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Objectives: To evaluate medical policy determinations for pharmacogenetic (PGx) testing for 65 clinically relevant drug-gene pairs and evidence cited to support determinations across major US health plans and laboratory benefit managers (LBMs)., Study Design: Landscape analysis of available PGx medical policies to determine coverage status of certain drug-gene pairs., Methods: PGx medical policies as of February 1, 2024, were ascertained through Policy Reporter for top national insurers, LBMs, and the Palmetto GBA Molecular Diagnostic Services (MolDX) Program, which determines whether a molecular diagnostic test is covered by Medicare. Data elements included date of last policy update, coverage status for each drug-gene pair, and evidence cited for or against coverage. A drug-gene pair was considered covered if the policy indicated that a PGx test was deemed medically necessary and/or meets coverage criteria., Results: Policies from 8 insurers, 3 LBMs, and MolDX were available and reviewed. MolDX covered all 65 individual drug-gene pairs, followed by Avalon Healthcare Solutions (n = 50) and UnitedHealthcare (n = 45); these 3 also covered multigene panels. Eight policies covered 10 or fewer drug-gene pairs. HLA-B*57:01 testing prior to abacavir initiation and HLA-B*15:02 testing prior to carbamazepine initiation were covered across all policies. Drug-gene pairs with Clinical Pharmacogenetics Implementation Consortium guidelines and/or included in the FDA's Table of Pharmacogenetic Associations Section 1 were more commonly covered. Society guidelines were the most frequently cited evidence (413 times), and cost-effectiveness studies were infrequently cited (43 times)., Conclusions: We found significant variability in medical policy determinations and evidence cited for clinically relevant PGx tests among major US health insurers and LBMs. A collaborative effort between payers and the PGx community to standardize evidence evaluation may lead to more consistent coverage and improve patient access to PGx tests meeting evidence requirements.

Background and Objective: Gene therapies for sickle cell disease (SCD) may offer meaningful benefits for patients and society. This study evaluated the cost-effectiveness of lovotibeglogene autotemcel (lovo-cel), a one-time gene therapy administered via autologous hematopoietic stem cell transplantation, compared with common care for patients in the United States (US) with SCD aged ≥ 12 years with ≥ 4 vaso-occlusive events (VOEs) in the past 24 months., Methods: We developed a patient-level simulation model accounting for lovo-cel and SCD-related events, complications, and mortality over a lifetime time horizon. The pivotal phase 1/2 HGB-206 clinical trial (NCT02140554) served as the basis for lovo-cel efficacy and safety. Cost, quality-of-life, and other clinical data were sourced from HGB-206 data and the literature. Analyses were conducted from US societal and third-party payer perspectives. Uncertainty was assessed through probabilistic sensitivity analysis and extensive scenario analyses., Results: Patients treated with lovo-cel were predicted to survive 23.84 years longer on average (standard deviation [SD], 12.80) versus common care (life expectancy, 62.24 versus 38.40 years), with associated discounted patient quality-adjusted life-year (QALY) gains of 10.20 (SD, 4.10) and direct costs avoided of $1,329,201 (SD, $1,346,446) per patient. Predicted societal benefits included discounted caregiver QALY losses avoided of 1.19 (SD, 1.38) and indirect costs avoided of $540,416 (SD, $262,353) per patient. Including lovo-cel costs ($3,282,009 [SD, $29,690] per patient) resulted in incremental cost-effectiveness ratios of $191,519 and $124,051 per QALY gained from third-party payer and societal perspectives, respectively. In scenario analyses, the predicted cost-effectiveness of lovo-cel also was sensitive to baseline age and VOE frequency and to the proportion of patients achieving and maintaining complete resolution of VOEs., Conclusions: Our analysis of lovo-cel gene therapy compared with common care for patients in the US with SCD with recurrent VOEs estimated meaningful improvements in survival, quality of life, and other clinical outcomes accompanied by increased overall costs for the health care system and for broader society. The predicted economic value of lovo-cel gene therapy was influenced by uncertainty in long-term clinical effects and by positive spillover effects on patient productivity and caregiver burden., (© 2024. The Author(s).)

