Recommendations for Emerging Good Practice and Future Research in Relation to Family and Caregiver Health Spillovers in Health Economic Evaluations:A Report of the SHEER Task Force

BackgroundOmission of family and caregiver health spillovers from the economic evaluation of healthcare interventions remains common practice. When reported, a high degree of methodological inconsistency in incorporating spillovers has been observed.AimTo promote emerging good practice, this paper from the Spillovers in Health Economic Evaluation and Research (SHEER) task force aims to provide guidance on the incorporation of family and caregiver health spillovers in cost-effectiveness and cost-utility analysis. SHEER also seeks to inform the basis for a spillover research agenda and future practice.MethodsA modified nominal group technique was used to reach consensus on a set of recommendations, representative of the views of participating subject-matter experts. Through the structured discussions of the group, as well as on the basis of evidence identified during a review process, recommendations were proposed and voted upon, with voting being held over two rounds.ResultsThis report describes 11 consensus recommendations for emerging good practice. SHEER advocates for the incorporation of health spillovers into analyses conducted from a healthcare/health payer perspective, and more generally inclusive perspectives such as a societal perspective. Where possible, spillovers related to displaced/foregone activities should be considered, as should the distributional consequences of inclusion. Time horizons ought to be sufficient to capture all relevant impacts. Currently, the collection of primary spillover data is preferred and clear justification should be provided when using secondary data. Transparency and consistency when reporting on the incorporation of health spillovers are crucial. In addition, given that the evidence base relating to health spillovers remains limited and requires much development, 12 avenues for future research are proposed.ConclusionsConsideration of health spillovers in economic evaluations has been called for by researchers and policymakers alike. Accordingly, it is hoped that the consensus recommendations of SHEER will motivate more widespread incorporation of health spillovers into analyses. The developing nature of spillover research necessitates that this guidance be viewed as an initial roadmap, rather than a strict checklist. Moreover, there is a need for balance between consistency in approach, where valuable in a decision making context, and variation in application, to reflect differing decision maker perspectives and to support innovation

Dinutuximab beta for treating neuroblastoma: an evidence review group and decision support unit perspective of a NICE single technology appraisal

As part of its Single Technology Appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer (EUSA Pharma) of dinutuximab beta (Qarziba®) to submit evidence of its clinical and cost effectiveness for treating neuroblastoma. The BMJ Technology Assessment Group (BMJ-TAG) was commissioned to act as the Evidence Review Group (ERG), reviewing the submission from the company. The Decision Support Unit (DSU) was commissioned to review additional evidence submitted by the company and to undertake further analyses. This article presents the critical review of the company’s submissions by the ERG and DSU, further analyses undertaken by the DSU, and the outcome of the NICE guidance. The clinical effectiveness for dinutuximab beta was derived from a phase III randomised controlled trial (RCT) that assessed the safety and efficacy of the addition of interleukin (IL)-2 to dinutuximab beta plus isotretinoin. This trial did not inform the relative effectiveness of dinutuximab beta versus isotretinoin alone, which was established practice in the UK for maintenance treatment. In the absence of direct evidence, the company initially conducted a naïve indirect treatment comparison against a historical control, and later performed a matching-adjusted indirect comparison (MAIC) against the isotretinoin arm of an RCT comparing dinutuximab alpha and isotretinoin. The company submitted a partitioned survival analysis model that calculated the incremental cost effectiveness of dinutuximab beta versus isotretinoin. The company’s original incremental cost-effectiveness ratio (ICER) was £22,338 per quality-adjusted life-year (QALY) gained. However, the ERG were concerned that the company’s ICER was not suitable for decision making, and thus carried out initial exploratory analysis as a first step to overcome the naïve estimation of treatment effectiveness in the model. The ERG’s analysis estimated an ICER of £111,858 per QALY gained. In their revised analysis incorporating the MAIC and other changes as requested by the appraisal committee, the company’s ICER was £24,661 per QALY gained. When the DSU incorporated longer-term isotretinoin data and made corrections to the model, the ICER increased to between £62,886 and £87,164 per QALY gained depending on the choice of survival model. A confidential Patient Access Scheme (PAS) decreased the ICERs. The ICERs with the PAS were over £40,000 per QALY gained, but the NICE committee additionally considered the patient population and its size, the disease severity, the potential for significant survival benefit and uncaptured health benefits, and recommended dinutuximab beta as a treatment option, subject to the company providing the agreed discount in the PAS

Patient-reported utilities in advanced or metastatic melanoma, including analysis of utilities by time to death

