In search of a 'pan-European value set'; application for EQ-5D-3L.

OBJECTIVES: Country-specific value sets for the EQ-5D are available which reflect preferences for health states elicited from the general population. This allows the transformation of responses on EQ-5D to health state utility values. Only twelve European countries possess country-specific value sets and no value set reflecting the preferences of Europe exists. We aim to estimate a 'pan-European' value set for the EQ-5D-3L, reflecting the preferences for health states of the European population that could help to evaluate health care from the perspective of the European decision-maker. METHODS: We systematically assessed and compared the methodologies of available EQ-5D-3L time trade-off (TTO) value sets from twelve European countries: Denmark, France, Germany, Hungary, Italy, Netherlands, Poland, Portugal, Romania, Slovenia, Spain and UK. Using their published coefficients, a dataset with utility values for all 243 health states was simulated. Different modelling techniques and model specifications including interaction terms were tested. Model selection was based on goodness-of-fit criteria. We also explored results with application of population size weights. RESULTS: Methodological, procedural and analytical characteristics of the included EQ-5D-3L valuation studies were quite comparable. An OLS based model was the preferred model to represent European preferences. Weighting with population size made little difference. CONCLUSIONS: EQ-5D-3L valuation studies were considered of sufficient comparability to form the basis for a new 'pan-European' value set. The method used allows for an easy update when new national value sets become available.

Effectiveness and Cost-Effectiveness of 360 Disease-Modifying Treatment Escalation Sequences in Multiple Sclerosis.

OBJECTIVES: The rapid expansion in treatment options for relapsing-remitting multiple sclerosis (RRMS) of the past decade requires clinical decision making on the sequential prescription of these treatments. Here, we compare 360 treatment escalation sequences for patients with RRMS in terms of health outcomes and societal costs in The Netherlands. METHODS: We use a microsimulation model with a societal perspective, developed in collaboration with MS neurologists, to estimate the effectiveness and cost-effectiveness of 360 treatment sequences starting with first-line therapies in RRMS. This model integrated data on disease progression, disease-modifying treatment efficacy, clinical decision rules, age-dependent relapse rates, quality of life, healthcare, and societal costs. RESULTS: Costs and health outcomes were overlapping among different treatment escalation sequences. In our model for RRMS treatment, optimal lifetime health outcomes (20.24 ± 1.43 quality-adjusted life-years [QALYs], 6.11 ± 0.30 relapses) were achieved with the sequence peginterferon-dimethyl fumarate-ocrelizumab-natalizumab-alemtuzumab. The most cost-effective sequence (peginterferon-glatiramer acetate-ocrelizumab-cladribine-alemtuzumab) yielded numerically worse health outcomes per patient (19.59 ± 1.43 QALYs, 6.64 ± 0.43 relapses), but resulted in €98 127 ± €19 134 less costs than the most effective treatment sequence. CONCLUSIONS: Effectiveness estimates of treatments have overlapping confidence intervals but the treatment sequence that yields most QALYs is not the most cost-effective option, also when taking uncertainty into account. It is important that neurologists are aware of cost constraints and its relationship with prescription behavior, but treatment decisions should be individually tailored.

Correcting for discounting and loss aversion in composite time trade-off.

Time trade-off utilities have been suggested to be biased upwards. This bias is a result of the method being applied assuming linear utility of life duration, which is violated when individuals discount future life years or are loss averse for health. Applying a "corrective approach", that is, measuring individuals' discount function and loss aversion and correcting time trade-off utilities for these individual characteristics, may reduce this bias in utilities. Earlier work has developed this approach for time trade-off in a student sample. In this study, the corrective approach was extended to composite time trade-off (cTTO) methodology, which enabled correcting utilities for health states worse than dead. In digital interviews a sample of 150 members of the general public completed cTTO tasks for six health states, and afterward they completed measurements of loss aversion and discounting. cTTO utilities were corrected using these measurements under multiple specifications. Respondents were also asked to reflect on and adjust their cTTO utilities directly. Our results show considerable loss aversion and both positive and negative discounting were prevalent. As predicted, correction generally resulted in lower utilities. This was in accordance with the direction of adjustments made by respondents themselves.

Burden of Providing Informal Care for Patients with Atrial Fibrillation.

