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CYP2C19 loss of function (LOF) carriers undergoing percutaneous coronary intervention (PCI) have an increased risk of ischemic events when treated with clopidogrel. PCI patients in TAILOR-PCI were randomized to clopidogrel or genotype-guided (GG) therapy in which LOF carriers received ticagrelor and non-carriers clopidogrel. Direct medical costs associated with a GG approach have not been described before. TAILOR-PCI participants for whom direct medical costs were available for the duration from the date of PCI to one-year post PCI were included. Primary cost estimates were obtained from the Mayo Clinic Cost Data Warehouse. There were no differences in direct medical costs between the GG and clopidogrel groups (mean $20,682 versus $19,747, p  = 0.11) however total costs were greater in the GG group (mean $21,245 versus $19,891, p  = 0.02) which was primarily driven by ticagrelor costs. In conclusion the increased expense of a GG strategy post PCI as compared to clopidogrel for all is primarily driven by the cost of ticagrelor.

IntroductionGenetic variations impact drug response, driving the need for personalised medicine through pre-emptive pharmacogenetic testing. However, the adoption of pre-emptive pharmacogenetic testing for commonly prescribed drugs, such as statins, outside of tertiary hospitals is limited due to a lack of pharmacoeconomic evidence to support widespread implementation by healthcare policy-makers. The Spanish Consortium for the Implementation of Pharmacogenetics (iPHARMGx Consortium) addresses this by developing a clinical trial master protocol that will govern multiple nested adaptive clinical trials that compare genotype-guided treatments to standard care in specific drug–gene–population triads, asses their cost-efficacy and identify novel biomarkers through advanced sequencing techniques. The first of these studies aims to assess whether a pre-emptive statin therapy genotyping scheme reduces the incidence of statin-associated muscle symptoms (SAMS) in a population at risk of cardiovascular disease susceptible of receiving high-intensity or moderate-intensity doses of statins: The PREVESTATGx trial.Methods and analysisthe PREVESTATGX trial is a multicentre, adaptive randomised controlled pragmatic phase IV clinical trial nested to the iPHARMGx master protocol with two parallel arms, aiming for superiority. Randomisation will be conducted on an individual basis with a centralised approach and stratification by centre. After inclusion in the trial and genotyping has been performed, subjects will be randomly allocated to experimental group (pharmacogenetic genotype-guided statin prescription) or standard-of-care statin prescription (as deemed by attending physician). The main objective is to assess the efficacy of a statin pre-emptive genotyping strategy in reducing the incidence of SAMS. A total of 225 subjects will be recruited among the 10 participating centres if no futility/efficacy boundary is reached in the prespecified interim analyses. Recruitment will be carried out during a 12-month period and subjects will be followed for a 9-month period.Ethics and disseminationThe PREVESTATGx trial received ethical approval on 24 April 2024. Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. Trial results will be submitted for publication in an open-access peer-reviewed medical speciality-specific publication.Trial registration numberEU CT number: 2023-509418-12-00/Clinical trial Identifier (ClinicalTrials.gov): NCT06262685. Protocol version 1.2 12 April 2024 (includes non-substantial modification number 14 June 2024). Trial registration of this study can be located at both the EU Clinical Trials Register available from https:// euclinicaltrials.eu/search-for-clinical-trials/?lang=en and https://clinicaltrials.gov. Registration on both websites was done before the enrolment of the first patient complying with European regulations. EU Clinical Trials Register is a primary registry according to the WHO.

The University of Florida Health conducted a pragmatic implementation of a pharmacogenetics (PGx) panel‐based test to guide medications used for supportive care prescribed to patients undergoing chemotherapy. The implementation was in the context of a pragmatic clinical trial for patients with non‐hematologic cancers being treated with chemotherapy. Patients were randomized to either the intervention arm or control arm and received PGx testing immediately or at the end of the study, respectively. Patients completed the MD Anderson Symptom Inventory (MDASI) to assess quality of life (QoL). A total of 150 patients received PGx testing and enrolled in the study. Clinical decision support and implementation infrastructure were developed. While the study was originally planned for 500 patients, we were underpowered in our sample of 150 patients to test differences in the patient‐reported MDASI scores. We did observed a high completion rate (92%) of the questionnaires; however, there were few medication changes (n = 6 in the intervention arm) based on PGx test results. Despite this, we learned several lessons through this pragmatic implementation of a PGx panel‐based test in an outpatient oncology setting. Most notably, patients were less willing to undergo PGx testing if the cost of the test exceeded $100. In addition, to enhance PGx implementation success, reoccurring provider education is necessary, clinical decision support needs to appear in a more conducive way to fit in with oncologists' workflow, and PGx test results need to be available earlier in treatment planning.

