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A recent study found that negative utility values elicited using composite time trade-off (TTO) were barely associated with the severity of EQ-5D-5L health states, suggesting poor discriminative ability. Assuming negative values provide limited information, this study aimed to explore the usefulness of censoring negative TTO values at 0 in modeling EQ-5D-5L valuation data.We analyzed EQ-5D-5L valuation data from China, The Netherlands, Canada, Singapore, and Thailand. For each data set, we estimated value sets using 2 Tobit models, one left-censored at -1 (current practice) and one left-censored at 0 (our proposed method), and compared the model performances. We hypothesized that censoring at 0 and censoring at -1 would produce similar values, though on slightly different scales.When censoring at 0, logical inconsistencies and statistical significance were improved but the value range was compressed. In the cross-attribute level effects model, the 3-level parameters were similar between the models censored at 0 and -1, but the rank order of some dimension parameters was altered. Health state values predicted by the 2 censoring models approximated a perfect agreement after rescaling.Censoring TTO values at 0 improved model estimation and fit but produced higher utility values than models censoring at -1. Investigators of future EQ-5D value set studies using the composite TTO method are advised to examine the validity of negative TTO values before choosing modeling strategies.

During the first year of life, B-cell level is a valuable indicator of whether external factors, such as exposure to B-cell-depleting therapies, have an adverse impact on immune system development. However, there are no standard reference ranges of B-cell levels in healthy infants by age.Our aim was to estimate the normal range of B-cell levels in infants, by age, during the first year of life by pooling data from published studies.Studies reporting B-cell levels measured by using flow cytometry and CD19 markers in healthy infants were identified via a systematic literature review. Quality and feasibility assessments determined suitability for inclusion in meta-analyses by age group and/or continuous age. Means and normal ranges (2.5th-97.5th percentile) were estimated for absolute and percentage B-cell levels. Sensitivity analyses assessed the impact of various assumptions.Of the 37 relevant studies identified, 28 were included in at least 1 meta-analysis. The means and normal ranges of B-cell levels were found to be 707 cells/μL in cord blood (range 123-2324 cells/μL), 508 cells/μL in infants aged 0 to 1 month (range 132-1369 cells/μL), 1493 cells/μL in infants aged 1 to 6 months (range 416-3877 cells/μL), and 1474 cells/μL in infants older than 6 months (range 416-3805 cells/μL). The continuous age model showed that B-cell levels peaked at week 26. Trends were similar for the percentage B-cell estimates and in sensitivity analyses.These meta-analyses provide the first normal reference ranges for B-cell levels in infants, by week of age, during the first year of life.

The left censoring of values at -1 by design of the composite time trade-off (cTTO) tasks leads to excessive amount of -1 values in some EQ-5D-5L valuation studies. This study aimed to investigate whether a time-based willingness-to-accept (tWTA) question can be used to elicit values lower than -1 and improve the estimation of EQ-5D-5L values.At the end of each cTTO task in the Taiwanese EQ-5D-5L valuation study, if the value of the health state was indicated to be lower than -1, a tWTA question eliciting the indifference point between a hypothetical life (i.e. x number of years in full health followed by 10 years in the health state) and immediate death was used to estimate its uncensored value. We compared the statistical characteristics of the censored and uncensored data.Four hundred and twenty-nine of 1,000 respondents were offered the tWTA question in a total of 1,071 cTTO tasks. In 79.55% of those tasks, indifference was not reached. Spearman's correlation with level summary score was -0.41 and -0.40 for negative uncensored and censored data, respectively. The logical inconsistency rates of the uncensored and censored data were 0.88% vs. 0.29%, respectively. Modelling of the uncensored data resulted in coefficients with greater uncertainty and much lower predictions.The elicitation of values lower than -1 using a tWTA question that grants more time for trading seems not a promising solution to the value censoring of the cTTO tasks. Other strategies for valuation of very poor health states should be explored.

Background The TTO task involves giving up life years, i.e. living a shorter life, to avoid an undesirable health state. Despite being a hypothetical task, some respondents take other life factors into account when completing the task. This study explored the effect of having children and/or a partner on TTO valuations of hypothetical EQ-5D-5L health states in a valuation study of the general population. Methods The study used TTO data collected in a Norwegian EQ-5D-5L valuation study in 2019–2020, by one-to-one pc-assisted interviews following the EQ-VT protocol. We used regression modelling to determine the effect of significant others (having children or a partner) on disutility per health state from the TTO valuations. Results 430 respondents were included [mean age 43.8 (SD 15.9) years, 58% female, 48% with children, 68% with a partner, 25% with neither children nor partner]. Having children and/or a partner was associated with lowered willingness to trade life years translating to higher elicited health state utilities (p Conclusion Having significant others, or the lack of having significant others, was associated with respondents’ valuation of hypothetical health states using TTO, more so than traditional sampling variables such as age and sex. Inadequate representativeness in terms of having significant others could bias health state preference values in valuation studies.

