The 50 most-cited articles in Value in Health, 2019

OBJECTIVE: To derive a US-based value set for the EQ-5D-5L questionnaire using an international, standardized protocol developed by the EuroQol Group. METHODS: Respondents from the US adult population were quota-sampled on the basis of age, sex, ethnicity, and race. Trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete choice experiment (DCE) tasks using the EuroQol Valuation Technology software and routine quality control measures. Data were modeled using a Tobit model for cTTO data, a mixed logit model for DCE data, and a hybrid model that combined cTTO and DCE data. Model performance was compared on the basis of logical ordering of coefficients, statistical significance, parsimony, and theoretical considerations. RESULTS: Of 1134 respondents, 1062, 1099, and 1102 respondents provided useable cTTO, DCE, and cTTO or DCE responses, respectively, on the basis of quality control criteria and interviewer judgment. Respondent demographic characteristics and health status were similar to the 2015 US Census. The Tobit model was selected as the…

A standardized 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L) valuation protocol was first used in national studies in the period 2012 to 2013. A set of problems encountered in this initial wave of valuation studies led to the subsequent refinement of the valuation protocol. To clarify lessons learned and how the protocol was updated when moving from version 1.0 to the current version 2.1 and 2.0, this article will (1) present the challenges faced in EQ-5D-5L valuation since 2012 and how these were resolved and (2) describe in depth a set of new challenges that have become central in currently ongoing research on how EQ-5D-5L health states should be valued and modeled.

OBJECTIVES: Within health economic studies, it is often necessary to adjust costs obtained from different time periods for inflation. Nevertheless, many studies do not report the methods used for this in sufficient detail. In this article, we outline the principal methods used to adjust for inflation, with a focus on studies relating to healthcare interventions in low- and middle-income countries. We also discuss issues relating to converting local currencies to international dollars and US$ and adjusting cost data collected from other countries or previous studies. METHODS: We outlined the 3 main methods used to adjust for inflation for studies in these settings: exchanging the local currency to US$ or international dollars and then inflating using US inflation rates (method 1); inflating the local currency using local inflation rates and then exchanging to US$ or international dollars (method 2); splitting the costs into tradable and nontradable resources and using method 1 on the tradable resources and method 2 on the nontradable resources (method 3). RESULTS: In a hypothetical…

OBJECTIVE: Recent years have witnessed an increased interest in the use of multicriteria decision analysis (MCDA) to support health technology assessment (HTA) agencies for setting healthcare priorities. However, its implementation to date has been criticized for being "entirely mechanistic," ignoring opportunity costs, and not following best practice guidelines. This article provides guidance on the use of MCDA in this context. METHODS: The present study was based on a systematic review and consensus development. We developed a typology of MCDA studies and good implementation practice. We reviewed 36 studies over the period 1990 to 2018 on their compliance with good practice and developed recommendations. We reached consensus among authors over the course of several review rounds. RESULTS: We identified 3 MCDA study types: qualitative MCDA, quantitative MCDA, and MCDA with decision rules. The types perform differently in terms of quality, consistency, and transparency of recommendations on healthcare priorities. We advise HTA agencies to always include a deliberative component.…

OBJECTIVES: Interest in the measurement of health-related quality of life (HRQoL) in children and adolescents has been increasing, and appropriate instruments are required for this target group. This article focuses on the EQ-5D-Y instrument, presenting an overview of its characteristics, development, and current use, and includes a discussion of methodological and conceptual issues related to the valuation of child health and the development of an EQ-5D-Y value set. METHODS: This article brings together the experiences of the research team that developed and validated the EQ-5D-Y, supplemented by information derived from EQ-5D-Y study registrations on the EuroQol Group's website. RESULTS: EQ-5D-Y is a child-specific and age-appropriate measure of HRQoL. Study registration data show that the instrument's use has steadily increased since its first publication. It has been used in various types of studies and in different disease areas. Currently there is no value set for EQ-5D-Y, and so its use in cost-utility analysis (CUA) is limited. There are methodological and conceptual issues…