We aimed to assess the cost-effectiveness of pharmacogenetic-guided dosing of warfarin in patients with atrial fibrillation (AF) in the United Kingdom and Sweden. Data from EU-PACT, a randomized controlled trial in newly diagnosed AF patients, were used to model the incremental costs per quality-adjusted life-year (QALY) gained by pharmacogenetic-guided warfarin dosing versus standard treatment over a lifetime horizon. Incremental lifetime costs were £26 and 382 Swedish kronor (SEK) and incremental QALYs were 0.0039 and 0.0015 in the United Kingdom and Sweden, respectively. The corresponding incremental cost-effectiveness ratios (ICERs) were £6 702 and 253 848 SEK per QALY gained. The ICER was below the willingness-to-pay threshold of £20 000 per QALY gained in 93% of the simulations in the United Kingdom and below 500 000 SEK in 67% of the simulations in Sweden. Our data suggest that pharmacogenetic-guided dosing of warfarin is a cost-effective strategy to improve outcomes of patients with AF treated with warfarin in the United Kingdom and in Sweden.

Preemptive pharmacogenetic testing aims to optimize medication use by having genetic information at the point of prescribing. Payers' decisions influence implementation of this technology. We investigated US payers' knowledge, awareness, and perspectives on preemptive pharmacogenetic testing. A qualitative study was conducted using semistructured interviews. Participants were screened for eligibility through an online survey. A blended inductive and deductive approach was used to analyze the transcripts. Two authors conducted an iterative reading process to code and categorize the data. Medical or pharmacy directors from 14 payer organizations covering 122 million US lives were interviewed. Three concept domains and ten dimensions were developed. Key findings include clinical utility concerns and limited exposure to preemptive germ-line testing, continued preference for outcomes from randomized controlled trials, interest in guideline development, importance of demonstrating an impact on clinical decision making, concerns of downstream costs and benefit predictability, and the impact of public stakeholders such as the Food and Drug Administration and Centers for Medicare and Medicaid Services. Both barriers and potential facilitators exist to developing cohesive reimbursement policy for pharmacogenetics, and there are unique challenges for the preemptive testing model. Prospective outcome studies, more precisely defining target populations, and predictive economic models are important considerations for future research.

Pharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene–drug associations have been discovered, but PGx-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health-care. We reviewed economic evaluations for PGx associations listed in the US Food and Drug Administration (FDA) Table of Pharmacogenomic Biomarkers in Drug Labeling. We determined the proportion of evaluations that found PGx-guided treatment to be cost-effective or dominant over the alternative strategies, and estimated the impact on this proportion of removing the cost of genetic testing. Of the 137 PGx associations in the FDA table, 44 economic evaluations, relating to 10 drugs, were identified. Of these evaluations, 57% drew conclusions in favour of PGx testing, of which 30% were cost-effective and 27% were dominant (cost-saving). If genetic information was freely available, 75% of economic evaluations would support PGx-guided treatment, of which 25% would be cost-effective and 50% would be dominant. Thus, PGx-guided treatment can be a cost-effective and even a cost-saving strategy. Having genetic information readily available in the clinical health record is a realistic future prospect, and would make more genetic tests economically worthwhile.

