Cost-Effectiveness of Tepotinib Versus Capmatinib for the Treatment of Adult Patients With Metastatic Non-Small Cell Lung Cancer Harboring Mesenchymal-Epithelial Transition Exon 14 Skipping.

OBJECTIVES: From the US Medicare perspective, this study compared the cost-effectiveness of tepotinib and capmatinib for treating metastatic non-small cell lung cancer with tumors harboring mesenchymal-epithelial transition factor gene exon 14 skipping. METHODS: A 3-state partitioned survival model assessed outcomes over a lifetime horizon. Parametric survival analysis of the phase 2 VISION trial informed clinical inputs for tepotinib. Capmatinib inputs were captured using hazard ratios derived from an unanchored matching-adjusted indirect comparison study and published literature. National cost databases, trial data, and literature furnished drug, treatment monitoring, and disease/adverse event management expenditures (2021 US dollars) and utility inputs. Outcomes were discounted at 3% annually. RESULTS: In the base case, tepotinib dominated capmatinib in frontline settings (incremental discounted quality-adjusted life-years [QALYs] and costs of 0.2127 and -$47 756, respectively) while realizing an incremental cost-effectiveness ratio of $274 514/QALY in subsequent lines (incremental QALYs and costs of 0.3330 and $91 401, respectively). In a line agnostic context, tepotinib produced an incremental cost-effectiveness ratio of $105 383/QALY (incremental QALYs and costs of 0.2794 and $29 447, respectively). Sensitivity and scenarios analyses for individual lines typically supported the base case, whereas those for the line agnostic setting suggested sensitivity to drug acquisition costs and efficacy inputs. CONCLUSIONS: Tepotinib could be cost-effective versus capmatinib in frontline and line agnostic contexts, considering the range of willingness-to-pay thresholds recommended by the Institute for Clinical and Economic Review ($100 000-$150 000/QALY). Tepotinib could be cost-effective in subsequent lines at higher willingness-to-pay levels. These results are to be interpreted cautiously, considering uncertainty in key model inputs.

Belantamab mafodotin for the treatment of relapsed/refractory multiple myeloma in heavily pretreated patients: a US cost-effectiveness analysis.

BACKGROUND: Patients with relapsed/refractory multiple myeloma (RRMM) require several lines of therapy, with typically shorter remission duration with each additional line. RESEARCH DESIGN AND METHODS: The cost-effectiveness of belantamab mafodotin (belamaf; DREAMM-2; NCT03525678) was compared with selinexor plus dexamethasone (SEL+DEX; STORM Part 2; NCT02336815) among patients with RRMM who have received at least four prior therapies. The base case used a US commercial payer's perspective over a 10-year time horizon. Efficacy data were based on parametric survival analysis of DREAMM-2 and matching-adjusted indirect treatment comparison between DREAMM-2 and STORM Part 2, which assessed relative treatment effects between belamaf and SEL+DEX. Cost inputs included drug treatment, concomitant medications, adverse event management, subsequent treatments, and disease management. RESULTS: Belamaf decreased total treatment costs per patient by $14,267 and increased patient life years by 0.74 and quality-adjusted life years (QALYs) by 0.49 versus SEL+DEX. Patients receiving belamaf accrued 0.12 fewer progression-free life years versus patients on SEL+DEX. CONCLUSIONS: From a US commercial payer's perspective, belamaf had lower costs, and increased QALYs and life-year gain, compared with SEL+DEX. Belamaf is therefore likely to be a cost-effective treatment option for patients with RRMM who have received four or more prior lines of therapy.

Budget impact of tepotinib in the treatment of adult patients with metastatic non-small cell lung cancer harboring METex14 skipping alterations in the United States.