Objectives To determine the effects of age, immigrant background, and poor self-reported health in a general population sample on the probability of non-completion or slow completion of the time trade-off (TTO). Methods We used data from an interrupted Norwegian EQ-5D-5L valuation study conducted between 2019 and 2020. All participants responded to background items, irrespective of completion. We used mixed effect logistic regression analysis to assess the effect of old age, poor health, and immigrant background on the probability of non-completion of the TTO, and, for those who completed the TTO, of slow completion times. Results First experiences from a Norwegian valuation study were that 29 (5.5%) respondents failed to complete the TTO tasks. For those reporting age over 65 years, poor health, or an immigrant background, 12% failed to complete the TTO. Adjusted odds ratios for predictors of non-completion were statistically significant (age > 65 years, 8.3; EQ-VAS ≤ 50, 3.49; immigrant background, 4.56). Being over 65 years or with an immigrant background also predicted slow completion of both the introduction and TTO tasks. Conclusions High age, poor health, and immigrant status increased the risk of not being able to complete the TTO tasks, and of slow completion. Higher non-completion rates and increased completion times suggest that elements of the TTO may be demanding for some respondent groups, with possible implications for representativeness.

Purpose To provide the first Norwegian EQ-5D-5L and EQ VAS population norms for the adult general population. Methods Postal survey of a random sample of 12,790 Norwegians identified through the National Registry of the Norwegian Tax Administration. Norms, weighted for Norwegian general population characteristics, are shown for the five EQ-5D-5L dimensions, EQ-5D index, and EQ VAS scores for seven age categories, females, males, and education level. Results There were 3200 (25.9%) respondents to 12,263 correctly addressed questionnaires. The EQ-5D-5L dimensions, EQ VAS, and background questions were completed by 3120 (24.6%) respondents. The mean age (SD) was 50.9 (21.7) and range was 18–97 years. The youngest age group of 18–29 years and oldest of 80 years and over had the highest (n = 691) and lowest (n = 239) number of respondents, respectively. Compared to the general population, the respondents comprised a greater number of females, younger and older ages, and had a higher education level. 32% of respondents reported no health problems on the EQ-5D-5L. From the youngest to oldest age groups, there was a general decline in health as assessed by the EQ-5D-5L. The exception was for anxiety/depression, where the youngest age groups had the poorest health. Apart from self-care, women reported poorer health than men, as assessed by the EQ-5D-5L; EQ VAS scores were similar for men and women. Higher levels of health (EQ-5D index, EQ VAS scores) were found with increasing levels of education. Conclusion The population norms will improve interpretation of EQ-5D-5L and EQ VAS scores in Norwegian applications including clinical practice, clinical and health services research, and national quality registers where EQ-5D-5L is the most widely used patient-reported instrument.

Background Stated preference research currently lacks a form of evidence that is well suited for small samples. A preference path is a sequence of two or more choices showing the evolution of an object following an adaptive process. Objectives The aims were to introduce preference paths and their kaizen tasks and to demonstrate how to analyze their evidence using a small sample. Methods Twenty respondents were assigned the same 16 profiles generated from an orthogonal array based on the five attributes of the EQ-5D-5L descriptive system. Each kaizen task began with an opt-out paired comparison (i.e., choosing between the initial 10-year profile and the opt-out “dying immediately”), followed by choosing three changes, and ended with a second paired comparison (final profile versus opt-out) if the respondent chose opt-out initially. By maximum likelihood with respondent clusters, we estimated the 20 main effects using conditional logit and Zermelo–Bradley–Terry (ZBT) specifications. Results Apart from demonstrating heterogeneity and profile effects, all main effect estimates were non-negative, and most were significant (15 for logit and all 20 for ZBT; p value < 0.05). Under the logit and ZBT specifications, the value of the worst EQ-5D-5L profile (55555) is − 0.920 quality-adjusted life years (QALYs) or − 1.478 QALYs, respectively. Furthermore, the findings illustrate a log-linear relationship between the logit and ZBT main effects. Conclusion This paper demonstrates the feasibility of a stated-preference study that estimates 20 main effects using path evidence from 20 respondents (16 kaizen tasks, 15-min interviews). This approach shows promise for future application in stated-preference research, particularly in small samples. Supplementary Information The online version contains supplementary material available at 10.1007/s40271-021-00541-z.

