Cost-Effectiveness of Neoadjuvant Pembrolizumab plus Chemotherapy Followed by Adjuvant Pembrolizumab in Patients with High-Risk, Early-Stage, Triple-Negative Breast Cancer in Switzerland.

AIM: This study assessed the cost-effectiveness of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab versus neoadjuvant chemotherapy plus placebo followed by adjuvant placebo for patients with high-risk, early-stage, triple-negative breast cancer (TNBC) from a Swiss third-party payer perspective over a lifetime horizon (51 years). MATERIALS AND METHODS: A transition model with four health states (event-free, locoregional recurrence, distant metastasis, and death) was developed to assess the cost-effectiveness of pembrolizumab plus chemotherapy versus chemotherapy alone for the treatment of high-risk, early-stage TNBC. Data were utilized from the KEYNOTE-522 randomized controlled trial (ClinicalTrials.gov, NCT03036488). The incremental cost-effectiveness ratio (ICER) was calculated, which was reported as cost per life year or quality-adjusted life year (QALY) gained. A one-way deterministic sensitivity analysis, a probabilistic sensitivity analysis (PSA) and scenario analyses were conducted to assess the robustness of the model results. RESULTS: Base-case results estimated an ICER of 14,114 Swiss francs (CHF)/QALY for pembrolizumab plus chemotherapy versus chemotherapy alone. Results were most sensitive to changes in the extrapolation of event-free survival (EFS). All sensitivity and scenario analyses generated ICERs below the willingness-to-pay threshold of CHF100,000/QALY, and the PSA showed a 98.8% probability that the ICER would be below this threshold. LIMITATIONS: Due to the limited follow-up period in the KEYNOTE-522 trial, EFS data were extrapolated over the lifetime horizon to inform transition probabilities. Extensive validation and scenario analyses ensured the results were robust. CONCLUSION: The model demonstrated that neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab was cost-effective versus chemotherapy alone in patients with high-risk, early-stage TNBC in Switzerland.

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.

Cost-effectiveness of pembrolizumab as an adjuvant treatment for patients with resected stage IIB or IIC melanoma in Switzerland.

AIM: To assess the cost-effectiveness of adjuvant pembrolizumab versus observation for patients with resected stage IIB/IIC melanoma from a third-party payers' perspective in Switzerland over a lifetime horizon. MATERIALS AND METHODS: A Markov state transition model with four health states (recurrence-free [RF], locoregional recurrence, distant metastases [DM], and death) was developed to determine the cost-effectiveness of pembrolizumab versus observation as an adjuvant treatment in patients with stage IIB/IIC melanoma who have undergone complete resection. The model utilized data from the KEYNOTE-716 randomized controlled trial (ClinicalTrials.gov, NCT03553836). The incremental cost-effectiveness ratio (ICER) (Swiss Franc [CHF] per life year or quality-adjusted life years [QALYs] gained) was calculated. A probabilistic sensitivity analysis and deterministic sensitivity analysis were conducted to assess the robustness of the base case results. RESULTS: Model results demonstrated that pembrolizumab is highly cost-effective as an adjuvant treatment for resected stage IIB/IIC melanoma versus observation in Switzerland. Base case results showed an ICER of CHF 27,424/QALY (EUR 27,342/QALY; exchange rate: 1 CHF = 0.997 EUR) for pembrolizumab versus observation. Results were most sensitive to changes to transition probabilities from the RF state. Most sensitivity and scenario analyses resulted in ICERs below the willingness-to-pay threshold (WTP) of CHF 100,000. At this WTP, pembrolizumab had a 78.9% probability of being cost-effective versus observation. LIMITATIONS: Due to a limited follow-up period in the KEYNOTE-716 trial, data from other clinical trials in the advanced melanoma setting were synthesized in a network meta-analysis and used to inform transition probabilities from DM to death in the cost-effectiveness model, to overcome the absence of these data from the trial. CONCLUSION: The model demonstrated that pembrolizumab is highly cost-effective versus observation in patients with resected stage IIB/IIC melanoma in Switzerland. The ICER was below the WTP threshold of CHF 100,000, commonly used for cost-effectiveness models in Switzerland.

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 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.

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.

Systematic Review of Cost-Utility Analyses That Have Included Carer and Family Member Health-Related Quality of Life.