Aims: CYP2C19-guided P2Y12 inhibitor selection can reduce cardiovascular (CV) events and bleeding in patients with acute coronary syndromes (ACSs) post-percutaneous coronary intervention (PCI). The 12-month cost-effectiveness of CYP2C19-guided P2Y12 inhibitor selection for Veterans post-ACS/PCI was evaluated from the Veterans Health Administration's (VHA) perspective., Methods and Results: Using average annualized PCI volumes and P2Y12 inhibitor use from VA data, a decision-analytic model simulated CYP2C19 testing vs. no testing outcomes in 2800 hypothetical Veterans receiving PY212 inhibitor for 12 months post-ACS/PCI (74% clopidogrel, 5% prasugrel, and 21% ticagrelor use at baseline without testing). CYP2C19 loss-of-function (LOF) carrier prevalence was 28%. Model inputs were from studies (bleeding/ischaemic events, CYP2C19-guided therapy effect, health state utilities, CYP2C19 LOF carrier prevalence) and VHA administrative data (costs of events, drugs, CYP2C19 testing; PCI volumes, and P2Y12 inhibitor prescriptions). The primary outcome was cost (2020 US${\$}$) per quality-adjusted life year (QALY) gained. Base-case scenarios, probabilistic sensitivity analyses, and scenario analyses were completed. CYP2C19-guided therapy resulted in 496 (24%) escalations (clopidogrel to prasugrel/ticagrelor) and 465 (65%) de-escalations (prasugrel/ticagrelor to clopidogrel). CYP2C19 testing averted 1 stroke, 27 myocardial infarctions, 8 CV-related deaths, and caused 3 bleeds. CYP2C19 testing (vs. no testing) was dominant in the base-case scenario (0.0027 QALYs gained, ${\$}$527 saved/person) and in 97.1% of simulations, making it cost-effective and high-value. In scenario analyses, de-escalation in conjunction with escalation is required for CYP2C19 testing to be cost-effective and high-value., Conclusion: In Veterans post-ACS/PCI, CYP2C19-guided P2Y12 inhibitor selection can improve CV outcomes and lower costs for the VHA within 12 months of implementation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Healthcare policy makers should ensure optimal patient access to medical nutrition (MN) as part of the management of nutrition-related disorders and conditions. Questions remain whether current healthcare policies reflect the clinical and economic benefits of MN. The objective of this article is to characterize coverage and reimbursement of MN, defined as food for special medical purposes/medical food for a diverse set of countries, including Australia, Belgium, Brazil, Canada, China, France, Germany, Hong Kong, Italy, Japan, The Netherlands, Singapore, Spain, United Kingdom, and United States., Methods: Data sources included published literature and online sources. ISPOR's Nutrition Economics Special Interest Group developed a data collection form to guide data extraction that included reimbursement coverage, years that reimbursement policies were established, and presence of a formal health technology assessment (HTA) for MN technologies., Results: Reimbursement coverage of MN technologies varied across the countries that were reviewed. All but 3 countries limited coverage to specific formulations of products, regardless of demonstrated clinical benefit. The year that reimbursement policies were established varied across countries (ranging from 1984 to 2017), and only 4 countries regularly update policies. France and Brazil are the only countries with a formal HTA process for MN technologies., Conclusions: Most countries have limited MN reimbursement, have not updated reimbursement policies, and lack HTA for MN technologies. These limitations may lead to suboptimal access to MN technologies where they are indicated to manage nutrition-related disorders and conditions, with the potential of negatively affecting patient and healthcare system outcomes., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: A cost-effectiveness analysis comparing comprehensive genomic profiling (CGP) of 10 oncogenes, targeted gene panel testing (TGPT) of 4 oncogenes, and no tumor profiling over the lifetime for patients with metastatic lung adenocarcinoma from the Centers for Medicare and Medicaid Services' perspective was conducted., Methods: A decision analytic model used 10 000 hypothetical Medicare beneficiaries with metastatic lung adenocarcinoma to simulate outcomes associated with CGP (ALK, BRAF, EGFR, ERBB2, MET, NTRK1, NTRK2, NTRK3, RET, ROS1), TGPT (ALK, BRAF, EGFR, ROS1), and no tumor profiling (no genes tested). First-line targeted cancer-directed therapies were assigned if actionable gene variants were detected; otherwise, nontargeted cancer-directed therapies were assigned. Model inputs were derived from randomized trials (progression-free survival, adverse events), the Veterans Health Administration and Medicare (drug costs), published studies (nondrug cancer-related management costs, health state utilities), and published databases (actionable variant prevalences). Costs (2019 US$) and quality-adjusted life-years (QALYs) were discounted at 3% per year. Probabilistic sensitivity analyses used 1000 Monte Carlo simulations., Results: No tumor profiling was the least costly/person ($122 613 vs $184 063 for TGPT and $188 425 for CGP) and yielded the least QALYs/person (0.53 vs 0.73 for TGPT and 0.74 for CGP). The costs per QALY gained and corresponding 95% confidence interval were $310 735 ($278 323-$347 952) for TGPT vs no tumor profiling and $445 545 ($322 297-$572 084) for CGP vs TGPT. All probabilistic sensitivity analysis simulations for both comparisons surpassed the willingness-to-pay threshold ($150 000 per QALY gained)., Conclusion: Compared with no tumor profiling in patients with metastatic lung adenocarcinoma, tumor profiling (TGPT, CGP) improves quality-adjusted survival but is not cost-effective., (Copyright © 2021 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: The first Plan-Do-Study-Act cycle for the Veterans Affairs Pharmacogenomic Testing for Veterans pharmacogenomic clinical testing program is described. Materials & methods: Surveys evaluating implementation resources and processes were distributed to implementation teams, providers, laboratory and health informatics staff. Survey responses were mapped to the Consolidated Framework for Implementation Research constructs to identify implementation barriers. The Expert Recommendation for Implementing Change strategies were used to address implementation barriers. Results: Survey response rate was 23-73% across personnel groups at six Veterans Affairs sites. Nine Consolidated Framework for Implementation Research constructs were most salient implementation barriers. Program revisions addressed these barriers using the Expert Recommendation for Implementing Change strategies related to three domains. Conclusion: Beyond providing free pharmacogenomic testing, additional implementation barriers need to be addressed for improved program uptake.

