Characteristics Predicting Short-Term and Long-Term Health-Related Quality of Life in Patients with Esophageal Cancer After Neoadjuvant Chemoradiotherapy and Esophagectomy.

BACKGROUND: Esophagectomy is associated with lasting effect on health-related quality of life (HRQOL). Patients desire detailed information on the expected impact of treatment on their postoperative HRQOL. The aim of the present study is to identify clinicopathological characteristics predictive for changes in short-term and long-term HRQOL after neoadjuvant chemoradiotherapy (nCRT) and surgery. METHODS: HRQOL was measured using EORTC-QLQ-C30 and QLQ-OES24 questionnaires prior to nCRT, three, six, nine and twelve months postoperatively and at a minimum of six years postoperatively. Based on previous experience and available literature, several subgroups were predefined for different clinicopathological characteristics: baseline global HRQOL, WHO performance status, histology, tumor stage and tumor location. The primary endpoints of the present study were the change compared to baseline in the HRQOL dimensions physical functioning and eating problems. Secondary endpoints were global HRQOL, fatigue and emotional problems. RESULTS: In total, 134 (76%) of 177 patients who received HRQOL questionnaires, responded at baseline. Patients who reported a high baseline global HRQOL had a more severe deterioration in eating problems (+14.5 to + 18.0), global HRQOL (-16.0 to -28.0) and fatigue (+10.5 to +14.9) up to six years postoperatively compared to patients who reported a low baseline global HRQOL. Patients who had stage 2 tumor (UICC 6th edition) had a more severe deterioration in eating problems (+14.6 to +19.0) and global HRQOL (-10.1 to -17.1) than patients who had stage 3 tumor. CONCLUSIONS: The results suggest that patients with locally advanced esophageal cancer in favorable condition at baseline decline more in terms of various HRQOL outcomes.

Health state utilities for beta-thalassemia: a time trade-off study.

BACKGROUND: Beta-thalassemia (BT) is an inherited blood disorder characterized by reduced levels of functional hemoglobin resulting in phenotypes ranging from clinically asymptomatic to severely anemic. Patients with BT may require lifelong regular blood transfusions supported by appropriate iron chelation therapy (ICT). This study aimed to determine how the UK general population values BT health states associated with differing transfusion burden and ICT. METHODS: Composite time trade-off (cTTO) methodology was employed to elicit health state utilities in BT. Relevant BT literature related to symptom and quality-of-life impact, including physical, functional, and emotional well-being, and safety profiles of BT treatments were considered when drafting health state descriptions. Eleven health state descriptions were developed and validated by hematologists and patient advocates for clinical accuracy and completeness. 200 individuals from the UK general population participated in the cTTO interviews. RESULTS: The mean age of participants was 41.50 years (SD 16.01, range 18-81); 88 (46.8%) were female. Utility values ranged from 0.78 (SD 0.34) for non-transfusion dependent BT with oral ICT to 0.37 (SD 0.50) for high transfusion burden with subcutaneous ICT in transfusion-dependent BT. CONCLUSIONS: This study provides health utilities for a range of BT health states from the UK general population perspective. Importantly, lower transfusion burden and lower burden of anemia were associated with higher utilities. To a lesser extent, differential modes of ICT were found to impact utility valuations in patients with BT. The utilities obtained in this study can be employed as inputs in cost-effectiveness analyses of BT therapies.

Budget impact of introducing subcutaneous vedolizumab as a maintenance therapy in biologic-naïve and biologic-experienced patients with ulcerative colitis in France.