OBJECTIVES: Patients with atrial fibrillation (AF) have rapid and irregular heart rates, increasing the risk of comorbidities and mortality. Next to formal medical care, many patients receive informal care from their social environment. The objective of this study was to examine the well-being and economic burden of providing informal care to patients with AF in the UK, Italy, and Germany. METHODS: Caregivers of patients with AF completed an online survey based on the iMTA Valuation of Informal Care Questionnaire, with questions about their caregiving situation, perceived burden of caregiving, and absence from work due to health problems resulting from caregiving. Care-related quality-of-life utilities were calculated using the Care-related Quality of Life instrument and associated tariffs. Societal costs of caregiving were calculated based on the proxy good method. RESULTS: A total of 585 caregivers participated in this study. On average, caregivers provided 33 hours of informal care per week to patients (SD 29 hours). On a scale from 0 to 10, their self-rated burden was 5.4. The average Care-related Quality of Life utility was 72. Caregivers primarily indicated problems with daily activities, mental health, and physical health. Still, the vast majority of caregivers (87%) derived fulfillment from providing care. Weekly societal costs of caregiving were on average €636. Comorbidities contributed substantially to the caregiver time and burden. CONCLUSIONS: Caring for a patient with AF is associated with substantial objective and subjective burden, but also provides fulfillment from being able to care for a loved one.

Evaluation of the performance of algorithms mapping EORTC QLQ-C30 onto the EQ-5D index in a metastatic colorectal cancer cost-effectiveness model.

BACKGROUND: Cost-effectiveness models require quality of life utilities calculated from generic preference-based questionnaires, such as EQ-5D. We evaluated the performance of available algorithms for QLQ-C30 conversion into EQ-5D-3L based utilities in a metastatic colorectal cancer (mCRC) patient population and subsequently developed a mCRC specific algorithm. Influence of mapping on cost-effectiveness was evaluated. METHODS: Three available algorithms were compared with observed utilities from the CAIRO3 study. Six models were developed using 5-fold cross-validation: predicting EQ-5D-3L tariffs from QLQ-C30 functional scale scores, continuous QLQ-C30 scores or dummy levels with a random effects model (RE), a most likely probability method on EQ-5D-3L functional scale scores, a beta regression model on QLQ-C30 functional scale scores and a separate equations subgroup approach on QLQ-C30 functional scale scores. Performance was assessed, and algorithms were tested on incomplete QLQ-C30 questionnaires. Influence of utility mapping on incremental cost/QALY gained (ICER) was evaluated in an existing Dutch mCRC cost-effectiveness model. RESULTS: The available algorithms yielded mean utilities of 1: 0.87 ± sd:0.14,2: 0.81 ± 0.15 (both Dutch tariff) and 3: 0.81 ± sd:0.19. Algorithm 1 and 3 were significantly different from the mean observed utility (0.83 ± 0.17 with Dutch tariff, 0.80 ± 0.20 with U.K. tariff). All new models yielded predicted utilities drawing close to observed utilities; differences were not statistically significant. The existing algorithms resulted in an ICER difference of €10,140 less and €1765 more compared to the observed EQ-5D-3L based ICER (€168,048). The preferred newly developed algorithm was €5094 higher than the observed EQ-5D-3L based ICER. Disparity was explained by minimal diffences in incremental QALYs between models. CONCLUSION: Available mapping algorithms sufficiently accurately predict utilities. With the commonly used statistical methods, we did not succeed in developping an improved mapping algorithm. Importantly, cost-effectiveness outcomes in this study were comparable to the original model outcomes between different mapping algorithms. Therefore, mapping can be an adequate solution for cost-effectiveness studies using either a previously designed and validated algorithm or an algorithm developed in this study.

Cost Effectiveness of the Angiotensin Receptor Neprilysin Inhibitor Sacubitril/Valsartan for Patients with Chronic Heart Failure and Reduced Ejection Fraction in the Netherlands: A Country Adaptation Analysis Under the Former and Current Dutch Pharmacoeconomic Guidelines.