BACKGROUND: Lack of evidence about the external validity of discrete choice experiments (DCEs) is one of the barriers that inhibit greater use of DCEs in healthcare decision making. OBJECTIVES: To determine whether the number of alternatives in a DCE choice task should reflect the actual decision context, and how complex the choice model needs to be to be able to predict real-world healthcare choices. METHODS: Six DCEs were used, which varied in (1) medical condition (involving choices for influenza vaccination or colorectal cancer screening) and (2) the number of alternatives per choice task. For each medical condition, 1200 respondents were randomized to one of the DCE formats. The data were analyzed in a systematic way using random-utility-maximization choice processes. RESULTS: Irrespective of the number of alternatives per choice task, the choice for influenza vaccination and colorectal cancer screening was correctly predicted by DCE at an aggregate level, if scale and preference heterogeneity were taken into account. At an individual level, 3 alternatives per choice task and…

BACKGROUND: Despite increasing informal and formal use of unmet medical need (UMN) in drug development, regulation, and assessment, there is no insight into its definitions in use. This study aims to provide insight into the current definitions in use and to provide a starting point for a multi-stakeholder discussion on alignment. METHODS: A scoping and a gray literature review were performed to locate definitions of UMN in literature and on stakeholder websites. These definitions were categorized and then discussed among the multi-stakeholder author group via semistructured group discussions and open session workshops with a broader stakeholder audience. Issues with the formation of a common definition and mechanisms for use were discussed. RESULTS: The reviews yielded 16 definitions. Differences were evident, but all included 1 or more of the following elements: (adequacy of) available treatments (16 of 16: 100%), disease severity or burden (6 of 16: 38%), and patient population size (1 of 16: 6%). The stakeholder discussions led to a suggestion for a definition including the…

BACKGROUND: Research has been mainly focused on how to elicit patient preferences, with less attention on why patients form certain preferences. OBJECTIVES: To assess which psychological instruments are currently used and which psychological constructs are known to have an impact on patients' preferences and health-related decisions including the formation of preferences and preference heterogeneity. METHODS: A systematic database search was undertaken to identify relevant studies. From the selected studies, the following information was extracted: study objectives, study population, design, psychological dimensions investigated, and instruments used to measure psychological variables. RESULTS: Thirty-three studies were identified that described the association between a psychological construct, measured using a validated instrument, and patients' preferences or health-related decisions. We identified 33 psychological instruments and 18 constructs, and categorized the instruments into 5 groups, namely, motivational factors, cognitive factors, individual differences, emotion and…

The widespread adoption of the EuroQol 5-dimensional questionnaire (EQ-5D) has been important for the comparability, transparency, and consistency of economic evaluations for informing resource allocation in healthcare. The objectives of this article were to (1) critically assess whether the widespread adoption of the EQ-5D and its time trade-off-based value sets to inform economic evaluation is likely to continue and (2) speculate about how benefits may be measured and valued to inform economic evaluation in the future. Evidence supports the use of the EQ-5D in many areas of health, but there are notable gaps. Furthermore, there has been interest among some policy makers in measuring changes in well-being, and in using common outcomes across sectors. Possibilities for measuring well-being alongside health can be achieved through bolt-on dimensions or an entirely new measure capturing both health and well-being. Nevertheless, there are significant concerns about the logic of estimating a common utility function. The development of online valuation methods has had a major impact on…

BACKGROUND: Priority setting in healthcare can be guided by both efficiency and equity principles. The latter principle is often explicated in terms of disease severity and, for example, defined as absolute or proportional shortfall. These severity operationalizations do not explicitly consider patients' age, even though age may be inextricably related to severity and an equity-relevant characteristic. OBJECTIVE: This study examines the relative strength of societal preferences for severity and age for informing allocation decisions in healthcare. METHODS: We elicited preferences for severity and age in a representative sample of the public in The Netherlands (N = 1025) by applying choice tasks and person-trade-off tasks in a design in which severity levels and ages varied both separately and simultaneously between patient groups. We calculated person trade-off ratios and, in addition, applied ordinary least squares regression models to aid interpretation of the ratios when both severity and age varied. RESULTS: Respondents attached a higher weight (median of ratios: 2.46-3.50) to…

BACKGROUND: Pneumococcal diseases cause substantial mortality, morbidity, and economic burden. Evidence on data inputs for economic evaluations of interventions targeting pneumococcal disease is critical. OBJECTIVES: To summarize evidence on resource use, costs, health utilities, and cost-effectiveness for pneumococcal disease and associated interventions to inform future economic analyses. METHODS: We searched MEDLINE, Embase, Web of Science, CINAHL, PsycINFO, EconLit, and Cochrane databases for peer-reviewed studies in English on pneumococcal disease that reported health utilities using direct or indirect valuation methods, resource use, costs, or cost-effectiveness of intervention programs, and summarized the evidence descriptively. RESULTS: We included 383 studies: 9 reporting health utilities, 131 resource use, 160 economic costs of pneumococcal disease, 95 both resource use and costs, and 178 economic evaluations of pneumococcal intervention programs. Health state utility values ranged from 0 to 1 for both meningitis and otitis media and from 0.3 to 0.7 for both pneumonia and…