BACKGROUND: Inflammatory bowel disease poses significant social and economic burdens. We assessed the budget impact of including the recently approved subcutaneous (SC) formulation of vedolizumab as maintenance therapy (MT) in patients with ulcerative colitis (UC) in France. METHODS: A decision-analytic model was developed from a French payer's perspective over 5 years to assess budget impact of including vedolizumab SC as MT for UC following induction therapy with vedolizumab intravenous (IV), by subtracting outcomes of a 'world without vedolizumab SC' from a 'world with vedolizumab SC.' Comparators included approved therapies: infliximab (branded/biosimilar), adalimumab (branded/biosimilar), golimumab, ustekinumab, and vedolizumab IV. The model predicts drug, medical, and total costs, including indirect costs in a scenario analysis. A one-way sensitivity analysis explored the impact of varying individual parameters. RESULTS: Including vedolizumab SC as MT following vedolizumab IV induction yielded total cost savings of €59,176,842 (biologic-naïve) and €22,004,135 (biologic-experienced) versus a world without vedolizumab SC. Including indirect costs yielded cost savings in biologic-naïve (€62,600,716) and biologic-experienced (€24,314,915) populations in a world with vedolizumab SC. CONCLUSIONS: Introducing vedolizumab SC as MT after IV induction is expected to have substantial cost savings to a health plan from a French payer's perspective versus a world without vedolizumab SC.

Accounting for Unobservable Preference Heterogeneity and Evaluating Alternative Anchoring Approaches to Estimate Country-Specific EQ-5D-Y Value Sets: A Case Study Using Spanish Preference Data.

OBJECTIVES: The EuroQol Group published the EQ-5D-Y valuation protocol that recommends 2 valuation techniques to elicit preferences: composite time trade-off (C-TTO) and discrete choice experiments (DCEs). The protocol left the decision of what modeling approach to use open for researchers. Our aims were to explore modeling strategies allowing generation of EQ-5D-Y value sets and to produce an EQ-5D-Y Spanish value set. METHODS: We used EQ-5D-Y DCE and C-TTO data collected in Spain following the protocol and adopted a staged approach for our modeling exercise. First, we selected the best performing DCE latent class model and evaluated models from 2 to 10 classes. We selected the preferred model based on best goodness of fit in terms of the Bayesian information criterion. We considered 2 anchoring approaches to estimate utility values: (1) pits state anchoring and (2) hybrid models (using all available C-TTO responses). All analysis were weighted to be representative of the Spanish population. RESULTS: We collected 1005 DCE and 200 C-TTO interviews. We selected a DCE model including 4 classes. Hybrid models using all available C-TTO observations produced a narrower range of values than the pits state anchoring approach. CONCLUSIONS: In this article, we have presented an EQ-5D-Y value set that can be used for cost-utility analysis in Spain. The international EQ-5D-Y valuation protocol should be updated to include a different set of health states for the C-TTO experiment if researchers wish to use alternative anchoring approaches to the "pits state."

Cost Effectiveness of Subcutaneous Vedolizumab for Maintenance Treatment of Ulcerative Colitis in Canada.

BACKGROUND AND OBJECTIVES: Ulcerative colitis is highly prevalent in Canada and cost-effective ulcerative colitis therapies are warranted. Vedolizumab subcutaneous (SC) formulation was recently approved for ulcerative colitis maintenance therapy. We assessed vedolizumab SC cost effectiveness vs conventional and advanced therapeutics in patients with moderately to severely active ulcerative colitis from a Canadian public healthcare payer perspective. METHODS: A hybrid decision tree/Markov model was developed to evaluate vedolizumab SC costs, quality-adjusted life-years, and cost effectiveness vs conventional therapy, adalimumab SC, infliximab intravenous, golimumab SC, tofacitinib, ustekinumab SC, and vedolizumab intravenous. This model predicts the number of patients achieving clinical response and remission after treatment induction, and sustained benefit during maintenance treatment. To account for statistical uncertainties, the base-case analysis was conducted in a probabilistic manner. Scenario analyses examined the impact of previous treatment with anti-tumor necrosis factor agents, dose escalation, loss of efficacy, and treatment adherence. RESULTS: In the base-case analysis, conventional therapy was the most cost-effective therapeutic option in the overall population. Vedolizumab SC was cost effective and dominant compared with other advanced therapies (adalimumab, golimumab, infliximab, tofacitinib 5 mg, ustekinumab, and vedolizumab intravenous). The annual vedolizumab SC cost per patient was reduced vs ustekinumab SC, tofacitinib 5 mg, vedolizumab intravenous, and golimumab SC by $47,024, $3251, $2120, and $2004 (Canadian dollars), respectively, and exceeded that of infliximab, adalimumab, and conventional therapy by $582, $3293, and $41,024, respectively. Among the treatments, vedolizumab SC generated the highest quality-adjusted life-years overall (14.21), which translated into the best incremental cost per quality-adjusted life-years gained over conventional therapy in the overall population ($109,374) and in anti-tumor necrosis factor-naïve and anti-tumor necrosis factor-experienced patients ($41,658/$114,287). CONCLUSIONS: Conventional therapy offered the most cost-effective therapeutic option followed by vedolizumab SC. Based on a $50,000/quality-adjusted life-year threshold, vedolizumab was cost effective in anti-tumor necrosis factor-naïve patients but not the overall population also when compared to conventional therapy.

