Cost Effectiveness and Budget Impact of Nivolumab Plus Ipilimumab Versus Platinum Plus Pemetrexed (with and Without Bevacizumab) in Patients with Unresectable Malignant Pleural Mesothelioma in Switzerland.

BACKGROUND Malignant pleural mesotheliomas (MPMs) are aggressive and often unresectable. In the past, chemotherapy was the standard for palliative treatment. However, immunotherapy with nivolumab+ipilimumab has recently received marketing approval. OBJECTIVES This study evaluated the cost effectiveness of nivolumab+ipilimumab versus pemetrexed+platinum (with/without bevacizumab) for Swiss patients with unresectable MPM, overall and by histological subtype. METHODS We developed a three-state Markov cohort model with a cycle length of 1 month, a 30-year time horizon, and a discount rate of 3% per year for costs and benefits. The model included the updated survival and treatment-dependent utility results from the Checkmate-743 and MAPS registration trials. A Swiss statutory health insurance perspective was considered with unit costs for 2022 from publicly available and real-world sources. We assumed a willingness-to-pay (WTP) threshold of CHF100,000/QALY. Model robustness was explored in sensitivity and scenario analyses. RESULTS Compared with chemotherapy, nivolumab+ipilimumab incurred additional costs of CHF109,115 and 0.57 additional quality-adjusted life-years (QALYs), yielding an incremental cost-effectiveness ratio (ICER) of CHF192,585/QALY (i.e. USD201,829/QALY) gained. Relative to their 2022 list price, nivolumab+ipilimumab may be cost effective if priced at 48% across all histologies. Assuming cisplatin-based instead of carboplatin-based chemotherapy reduced the ICER to CHF158,911/QALY (i.e. USD166,539/QALY). For the non-epithelioid subtype, nivolumab+ipilimumab was cost effective compared with chemotherapy (ICER of CHF97,894/QALY, i.e. USD102,593/QALY). Chemotherapy+bevacizumab was often a dominated strategy or would require a bevacizumab cost reduction to 28%. CONCLUSIONS Our model projected nivolumab+ipilimumab to be cost effective for the non-epithelioid subtype but not for all histologies. Substantial discounts for nivolumab+ipilimumab would be necessary to achieve cost effectiveness for all histologies

A Comparison of the Validity and Responsiveness of the EQ-5D-5L and SF-6D for Measuring Health Spillovers: A Study of the Family Impact of Meningitis

The “health spillover” of patient illness on family members is important to capture in economic evaluation. This study compares the construct validity and responsiveness of 2 widely used health-related quality-of-life instruments, the EQ-5D-5L and SF-6D, in capturing health spillover effects for family members with and without an informal care role (carers and noncarers). Construct validity and responsiveness were assessed using data from a 2012 UK survey of the family impact of meningitis-related sequelae. Construct validity was assessed by testing associations between family members’ health status and variables anticipated to be associated with spillover effects (patient health status and informal care). Responsiveness was assessed by testing associations between the longitudinal change in family members’ health status and longitudinal change in patient health and caring hours. Among noncarers, both the EQ-5D-5L and the SF-6D exhibited construct validity with 10 of the 11 associations that were hypothesized being statistically significant on both measures. There was less clear evidence of responsiveness of the measures for noncarers. Among carers, the EQ-5D-5L exhibited greater construct validity, as well as responsiveness, with respect to spillovers from patient health. This was evidenced by the EQ-5D-5L detecting 9 significant associations compared with 4 on the SF-6D. However, the SF-6D exhibited greater construct validity with respect to spillovers generated from informal care provision (5 associations significant compared with 2 on the EQ-5D-5L). Both the EQ-5D-5L and the SF-6D exhibited a degree of validity that could justify their use as measures of health-related quality-of-life spillovers on family members in economic evaluation

Cost-effectiveness of voretigene neparvovec in the treatment of patients with inherited retinal disease with RPE65 mutation in Switzerland