BACKGROUND: Health inequalities can be partially addressed through the range of treatments funded by health systems. Nevertheless, although health technology assessment agencies assess the overall balance of health benefits and costs, no quantitative assessment of health inequality impact is consistently undertaken. OBJECTIVES: To assess the inequality impact of technologies recommended under the NICE single technology appraisal process from 2012 to 2014 using an aggregate distributional cost-effectiveness framework. METHODS: Data on health benefits, costs, and patient populations were extracted from the NICE website. Benefits for each technology were distributed to social groups using the observed socioeconomic distribution of hospital utilization for the targeted disease. Inequality measures and estimates of cost-effectiveness were compared using the health inequality impact plane and combined using social welfare indices. RESULTS: Twenty-seven interventions were evaluated. Fourteen interventions were estimated to increase population health and reduce health inequality, 8 to…

BACKGROUND: Integrating patient preferences in Health Technology Assessment (HTA) is argued to improve uptake, adherence, and patient satisfaction. However, how to elicit and incorporate these preferences in HTA in a systematic and scientifically valid manner is subject to debate. OBJECTIVE: This article provides a systematic review of the challenges to integrating patient preferences in HTA that have been raised in the literature about patient preferences in HTA. METHODS: A systematic review of articles published between 2013 and 2017 addressing challenges to the integration of patient preferences in HTA was conducted in 7 databases. All issues with respect to the integration of patient preferences in HTA were extracted and divided into 5 categories: conceptual, normative, procedural, methodological, and practical issues. The issues were ranked according to how often they were mentioned. RESULTS: Of 2147 retrieved articles, 67 were included in the analysis. Thirty-seven unique research issues were identified. In the majority of the articles, methodological issues were posed (82%),…

OBJECTIVES: A new patient-reported outcome (PRO) instrument to measure fatigue symptoms and impacts in relapsing multiple sclerosis (RMS) was developed in a qualitative stage, followed by psychometric validation and migration from paper to an electronic format. METHODS: Adult patients with relapsing-remitting multiple sclerosis (RRMS) were interviewed to elicit fatigue-related symptoms and impacts. A draft questionnaire was debriefed in cognitive interviews with further RRMS patients, and revised. Content confirmation interviews were conducted with patients with progressive-relapsing multiple sclerosis (PRMS) and relapsing secondary-progressive multiple sclerosis (RSPMS). Psychometric analyses used data from adult patients with different RMS subtypes and matched non-RMS controls in a multicenter, observational study. After item reduction, the final instrument was migrated to a smartphone (eDiary) and usability was confirmed in interviews with additional adult RMS patients. RESULTS: The qualitative stage included 37 RRMS, 5 PRMS, and 5 RSPMS patients. Saturation of concepts was…

BACKGROUND: Many high cost treatments for advanced melanoma have become available in recent years. National health technology assessment agencies have raised concerns regarding uncertainty in their clinical and cost-effectiveness. OBJECTIVE: The aim of this systematic review is to identify economic evaluations of treatments for advanced melanoma and review model assumptions, outcomes, and quality as preparation for a health technology assessment. METHODS: A search of Embase, MEDLINE, EconLit, and the Cochrane Database was conducted. Only studies using decision-analytic models were included. Two authors independently completed full-text review and data extraction. RESULTS: Fifteen studies were identified. There were major differences in the structural assumptions underpinning the models. There was general agreement in study conclusions, although the predicted costs and quality-adjusted life years for each treatment varied. BRAF monotherapy (vemurafenib, dabrafenib) or BRAF/MEK combination therapy (BRAF monotherapy with cobimetinib or trametinib) has not been shown to be…