Does Changing the Age of a Child to be Considered in 3-Level Version of EQ-5D-Y Discrete Choice Experiment-Based Valuation Studies Affect Health Preferences?

OBJECTIVES: There has been some debate about the choice of perspective and the age of the child considered when completing preference elicitation tasks in the 3-level version of EQ-5D-Y (EQ-5D-Y-3L) valuation protocol. This study aimed to clarify the impact on latent scale EQ-5D-Y-3L values of varying the age of the child experiencing the health state considered by respondents completing the discrete choice experiment (DCE) tasks of the protocol. METHODS: We conducted an online DCE with a representative sample of 1000 adults in the United Kingdom and 1000 adults in the United States. Respondents selected the health state they prefer from a series of DCE paired EQ-5D-Y-3L health state comparisons using their own perspective and that of a hypothetical child from the following age groups: "5-7 years old," "8-10 years old," "11-13 years old," and "14-15 years old." Data analysis was conducted using separate multinomial logit models for each perspective and country. We also estimated combined models including data from each possible pair of perspectives and used interactions between EQ-5D-Y-3L levels and perspective to determine whether any differences were statistically significant. RESULTS: No statistically significant differences in coefficients between perspectives were found in the United States. In the United Kingdom, there were differences between the own perspective and the 5 to 7 years old perspective (looking after myself level 3) and between the 5 to 7 years old perspective and the 8 to 10 years old perspective (usual activities level 3). CONCLUSIONS: Our results suggest that there is minimal impact on latent scale values when using different ages of the hypothetical child in the current EQ-5D-Y-3L valuation protocol.

Exploring the Comparability of Face-to-Face Versus Video Conference-Based Composite Time Trade-Off Interviews: Insights from EQ-5D-Y-3L Valuation Studies in Belgium and Spain.

BACKGROUND: Face-to-face interviews are recommended for the collection of composite time trade-off (cTTO) data. The coronavirus disease 2019 (COVID-19) social distancing measures made researchers consider videoconferencing interviews as an alternative mode of administration, but little evidence about the implementation of videoconferencing in valuation studies is available. This study provides insights into the effect of videoconferencing on the quality of data, evaluating interviewers' and respondents' engagement level in videoconferences compared with face-to-face interviews. METHODS: We used cTTO data collected in Belgium and Spain following the EQ-5D-Y-3L valuation protocol. Due to the COVID-19 pandemic, both projects interrupted the face-to-face data collection before reaching the target sample. The remaining interviews were conducted by videoconference. We compared both modes of administration in terms of interviewers' engagement (task duration and number of moves in each example) and respondents' engagement (task duration and proportions of specific response values, in half-year units). To minimise interviewers' learning effects, we split our sample into three groups: (1) first 20 interviews conducted face-to-face; (2) subsequent interviews conducted face-to-face; and (3) videoconferencing interviews. RESULTS: The comparison between videoconferencing and subsequent face-to-face interviews showed the interviewer's engagement was not affected by the mode of administration as almost no significant results were found either in the task duration or the numbers of moves shown in the examples. Similarly, none of the respondents' task duration or proportion of specific responses or half-year units were affected by the mode of administration in either of the two countries. CONCLUSIONS: No evidence suggested that the quality of cTTO data is reduced when using videoconferencing compared with face-to-face interviews.