AIMS: To estimate the budget impact of adding tepotinib to United States (US) health plans for treating adult patients with metastatic non-small cell lung cancer (mNSCLC) harboring mesenchymal-epithelial transition exon 14 (METex14) skipping alterations. METHODS: The base-case analysis was conducted from the perspective of a hypothetical Medicare plan of 1 million members. Scenarios were analysed for other US health plans. Treatments included tepotinib, capmatinib, crizotinib, and standard of care (SoC). Patients eligible for tepotinib were estimated from published epidemiological data and literature, and real-world evidence. Clinical inputs were derived from the phase II VISION trial, US prescribing information, and published literature. Tepotinib uptake and projected testing rates for METex14 skipping alterations were based on market research. Unit costs (2020 US dollars (USD)) and resource utilization associated with drug acquisition and administration, treatment monitoring, disease and adverse event (AE) management, and subsequent treatment were derived primarily from public sources. RESULTS: In the base-case, 38-65 patients were eligible for tepotinib each year over the three-year time horizon. The cumulative net budgetary impact of tepotinib was -$692,541 (-2.6%); $26,531,670 in the scenario without tepotinib and $25,839,129 in the scenario with tepotinib. A negligible net budget impact was observed per member per month (PMPM) at $0.2457 and $0.2393, respectively, before and after tepotinib's introduction. Results were most sensitive to variability in unit costs of capmatinib and tepotinib and their corresponding median treatment durations. Sensitivity and scenario analyses support the conclusion that introducing tepotinib will have minimal budgetary impact for Medicare health plans. Similar results were obtained for other US health plans. LIMITATIONS: Assumptions and expert opinion were applied to address data gaps in key model inputs. CONCLUSIONS: The estimated budgetary impact of tepotinib for the treatment of adult patients with mNSCLC harboring METex14 skipping alterations is minimal from the perspective of US health plans.

Health Economic Analysis of Access Site Practice in England During Changes in Practice: Insights From the British Cardiovascular Interventional Society.

BACKGROUND: Transradial access (TRA) for percutaneous coronary intervention (PCI) is associated with a reduced risk of mortality compared with transfemoral access, access site-related bleeding complications, and shorter length of stay. The budget impact from a healthcare system that has largely transitioned to TRA for PCI has not been previously published. METHODS AND RESULTS: Data from 323 656 patients undergoing PCI between 2010 and 2014 were obtained from the British Cardiovascular Intervention Society database. Costs for TRA and transfemoral access PCI were estimated based on procedure cost, length of stay, and differences in the rates of complications (major bleeding and vascular complications). In the base case, a propensity-matched data set between transfemoral access and TRA was used to directly compare the cost per PCI, whereas in the real-world analysis, the full data set was used. Across all indications and all years, TRA offered an average cost saving of £250.59 per procedure (22% reduction) versus transfemoral access with the majority of cost saving derived from reduced length of stay (£190.43) rather than direct costs of complications (£3.71). In the real-world analysis, adoption of TRA was estimated to have provided cost savings of £13.31 million across England between 2010 and 2014; however, if operators in all regions had adopted TRA at the rate of the region with the highest utilization, cost savings of £33.40 million could have been achieved. CONCLUSIONS: The transition to TRA in England has been associated with significant cost savings across the national healthcare system, in addition to the well-established clinical benefits.

A cost-effectiveness analysis of condom distribution programmes for the prevention of sexually transmitted infections in England.

BACKGROUND: Prevention of sexually transmitted infection (STI) incidence in England is a high priority, particularly among young people, men who have sex with men (MSM) and black ethnic minorities. An economic evaluation of condom distribution programmes (CDPs) to reduce STI transmission is presented. METHODS: An economic model using a Bernoulli process estimated the number of people acquiring an STI as a function of its prevalence, transmission rate, condom use, condom failure rate and number of sexual contacts. Models were developed for young people (13-24 years), black ethnic minorities, MSM and the general English population. Effectiveness evidence came from a recent systematic review. For young people, a CDP was modelled (relative risk for condom use=1.23), along with an exploratory analysis of the impact on unintended pregnancies. For other populations, threshold analyses were used to identify the combination of costs and effect size required to make a programme cost-effective. RESULTS: The base case predicted that CDP for all young people in England could avert 5123 STI cases per annum, with an incremental cost-effectiveness ratio of £17 411. In addition, it could avert 118 pregnancies and 82 abortions and save £333 000 in associated costs. Schemes for black ethnic minorities and MSM could also be cost-effective even with relatively high costs and small effect sizes. CONCLUSION: CDPs for young people are likely to be cost-effective or cost-saving. CDPs for other high-risk populations may also be cost-effective if they can increase condom use, since high HIV prevalence in these groups imposes a considerable health and cost burden.

Constrained Optimization Methods in Health Services Research-An Introduction: Report 1 of the ISPOR Optimization Methods Emerging Good Practices Task Force.