OBJECTIVES: To describe the adaptation of a global health economic model to determine whether treatment with the angiotensin receptor neprilysin inhibitor LCZ696 is cost effective compared with the angiotensin-converting enzyme inhibitor enalapril in adult patients with chronic heart failure with reduced left ventricular ejection fraction in the Netherlands; and to explore the effect of performing the cost-effectiveness analyses according to the new pharmacoeconomic Dutch guidelines (updated during the submission process of LCZ696), which require a value-of-information analysis and the inclusion of indirect medical costs of life-years gained. METHODS: We adapted a UK model to reflect the societal perspective in the Netherlands by including travel expenses, productivity loss, informal care costs, and indirect medical costs during the life-years gained and performed a preliminary value-of-information analysis. RESULTS: The incremental cost-effectiveness ratio obtained was €17,600 per quality-adjusted life-year (QALY) gained. This was robust to changes in most structural assumptions and across different subgroups of patients. Probability sensitivity analysis results showed that the probability that LCZ696 is cost-effective at a €50,000 per QALY threshold is 99.8%, with a population expected value of perfect information of €297,128. On including indirect medical costs of life-years gained, the incremental cost-effectiveness ratio was €26,491 per QALY gained, and LCZ696 was 99.46% cost effective at €50,000 per QALY, with a population expected value of perfect information of €2,849,647. CONCLUSIONS: LCZ696 is cost effective compared with enalapril under the former and current Dutch guidelines. However, the (monetary) consequences of making a wrong decision were considerably different in both scenarios.

Are Health State Valuations from the General Public Biased? A Test of Health State Reference Dependency Using Self-assessed Health and an Efficient Discrete Choice Experiment.

Health state valuations of patients and non-patients are not the same, whereas health state values obtained from general population samples are a weighted average of both. The latter constitutes an often-overlooked source of bias. This study investigates the resulting bias and tests for the impact of reference dependency on health state valuations using an efficient discrete choice experiment administered to a Dutch nationally representative sample of 788 respondents. A Bayesian discrete choice experiment design consisting of eight sets of 24 (matched pairwise) choice tasks was developed, with each set providing full identification of the included parameters. Mixed logit models were used to estimate health state preferences with respondents' own health included as an additional predictor. Our results indicate that respondents with impaired health worse than or equal to the health state levels under evaluation have approximately 30% smaller health state decrements. This confirms that reference dependency can be observed in general population samples and affirms the relevance of prospect theory in health state valuations. At the same time, the limited number of respondents with severe health impairments does not appear to bias social tariffs as obtained from general population samples. Copyright © 2016 John Wiley & Sons, Ltd.

Testing mapping algorithms of the cancer-specific EORTC QLQ-C30 onto EQ-5D in malignant mesothelioma.

BACKGROUND: In order to estimate utilities for cancer studies where the EQ-5D was not used, the EORTC QLQ-C30 can be used to estimate EQ-5D using existing mapping algorithms. Several mapping algorithms exist for this transformation, however, algorithms tend to lose accuracy in patients in poor health states. The aim of this study was to test all existing mapping algorithms of QLQ-C30 onto EQ-5D, in a dataset of patients with malignant pleural mesothelioma, an invariably fatal malignancy where no previous mapping estimation has been published. METHODS: Health related quality of life (HRQoL) data where both the EQ-5D and QLQ-C30 were used simultaneously was obtained from the UK-based prospective observational SWAMP (South West Area Mesothelioma and Pemetrexed) trial. In the original trial 73 patients with pleural mesothelioma were offered palliative chemotherapy and their HRQoL was assessed across five time points. This data was used to test the nine available mapping algorithms found in the literature, comparing predicted against observed EQ-5D values. The ability of algorithms to predict the mean, minimise error and detect clinically significant differences was assessed. RESULTS: The dataset had a total of 250 observations across 5 timepoints. The linear regression mapping algorithms tested generally performed poorly, over-estimating the predicted compared to observed EQ-5D values, especially when observed EQ-5D was below 0.5. The best performing algorithm used a response mapping method and predicted the mean EQ-5D with accuracy with an average root mean squared error of 0.17 (Standard Deviation; 0.22). This algorithm reliably discriminated between clinically distinct subgroups seen in the primary dataset. CONCLUSIONS: This study tested mapping algorithms in a population with poor health states, where they have been previously shown to perform poorly. Further research into EQ-5D estimation should be directed at response mapping methods given its superior performance in this study.

Would you rather be ill now, or later?