OBJECTIVES: Health interventions for patients can also affect the health of their informal carers and family members. These changes in carer or family member health could be reflected in cost-utility analyses (CUAs) through the inclusion of their quality-adjusted life-years (QALYs). We conducted a systematic review to identify and describe all CUAs that have included family member health-related QALYs. METHODS: A total of 4 bibliographic databases were searched from inception to July 2021. A 2-stage sifting process for inclusion of studies was undertaken. We performed data extraction using a standardized data extraction form and performed a narrative synthesis of the evidence. RESULTS: A total of 40 CUAs published between 1999 and 2021 were identified. CUAs were conducted in 15 different countries. CUAs examined 13 different conditions including 15 CUAs on vaccination, 5 on Alzheimer's disease, 2 on Parkinson's disease, 3 on dementia, and 2 on terminal illness. The EQ-5D was the most commonly used measure of family member health. Generally, including carer QALYs resulted in lower incremental cost-effectiveness ratios. CONCLUSIONS: When considering the total number of economic evaluations published, few have included family member QALYs and the methods for doing so are often inconsistent and data sources often limited. Estimation of family member QALYs in patient CUAs was regularly uncertain and often substantial in magnitude. The findings highlight the variation among methods and call for greater consistency in methods for incorporating family member QALYs in patient CUAs.

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.

Self-managed, computerised word finding therapy as an add-on to usual care for chronic aphasia post-stroke: An economic evaluation.

OBJECTIVE: To examine the cost-effectiveness of self-managed computerised word finding therapy as an add-on to usual care for people with aphasia post-stroke. DESIGN: Cost-effectiveness modelling over a life-time period, taking a UK National Health Service (NHS) and personal social service perspective. SETTING: Based on the Big CACTUS randomised controlled trial, conducted in 21 UK NHS speech and language therapy departments. PARTICIPANTS: Big CACTUS included 278 people with long-standing aphasia post-stroke. INTERVENTIONS: Computerised word finding therapy plus usual care; usual care alone; usual care plus attention control. MAIN MEASURES: Incremental cost-effectiveness ratios (ICER) were calculated, comparing the cost per quality adjusted life year (QALY) gained for each intervention. Credible intervals (CrI) for costs and QALYs, and probabilities of cost-effectiveness, were obtained using probabilistic sensitivity analysis. Subgroup and scenario analyses investigated cost-effectiveness in different subsets of the population, and the sensitivity of results to key model inputs. RESULTS: Adding computerised word finding therapy to usual care had an ICER of £42,686 per QALY gained compared with usual care alone (incremental QALY gain: 0.02 per patient (95% CrI: -0.05 to 0.10); incremental costs: £732.73 per patient (95% CrI: £674.23 to £798.05)). ICERs for subgroups with mild or moderate word finding difficulties were £22,371 and £21,262 per QALY gained respectively. CONCLUSION: Computerised word finding therapy represents a low cost add-on to usual care, but QALY gains and estimates of cost-effectiveness are uncertain. Computerised therapy is more likely to be cost-effective for people with mild or moderate, as opposed to severe, word finding difficulties.

Measurement properties of EQ-5D-3L and EQ-5D-5L in recording self-reported health status in older patients with substantial multimorbidity and polypharmacy.

BACKGROUND: The EQ-5D-3L and EQ-5D-5L are two generic health-related quality of life measures, which may be used in clinical and health economic research. They measure impairment in 5 aspects of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The aim of this study was to assess the performance of the EQ-5D-3L and EQ-5D-5L in measuring the self-reported health status of older patients with substantial multimorbidity and associated polypharmacy. METHODS: Between 2017 and 2019, we administered EQ-5D-3L and EQ-5D-5L to a subset of patients participating in the OPERAM trial at 6 months and 12 months after enrolment. The OPERAM trial is a two-arm multinational cluster randomised controlled trial of structured medication review assisted by a software-based decision support system versus usual pharmaceutical care, for older people (aged ≥ 70 years) with multimorbidity and polypharmacy. In the psychometric analyses, we only included participants who completed the measures in full at 6 and 12 months. We assessed whether responses to the measures were consistent by assessing the proportion of EQ-5D-5L responses, which were 2 or more levels away from that person's EQ-5D-3L response. We also compared the measures in terms of informativity, and discriminant validity and responsiveness relative to the Barthel Index, which measures independence in activities of daily living. RESULTS: 224 patients (mean age of 77 years; 56% male) were included in the psychometric analyses. Ceiling effects reported with the EQ-5D-5L (22%) were lower than with the EQ-5D-3L (29%). For the mobility item, the EQ-5D-5L demonstrated better informativity (Shannon's evenness index score of 0.86) than the EQ-5D-3L (Shannon's evenness index score of 0.69). Both the 3L and 5L versions of EQ-5D demonstrated good performance in terms of discriminant validity, i.e. (out of all items of the EQ-5D-3L and EQ-5D-5L, the pain/discomfort and anxiety/depression items had the weakest correlation with the Barthel Index. Both the 3L and 5L versions of EQ-5D demonstrated good responsiveness to changes in the Barthel Index. CONCLUSION: Both EQ-5D-3L and EQ-5D-5L demonstrated validity and responsiveness when administered to older adults with substantial multimorbidity and polypharmacy who were able to complete the measures.