Background The Philippines has recommended the use of Quality-Adjusted Life Years (QALYs) in government health technology assessments (HTA). We aimed to develop a value set for the EQ-5D-5L based on health preferences of the healthy general adult population in the Philippines. Methods Healthy, literate adults were recruited from the Philippine general population with quota targets based on age, sex, administrative region, type of residence, education, income, and ethnolinguistic groups. Each participant’s preference was elicited by completing Composite Time Trade-Off (C-TTO) and Discrete Choice Experiment (DCE) tasks. Tasks were computer-assisted using the EuroQol Valuation Technology 2.0. To estimate the value set, we explored 20- and 8-parameter models that either use c-TTO-only data or both c-TTO and DCE (also called hybrid models). Final model choice was guided by principles of monotonicity, out-of-sample likelihood, model fit, and parsimony. Results We recruited 1000 respondents with demographic characteristics that approximate the general population such as 49.6% Female, 82% Roman Catholic, 40% in urban areas, and 55% finished high school. None of the 20-parameter models demonstrated monotonicity (logical worsening of coefficients with increasing severity). From the 8-parameter models, the homoscedastic TTO-only model exhibited the best fit. From this model, mobility and pain/ discomfort had the highest effect on utilities. Conclusion The selected model for representing the Philippine general population preferences for EQ-5D-5L health states was an 8-parameter homoscedastic TTO-only model. This value set is recommended for use in QALY calculations in support of HTA-informed coverage decisions in the Philippines.

Recently, a constrained main-effects model called cross-attribute level effects (CALE) model was tested and was used to estimate both EQ-5D-5L and EQ-5D-3L value sets. In this study, we further tested this alternative model spcification in modelling two types of modified EQ-5D-5L states using a small cTTO design. Our results confirmed the good performance of the CALE model.

Objectives The EQ-5D-5L valuation protocol recommends combining time trade-off (TTO) and discrete choice experiments (DCEs). DCEs that include a duration attribute (DCETTO) allow modeling on the quality-adjusted life-year scale. Because the choice sequence in a TTO can be construed as a series of DCETTO, we used data from a single TTO study to investigate the extent to which DCE values match TTO values when based on identical preferences. Methods In a TTO design in which a fixed set of choices were administered without termination at preference indifference, 202 individuals each valued 10 EQ-5D health states. From identified indifference points, we estimated three sets of TTO values: (i) plotting means and (ii) applying censored regressions at −1 and 1. Using all strict preferences, we (iii) estimated DCETTO values with a logit model and a bootstrap procedure. Results Estimated DCETTO and TTO values agreed well at the severe end of the quality-adjusted life-year scale, but with decreasing severity, DCETTO values were higher than TTO-values, with the difference peaking at 0.37 for the mildest health state. Left-censoring TTO values at −1 worsen the agreement for the worst health states and did not affect health states. Right censoring at 1 improved the agreement for mild states. Conclusions TTO and the DCETTO values estimated from the same preference data diverged, with increasing difference for milder health states. Although the values converged when applying censored regression at +1, we question the validity of this adjustment.