The time tradeoff (TTO) method is frequently used to calculate the quality adjustment of the quality adjusted life year and is therefore an important element in the calculation of the benefits of medical interventions. New specifications of TTO, known as 'lead time' TTO and 'lag time' TTO, have been developed to overcome methodological issues of the 'classic' TTO. In the lead time TTO, ill-health is explicitly placed in the future, after a period of good health, whereas in lag time TTO, a health state starts immediately and is followed by a 'lag time' of good health. In this study, we take advantage of these timing properties of lead and lag time TTO. In particular, we use data from a previous study that employed lead and lag time TTO to estimate their implied discounting parameters. We show that individuals prefer being ill later, rather than now, with larger per-period discount rates for longer durations of the health states.

Lead time TTO: leading to better health state valuations?

Preference elicitation tasks for better than dead (BTD) and worse than dead (WTD) health states vary in the conventional time trade-off (TTO) procedure, casting doubt on uniformity of scale. 'Lead time TTO' (LT-TTO) was recently introduced to overcome the problem. We tested different specifications of LT-TTO in comparison with TTO in a within-subject design. We elicited preferences for six health states and employed an intertemporal ranking task as a benchmark to test the validity of the two methods. We also tested constant proportional trade-offs (CPTO), while correcting for discounting, and the effect of extending the lead time if a health state is considered substantially WTD. LT-TTO produced lower values for BTD states and higher values for WTD states. The validity of CPTO varied across tasks, but it was higher for LT-TTO than for TTO. Results indicate that the ratio of lead time to disease time has a greater impact on results than the total duration of the time frame. The intertemporal ranking task could not discriminate between TTO and LT-TTO.

Societal Utilities for Cognitive Impairment in Schizophrenia: Developing a Preference-Based Scoring Algorithm Based on the Schizophrenia Cognition Rating Scale.

INTRODUCTION: Loss of cognitive function is a common feature in schizophrenia. However, generic measures of health-related quality of life favored by decision-makers, such as the EQ-5D, are not designed to detect changes in cognitive function. We report the valuation of the Schizophrenia Cognition Rating Scale (SCoRS), a schizophrenia-specific measure of cognitive impairment. METHODS: Expert opinion and psychometric analysis of the SCoRS from clinical trial data was undertaken to select 5 key items from the measure. These items were combined orthogonally to develop health-state vignettes. Vignettes were valued using composite time trade-off (cTTO) in one-on-one video calls. Several econometric models were fitted to the data to estimate disutilities. Performance of EQ-5D- and SCoRS-based utilities were compared in the trial data. RESULTS: The SCoRS items selected for the valuation study represented attention, learning, processing speed, social cognition and memory. Four hundred respondents participated in the valuation study. The best observed health state was valued at 0.855 [standard deviation (SD) = 0.179] and the worst at 0.152 (SD = 0.575). At the most severe levels, 'social cognition' received the largest disutility followed by 'learning' and 'memory'. The final model to estimate utilities had 15 parameters. SCoRS-based utilities were sensitive to change in cognition, but the EQ-5D was not. CONCLUSION: It is feasible to value different dimensions of cognition separately using a validated instrument for proxy assessment. The resulting utilities indicate loss of quality of life due to reduced cognitive functioning.

Benefits of sphingosine-1-phosphate receptor modulators in relapsing MS estimated with a treatment sequence model.

BACKGROUND: Three sphingosine-1-phosphate receptor (S1PR) modulators are currently available as disease-modifying therapies (DMTs) for relapsing MS in the Netherlands (i.e. fingolimod, ozanimod and ponesimod). We aimed to identify which S1PR modulator yields the highest benefit from a health-economic and societal perspective during a patient's lifespan. METHODS: Incorporating Dutch DMT list prices, we used the ErasmusMC/iMTA MS model to compare DMT sequences, including S1PR modulators and eight other DMT classes, for treatment-naïve patients with relapsing MS in terms of health outcomes (number of lifetime relapses, time to Expanded Disability Status Scale (EDSS) 6, lifetime quality-adjusted life years (QALYs)) and cost-effectiveness (net health benefit (NHB)). We estimated the influence of list price and EDSS progression on cost-effectiveness outcomes. RESULTS: In deterministic and probabilistic analysis, DMT sequences with ponesimod have lower lifetime costs and higher QALYs resulting in a higher average NHB compared to sequences with other S1PR modulators. Ponesimod remains the most cost-effective S1PR modulator when EDSS progression is class-averaged. Given the variable effects on disability progression, list price reductions could make fingolimod but not ozanimod more cost-effective than ponesimod. CONCLUSION: Our model favours ponesimod among the S1PR modulators for the treatment of relapsing MS. This implies that prioritizing ponesimod over other S1PR modulators translates into a more efficacious spending of national healthcare budget without reducing benefit for people with MS. Prioritizing cost-effective choices when counselling patients contributes to affordable and accessible MS care.

