=6), food and health organizations (n=4), and a research organization (n=6). Key barriers included a potentially low degree of acceptance by regulatory authorities, technical issues (standardization, validation, and data storage), compliance and adherence, and lack of knowledge or comprehension regarding the opportunities VCTs have to offer. Involvement of regulators in development processes, stakeholder exposure to the results of pilot studies, and clear and simple instructions and assistance for patients were considered key facilitators.ConclusionsCollaboration among all stakeholders in VCT development is crucial to increase knowledge and awareness. Organizations should invest in accurate data collection technologies, and compliance of patients in VCTs needs to be ensured. Multicriteria decision analysis can help determine if a VCT is a preferred option by stakeholders. The findings of this study can be a good starting point to accelerate the development and widespread implementation of VCTs.
| S-EPMC8294122 | biostudies-literature
Project description:There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.
| S-EPMC4221931 | biostudies-literature