Computerised speech and language therapy or attention control added to usual care for people with long-term post-stroke aphasia: the Big CACTUS three-arm RCT.

BACKGROUND: People with aphasia may improve their communication with speech and language therapy many months/years after stroke. However, NHS speech and language therapy reduces in availability over time post stroke. OBJECTIVE: This trial evaluated the clinical effectiveness and cost-effectiveness of self-managed computerised speech and language therapy to provide additional therapy. DESIGN: A pragmatic, superiority, single-blind, parallel-group, individually randomised (stratified block randomisation, stratified by word-finding severity and site) adjunct trial. SETTING: Twenty-one UK NHS speech and language therapy departments. PARTICIPANTS: People with post-stroke aphasia (diagnosed by a speech and language therapist) with long-standing (> 4 months) word-finding difficulties. INTERVENTIONS: The groups were (1) usual care; (2) daily self-managed computerised word-finding therapy tailored by speech and language therapists and supported by volunteers/speech and language therapy assistants for 6 months plus usual care (computerised speech and language therapy); and (3) activity/attention control (completion of puzzles and receipt of telephone calls from a researcher for 6 months) plus usual care. MAIN OUTCOME MEASURES: Co-primary outcomes - change in ability to find treated words of personal relevance in a bespoke naming test (impairment) and change in functional communication in conversation rated on the activity scale of the Therapy Outcome Measures (activity) 6 months after randomisation. A key secondary outcome was participant-rated perception of communication and quality of life using the Communication Outcomes After Stroke questionnaire at 6 months. Outcomes were assessed by speech and language therapists using standardised procedures. Cost-effectiveness was estimated using treatment costs and an accessible EuroQol-5 Dimensions, five-level version, measuring quality-adjusted life-years. RESULTS: A total of 818 patients were assessed for eligibility and 278 participants were randomised between October 2014 and August 2016. A total of 240 participants (86 usual care, 83 computerised speech and language therapy, 71 attention control) contributed to modified intention-to-treat analysis at 6 months. The mean improvements in word-finding were 1.1% (standard deviation 11.2%) for usual care, 16.4% (standard deviation 15.3%) for computerised speech and language therapy and 2.4% (standard deviation 8.8%) for attention control. Computerised speech and language therapy improved word-finding 16.2% more than usual care did (95% confidence interval 12.7% to 19.6%; p < 0.0001) and 14.4% more than attention control did (95% confidence interval 10.8% to 18.1%). Most of this effect was maintained at 12 months (n = 219); the mean differences in change in word-finding score were 12.7% (95% confidence interval 8.7% to 16.7%) higher in the computerised speech and language therapy group (n = 74) than in the usual-care group (n = 84) and 9.3% (95% confidence interval 4.8% to 13.7%) higher in the computerised speech and language therapy group than in the attention control group (n = 61). Computerised speech and language therapy did not show significant improvements on the Therapy Outcome Measures or Communication Outcomes After Stroke scale compared with usual care or attention control. Primary cost-effectiveness analysis estimated an incremental cost per participant of £732.73 (95% credible interval £674.23 to £798.05). The incremental quality-adjusted life-year gain was 0.017 for computerised speech and language therapy compared with usual care, but its direction was uncertain (95% credible interval -0.05 to 0.10), resulting in an incremental cost-effectiveness ratio of £42,686 per quality-adjusted life-year gained. For mild and moderate word-finding difficulty subgroups, incremental cost-effectiveness ratios were £22,371 and £28,898 per quality-adjusted life-year gained, respectively, for computerised speech and language therapy compared with usual care. LIMITATIONS: This trial excluded non-English-language speakers, the accessible EuroQol-5 Dimensions, five-level version, was not validated and the measurement of attention control fidelity was limited. CONCLUSIONS: Computerised speech and language therapy enabled additional self-managed speech and language therapy, contributing to significant improvement in finding personally relevant words (as specifically targeted by computerised speech and language therapy) long term post stroke. Gains did not lead to improvements in conversation or quality of life. Cost-effectiveness is uncertain owing to uncertainty around the quality-adjusted life-year gain, but computerised speech and language therapy may be more cost-effective for participants with mild and moderate word-finding difficulties. Exploring ways of helping people with aphasia to use new words in functional communication contexts is a priority. TRIAL REGISTRATION: Current Controlled Trials ISRCTN68798818. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 19. See the NIHR Journals Library website for further project information. The Tavistock Trust for Aphasia provided additional support to enable people in the control groups to experience the intervention after the trial had ended.