Providing health services with the greatest possible value to patients and society given the constraints imposed by patient characteristics, health care system characteristics, budgets, and so forth relies heavily on the design of structures and processes. Such problems are complex and require a rigorous and systematic approach to identify the best solution. Constrained optimization is a set of methods designed to identify efficiently and systematically the best solution (the optimal solution) to a problem characterized by a number of potential solutions in the presence of identified constraints. This report identifies 1) key concepts and the main steps in building an optimization model; 2) the types of problems for which optimal solutions can be determined in real-world health applications; and 3) the appropriate optimization methods for these problems. We first present a simple graphical model based on the treatment of "regular" and "severe" patients, which maximizes the overall health benefit subject to time and budget constraints. We then relate it back to how optimization is relevant in health services research for addressing present day challenges. We also explain how these mathematical optimization methods relate to simulation methods, to standard health economic analysis techniques, and to the emergent fields of analytics and machine learning.

Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with disease-modifying antirheumatic drugs and after the failure of conventional disease-modifying antirheumatic drugs only: systematic review and economic evaluation.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increasing disability, reduced quality of life and substantial costs (as a result of both intervention acquisition and hospitalisation). The objective was to assess the clinical effectiveness and cost-effectiveness of seven biologic disease-modifying antirheumatic drugs (bDMARDs) compared with each other and conventional disease-modifying antirheumatic drugs (cDMARDs). The decision problem was divided into those patients who were cDMARD naive and those who were cDMARD experienced; whether a patient had severe or moderate to severe disease; and whether or not an individual could tolerate methotrexate (MTX). DATA SOURCES: The following databases were searched: MEDLINE from 1948 to July 2013; EMBASE from 1980 to July 2013; Cochrane Database of Systematic Reviews from 1996 to May 2013; Cochrane Central Register of Controlled Trials from 1898 to May 2013; Health Technology Assessment Database from 1995 to May 2013; Database of Abstracts of Reviews of Effects from 1995 to May 2013; Cumulative Index to Nursing and Allied Health Literature from 1982 to April 2013; and TOXLINE from 1840 to July 2013. Studies were eligible for inclusion if they evaluated the impact of a bDMARD used within licensed indications on an outcome of interest compared against an appropriate comparator in one of the stated population subgroups within a randomised controlled trial (RCT). Outcomes of interest included American College of Rheumatology (ACR) scores and European League Against Rheumatism (EULAR) response. Interrogation of Early Rheumatoid Arthritis Study (ERAS) data was undertaken to assess the Health Assessment Questionnaire (HAQ) progression while on cDMARDs. METHODS: Network meta-analyses (NMAs) were undertaken for patients who were cDMARD naive and for those who were cDMARD experienced. These were undertaken separately for EULAR and ACR data. Sensitivity analyses were undertaken to explore the impact of including RCTs with a small proportion of bDMARD experienced patients and where MTX exposure was deemed insufficient. A mathematical model was constructed to simulate the experiences of hypothetical patients. The model was based on EULAR response as this is commonly used in clinical practice in England. Observational databases, published literature and NMA results were used to populate the model. The outcome measure was cost per quality-adjusted life-year (QALY) gained. RESULTS: Sixty RCTs met the review inclusion criteria for clinical effectiveness, 38 of these trials provided ACR and/or EULAR response data for the NMA. Fourteen additional trials contributed data to sensitivity analyses. There was uncertainty in the relative effectiveness of the interventions. It was not clear whether or not formal ranking of interventions would result in clinically meaningful differences. Results from the analysis of ERAS data indicated that historical assumptions regarding HAQ progression had been pessimistic. The typical incremental cost per QALY of bDMARDs compared with cDMARDs alone for those with severe RA is > £40,000. This increases for those who cannot tolerate MTX (£50,000) and is > £60,000 per QALY when bDMARDs were used prior to cDMARDs. Values for individuals with moderate to severe RA were higher than those with severe RA. Results produced using EULAR and ACR data were similar. The key parameter that affected the results is the assumed HAQ progression while on cDMARDs. When historic assumptions were used typical incremental cost per QALY values fell to £38,000 for those with severe disease who could tolerate MTX. CONCLUSIONS: bDMARDs appear to have cost per QALY values greater than the thresholds stated by the National Institute for Health and Care Excellence for interventions to be cost-effective. Future research priorities include: the evaluation of the long-term HAQ trajectory while on cDMARDs; the relationship between HAQ direct medical costs; and whether or not bDMARDs could be stopped once a patient has achieved a stated target (e.g. remission). STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003386. FUNDING: The National Institute for Health Research Health Technology Assessment programme.