The two primary objectives of this paper were (a) to develop first logically consistent TTO based EQ-5D-3L value sets for Slovenia and (b) to revisit earlier developed VAS based EQ-5D-3L value sets.Between September 2005 and April 2006, face-to-face interviews with 225 individuals in Slovenia were conducted. Protocols from the Measurement and Value of Health study were followed closely. Each respondent valued 15 health states out of a total of 23. Model selection was informed by the criteria monotonicity/logical consistency. Predictive accuracy was assessed in terms of mean square difference between out-of-sample predictions and corresponding observed means, as well as Lin's Concordance Correlation Coefficient.Modelling was based on 2,717 VAS and 2,831 TTO values elicited from 225 respondents. A 6-parameter constrained regression model with a supplementary power term was selected for VAS and TTO value sets, as it produces monotonic values, and proved superior in terms of out-of-sample predictive accuracy over the tested alternatives.This is the first EQ-5D-3L TTO based value set in Slovenia and the second in Central and Eastern Europe (besides Poland). It is also the first monotonic and logically consistent VAS value set in Central and Eastern Europe. Comparisons with Polish and UK TTO values show considerable differences, mostly due to mobility with having a substantially greater weight in Slovenia. The UK value set generally produces lower values and the Polish value set higher values for mild states.Dva osnovna cilja raziskave sta (a) prikazati prvi logično konsistentni vrednostni set EQ-5D-3L za Slovenijo, ki temelji na metodi časovne izmenjave, (b) izboljšati prejšnji vrednostni set EQ-5D-3L za Slovenijo, ki temelji na vrednostni lestvici (VAS-metodi).Od septembra 2005 do aprila 2006 je bilo opravljenih 225 osebnih intervjujev s posamezniki iz 40 slovenskih občin. Študija je natančno sledila protokolu študije MVH o merjenju in vrednotenju zdravja, ki je bila izvedena v Združenem kraljestvu. Vsak anketiranec je ocenil 15 od skupno 23 zdravstvenih stanj. Izbira modela za izračun vrednosti zdravstvenih stanj je temeljila na dveh osnovnih merilih: monotonosti in logični doslednosti vrednosti. Napovedno moč smo vrednotili s povprečno kvadrirano razliko med napovedmi izven vzorca in pripadajočimi ocenjenimi povprečji ter s pomočjo Linovega konkordančnega korelacijskega koeficienta.Izbrana modela temeljita na vrednostih zdravstvenih stanj 2,717 VAS in 2,831 TTO, ki smo jih pridobili v 225 osebnih intervjujih. Za oceno vrednosti VAS in TTO smo izbrali šestparametrski regresijski model z omejitvami in dodanim potenčnim faktorjem, saj se je izkazalo, da so ocenjene vrednosti na temelju tega modela monotone in imajo boljšo napovedno moč ocen izven vzorca kot vsi drugi ocenjevani modeli.V študiji smo prikazali prvi slovenski vrednostni set EQ-5D, ki temelji na metodi TTO, hkrati pa je to drugi set, izračunan v srednji in vzhodni Evropi (poleg Poljske). Gre tudi za prvi monotoni in logično dosledni vrednostni VAS-set tako v Sloveniji kot srednji in vzhodni Evropi. Primerjave z vrednostmi poljskega in britanskega TTO kažejo precejšnje razlike med vrednostmi posameznih zdravstvenih stanj, predvsem zaradi dimenzije pokretnosti, ki ima bistveno večjo težo v Sloveniji. Vrednosti TTO v Združenem Kraljestvu so na splošno nižje za manj težavna zdravstvena stanja, poljske vrednosti zdravstvenih stanj pa so na splošne višje.

Background Healthcare workers have reported increased anxiety while working in hospitals during the COVID-19 pandemic, and the role of healthcare students in a health crisis has been discussed among clinicians and researchers. The simultaneous international shortage of personal protection equipment (PPE) during the first wave of the pandemic potentially exposed healthcare workers and students to the virus during their work and clinical training. Our aim was therefore to evaluate the extent to which paramedic students in Oslo, Norway, were exposed to the SARS-CoV-2 virus and were involved in voluntary and/or paid healthcare-related work. An evaluation was also made of the students’ COVID-19-related symptoms and of their health-related quality of life (HRQoL) during the first wave of the pandemic. Methods Paramedic students (n = 155) at Oslo Metropolitan University, Norway, were invited to complete an online survey five months after the first cases of COVID-19 were detected. The university was situated in the epicenter of the pandemic in Norway. The responses were analyzed using descriptive statistics, independent sample t-tests, and linear regression analysis. Results Of the 109 respondents (70.3%), 40 worked in patient-related healthcare work. Of those, seven (17.5%) students experienced insufficient supplies of PPE, six (15.0%) participated in aerosol-generating procedures without adequate PPE, and nine (22.5%) experienced insufficient time to don PPE. Seventy-five (70.1%) students experienced no COVID-19-related symptoms, and no students tested positive for COVID-19. HRQoL was scored 0.92 (sd 0.12), which was significantly higher than for the general population before the pandemic (p = 0.002). Students continued with their education and participated in a variety of pandemic-related emergency tasks during the first wave of the pandemic. Conclusions Paramedic students were valuable contributors to the national pandemic response. Despite potential exposure to SARS-CoV-2 in unpredictable emergency settings with limited supplies of personal protection equipment, no students tested positive for COVID-19. Their health-related quality of life remained high. Students’ participation and utilization in similar health crises should be considered in future health crises.