Aphasia is a communication disorder that can be caused by a stroke. It affects a person's understanding of spoken words and their talking, reading and writing abilities. Communication may improve months, or years, after a stroke with speech and language therapy. Many patients want more speech and language therapy than the NHS can provide. The Big CACTUS (clinical and cost-effectiveness of aphasia computer treatment versus usual stimulation or attention control long term post-stroke) trial evaluated the use of speech and language therapy software for people with aphasia to practise finding words independently at home on their own computer or one loaned by the NHS. People with aphasia who had had a stroke at least 4 months previously were randomly allocated to one of three groups: usual speech and language therapy caredaily use of computerised speech and language therapy for 6 months, tailored by a speech and language therapist and supported by a volunteer or speech and language therapy assistantdaily completion of puzzles and supportive telephone calls from a researcher to mimic the activity/attention the computerised speech and language therapy group received. All groups received usual speech and language therapy. A total of 278 people with aphasia took part in this trial, from 21 UK NHS speech and language therapy departments. They had their strokes between 4 months and 36 years previously. Computerised speech and language therapy enabled more practice (28 hours on average) than usual speech and language therapy (3.8 hours). The computerised speech and language therapy group significantly improved their ability to say words they chose to practise compared with those in the usual speech and language therapy or puzzle book groups. Although computerised speech and language therapy can help people with aphasia to learn new words for years after stroke, no improvements in conversation or quality of life were seen. The cost-effectiveness for the NHS is still uncertain. However, our best estimate is that it is unlikely to be cost-effective for everyone with aphasia, but it may be cost-effective for people with mild and moderate word-finding difficulties. Next steps will focus on how to encourage use of new words in conversation to have an impact on quality of life.

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 (FEV1). 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.

Cost effectiveness of pembrolizumab vs chemotherapy as first-line treatment for metastatic NSCLC that expresses high levels of PD-L1 in Switzerland.

AIM: The study aim was to evaluate the cost effectiveness of pembrolizumab monotherapy compared with chemotherapy as a first-line treatment for previously untreated metastatic non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50%, from a Swiss payer perspective. Cost effectiveness of pembrolizumab for this indication has not previously been evaluated in Switzerland. METHODS: We conducted an analysis using a partitioned survival model with a cycle length of one week, base-case time horizon of 20 years and discount rate of 3% for cost and health outcomes. KEYNOTE-024 randomised controlled trial data for pembrolizumab monotherapy compared with chemotherapy was used as a basis for projecting time-on-treatment, progression-free survival and overall survival, over a 20-year period. For overall survival and progression-free survival, we used Kaplan-Meier probabilities for a brief initial period of the model, followed by parametric curves that had the best fit with subsequent trial data. Quality-adjusted life years (QALYs) were calculated based on the EuroQol 5-dimensional 3-level (EQ-5D-3L) questionnaire administered to trial patients. Costs (in CHF, year 2018) of drug acquisition/administration, adverse events and disease management were included. RESULTS: For the base-case, pembrolizumab monotherapy resulted in mean incremental costs of CHF 77,060 (pembrolizumab CHF 223,324, chemotherapy CHF 146,264) and mean incremental QALYs of 1.34 (pembrolizumab 3.05, chemotherapy 1.71), leading to an incremental cost-effectiveness ratio of CHF 57,402 per QALY gained. Cost-effectiveness results were most sensitive to overall survival and relatively insensitive to other parameters varied. In probabilistic sensitivity analysis, the probability of cost effectiveness of pembrolizumab, with an assumption of a willingness-to-pay threshold of CHF 100,000 per QALY gained, was 88%. CONCLUSION: Pembrolizumab is likely to be cost effective for treating Swiss patients with previously untreated metastatic NSCLC expressing PD-L1 TPS ≥50%. (This economic evaluation was based on the KEYNOTE-024 trial. The trial identifier is NCT02142738.).

Economic evaluation of a novel genetic screening test for risk of venous thromboembolism compared with standard of care in women considering combined hormonal contraception in Switzerland.