Background: Health-related quality of life is often collected in clinical studies, and forms a cornerstone of economic evaluation. This study had two objectives, firstly to report and compare pre- and post-progression health state utilities in advanced melanoma when valued by different methods and secondly to explore the validity of progression-based health state utility modelling compared to modelling based upon time to death. Methods: Utilities were generated from the ipilimumab MDX010-20 trial (Clinicaltrials.gov Identifier: NCT00094653) using the condition-specific EORTC QLQ-C30 (via the EORTC-8D) and generic SF-36v2 (via the SF-6D) preference-based measures. Analyses by progression status and time to death were conducted on the patient-level data from the MDX010-20 trial using generalised estimating equations fitted in Stata®, and the predictive abilities of the two approaches compared. Results: Mean utility showed a decrease on disease progression in both the EORTC-8D (0.813 to 0.776) and the SF-6D (0.648 to 0.626). Whilst higher utilities were obtained using the EORTC-8D, the relative decrease in utility on progression was similar between measures. When analysed by time to death, both EORTC-8D and SF-6D showed a large decrease in utility in the 180 days prior to death (from 0.831 to 0.653 and from 0.667 to 0.544, respectively). Compared to progression status alone, the use of time to death gave similar or better estimates of the original data when used to predict patient utility in the MDX010-20 study. Including both progression status and time to death further improved model fit. Utilities seen in MDX010-20 were also broadly comparable with those seen in the literature. Conclusions: Patient-level utility data should be analysed prior to constructing economic models, as analysis solely by progression status may not capture all predictive factors of patient utility and time to death may, as death approaches, be as or more important. Additionally this study adds to the body of evidence showing that different scales lead to different health state values. Further research is needed on how different utility instruments (the SF-6D, EORTC-8D and EQ-5D) relate to each other in different disease areas

The Impact of Moving from EQ-5D-3L to -5L in NICE Technology Appraisals

Background: The EuroQol-5 Dimension (EQ-5D) instrument is the National Institute for Health and Care Excellence (NICE)’s preferred measure of health-related quality of life (QoL) in adults. The three-level (3L) value set is currently recommended for use, but the five-level (5L) set is increasingly being used in practice. Objective: We aimed to explore the impact of moving from 3L to 5L in NICE appraisals. Methods: We adapted our existing mapping for use with health state utility values derived from a population where the original distribution of utilities was unknown. We used this mapping to estimate 5L utilities for 21 comparisons of interventions from models used in NICE technology appraisal decision making, covering a range of disease areas. Results: All utilities increased using 5L, and the differences between highest and lowest utilities decreased. In ten oncology comparisons, using 5L generally increased the incremental quality-adjusted life-years (QALYs) as the benefit from improving survival increased. In four non-oncology comparisons where the intervention improved QoL only, the incremental QALYs decreased as the benefit of improving QoL was reduced. In seven non-oncology comparisons where interventions improved survival and QoL, there was a trade-off between increasing the benefit from survival and decreasing the benefit from improving QoL. Conclusion: 3L and 5L lead to substantially different estimates of incremental QALYs and cost effectiveness. The direction and magnitude of the change is not consistent across case studies. Using 5L instead of 3L may lead to different reimbursement decisions. NICE will face inconsistencies in decision making if it uses 3L and 5L concurrently

Inclusion of carer health-related quality of life in national institute for health and care excellence appraisals

Objectives Health interventions for patients can have effects on their carers too. For consistency, decision makers may wish to specify whether carer outcomes should be included. One example is the National Institute for Health and Care Excellence (NICE), whose reference case specifies that economic evaluations should include direct health effects for patients and carers where relevant. We aimed to review the methods used in including carer health-related quality of life (HRQL) in NICE appraisals. Methods We reviewed all published technology appraisals (TAs) and highly specialized technologies (HSTs) to identify those that included carer HRQL and discussed the methods and data sources. Results Twelve of 414 TAs (3%) and 4 of 8 HSTs (50%) included carer HRQL in cost-utility analyses. Eight were for multiple sclerosis, the remainder were each in a unique disease area. Twelve of the 16 appraisals modeled carer HRQL as a function of the patient’s health state, 3 modeled carer HRQL as a function of the patient’s treatment, and 1 included family quality-adjusted life year (QALY) loss. They used 5 source studies: 2 compared carer EQ-5D scores with controls, 2 measured carer utility only (1 health utilities index and 1 EQ-5D), and 1 estimated family QALY loss from a child’s death. Two used disutility estimates not from the literature. Including carer HRQL increased the incremental QALYs and decreased incremental cost-effectiveness ratios in all cases. Conclusions The inclusion of carer HRQL in NICE appraisals is relatively uncommon and has been limited by data availability

Evaluation of Intervention Impact on Health Inequality for Resource Allocation

Introduction. We describe a simplified distributional cost-effectiveness analysis based on aggregate data to estimate the health inequality impact of public health interventions. Methods. We extracted data on costs, health outcomes expressed as quality-adjusted life years (QALYs), and target populations for interventions within National Institute for Health and Care Excellence (NICE) public health guidance published up to October 2016. Evidence on variation by age, gender, and index of multiple deprivation informed socioeconomic distributions of incremental QALYs, health opportunity costs, and the baseline distribution of health. Total population QALYs, summary measures of inequality, and a health equity impact plane show results by intervention and by guideline. A value for inequality aversion from a general population survey in England let us combine impacts on health inequality and total health into a single measure of intervention value. Results. Our estimates suggest that of 134 interventions considered by NICE, 70 (52%) reduce inequality and increase health, 21 (16%) involve a tradeoff between improving health and improving health inequality, and 43 (32%) reduce health and increase health inequality. Fully implemented, the potential impact of all recommendations was 23,336,181 additional QALYs for the population of England and Wales and a reduction of the gap in quality-adjusted life expectancy between the healthiest and least healthy from 13.78 to 13.34 QALYs. The combined value of the additional health and reduction in inequality was 28,723,776 QALYs. Discussion. Our analysis takes account of the fact that existing public health spending likely benefits the most disadvantaged. This simple method applied separately to economic evaluation produces evidence of intervention impacts on the distribution of health that is vital in determining value for money when health inequality reduction is a policy goal

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

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. Keywords carer quality of lif