Background. National valuation studies are costly, with ∼1000 face-to-face interviews recommended, and some countries may deem such studies infeasible. Building on previous studies exploring sample size, we determined the effect of sample size and alternative model specifications on prediction accuracy of modeled coefficients in EQ-5D-5L value set generating regression analyses. Methods. Data sets ( n = 50 to ∼1000) were simulated from 3 valuation studies, resampled at the respondent level and randomly drawn 1000 times with replacement. We estimated utilities for each subsample with leave-one-out at the block level using regression models (8 or 20 parameter; with or without a random intercept; time tradeoff [TTO] data only or TTO + discrete choice experiment [DCE] data). Prediction accuracy, root mean square error (RMSE), was calculated by comparing to censored mean predicted values to the left-out block in the full data set. Linear regression was used to estimate the relative effect of changes in sample size and each model specification. Results. Results showed that doubling the sample size decreased RMSE by on average 0.012. Effects of other model specifications were smaller but can when combined compensate for loss in prediction accuracy from a small sample size. For models using TTO data only, 8-parameter models clearly outperformed 20-parameter models. Adding a random intercept, or including DCE responses, also improved mean RMSE, most prominently for variants of the 20-parameter models. Conclusions. The prediction accuracy impact of further increases in sample size after 300 to 500 were smaller than the impact of combining alternative modeling choices. Hybrid modeling, use of constrained models, and inclusion of random intercepts all substantially improve the expected prediction accuracy. Beyond a minimum of 300 to 500 respondents, the sample size may be better informed by other considerations, such as legitimacy and representativeness, than by the technical prediction accuracy achievable. Highlights Increases in sample size beyond a minimum in the range of 300 to 500 respondents provide smaller gains in expected prediction accuracy than alternative modeling approaches. Constrained, nonlinear models; time tradeoff + discrete choice experiment hybrid modeling; and including a random intercept all improved the prediction accuracy of models estimating values for the EQ-5D-5L based on data from 3 different valuation studies. The tested modeling choices can compensate for smaller sample sizes.

Background Stroke incidence rates have fallen in high-income countries over the last several decades, but findings regarding the trend over recent years have been mixed. The aim of the study was to describe and model temporal trends in incidence of stroke by age and sex between 2010 and 2015 in Norway, and to generate incidence projections towards year 2040. Methods All recorded strokes in Norway between 2010 and 2015 were extracted from the National Patient Registry and the National Cause of Death Registry. We report incidence by age, sex, and year; in raw numbers, per 100,000 person-years, by WHO and European standard populations; and generated statistical models by stroke type, age, sex, and year; and projected stroke incidence toward year 2040. Results The data covered 30.1 million person-years at risk, 53431 unique individuals hospitalized with a primary stroke diagnosis, and 6315 additional individuals registered as dead due to stroke. From 2010 to 2015, individuals suffering stroke per 100,000 person-years dropped from 239 to 195 (208 to 177 excluding immediate deaths). The decline was driven by ischemic strokes, with a statistically non-significant time trend for hemorrhagic stroke. Conclusions The age-dependent incidence of ischemic strokes in Norway is declining rapidly, and more than compensates for the growth and ageing of the population. Comparisons with historic incidence statistics show that the reduction in incidence rates has accelerated over the last two decades.

OBJECTIVES To evaluate the discriminative ability of negative values measured in 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L) value set studies. METHODS This is a secondary analysis of EQ-5D-5L value set studies from Singapore, the Netherlands, China, Thailand, and Canada in which health state values were elicited from a general population sample using a composite time trade-off (TTO) method. Mean values were calculated for health states with same severity. The association between the mean values and severity was evaluated using Pearson correlation (r). A linear mixed model using severity as the fixed effect was fitted for values. The analyses were performed separately for positive values (from a conventional TTO for health states considered "better than death") and negative values (from a lead time TTO for health states considered "worse than death"). RESULTS In Singapore (N = 1000; negative values 32.6%), the mean decreased with severity from 0.89 to 0.21 for positive values and increased with severity from -0.98 to -0.89 for negative values. The correlation between values and severity was much lower for negative values (r = -0.016) than for positive values (r = -0.614). The coefficient of severity in the linear mixed model for negative values was much smaller (coefficient = -0.009; pseudo-R2 < 0.001) compared with the model for positive values (coefficient = -0.041; pseudo-R2 = 0.337). Results using data sets from the other countries were similar. CONCLUSIONS Negative values are not associated with severity of health states in EQ-5D-5L valuation studies, suggesting poor discriminative ability of the lead time TTO method in valuing health states considered worse than death.