Condition-specific preference-based measures: benefit or burden?

OBJECTIVES: Some argue that generic preference-based measures (PBMs) are not sensitive to certain disease-specific improvements. To overcome this problem, new condition-specific PBMs (CS-PBMs) are being developed, but it is not yet clear how such measures compare with existing generic PBMs. METHOD: We generated CS-PBMs from three condition-specific questionnaires (Health Assessment Questionnaire for arthritis, Quality of Life Questionnaire for Cancer 30 for cancer, and Multiple Sclerosis Impact Scale 29 for multiple sclerosis). First, the questionnaires were reduced in content, and then, a time trade-off study was conducted in the general public (N = 402) to obtain weights associated with the dimensions and levels of the new questionnaire. Finally, we compared utilities obtained by using the CS-PBMs with utilities obtained by using the EuroQol five-dimensional (EQ-5D) questionnaire in four data sets. RESULTS: Utility values generated by the CS-PBMs were higher than those of the EQ-5D questionnaire. The Health Assessment Questionnaire-based measure for arthritis proved to be insensitive to comorbidities. Measures based on the Multiple Sclerosis Impact Scale 29 and the Quality of Life Questionnaire for Cancer 30 discriminated comorbidities and side effect equally well as the EQ-5D questionnaire and were more sensitive than the EQ-5D questionnaire for mild impairments. CONCLUSIONS: The introduction of PBMs that are specific to a certain disease may have the merit of sensitivity to disease-specific effects of interventions. That gain, however, is traded off to the loss of comparability of utility values and, in some cases, insensitivity to side effects and comorbidity. The use of a CS-PBM for cost-utility analysis is warranted only under strict conditions.

Incremental benefits of novel pharmaceuticals in the UK: a cross-sectional analysis of NICE technology appraisals from 2010 to 2020.

OBJECTIVES: To evaluate the incremental value of new drugs across disease areas receiving favourable coverage decisions by the UK's National Institute for Health and Care Excellence (NICE) over the past decade. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study assessed favourable appraisal decisions of drugs between 1 January 2010 and 31 December 2020. Estimates of incremental benefit were extracted from NICE's evidence review groups reports. PRIMARY OUTCOME MEASURE: Incremental benefit of novel drugs relative to the best alternative therapeutic option, expressed in quality-adjusted life-years (QALYs). RESULTS: 184 appraisals of 129 drugs provided QALYs. The median incremental value was 0.27 QALY (IQR: 0.07-0.73). Benefits varied across drug-indication pairs (range: -0.49 to 5.22 QALY). The highest median benefits were found in haematology (0.70, IQR: 0.55-1.22) and oncology (0.46, IQR: 0.20-0.88), the lowest in ophthalmology (0.09, IQR: 0.04-0.22) and endocrinology (0.02, IQR: 0.01-0.06). Eight appraisals (4.3%) found contributions of more than two QALYs, but one in four (50/184) drug-indication pairs provided less than the equivalent of 1 month in perfect health compared to existing treatments. CONCLUSIONS: In our review period, the median incremental value of novel drugs approved for use within the English National Health System, relative to the best alternative therapeutic option, was equivalent to 3-4 months of life in perfect health, but data were heterogeneous. Objective evaluations of therapeutic value helps patients and physicians to develop reasonable expectations of drugs and delivers insights into disease areas where medicinal therapeutic progress has had the most and least impact.

Methodological Challenges in the Economic Evaluation of a Gene Therapy for RPE65-Mediated Inherited Retinal Disease: The Value of Vision.