A dynamic Markov model to assess the cost-effectiveness of the Kidney Team at Home intervention in The Netherlands.

OBJECTIVES: The Kidney Team at Home program is an educational intervention aimed at patients with chronic kidney disease to assist them in their choice for kidney replacement therapy. Previous studies have shown that the intervention results in an increase in knowledge and communication on kidney replacement therapy, and eventually in an increase in the number of living donor kidney transplantations. The study assesses the cost-effectiveness of the intervention compared to standard care. METHODS: A dynamic probabilistic Markov model was used to estimate the monetary and health benefits of the intervention in The Netherlands over 10 years. Data on costs and health-related quality of life were derived from the literature. Transition probabilities, prevalence, and incidence rates were calculated using a large national database. An optimistic and a pessimistic implementation scenario were compared to a base case scenario with standard care. RESULTS: In both the optimistic and pessimistic scenario, the intervention is cost-effective and dominant compared to standard care: savings were €108,681,985 and €51,770,060 and the benefits were 1382 and 695 QALYs, respectively. CONCLUSIONS: The superior cost-effectiveness of the intervention is caused by the superior health effects and the reduction of costs associated with transplantation, and the relatively small incremental costs of the intervention. The favorable findings of this implementation project resulted in national uptake of the intervention in The Netherlands as of 2021. This is the first time a psychosocial intervention has been implemented as part of standard care in a kidney replacement therapy program worldwide.

To What Extent Do Patient Preferences Differ From General Population Preferences?

OBJECTIVES: In some countries including Germany, value sets based on general population preferences are not acceptable for decision-makers in healthcare because the impact of the reference group-general population versus patients-on utility decrements is questioned. The objective of this study was to explore potential differences in patient versus general population health preferences and a way of combining both preferences in economic evaluation. METHODS: EQ-5D-5L general population preferences were available from national value sets in Germany and Spain. Patient preferences were obtained by conducting discrete choice experiments with patients with rheumatism and patients with diabetes mellitus in Germany and Spain using an online panel. The econometric approach was based on the conditional logit framework. Latent values were anchored using the national value sets. RESULTS: A total of 1700 patients (Germany, n = 937; Spain, n = 763) were included in the analysis. In both countries, patients gave more importance to mobility, self-care, or usual activities and less importance to pain/discomfort and anxiety/depression than the general population. The size of these differences was larger in Germany than in Spain. In Germany, preferences reported by both patient groups were more similar than in Spain. CONCLUSION: Patient preferences differ from preferences derived from the general population. In contrast to the general population, patients gave more importance to the functional dimensions than to symptoms in both countries. The extent of the differences depends on the disease and the country. For countries preferring patient preferences, a possible way of incorporating the patient perspective in health state valuation was suggested and needs to be further explored.

Adapting preference-based utility measures to capture the impact of cancer treatment-related symptoms.