Objectives: Several studies have shown that patients with heart disease value hypothetical health states differently from the general population. We aimed to investigate the health preferences of patients with heart disease and develop a value set for the 5-level EQ-5D (EQ-5D-5L) based on these patient preferences. Methods: Patients with confirmed heart disease were recruited from 2 hospitals in Singapore. A total of 86 EQ-5D-5L health states (10 per patient) were valued using a composite time trade-off method according to the international valuation protocol for EQ-5D-5L; 20-parameter linear models and 8-parameter cross-attribute level effects models with and without an N45 term (indicating whether any health state dimension at level 4 or 5 existed) were estimated. Each model included patient-specific random intercepts. Model performance was evaluated for out-of-sample and in-sample predictive accuracy in terms of root mean square error. The discriminative ability of the utility values was assessed using heart disease-related functional classes. Results: A total of 576 patients were included in the analysis. The preferred model, with the lowest out-of-sample root mean square error, was a 20-parameter linear model including N45. Predicted utility values ranged from −0.727 for the worst state to 1 for full health; the value for the second-best state was 0.981. Utility values demonstrated good discriminative ability in differentiating among patients of varied functional classes. Conclusions: An EQ-5D-5L value set representing the preferences of patients with heart disease was developed. The value set could be used for patient-centric economic evaluation and health-related quality of life assessment for patients with heart disease. acceptedVersion

Introduction EQ-5D is an instrument which has been utilized for a variety of purposes, including in health-economic appraisals as an input into quality-adjusted life year (QALY) calculations. Indeed, it is the most-widely applied instrument for health-economic appraisal worldwide, and is recommended for use in QALY calculations by many national Health Technology Assessment (HTA) agencies. There is also a growing body of evidence for its usefulness in a variety of settings other than economic appraisals, but such use has not been well-documented. This study addresses this issue and documents how EQ-5D has been applied in both the non-economic and economic contexts. Methods The PubMed database was searched using the terms ‘EQ-5D’, ‘EQ-5D AND cost’, and ‘EQ-5D AND cost AND QALY’ from 1 January 1980 to 31 December 2019. We concentrated on 2019 publications for more detailed analyses. All the data collected for 2019 were downloaded and collected in EndNote. For 2019 only, we classified economic and non-economic use based on the inclusion of ‘cost’. We also checked by manual inspection whether the search terms were suitable in correctly identifying economic and non-economic use. Variants of the non-economic use of EQ-5D were classified as follows: (a) as a quality of life outcome measure; (b) as a tool for methodological research; (c) methodological issues of EQ-5D itself; (d) comparisons with other quality of life questionnaires; (e) mapping studies; (f) value sets; (g) alongside costs but no QALY calculated; and (h) other. Results The first publication found was from 1990. Up to and including 2019, 10,817 publications were identified, of which more than two in three did not contain any reference to costs or QALYs. In 2019, a total of 1409 manuscripts were identified, of which 239 were specifically for EQ-5D-5L. Four hundred and seven (28.9%) included some form of ‘costs’ and 157 (11.1%) both ‘costs’ AND ‘QALYs’ terms. For EQ-5D-5L, the corresponding numbers were 104 (43.5%) and 29 (12.1%), respectively. After manually checking all the 1409 papers, three were duplicated records, which were omitted. In the remaining 1406 papers, only 40 (2.8%) contained the term ‘cost’, but not ‘cost per QALY’, and only 117 (8.3%) were identifiable as economic evaluations using the term ‘cost per QALY’. Most non-economic use of EQ-5D was as a quality-of-life outcome measure (72.8%). Other applications were: as a tool for methodological research (6.7%); comparison studies (3.7%); EQ-5D methodological issues (3.5%); containing costs but not QALYs (2.8%); mapping (1.3%); value sets (0.4%); and other papers (0.4%). Conclusions The majority of the studies retrieved, covering a wide variety of research areas, reported upon the non-economic use of EQ-5D. Despite being the most-used instrument worldwide for QALY calculations, economic appraisal accounted for only a small, but important, part of published use.

IntroductionNorway is one of several European countries that lacks a national value set and scoring algorithm for the EuroQol five dimensions (EQ-5D). Recent studies have found differences between countries in terms of health values or preferences for health states described by instruments such as the EQ-5D. The project aims to model a national value set for the five level version of the EQ-5D based on values elicited from a representative sample of the Norwegian adult general population in terms of region, age, sex and level of education. Using a sampling strategy supporting the collection of values for both hypothetical and experienced health states, the study will have the additional aim of assessing the feasibility of collecting experience-based values in accordance with the latest EQ-5D valuation study protocol, and comparing values with those given for hypothetical health states.Methods and analysisMultistage random sampling and quota-sampling will contribute to representativeness. To increase the number of valuations of experienced health states, those with less than perfect health will be oversampled, increasing the total number of interviews from 1000 to 1300–1500. The most recent EQ-5D valuation protocol will be followed which includes computer assisted face-to-face, one-to-one interviews and use of composite time trade-off and discrete choice experiments.Ethics and disseminationThe study has been reviewed and found to be outside of the scope of the ethics committee and thus not in need of ethical approval. The study findings will be disseminated through peer-reviewed publications, conference presentations and summaries for key stakeholders and partners in the field. The scoring algorithms will be available for widely used statistical software.