Purpose Although already a lot of research has been done on pharmacogenetic tests to inform the choice and/or dosing of medicines, the implementation and clinical uptake remain limited. This study assessed the implementation of pharmacogenetic (PGx) testing on a national scale by analyzing access to and volumes of reimbursed PGx. Methods The use of pharmacogenetic tests was examined via a cross-sectional online survey among the Belgian laboratories, collecting data on PGx targets, testing volumes and technologies used. The focus was on reimbursed tests. Additional data were sourced from the national reimbursement database to describe uptake of testing per medication. Results The uptake of PGx testing in Belgium varied by medication, with significant implementation for fluoropyrimidines, abacavir, and thiopurines. DPYD gene testing was the most frequently performed PGx test, due to endorsed (inter)national guidelines. Reimbursement rules shape access to PGx, with the majority of PGx tests performed in dedicated centers for human genetics (CHG). Access to HLA laboratories for HLA targets was not optimal and some laboratories without a CHG also included constitutional PGx targets in somatic oncology panels. Conclusion This nationwide study demonstrates that in a country where the prescribers have access to a relatively extensive list of reimbursable PGx tests, the implementation of PGx testing is shaped by the presence of endorsed evidence-based clinical practice guidelines, as well as organizational and logistical factors.

SUMMARYGenetic testing, including pharmacogenetic testing, is transforming personalized healthcare by improving risk assessment and treatment decisions. However, these advancements raise ethical, practical, and legal concerns for data privacy and security, as test results are often stored in EHRs. Additional concerns include the use of genetic data in underwriting for policies not covered under the federal Genetic Information Nondiscrimination Act of 2008, including life, disability, and long-term care insurance.These issues affect patients, consumers, and the broader healthcare system by increasing costs when patients delay testing or treatment out of fear of discrimination. They also strain public health programs when individuals are denied coverage because of genetic risks, leading to a \"genetic underclass,\" in which people with certain genetic predispositions are marginalized from the insurance market. Applying a bioethics framework of autonomy, beneficence, nonmaleficence, and justice allows these issues to be examined, and current protections to be evaluated for the purpose of instituting change.

Background Pharmacogenetics offers the potential to improve health outcomes by identifying individuals who are at greater risk of harm from certain medicines. Routine adoption of pharmacogenetic tests requires evidence of their cost effectiveness. Objective The present review aims to systematically review published economic evaluations of pharmacogenetic tests that aim to prevent or reduce the incidence of ADRs. Methods We conducted a systematic literature review of economic evaluations of pharmacogenetic tests aimed to reduce the incidence of adverse drug reactions. Literature was searched using Embase, MEDLINE and the NHS Economic Evaluation Database with search terms relating to pharmacogenetic testing, adverse drug reactions, economic evaluations and pharmaceuticals. Titles were screened independently by two reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts reviewed. Results We identified 852 articles, of which 47 met the inclusion criteria. There was evidence supporting the cost effectiveness of testing for HLA - B*57:01 (prior to abacavir), HLA - B*15:02 and HLA - A*31:01 (prior to carbamazepine), HLA - B*58:01 (prior to allopurinol) and CYP2C19 (prior to clopidogrel treatment). Economic evidence was inconclusive with respect to TPMT (prior to 6-mercaptoputine, azathioprine and cisplatin therapy), CYP2C9 and VKORC1 (to inform genotype-guided dosing of coumarin derivatives), MTHFR (prior to methotrexate treatment) and factor V Leiden testing (prior to oral contraception). Testing for A1555G is not cost effective before prescribing aminoglycosides. Conclusions Our systematic review identified robust evidence of the cost effectiveness of genotyping prior to treatment with a number of common drugs. However, further analyses and (or) availability of robust clinical evidence is necessary to make recommendations for others.

Evaluate the cost–effectiveness of combinatorial pharmacogenomic (PGx) testing, versus treatment as usual (TAU), to guide treatment for patients with depression, from the Canadian public healthcare system perspective. Clinical and economic data associated with depression were extracted from published literature. Clinical (quality-adjusted life years; QALYs) and economic (incremental cost–effectiveness ratio) outcomes were modeled using combinatorial PGx and TAU treatment strategies across a 5-year time horizon. With the combinatorial PGx strategy to guide treatment, patients were projected to gain 0.14–0.19 QALYs versus TAU. Accounting for test price, combinatorial PGx saved CAD $1,687–$3,056 versus TAU. Incremental cost–effectiveness ratios ranged from -$11,861 to -$16,124/QALY gained. Combinatorial PGx testing was more efficacious and less costly compared with the TAU for depression.