It is important that patient-reported outcome (PRO) measures used to assess cancer therapies adequately capture the benefits and risks experienced by patients, particularly when adverse event profiles differ across therapies. This study explores the case for augmenting preference-based utility measures to capture the impact of cancer treatment-related symptoms. Additional cancer treatment-related items could be specific (e.g., rash) or global. While specific items are easier to describe and understand, their use may miss rarer symptoms and those that are currently unknown but will arise from future medical advancements. The appropriate number of additional items, the independence of those items, and their impact on the psychometric properties of the core instrument require consideration. Alternatively, a global item could encompass all potential treatment-related symptoms, of any treatments for any disease. However, such an item may not be well understood by general public respondents in valuation exercises. Further challenges include the decision about whether to generate de novo value sets for the modified instrument or to map to existing tariffs. The fluctuating and transient nature of treatment-related symptoms may be inconsistent with the methods used in conventional valuation exercises. Fluctuating symptoms could be missed by sub-optimal measure administration timing. The addition of items also poses double-counting risks. In summary, the addition of treatment-related symptom items could increase the sensitivity of existing utility measures to capture known and unknown treatment effects in oncology, while retaining the core domains. However, more research is needed to investigate the challenges, particularly regarding valuation.

Cost-effectiveness of adding Sativex® spray to spasticity care in Belgium: using bootstrapping instead of Monte Carlo simulation for probabilistic sensitivity analyses.

BACKGROUND: Uncertainty in model-based cost-utility analyses is commonly assessed in a probabilistic sensitivity analysis. Model parameters are implemented as distributions and values are sampled from these distributions in a Monte Carlo simulation. Bootstrapping is an alternative method that requires fewer assumptions and incorporates correlations between model parameters. METHODS: A Markov model-based cost-utility analysis comparing oromucosal spray containing delta-9-tetrahidrocannabinol + cannabidiol (Sativex®, nabiximols) plus standard care versus standard spasticity care alone in the management of multiple sclerosis spasticity was performed over a 5-year time horizon from the Belgian healthcare payer perspective. The probabilistic sensitivity analysis was implemented using a bootstrap approach to ensure that the correlations present in the source clinical trial data were incorporated in the uncertainty estimates. RESULTS: Adding Sativex® spray to standard care was found to dominate standard spasticity care alone, with cost savings of €6,068 and a quality-adjusted life year gain of 0.145 per patient over the 5-year analysis. The probability of dominance increased from 29% in the first year to 94% in the fifth year, with the probability of QALY gains in excess of 99% for all years considered. CONCLUSIONS: Adding Sativex® spray to spasticity care was found to dominate standard spasticity care alone in the Belgian healthcare setting. This study showed the use of bootstrapping techniques in a Markov model probabilistic sensitivity analysis instead of Monte Carlo simulations. Bootstrapping avoided the need to make distributional assumptions and allowed the incorporation of correlating structures present in the original clinical trial data in the uncertainty assessment.

Health-related quality of life after traumatic brain injury: deriving value sets for the QOLIBRI-OS for Italy, The Netherlands and The United Kingdom.

PURPOSE: The Quality of Life after Brain Injury overall scale (QOLIBRI-OS) measures health-related quality of life (HRQoL) after traumatic brain injury (TBI). The aim of this study was to derive value sets for the QOLIBRI-OS in three European countries, which will allow calculation of utility scores for TBI health states. METHODS: A QOLIBRI-OS value set was derived by using discrete choice experiments (DCEs) and visual analogue scales (VAS) in general population samples from the Netherlands, United Kingdom and Italy. A three-stage procedure was used: (1) A selection of health states, covering the entire spectrum of severity, was defined; (2) General population samples performed the health state valuation task using a web-based survey with three VAS questions and an at random selection of sixteen DCEs; (3) DCEs were analysed using a conditional logistic regression and were then anchored on the VAS data. Utility scores for QOLIBRI-OS health states were generated resulting in estimates for all potential health states. RESULTS: The questionnaire was completed by 13,623 respondents. The biggest weight increase for all attributes is seen from "slightly" to "not at all satisfied", resulting in the largest impact on HRQoL. "Not at all satisfied with how brain is working" should receive the greatest weight in utility calculations in all three countries. CONCLUSION: By transforming the QOLIBRI-OS into utility scores, we enabled the application in economic evaluations and in summary measures of population health, which may be used to inform decision-makers on the best interventions and strategies for TBI patients.