There is a well-validated association between SLCO1B1 (rs4149056) and statin-associated muscle symptoms (SAMS). Preemptive SLCO1B1 pharmacogenetic (PGx) testing may diminish the incidence of SAMS by identifying individuals with increased genetic risk before statin initiation. Despite its potential clinical application, the cost implications of SLCO1B1 testing are largely unknown. We conducted a cost-consequence analysis of preemptive SLCO1B1 testing (PGx+) versus usual care (PGx-) among Veteran patients enrolled in the Integrating Pharmacogenetics in Clinical Care (I-PICC) Study. The assessment was conducted using a health system perspective and 12-month time horizon. Incremental costs of SLCO1B1 testing and downstream medical care were estimated using data from the U.S. Department of Veterans Affairs' Managerial Cost Accounting System. A decision analytic model was also developed to model 1-month cost and SAMS-related outcomes in a hypothetical cohort of 10,000 Veteran patients, where all patients were initiated on simvastatin. Over 12 months, 13.5% of PGx+ (26/193) and 11.2% of PGx- (24/215) participants in the I-PICC Study were prescribed Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline-concordant statins (Δ2.9%, 95% CI -4.0% to 10.0%). Differences in mean per-patient costs for lipid therapy prescriptions, including statins, for PGx+ compared to PGx- participants were not statistically significant (Δ USD 9.53, 95% CI -0.86 to 22.80 USD). Differences in per-patient costs attributable to the intervention, including PGx testing, lipid-lowering prescriptions, SAMS, laboratory and imaging expenses, and primary care and cardiology services, were also non-significant (Δ- USD 1004, 95% CI -2684 to 1009 USD). In the hypothetical cohort, SLCO1B1 -informed statin therapy averted 109 myalgias and 3 myopathies at 1-month follow up. Fewer statin discontinuations (78 vs. 109) were also observed, but the SLCO1B1 testing strategy was 96 USD more costly per patient compared to no testing (124 vs. 28 USD). The implementation of SLCO1B1 testing resulted in small, non-significant increases in the proportion of patients receiving CPIC-concordant statin prescriptions within a real-world primary care context, diminished the incidence of SAMS, and reduced statin discontinuations in a hypothetical cohort of 10,000 patients. Despite these effects, SLCO1B1 testing administered as a standalone test did not result in lower per-patient health care costs at 1 month or over 1 year of treatment. The inclusion of SLCO1B1 , among other well-validated pharmacogenes, into preemptive panel-based testing strategies may provide a better balance of clinical benefit and cost.

The complexity of genomic medicine can be streamlined by implementing some form of clinical decision support (CDS) to guide clinicians in how to use and interpret personalized data; however, it is not yet clear which strategies are best suited for this purpose. In this study, we used implementation science to identify common strategies for applying provider-based CDS interventions across six genomic medicine clinical research projects funded by an NIH consortium. Each project's strategies were elicited via a structured survey derived from a typology of implementation strategies, the Expert Recommendations for Implementing Change (ERIC), and follow-up interviews guided by both implementation strategy reporting criteria and a planning framework, RE-AIM, to obtain more detail about implementation strategies and desired outcomes. We found that, on average, the three pharmacogenomics implementation projects used more strategies than the disease-focused projects. Overall, projects had four implementation strategies in common; however, operationalization of each differed in accordance with each study's implementation outcomes. These four common strategies may be important for precision medicine program implementation, and pharmacogenomics may require more integration into clinical care. Understanding how and why these strategies were successfully employed could be useful for others implementing genomic or precision medicine programs in different contexts.