Objective: We aimed to evaluate the cost-effectiveness of voretigene neparvovec (VN) compared with standard of care (SoC) for patients with inherited retinal disease (IRD) caused by a biallelic RPE65-mutation. VN is a live, non-replicating adeno-associated virus serotype 2 (AAV2). SoC is best supportive care provided to patients with visual impairment. Patients under SoC may experience progressive vision loss leading to complete blindness. Methods: We adapted a previously published Markov cohort model for IRD. An annual cycle length, life-long time horizon, discount rate of 3% for cost and health outcomes, and Swiss health system perspective were used. Data from a randomised controlled phase III trial of VN versus SoC (ClinicalTrials.gov: NCT00999609) were used to estimate transitions between health states in the first year, after which VN patients were assumed to remain for 39 subsequent years in the health state they were in at the end of the first year. After the 40th year for VN patients and 1st year for SoC patients, visual decline was modelled based on observational data on the natural progression of the disease. Quality-adjusted life years (QALYs) were calculated based on an external study which elicited clinicians' EQ-5D-5L-based utility estimates for IRD patients with a RPE65-mutation. Costs (Swiss Francs (CHF), year 2018-2019) included drug acquisition/ administration, adverse events, testing for sufficient viable retinal cells, and healthcare-related costs of blindness. Societal costs of blindness were added in a complementary analysis. Robustness of the model results were tested in sensitivity and scenario analyses. Results: For the base-case, VN resulted in incremental costs per patient of CHF 764'402 (VN: CHF 901'654, SoC: CHF 137'252), incremental blindness-free years of 7.67 (VN: 28.32, SoC: 20.65) and incremental QALYs of 6.73 (VN: 18.35, SoC: 11.62), leading to an incremental cost-effectiveness ratio of CHF 113'526 per QALY gained. In probabilistic sensitivity analysis, the cost-effectiveness of VN was better than CHF 100,000 per QALY gained in 41% of iterations. For the scenario analysis in which a societal perspective was adopted and for which a 50% work-related productivity loss from blindness was assumed, incremental costs of CHF 423,837 and an ICER of CHF 62'947 per QALY gained were produced. The scenario assuming VN treatment effect lasts for 20 years produced an ICER of CHF 156'171 per QALY gained, whereas assuming a life-long VN treatment effect resulted in an ICER of CHF 96'384 per QALY gained. Conclusion: The incremental cost-effectiveness ratio of VN compared to the SoC was estimated to be CHF 113'526 and CHF 62'947 per QALY gained, respectively, from a Swiss healthcare system, and societal perspective assuming a 50% productivity loss. Keywords: Cost effectiveness; Health Economics; Inherited retinal disease; RPE65; Switzerland; Voretigene neparvove

Cost Effectiveness and Budget Impact of Siponimod Compared to Interferon Beta-1a in the Treatment of Adult Patients with Secondary Progressive Multiple Sclerosis with Active Disease in Switzerland

OBJECTIVE The study aim was to evaluate the cost effectiveness and budget impact of siponimod compared to interferon beta-1a for adult patients with secondary progressive multiple sclerosis (SPMS) with active disease, from a Swiss health insurance perspective. METHODS We conducted an analysis using a Markov cohort model with a cycle length of 1 year, life-long time horizon, and discount rate of 3% for cost and health outcomes. We used a matching-adjusted indirect comparison to estimate clinical outcomes using data from the EXPAND randomised controlled trial of siponimod vs placebo and the Nordic SPMS randomised controlled trial of interferon beta-1a vs placebo as the basis for estimates of disability progression and relapse outcomes. We used 6-month confirmed disability progression results to estimate disability progression in the base-case analysis. We calculated quality-adjusted life-years (QALYs) based on an external study that administered the EQ-5D-3L questionnaire to European patients with multiple sclerosis. We included costs (Swiss Franc (CHF), year 2020) of drug acquisition/administration, adverse events and disease management. We also performed a budget impact analysis to estimate the cost over the first 3 years of introducing siponimod. RESULTS For the base case, siponimod resulted in mean incremental costs of CHF 84,901 (siponimod: CHF 567,838, interferon beta-1a: CHF 482,937) and mean incremental QALYs of 1.591 (siponimod: 7.495, interferon beta-1a: 5.905), leading to an incremental cost-effectiveness ratio of CHF 53,364 per QALY gained. In the probabilistic sensitivity analysis, the probability of the cost effectiveness of siponimod assuming a willingness-to-pay threshold of CHF 100,000 per QALY gained was 90%. Siponimod was projected to result in drug administration costs for siponimod of CHF 23,817,856 in the first 3 years after introduction, accompanied by large cost offsets in drug acquisition of other multiple sclerosis drugs. Considering drug administration, monitoring and adverse event management costs, it was estimated to result in additional healthcare costs in Switzerland of CHF 2,177,021. CONCLUSIONS In the base-case analysis, we found that siponimod may be cost effective for treating Swiss adult patients with SPMS with active disease. The results of the cost-effectiveness analyses are valid under the assumption that the efficacy of siponimod and the comparators on disability progression for the overall SPMS population would be the same in the active SPMS population. CLINICAL TRIAL IDENTIFIER NCT01665144. This economic evaluation was based on the EXPAND trial

Health state utility data in Cystic Fibrosis: A systematic review

Introduction: Cystic fibrosis (CF) is a life-limiting, hereditable condition, with the highest prevalence in Europe. CF treatments have led to improvements in clinical symptoms, disease management and decelerated disease progression. However, little is known about the health state utility (HSU) associated with CF disease states, adverse events, and changes in disease severity. Although HSU data have contributed to existing health economic modelling studies, a lack of such data have been highlighted. This systematic review aims to provide a summary of HSU-related research in CF and highlight related research gaps. Methods: Online searches were performed in six databases and studies in any of the following categories were included: (1) estimation of HSUs in CF; (2) mapping studies between patient-reported outcome measures (PROMs) and HSUs; (3) economic evaluations on the management of CF that report primary HSU data; and (4) any CF clinical trial that reported HSU as an outcome. Results: A total of 17 studies were reviewed, of which 12 provided HSU values for specific CF populations. The remaining five articles provided HSU data that were broken down by CF relevant health states, including lung transplantations, pulmonary exacerbation (PEx) events and forced expiratory volume in 1 s (FEV 1). Conclusion: Current HSU data in CF are limited and there is considerable scope for further research, both in providing HSU values for CF and in investigating methods for HSU elicitation/evaluation in CF populations

Healthcare Costs and Health-Related Quality of Life in Older Multimorbid Patients After Hospitalization.