International Valuation Protocol for the EQ-5D-Y-3L.

The EQ-5D-Y-3L is a generic, health-related, quality-of-life instrument for use in younger populations. Some methodological studies have explored the valuation of children's EQ-5D-Y-3L health states. There are currently no published value sets available for the EQ-5D-Y-3L that are appropriate for use in a cost-utility analysis. The aim of this article was to describe the development of the valuation protocol for the EQ-5D-Y-3L instrument. There were several research questions that needed to be answered to develop a valuation protocol for EQ-5D-Y-3L health states. Most important of these were: (1) Do we need to obtain separate values for the EQ-5D-Y-3L, or can we use the ones from the EQ-5D-3L? (2) Whose values should we elicit: children or adults? (3) Which valuation methods should be used to obtain values for child's health states that are anchored in Full health = 1 and Dead = 0? The EuroQol Research Foundation has pursued a research programme to provide insight into these questions. In this article, we summarized the results of the research programme concluding with the description of the features of the EQ-5D-Y-3L valuation protocol. The tasks included in the protocol for valuing EQ-5D-Y-3L health states are discrete choice experiments for obtaining the relative importance of dimensions/levels and composite time-trade-off for anchoring the discrete choice experiment values on 1 = Full Health and 0 = Dead. This protocol is now available for use by research teams to generate EQ-5D-Y-3L value sets for their countries allowing the implementation of a cost-utility analysis for younger populations.

A French Value Set for the EQ-5D-5L.

OBJECTIVE: The objective of this study was to develop a French value set for the EQ-5D-5L, for academic and clinical research, and for regulatory requirements for price-setting of drugs and medical devices. METHOD: This study used the standardized valuation protocol developed by EuroQol, using computer-assisted personal interview software. A representative sample of 1048 French residents were interviewed by a market research company, under the supervision of the research team. Health states were valued using composite time trade-off and a discrete choice experiment. Modeling was used to create values for the 3125 possible health states. The composite time trade-off data were modeled using a Tobit model with censored observations at -1 and correcting for heteroscedasticity. A conditional logit model was used for the discrete choice results, and both models were combined using a hybrid model. An adjusted hybrid model was tested to correct for imbalance in the sample on age and sex compared with the general population. A comparison with the 3-level (3L) value set was performed. RESULTS: The adjusted model was preferred to comply with the representativeness of the general population. It provided a value set for which all coefficients were logically consistent. Values ranged from - 0.525 to 1. The distribution of values presented a shift towards higher values versus the 3L value set. Ranking of dimensions changed. Pain and discomfort and mobility were the dimensions with the highest potential for disutility compared with mobility and self-care for the 3L instrument. CONCLUSIONS: This study provides a value set based on societal preferences of the French population, using an improved descriptive instrument of health-related quality-of-life health states. It will contribute to improve the quality of cost-effectiveness analysis in the French context and help stimulate disease-specific quality-of-life references for academic-, institutional-, and industry-promoted studies.

Toward a Smaller Design for EQ-5D-5L Valuation Studies.

BACKGROUND: To construct an EQ-5D-5L value set, the EuroQol Group developed a standard protocol named EuroQol Valuation Technology (EQ-VT), prescribing the valuation of 86 health states utilizing the composite time trade-off (cTTO) approach, and subsequently modeled the observed values to yield values for all 3125 states. OBJECTIVE: A recent study demonstrated that a 25-state orthogonal design could provide as accurate predictions as the EQ-VT design applying visual analogue scale data. We aimed to test that design using time trade-off (TTO) data. METHOD: We collected TTO values utilizing EQ-VT, orthogonal, and D-efficient designs. The EQ-VT design included 86 health states distributed over 3 blocks of 30 states with some duplicates. The orthogonal and D-efficient designs each comprised 1 block of 30 states. A total of 525 university students were asked to value a random block of health states using EQ-PVT (a PowerPoint replica of EQ-VT software), which generated 100 observations per health state in all 3 designs. We modeled data by design and compared the root mean square error (RMSE) between observed and predicted values within and across the designs. RESULTS: The EQ-VT design had the lowest RMSE of 0.052; the RMSEs for the orthogonal and the D-efficient designs were 0.066 and 0.063, respectively. RMSE results between designs differed for more severe health states. Some coefficients differed between designs. CONCLUSION: Smaller designs did not lead to significant increases in prediction errors when modeling TTO data (measuring 0.01 on a utility scale). Resource-constrained countries may use small designs for valuation studies, especially when other types of preference data, such as those from discrete choice experiments, are collected and modeled jointly.