The emergence of gene therapies challenge health economists to evaluate interventions that are often provided to a small patient population with a specific gene mutation in a single dose with high upfront costs and uncertain long-term benefits. The objective of this study was to illustrate the methodological challenges of evaluating gene therapies and their implications by discussing four economic evaluations of voretigene neparvovec (VN) for the treatment of RPE65-mediated inherited retinal disease. The checklist for economic evaluations of gene therapies of Drummond et al. was applied to the economic evaluations of VN performed by US Institute for Clinical and Economic Review, two country adaptations of the company model in the UK and the Netherlands, and another US publication. The main differences in methodological choices and their impact on cost-effectiveness results were assessed and further explored with sensitivity analyses using the Dutch model. To enable comparison between the economic evaluations, costs were converted to US dollars. Different methodological choices were made in the economic evaluations of VN resulting in large differences in the incremental cost-effectiveness ratio varying from US$79,618 to US$643,813 per QALY. The chosen duration of treatment effect, source of utility values, discount rate and model structure had the largest impact on the cost-effectiveness. This study underlines the findings from Drummond et al. that standard methods can be used to evaluate gene therapies. However, given uncertainty about (particularly long-term) outcomes of gene therapies, guidance is required on the acceptable extrapolation of treatment effect of gene therapies and on how to handle the uncertainty around this extrapolation in scenario and sensitivity analyses to aid health technology assessment research and align submissions of future gene therapies.

Mapping onto Eq-5 D for patients in poor health.

BACKGROUND: An increasing amount of studies report mapping algorithms which predict EQ-5 D utility values using disease specific non-preference-based measures. Yet many mapping algorithms have been found to systematically overpredict EQ-5 D utility values for patients in poor health. Currently there are no guidelines on how to deal with this problem. This paper is concerned with the question of why overestimation of EQ-5 D utility values occurs for patients in poor health, and explores possible solutions. METHOD: Three existing datasets are used to estimate mapping algorithms and assess existing mapping algorithms from the literature mapping the cancer-specific EORTC-QLQ C-30 and the arthritis-specific Health Assessment Questionnaire (HAQ) onto the EQ-5 D. Separate mapping algorithms are estimated for poor health states. Poor health states are defined using a cut-off point for QLQ-C30 and HAQ, which is determined using association with EQ-5 D values. RESULTS: All mapping algorithms suffer from overprediction of utility values for patients in poor health. The large decrement of reporting 'extreme problems' in the EQ-5 D tariff, few observations with the most severe level in any EQ-5 D dimension and many observations at the least severe level in any EQ-5 D dimension led to a bimodal distribution of EQ-5 D index values, which is related to the overprediction of utility values for patients in poor health. Separate algorithms are here proposed to predict utility values for patients in poor health, where these are selected using cut-off points for HAQ-DI (> 2.0) and QLQ C-30 (< 45 average of QLQ C-30 functioning scales). The QLQ-C30 separate algorithm performed better than existing mapping algorithms for predicting utility values for patients in poor health, but still did not accurately predict mean utility values. A HAQ separate algorithm could not be estimated due to data restrictions. CONCLUSION: Mapping algorithms overpredict utility values for patients in poor health but are used in cost-effectiveness analyses nonetheless. Guidelines can be developed on when the use of a mapping algorithms is inappropriate, for instance through the identification of cut-off points. Cut-off points on a disease specific questionnaire can be identified through association with the causes of overprediction. The cut-off points found in this study represent severely impaired health. Specifying a separate mapping algorithm to predict utility values for individuals in poor health greatly reduces overprediction, but does not fully solve the problem.

Summarizing Patient Preferences for the Competitive Landscape of Multiple Sclerosis Treatment Options.

Objective. Quantitatively summarize patient preferences for European licensed relapsing-remitting multiple sclerosis (RRMS) disease-modifying treatment (DMT) options. Methods. To identify and summarize the most important RRMS DMT characteristics, a literature review, exploratory physician interviews, patient focus groups, and confirmatory physician interviews were conducted in Germany, the United Kingdom, and the Netherlands. A discrete choice experiment (DCE) was developed and executed to measure patient preferences for the most important DMT characteristics. The resulting DCE data (n=799 and n=363 respondents in the United Kingdom and Germany, respectively) were analyzed using Bayesian mixed logit models. The estimated individual-level patient preferences were subsequently summarized using 3 additional analyses: the quality of the choice data was assessed using individual-level R2 estimates, individual-level preferences for the available DMTs were aggregated into DMT-specific preference shares, and a principal component analysis was performed to explain the patients' choice process. Results. DMT usage differed between RRMS patients in Germany and the United Kingdom but aggregate patient preferences were similar. Across countries, 42% of all patients preferred oral medications, 38% infusions, 16% injections, and 4% no DMT. The most often preferred DMT was natalizumab (26%) and oral DMT cladribine tablets (22%). The least often preferred were mitoxantrone and the beta-interferon injections (1%-3%). Patient preferences were strongly correlated with patients' MS disease duration and DMT experience, and differences in patient preferences could be summarized using 8 principle components that together explain 99% of the variation in patients' DMT preferences. Conclusion. This study summarizes patient preferences for the included DMTs, facilitates shared decision making along the dimensions that are relevant to RRMS patients, and introduces methods in the medical DCE literature that are ideally suited to summarize the impact of DMT introductions in preexisting treatment landscapes.