Objectives There are several issues of concern for the composite time trade-off (c-TTO) used to estimate EQ-5D-5L value sets. The “nonstopping” TTO (n-TTO) differs from the c-TTO mainly in 2 aspects: (1) n-TTO uses a standardized top-down or bottom-up routing; and (2) n-TTO continues when indifference is indicated by respondents. In this study, we aimed to test the feasibility of n-TTO and compared it with c-TTO. Methods The study was conducted in parallel in Norway and Singapore. In both countries, members of the general population were invited to complete 10 n-TTO or c-TTO tasks. Acceptability and feasibility of n-TTO were assessed using respondents’ feedback, administration time, and valuation success rate. Characteristics of the TTO data derived from c-TTO and n-TTO tasks were examined at task, individual, as well as group levels. Results In both Norway and Singapore, the success rate of n-TTO tasks was high (> 95%) and the n-TTO tasks took less time to complete than the c-TTO tasks, and there were fewer or smaller “spikes” in the distributions of n-TTO data compared to c-TTO data. In Norway, the individual-level n-TTO and c-TTO data had similar distribution and logical consistency profiles. In Singapore, n-TTO was inferior to c-TTO in logical consistency; however, a similar degree of nonmonotonicity was observed in modeling of n-TTO and c-TTO data. Conclusions The noniterative n-TTO appeared to be feasible and may generate data with better distribution in shorter time than c-TTO. Further research is needed to assess this new health-state valuation method.

Purpose So far there is no Norwegian value algorithm to inform healthcare decision making. The 15D health state values estimated with the original 15D valuation procedure tend to be higher than the values of other generic preference-based health-related quality of life (HRQoL) instruments. The main purpose of this study was to use a new 15D valuation procedure to estimate Norwegian 15D health state values and to explore their empirical performance. Methods The visual analogue scale was used to collect 15D valuation data in a representative sample of the Norwegian general population. The new procedure used fewer valuation tasks and anchored the 15D health state values in an empirically assessed range. The Norwegian 15D health state values were compared to the values of five HRQoL instruments which were provided by Norwegian residents belonging to seven disease groups and a healthy population. Results The Norwegian 15D health state values ranged from 1 to − 0.52. Compared to 15D health state values estimated with the original procedure, the Norwegian 15D health state values were lower and more in line with values of other HRQoL instruments. Conclusions The new 15D valuation procedure is simpler, links the 15D health state values better to the requirements of the QALY model, and provides an empirically-based range. We recommend using the new valuation procedure in future 15D valuation studies, and the Norwegian health state values for use in 15D-based health economic analyses in Norway. Keywords Health-related quality of life 15D Visual analogue scale Value algorithm NORGES FORSKNINGSRÅD Prosjektkode: 213127 Prosjektkode: 229101

Introduction While there is a general agreement that stroke incidence among the elderly is declining in the developed world, there is a concern that it may be increasing among the young. The present study investigates this issue for the Norwegian population for the years 2010–2015. Cerebrovascular accidents (CVAs) for patients younger than 55 years were identified through the Norwegian Patient Registry and the Norwegian Cause-of-death Registry. Methods Negative binomial regression modelling was used to estimate temporal trends in the CVA incidence rates for the young, aged 15–54, with 10-year sub-intervals, and for children below the age of 18. The main outcomes were CVA incidence per 100,000 person-years at risk (PY), 30-day stroke mortality per 100,000 PY, and 30-day case-fatality rates. Results The analysis showed a negative and non-significant temporal trend in the CVA incidence (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 0.052$$\end{document}p=0.052) as well as for 30-day mortality (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 0.074$$\end{document}p=0.074) for the age group 15–54. Overall, the inclusion of an interaction for age in the bracket 45–54 suggested that any temporal decline is restricted to this age bracket. The analyses of the 10-year age brackets 15–24, 25–34, and 34–45, provided evidence neither for an increase, nor for a decrease, in incidence. Among the children, the estimated temporal coefficients were positive, but non-significant, consistent with a stationary trend. Conclusion Weak statistical evidence was found for a decline in CVA incidence and for overall stroke 30-day case fatality for 15–54 year olds, but the decline was significant only for the 45–54 age band. All results considered, the study suggests a stationary or decreasing temporal trend in CVA incidence and stroke fatality for children (0–18) and young (15–54) in Norway. Even larger data sets are needed to estimate these temporal trends accurately.