United States Valuation of EQ-5D-5L Health States Using an International Protocol.

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 preferred model to generate the value set. Values ranged from -0.573 (55 555) to 1 (11 111), with 20% of all predicted health states scores less than 0 (ie, worse than dead). CONCLUSIONS: A societal value set for the EQ-5D-5L was developed that can be used for economic evaluations and decision making in US health systems. The internationally established, standardized protocol used to develop this US-based value set was recommended by the EuroQol Group and can facilitate cross-country comparisons.

Exploring the Impact of Adding a Respiratory Dimension to the EQ-5D-5L.

Objectives. To evaluate the impact of adding a respiratory dimension (a bolt-on dimension) to the EQ-5D-5L health state valuations. Methods. Based on extensive regression and principal component analyses, 2 respiratory bolt-on candidates were formulated: R1, limitations in physical activities due to shortness of breath, and R2, breathing problems. Valuation interviews for the selected bolt-ons were performed with a representative sample from the Dutch general public using the standardized interview protocol and software of the EuroQol group. Hybrid models based on the combined time-tradeoff (TTO) and discrete choice experiment (DCE) data were estimated to assess whether the 5 levels of the respiratory bolt-on led to significant changes in utility values. Results. For each bolt-on candidate, slightly more than 200 valuation interviews were conducted. Mean TTO values and DCE choice probabilities for health states with a level 4 or 5 for the respiratory dimension were significantly lower compared with the same health states in the Dutch EQ-5D-5L valuation study without the respiratory dimension. Results of hybrid models showed that for the bolt-on "limitations in physical activities," the utility decrements were significant for level 3 (-0.055), level 4 (-0.087), and level 5 (-0.135). For "breathing problems," the utility decrements for the same levels were greater (-0.086, -0.219, and -0.327, respectively). Conclusions. The addition of each of the 2 respiratory bolt-ons to the EQ-5D-5L had a significant effect on the valuation of health states with severe levels for the bolt-on. The bolt-on dimension "breathing problems" showed the greatest utility decrements and therefore seems the most appropriate respiratory bolt-on dimension.

Cost-effectiveness of a home-based group educational programme on renal replacement therapies: a study protocol.

INTRODUCTION: Living donor kidney transplantation (LDKT) is the optimal treatment for most patients with end-stage renal disease (ESRD). However, there are numerous patients who cannot find a living kidney donor. Randomised controlled trials have shown that home-based education for patients with ESRD and their family/friends leads to four times more LDKTs. This educational intervention is currently being implemented in eight hospitals in the Netherlands. Supervision and quality assessment are being employed to maintain the quality of the intervention. In this study, we aim to: (1) conduct a cost-effectiveness analysis of the educational programme and its quality assurance system; (2) investigate the relationship between the quality of the implementation of the intervention and the outcomes knowledge, communication and LDKT activities; and (3) investigate policy implications. METHODS AND DESIGN: Patients with ESRD who do not have a living kidney donor are eligible to receive the home-based educational intervention. This is carried out by allied health transplantation professionals and psychologists across eight hospitals in the Netherlands. The cost-effectiveness analysis will be conducted with a Markov model. Cost data will be obtained from the literature. We will obtain the quality of life data from the patients who participate in the educational programme. Questionnaires on knowledge and communication will be used to measure the outcomes of the programme. Data on LDKT activities will be obtained from medical records up to 24 months after the education. A protocol adherence measure will be assessed by a third party by means of a telephone interview with the patients and the invitees. ETHICS AND DISSEMINATION: Ethical approval was obtained through all participating hospitals. Results will be disseminated through peer-reviewed publications and scientific presentations. Results of the cost-effectiveness of the educational programme will also be disseminated to the Dutch National Health Care Institute. TRIAL REGISTRATION NUMBER: NL6529.