Estimating Informal Caregiving Time from Patient EQ-5D Data: The Informal CARE Effect (iCARE) Tool.

BACKGROUND: Families and friends provide a considerable proportion of care for patients and elderly people. Caregiving can have substantial effects on caregivers' lives, health, and well-being. However, because clinical trials rarely assess these effects, no information on caregiver burden is available when evaluating the cost effectiveness of treatments. OBJECTIVE: This study develops an algorithm for estimating caregiver time using information that is typically available in clinical trials: the EQ-5D scores of patients and their gender. METHODS: Four datasets with a total of 8012 observations of dyads of caregivers and a gamma model with a log-link estimated with the Bayesian approach were used to estimate the statistical association between patient scores on the EQ-5D-3L dimensions and the numbers of hours of care provided by caregivers during the previous week. The model predicts hours of care as mean point estimates with 95% credible intervals or entire distributions. RESULTS: Model predictions of hours of care based on the five EQ-5D dimensions ranged from 13.06 (12.7-14.5) h/week for female patients reporting no health problems but receiving informal care to 52.82 (39.38-66.26) for male patients with the highest level of problems on all EQ-5D dimensions. CONCLUSIONS: The iCARE algorithm developed in this study allows researchers who only have patient-level EQ-5D data to estimate the mean hours of informal care received per week, including a 95% Bayesian credible interval. Caregiver time can be multiplied with a monetary value for caregiving, enabling the inclusion of informal care costs in economic evaluations. We recommend using the tool for samples that fall within the confidence intervals of the characteristics of our samples: men (age range 47.0-104.2 years), women (age range 55-103 years).

[Loss is gain? Discarding TNF-α inhibitors]. / Is verlies winst? Stoppen met TNF-α-blokkers.

According to a recent study, stopping the prescription of TNF inhibitors is a cost-effective decision at various willingness-to-accept thresholds. Discontinuing the prescription of the drug may lead to a minor loss in health - expressed in quality adjusted life years - but results in significant societal savings. In our commentary, we stress that willingness-to-pay thresholds should not be completely replaced by the willingness-to-accept threshold, also when it concerns health losses. Loss aversion can be viewed as either a relevant societal phenomenon or an irrationality that should not guide decision making.

Severity-Adjusted Probability of Being Cost Effective.

BACKGROUND: In the context of priority setting, a differential cost-effectiveness threshold can be used to reflect a higher societal willingness to pay for quality-adjusted life-year gains in the worse off. However, uncertainty in the estimate of severity can lead to problems when evaluating the outcomes of cost-effectiveness analyses. OBJECTIVES: This study standardizes the assessment of severity, integrates its uncertainty with the uncertainty in cost-effectiveness results and provides decision makers with a new estimate: the severity-adjusted probability of being cost effective. METHODS: Severity is expressed in proportional and absolute shortfall and estimated using life tables and country-specific EQ-5D values. We use the three severity-based cost-effectiveness thresholds (€20.000, €50.000 and €80.000, per QALY) adopted in The Netherlands. We exemplify procedures of integrating uncertainty with a stylized example of a hypothetical oncology treatment. RESULTS: Applying our methods, taking into account the uncertainty in the cost-effectiveness results and in the estimation of severity identifies the likelihood of an intervention being cost effective when there is uncertainty about the appropriate severity-based cost-effectiveness threshold. CONCLUSIONS: Higher willingness-to-pay thresholds for severe diseases are implemented in countries to reflect societal concerns for an equitable distribution of resources. However, the estimates of severity are uncertain, patient populations are heterogeneous, and this can be accounted for with the severity-adjusted probability of being cost effective proposed in this study. The application to the Netherlands suggests that not adopting the new method could result in incorrect decisions in the reimbursement of new health technologies.