Background The 5-level version of the EQ-5D (EQ-5D-5L) was introduced as an improvement on the original 3-level version (EQ-5D-3L). To date, 6 country-specific value sets have been published for EQ-5D-5L and 9 US value sets have been published for other instruments. Our aims were to (1) produce EQ-5D-5L values on a quality-adjusted life year (QALY) scale from the perspective of US adults and (2) compare them with US EQ-5D-3L values and the other country-specific EQ-5D-5L values. Methods In 2016, 8222 US respondents from all 50 states and Washington, DC completed an online survey including a discrete choice experiment with 20 paired comparisons. Each comparison asked respondents, "Which do you prefer?" regarding a pair of alternatives described using EQ-5D-5L and lifespan attributes. On the basis of more than 50 choices on each of the 3160 pairs, we estimated EQ-5D-5L values on a QALY scale and compared them with the US EQ-5D-3L values and the other country-specific EQ-5D-5L values. Results Ranging from -0.287 (55555) to 0.992 (11121) on a QALY scale, the estimated EQ-5D-5L values were similar to the US EQ-5D-3L values. Compared with the US EQ-5D-3L values, the values exhibited greater sensitivity and specificity and higher correlation with the EQ-5D-5L values of other countries, particularly England. Conclusions Like previous US valuation studies, this study produced nationally representative EQ-5D-5L values on a QALY scale. The results further demonstrate the advantages of the EQ-5D-5L over its 3-level predecessor as a preference-based summary measure of health-related quality of life from the perspective of US adults.

Utility values are critical for cost-utility analyses that guide healthcare decisions. We aimed to compare the utility values of the 5-level EuroQoL-5Dimension (EQ-5D-5L) health states elicited from members of the general public and patients with heart disease or cancer. In face-to-face interviews with 157 heart disease patients, 169 cancer patients, and 169 members from the general population, participants valued 10 EQ-5D-5L health states using a composite Time Trade-Off method. Pooling utility values for all health states, heart disease patients and cancer patients had mean utility values lower by 0.11 points (P value = 0.014) and 0.06 points (P value = 0.148), respectively, compared to the general population. Adjusting for sociodemographic characteristics, differences in health state utility values between the patient and the general populations were rendered non-significant, except that heart disease patients gave higher utility values (mean difference = 0.08; P value = 0.007) to mild health states than the general population. Difference in utility values, defined as utility value of a better health state minus that of a poorer health state, was higher among heart disease patients compared to the general population, before and after adjusting for sociodemographic characteristics. Patients may differ from members of the general population in the strength of their preferences for hypothetical health states. Using utility values derived from the general population may under-estimate the comparative effectiveness of healthcare interventions for certain diseases, such as heart diseases.

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. Copyright (c) 2019, ISPOR-The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The aim of this study was to develop an EQ-5D-5L value set reflecting the health preferences of the Malaysian adult population. Respondents were sampled with quotas for urbanicity, gender, age, and ethnicity to ensure representativeness of the Malaysian population. The study was conducted using a standardized protocol involving the EuroQol Valuation Technology (EQ-VT) computer-assisted interview system. Respondents were administered ten composite time trade-off (C-TTO) tasks and seven discrete choice experiment (DCE) tasks. Both linear main effects and constrained non-linear regression models of C-TTO-only data and hybrid models combining C-TTO and DCE data were explored to determine an efficient and informative model for value set prediction. Data from 1125 respondents representative of the Malaysian population were included in the analysis. Logical consistency was present in all models tested. Using cross-validation, eight-parameter models for C-TTO only and C-TTO + DCE hybrid data displayed greater out-of-sample predictive accuracy than their 20-parameter, main-effect counterparts. The hybrid eight-parameter model was chosen to represent the Malaysian value set, as it displayed greater out-of-sample predictive accuracy over C-TTO data than the C-TTO-only model, and produced more precise estimates. The estimated value set ranged from − 0.442 to 1. The constrained eight-parameter hybrid model demonstrated the best potential in representing the Malaysian value set. The presence of the Malaysian EQ-5D-5L value set will facilitate its application in research and health technology assessment activities.