Valuation of EuroQol Five-Dimensional Questionnaire, Youth Version (EQ-5D-Y) and EuroQol Five-Dimensional Questionnaire, Three-Level Version (EQ-5D-3L) Health States: The Impact of Wording and Perspective.

BACKGROUND: Valuations of health states were affected by the wording of the two instruments (EQ-5D-3L and EQ-5D-Y) and by the perspective taken (child or adult). OBJECTIVES: There is a growing demand for value sets for the EQ-5D-Y (EQ-5D instrument for younger populations). Given the similarities between EQ-5D-Y and EQ-5D-3L, we investigated whether valuations of health states were affected by the differences in wording between the two instruments and by the perspective taken in the valuation exercise (child or adult). STUDY DESIGN: Respondents were randomly assigned to EQ-5D-3L or EQ-5D-Y (instrument) and further into two groups that either valued health states for an adult or for a 10-year-old child (perspective). The valuation tasks were composite time trade-off (C-TTO) and discrete choice experiments (DCE), including comparisons with death (DCE + death). Members of the adult general population in four countries (Germany, Netherlands, Spain, England) participated in computer-assisted personal interviews. METHODS: Two-way multivariate analysis of variance (MANOVA) and post hoc tests were used to compare C-TTO responses and chi-square tests were conducted to compare DCE + death valuations. RESULTS: A significant interaction effect between instrument and perspective for C-TTO responses was found. Significant differences by perspective (adult and child) occurred only for the EQ-5D-3L. Significant differences in values between instruments (EQ-5D-3L and EQ-5D-Y) occurred only for the adult perspective. Both significant results were confirmed by the DCE + death results. When comparing EQ-5D-3L for adult perspective and EQ-5D-Y for child perspective, values were also significantly different. CONCLUSIONS: The results identified an interaction effect between wording of the instrument and perspective on elicited values, suggesting that current EQ-5D-3L value sets should not be employed to assign values to EQ-5D-Y health states.

Severity-Stratified Discrete Choice Experiment Designs for Health State Evaluations.

BACKGROUND: Discrete choice experiments (DCEs) are increasingly used for health state valuations. However, the values derived from initial DCE studies vary widely. We hypothesize that these findings indicate the presence of unknown sources of bias that must be recognized and minimized. Against this background, we studied whether values derived from a DCE are sensitive to how well the DCE design spans the severity range. METHODS: We constructed an experiment involving three variants of DCE tasks for health state valuation: standard DCE, DCE-death, and DCE-duration. For each type of DCE, an experimental design was generated under two different conditions, enabling a comparison of health state values derived from current best practice Bayesian efficient DCE designs with values derived from 'severity-stratified' designs that control for coverage of the severity range in health state selection. About 3000 respondents participated in the study and were randomly assigned to one of the six study arms. RESULTS: Imposing the severity-stratified restriction had a large effect on health states sampled for the DCE-duration approach. The unstratified efficient design returned a skewed distribution of selected health states, and this introduced bias. The choice probability of bad health states was underestimated, and time trade-offs to avoid bad states were overestimated, resulting in too low values. Imposing the same restriction had limited effect in the DCE-death approach and standard DCE. CONCLUSION: Variation in DCE-derived values can be partially explained by differences in how well selected health states spanned the severity range. Imposing a 'severity stratification' on DCE-duration designs is a validity requirement.