Objective: To evaluate the cost-effectiveness of multigene testing (CYP2C19, SLCO1B1, CYP2C9, VKORC1) compared with single-gene testing (CYP2C19) and standard of care (no genotyping) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) from Medicare's perspective., Methods: A hybrid decision tree/Markov model was developed to simulate patients post-PCI for ACS requiring antiplatelet therapy (CYP2C19 to guide antiplatelet selection), statin therapy (SLCO1B1 to guide statin selection), and anticoagulant therapy in those that develop atrial fibrillation (CYP2C9/VKORC1 to guide warfarin dose) over 12 months, 24 months, and lifetime. The primary outcome was cost (2016 US dollar) per quality-adjusted life years (QALYs) gained. Costs and QALYs were discounted at 3% per year. Probabilistic sensitivity analysis (PSA) varied input parameters (event probabilities, prescription costs, event costs, health-state utilities) to estimate changes in the cost per QALY gained., Results: Base-case-discounted results indicated that the cost per QALY gained was $59 876, $33 512, and $3780 at 12 months, 24 months, and lifetime, respectively, for multigene testing compared with standard of care. Single-gene testing was dominated by multigene testing at all time horizons. PSA-discounted results indicated that, at the $50 000/QALY gained willingness-to-pay threshold, multigene testing had the highest probability of cost-effectiveness in the majority of simulations at 24 months (61%) and over the lifetime (81%)., Conclusions: On the basis of projected simulations, multigene testing for Medicare patients post-PCI for ACS has a higher probability of being cost-effective over 24 months and the lifetime compared with single-gene testing and standard of care and could help optimize medication prescribing to improve patient outcomes., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Aim: This study assesses the technical performance and cost of a targeted next-generation sequencing (NGS) multigene pharmacogenetic (PGx) test. Materials & methods: A genetic test was developed for 21 PGx genes using molecular inversion probes to generate library fragments for NGS. Performance of this test was assessed using 53 unique reference control cell lines from the Genetic Testing Reference Materials Coordination Program (GeT-RM). Results: 93.7% of variants were successfully called and the repeatability rate was 99.9%. Reference calls were available for 78.4% of diplotype calls resulting from PGx testing, and concordance for the test was 85.7%. Cost per sample was $32-$56. Conclusion: A targeted NGS assay using molecular inversion probe technology is able to characterize the pharmacogenome efficiently.

Competing Interests: Competing interests: None declared.

Aim: To determine the projected impact of a multigene pharmacogenetic (PGx) test on medication prescribing., Materials & Methods: A retrospective analysis was conducted with 122 cardiac catheterization laboratory patients undergoing angiography for eligibility of potential PGx-guided interventions that could have occurred if multigene PGx information was pre-emptively available at the time of the procedure. Medication data and presence of actionable at-risk genotypes were used to determine eligibility of a PGx intervention., Results: 20% of the study population (n = 24) would have qualified for at least one PGx-based medication intervention per US FDA or Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines within 6 months of their cardiac catheterization procedure. Commonly encountered gene-drug pairs for these interventions included: CYP2C19 for clopidogrel and antidepressants, CYP2D6 for antidepressants and codeine, SLCO1B1 for simvastatin, and VKORC1/CYP2C9 for warfarin., Conclusion: Pre-emptive use of a multigene PGx test in the cardiac catheterization laboratory offers potential to reduce adverse medication outcomes.

Currently, there is sufficient evidence for the use of pharmacogenetic information to optimize medication prescribing, but why has this information not been integrated into the drug prescribing process to improve patient care? A discussion about the major contributing factors that have limited the use of pharmacogenetic information in the drug prescribing process, the solutions to ensure widespread uptake, and a vision for the future of the pharmacogenetic field will be explored.

Aim: Determine whether using CYP2C19 genotype to optimize antiplatelet therapy selection is cost effective over the initial 30 days and 1-year following percutaneous coronary intervention., Materials & Methods: A cost-effectiveness analysis compared 30-day and 1-year outcomes and cost across three treatment strategies (universal clopidogrel, universal prasugrel, genotype-guided) in a hypothetical cohort., Results: Base-case scenario results at 30 days indicated that the incremental cost per major cardiovascular or bleeding event avoided for genotype-guided treatment was US$8525 and US$42,198 compared with universal clopidogrel and prasugrel, respectively. Probabilistic sensitivity analysis demonstrated that genotype-guided treatment was cost effective over 30 days and 1 year in 62 and 70% of simulations, respectively., Conclusion: Implementing a CYP2C19 genotype-guided approach to antiplatelet therapy could have a positive economic impact by preventing readmissions following percutaneous coronary intervention.

The incorporation of precision medicine into the clinical setting is becoming increasingly feasible with the availability of more affordable genetic sequencing technologies and successful genetic associations with phenotypes, especially in the pharmacogenomic field. Although substantial progress has been made to ensure successful uptake of pharmacogenomic testing in the clinical setting already, many challenges still remain for sustainable implementation. The importance of pharmacogenomic information in patient care, identifying key barriers, and proposed solutions for advancing pharmacogenomic implementation will be discussed., (Copyright © 2017 the American Physiological Society.)