Objectives Type 2 diabetes mellitus (T2DM) and associated ailments are leading economic burdens to society. Sodium glucose cotransporter-2 (SGLT2) inhibitors are recent antidiabetic medications with beneficial clinical efficacy. This meta-analysis was conducted to quantitatively pool the incremental net benefit of SGLT2 inhibitors in T2DM patients who failed metformin monotherapy. Methods Relevant economic evaluation studies of T2DM patients were identified from PubMed, Scopus, ProQuest, the Cochrane Library, and the Tufts Cost-Effective Analysis Registry until June 2018. Studies were eligible if they studied T2DM patients who failed metformin monotherapy and assessed the cost-effectiveness/utility between SGLT2 inhibitors and other treatments. Details of the study characteristics, economic model inputs, costs, and outcomes were extracted. Risk of bias was assessed using the biases in economic studies (ECOBIAS) checklist. The incremental net benefit was calculated with monetary units adjusting for purchasing power parity for 2017 US dollars. This was then pooled across studies…

OBJECTIVE: To evaluate the cost-effectiveness of multigene testing (CYP2C19, SLCO1B1, CYP2C9, VKORC1) compared with single-gene testing (CYP2C19) and standard of care (no genotyping) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) from Medicare's perspective. METHODS: A hybrid decision tree/Markov model was developed to simulate patients post-PCI for ACS requiring antiplatelet therapy (CYP2C19 to guide antiplatelet selection), statin therapy (SLCO1B1 to guide statin selection), and anticoagulant therapy in those that develop atrial fibrillation (CYP2C9/VKORC1 to guide warfarin dose) over 12 months, 24 months, and lifetime. The primary outcome was cost (2016 US dollar) per quality-adjusted life years (QALYs) gained. Costs and QALYs were discounted at 3% per year. Probabilistic sensitivity analysis (PSA) varied input parameters (event probabilities, prescription costs, event costs, health-state utilities) to estimate changes in the cost per QALY gained. RESULTS: Base-case-discounted results indicated that the cost per QALY gained was $59…

OBJECTIVES: Universal healthcare coverage in low- and middle-income countries requires challenging resource allocation decisions. Health technology assessment is one important tool to support such decision making. The International Decision Support Initiative worked with the Ghanaian Ministry of Health to strengthen health technology assessment capacity building, identifying hypertension as a priority topic area for a relevant case study. METHODS: Based on guidance from a national technical working group of researchers and policy makers, an economic evaluation and budget impact analysis were undertaken for the main antihypertensive medicines used for uncomplicated, essential hypertension. The analysis aimed to address specific policy questions relevant to the National Health Insurance Scheme. RESULTS: The evaluation found that first-line management of essential hypertension with diuretics has an incremental cost per disability-adjusted life-year avoided of GH¢ 276 ($179 in 2017, 4% of gross national income per capita) compared with no treatment. Calcium channel blockers were more…

OBJECTIVES: To identify how monetary incentives affect influenza vaccination uptake rate using a randomized control experiment and to subsequently design an optimal incentive program in Singapore, a high-income country with a market-based healthcare system. METHODS: 4000 people aged ≥65 were randomly assigned to 4 treatment groups (1000 each) and were offered a monetary incentive (in shopping vouchers) if they chose to participate. The baseline group was invited to complete a questionnaire with incentives of 10 Singapore dollars (SGD; where 1 SGD ≈ 0.73 USD), whereas the other three groups were invited to complete the questionnaire and be vaccinated against influenza at their own cost of around 32 SGD, in return for incentives of 10, 20, or 30 SGD. RESULTS: Increasing the total incentive for vaccination and reporting from 10 to 20 SGD increased participation in vaccination from 4.5% to 7.5% (P < .001). Increasing the total incentive from 20 to 30 SGD increased the participation rate to 9.2%, but this was not statistically significantly different from a 20-SGD incentive. The group of…

OBJECTIVE: An adaptive design uses data collected as a clinical trial progresses to inform modifications to the trial. Hence, adaptive designs and health economics aim to facilitate efficient and accurate decision making. Nevertheless, it is unclear whether the methods are considered together in the design, analysis, and reporting of trials. This review aims to establish how health economic outcomes are used in the design, analysis, and reporting of adaptive designs. METHODS: Registered and published trials up to August 2016 with an adaptive design and health economic analysis were identified. The use of health economics in the design, analysis, and reporting was assessed. Summary statistics are presented and recommendations formed based on the research team's experiences and a practical interpretation of the results. RESULTS: Thirty-seven trials with an adaptive design and health economic analysis were identified. It was not clear whether the health economic analysis accounted for the adaptive design in 17/37 trials where this was thought necessary, nor whether health economic…