OBJECTIVES We identified factors associated with healthcare costs and health-related quality of life (HRQoL) of multimorbid older adults with polypharmacy. METHODS Using data from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid older people) trial, we described the magnitude and composition of healthcare costs, and time trends of HRQoL, during 1-year after an acute-care hospitalization. We performed a cluster analysis to identify groups with different cost and HRQoL trends. Using multilevel models, we also identified factors associated with costs and HRQoL. RESULTS Two months after hospitalization monthly mean costs peaked (CHF 7'124) and HRQoL was highest (0.67). They both decreased thereafter. Age, falls, and comorbidities were associated with higher 1-year costs. Being female and housebound were negatively associated with HRQoL, while moderate alcohol consumption had a positive association. Being independent in daily activities was associated with lower costs and higher HRQoL. CONCLUSION Although only some identified potential influences on costs and HRQoL are modifiable, our observations support the importance of prevention before health deterioration in older people with multimorbid illness and associated polypharmacy

Cost-effectiveness of a structured medication review approach for multimorbid older adults: Within-trial analysis of the OPERAM study

BACKGROUND Inappropriate polypharmacy has been linked with adverse outcomes in older, multimorbid adults. OPERAM is a European cluster-randomized trial aimed at testing the effect of a structured pharmacotherapy optimization intervention on preventable drug-related hospital admissions in multimorbid adults with polypharmacy aged 70 years or older. Clinical results of the trial showed a pattern of reduced drug-related hospital admissions, but without statistical significance. In this study we assessed the cost-effectiveness of the pharmacotherapy optimisation intervention. METHODS We performed a pre-planned within-trial cost-effectiveness analysis (CEA) of the OPERAM intervention, from a healthcare system perspective. All data were collected within the trial apart from unit costs. QALYs were computed by applying the crosswalk German valuation algorithm to EQ-5D-5L-based quality of life data. Considering the clustered structure of the data and between-country heterogeneity, we applied Generalized Structural Equation Models (GSEMs) on a multiple imputed sample to estimate costs and QALYs. We also performed analyses by country and subgroup analyses by patient and morbidity characteristics. RESULTS Trial-wide, the intervention was numerically dominant, with a potential cost-saving of CHF 3'588 (95% confidence interval (CI): -7'716; 540) and gain of 0.025 QALYs (CI: -0.002; 0.052) per patient. Robustness analyses confirmed the validity of the GSEM model. Subgroup analyses suggested stronger effects in people at higher risk. CONCLUSION We observed a pattern towards dominance, potentially resulting from an accumulation of multiple small positive intervention effects. Our methodological approaches may inform other CEAs of multi-country, cluster-randomized trials facing presence of missing values and heterogeneity between centres/countries

The effects of educational curricula and training on LGBT specific health issues for healthcare students and professionals: a mixed-methods systematic review

Introduction: Poor access of lesbian, gay, bisexual and transgender (LGBT) people to healthcare providers with clinical and cultural competency contributes to health inequalities between heterosexual/cisgender and LGBT people. This systematic review assesses the effect of educational curricula and training for healthcare students and professionals on LGBT healthcare issues. Methods: Systematic review; the search terms, strategy and process as well as eligibility criteria were predefined and registered prospectively on PROSPERO. A systematic search of electronic databases was undertaken. Screening for eligible studies and data extraction were done in duplicate. All the eligible studies were assessed for risk of bias. The outcome of interest was a change in participants’ knowledge, attitude and or practice. Results: Out of 1171 papers identified, 16 publications reporting 15 studies were included in the review. Three were non-randomized controlled studies and 12 had a pre/post-design; two had qualitative components. Bias was reported in the selection of participants and confounding. Risk reported was moderate/mild. Most studies were from the USA, the topics revolved around key terms and terminology, stigma and discrimination, sexuality and sexual dysfunction, sexual history taking, LGBT-specific health and health disparities. Time allotted for training ranged from 1 to 42 hours, the involvement of LGBT people was minimal. The only intervention in sub-Saharan Africa focused exclusively on men who have sex with men. All the studies reported statistically significant improvement in knowledge, attitude and/or practice post-training. Two main themes were identified from the qualitative studies: the process of changing values and attitudes to be more LGBT inclusive, and the constraints to the application of new values in practice.Conclusions: Training of healthcare providers will provide information and improve skills of healthcare providers which may lead to improved quality of healthcare for LGBT people. This review reports short-term improvement in knowledge, attitudes and practice of healthcare students and professionals with regards to sexual and LGBT-specific healthcare. However, a unified conceptual model for training in-terms of duration, content and training methodology was lacking