AIM: The aim of this study was to assess the cost effectiveness of the Pill Protect (PP) genetic screening test for venous thromboembolism (VTE) risk compared with standard of care (SoC), for women considering combined hormonal contraceptives (CHCs) in Switzerland. METHODS: A two-part microsimulation model was developed to estimate VTE events, costs and quality-adjusted life years (QALYs) associated with the PP and SoC strategies. In the first portion of the model, a cohort of 1 million Swiss first-time seekers of a CHC were simulated. It was determined whether each women would receive a CHC or non-CHC by using prescribing patterns elicited from a modified Delphi study. These results formed the basis of the SoC strategy. For the PP strategy, a PP test was included and the results considered in addition to SoC practice. Each woman then entered a Markov model that captured morbidity and mortality over a lifetime. The risk of having a VTE was derived from the risk algorithm that underpins the PP test. The remaining model inputs relating to population characteristics, costs, health resource use, mortality and utilities were derived from published studies or national sources. The model was validated and calibrated to align with population-based studies. Extensive uncertainty analyses were conducted. RESULTS: From a Swiss health system perspective, the PP strategy in comparison with the SoC strategy generated an additional CHF 231, and gained 0.003 QALYs per woman, leading to an incremental cost-effectiveness ratio of CHF 76 610 per QALY gained. Assuming a threshold of CHF 100 000 per QALY gained, the PP strategy is likely to be cost effective. Our results were generally robust to variations in the parameter values. CONCLUSIONS: The PP test may be cost effective in Switzerland for screening women seeking CHCs for their risk of VTE based on the current evidence.

Incorporating Household Spillovers in Cost Utility Analysis: A Case Study Using Behavior Change in COPD.

OBJECTIVES: It is important to capture all health effects of interventions in cost-utility analyses conducted under a societal or healthcare perspective. However, this is rarely done. Household spillovers (health effects on patients' other household members) may be particularly likely in the context of technologies and interventions to change behaviors that are interdependent in the household. Our objective was to prospectively collect outcome data from household members and illustrate how these can be included in a cost-utility analysis of a behavior change intervention in chronic obstructive pulmonary disease (COPD). METHODS: Data were collected from patients' household members (n = 153) alongside a randomized controlled trial of a COPD self-management intervention. The impact of the intervention on household members' EQ-5D-5L scores (primary outcome), was evaluated. Analyses were then carried out to estimate household members' quality-adjusted life-years (QALYs) and assess the impact of including these QALYs on cost-effectiveness. RESULTS: The intervention had a negligible spillover on household members' EQ-5D-5L scores (-0.007; p = .75). There were also no statistically significant spillovers at the 5 percent level in household member secondary outcomes. In the base-case model, the inclusion of household member QALYs in the incremental cost-effectiveness ratio (ICER) denominator marginally increased the ICER from GBP 10,271 (EUR 13,146) to GBP 10,991 (EUR 14,068) per QALY gained. CONCLUSIONS: This study demonstrates it is feasible to prospectively collect and include household members' outcome data in cost utility analysis, although the study highlighted several methodological issues. In this case, the intervention did not impact significantly on household members' health or health behaviors, but inclusion of household spillovers may make a difference in other contexts.

Health economic modelling in Cystic Fibrosis: A systematic review.

INTRODUCTION: Cystic Fibrosis (CF) is a heritable chronic condition. Due to the genetic and progressive nature of CF, a number of interventions are available for the condition. In the United Kingdom (U.K.) average annual cost of CF treatment is between €49,000 to €76,000 (2012) per patient [1]. A review of health economic modelling studies is warranted to provide decision makers and researchers with an in depth understanding of modelling practices in CF and guidance for future research. METHODS: Online searches were performed in the 5 databases, studies were included if they were: a) Model based economic evaluation for management of Cystic Fibrosis. Articles were restricted to English language only, but no restriction was applied on publication year. RESULTS: Nine studies were reviewed, most were Markov cohort models. Models evaluated pharmaceutical interventions and drug adherence. Modelling structure was consistent across most articles and a range of sources were used to populate the models. Cost and utility data were based on different sources and elicitation methods respectively. The majority of models failed to incorporate significant health events which impact both cost and disease progression. CONCLUSION: In our review we observed a lack of, application of European Medicines Agency (EMA) guidelines for clinical trial endpoints, model structure justifications and lastly, health-related quality of life derived utility information around important clinical events. Future work around conceptual modelling of CF progression, utility valuation of significant health events and meeting EMA guidelines for trial reporting is encouraged.

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

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.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.