Improving the Valuation of the EQ-5D-5L by Introducing Quality Control and Integrating TTO and DCE

Background: Recently, a new version of the standard EQ-5D questionnaire called EQ-5D-5L with 5 levels on each dimension was developed. To make the EQ-5D-5L suitable for use in economic evaluations, national value sets need to be developed. A standardized valuation protocol has been suggested for that purpose, to enable comparison of values across countries. This protocol included two elicitation techniques, the ‘composite time trade-off’ (C-TTO), and ‘discrete choice experiments’ (DCE). This thesis describes experiences with first use of that standardized protocol and major evolvements happening to it since, with a focus on the following three questions: 1) What problems may be encountered in the use of the EQ-5D-5L valuation protocol to generate national value sets? 2) How can the protocol be improved? 3) How can the produced data best be modelled to develop a value set? Conclusions: The studies presented in this thesis, together with similar work accomplished elsewhere, have resulted in an evolved valuation protocol for the EQ-5D-5L instrument, paired with a quality assurance procedure and novel analytical approaches. The updated protocol has enabled teams from all over the world to successfully establish EQ-5D-5L value sets

EQ-5D-5L valuation project for the Spanish population: a descriptive overview and preliminary results

The latest EQ-5D instrument, EQ-5D-5L, needs new country-specific valuation studies to obtain a value set adapted to the characteristics of the updated instrument. Eight countries from Europe, North and South America and Asia have participated on pilot exercises to develop a final protocol which will be commonly used to perform the valuation studies in each country. Spain is the first country where this protocol has been introduced as part of the Valuation Project for the Spanish Population. This discussion paper reports a descriptive overview of EQ-5D-5L valuation results in the Spanish population and its preliminary results.The survey has a two-stage sample plan. The first stage concentrates on the selection of Spanish regions. The 50 Spanish regions were ordered by population size, and the first 20 regions covering 80% of the total Spanish population were selected. In the second stage, a simple random sampling strategy on each of the selected regions was conducted. The sample size on each region was calculated multiplying the total sample size (1,000) by the percentage of the population on the region respect the total population of the select 20 regions. Data will be collected between 21st May and 15th June 2012 using the final agreed protocol by the EuroQol group. Primary data collection will be conducted by a specialist survey company with a second company conducting a strict quality control process to ensure interviews and data collection of highest quality. The final survey has three blocks of questions. The first block includes patient characteristics (age, gender, socioeconomic status and so on), and a respondent valuation of own health using the EQ-5D-5L. The second block contains 10 composite time trade-offs (TTO) questions, for states better than death classic TTO is used and the “Lead Time” TTO is used for those health states considered worse than death. In this case the lead time (period in full health) is 10 years and the time in the disease is another 10 years to be comparable with the classical TTO were there are 10 years in full health and 10 years in the disease. The last block contains 7 discrete choice experiments questions, where the participant has to choose between two states. Finally some questions about the difficulties of the survey are also included. Descriptive statistics of the final sample are reported. A detailed overview of summary statistics for the health state valuations is included. Different models were explored; hybrid TTO and DC model and DC conditional logistic rescaled with TTO values were used and compared

Using a stated preference discrete choice experiment to assess societal value from the perspective of patients with rare diseases in Italy

Background: Decision makers have huge problems when attempting to attribute social value to the improvements achieved by new drugs, especially when considering the use of orphan drugs for rare diseases. We present the results of a pilot study aimed to investigate patient preferences regarding public funding for drugs used to treat rare diseases. Methods: An online questionnaire was used as a discrete choice experiment (DCE) survey to explore the preferences of patients with cystic fibrosis and haemophilia in Italy. The questionnaire focused on relevant issues that were defined in a review of the literature. A conditional logistic model showed preferences for specific attributes. Results: A total of 54 questionnaires (20% response rate) were completed. The issues that received the greatest attention were improvement in health, treatment cost and value for money. However, disease severity and the availability of other treatments were important social values that could not be ignored. Conclusions: The findings presented here provide evidence as to what patients with cystic fibrosis or haemophilia think are the most important considerations on which to base decisions in health technology scenarios, and regarding the priorities for funding

Quality Control Process for EQ-5D-5L Valuation Studies

Background: The values of the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) are elicited using composite time trade-off and discrete choice experiments. Unfortunately, data quality issues and interviewer effects were observed in the first few EQ-5D-5L valuation studies. To prevent these issues from occurring in later studies, the EuroQol Group established a cyclic quality control (QC) process. Objectives: To describe this QC process and show its impact on data quality. Methods: A newly developed QC tool provided information about protocol compliance, interviewer effects, and mean values by health state severity. In a cyclic process, this information is initially used to evaluate whether new interviewers meet minimal quality requirements and later to provide feedback about how their performance may be improved. To investigate the impact of this cyclic process, we compared the quality of the data in Dutch and Spanish valuation studies that did not have this QC process with that in the follow-up studies in the same countries that used the QC process. Data quality was measured using protocol violations, variability between interviewers, the proportion of inconsistent responders, and clustering of composite time trade-off values. Results: In Spain, protocol violations were reduced from 87% in the valuation study to 5% in the follow-up study and in the Netherlands from 20% to 8%. In both countries, interviewers performed more homogeneously in the follow-up studies. The number of inconsistent respondents was reduced by 23.2% in Spain and 23.6% in the Netherlands. Values were less clustered in the follow-up studies. Conclusions: The implementation of a strict QC process in EQ-5D-5L valuation studies increases interviewer protocol compliance and promotes data quality

High-Dimensional Analysis of Single-Cell Flow Cytometry Data Predicts Relapse in Childhood Acute Lymphoblastic Leukaemia

B-cell Acute Lymphoblastic Leukaemia is one of the most common cancers in childhood, with 20% of patients eventually relapsing. Flow cytometry is routinely used for diagnosis and follow-up, but it currently does not provide prognostic value at diagnosis. The volume and the high-dimensional character of this data makes it ideal for its exploitation by means of Artificial Intelligence methods. We collected flow cytometry data from 56 patients from two hospitals. We analysed differences in intensity of marker expression in order to predict relapse at the moment of diagnosis. We finally correlated this data with biomolecular information, constructing a classifier based on CD38 expression. Artificial intelligence methods may help in unveiling information that is hidden in high-dimensional oncological data. Flow cytometry studies of haematological malignancies provide quantitative data with the potential to be used for the construction of response biomarkers. Many computational methods from the bioinformatics toolbox can be applied to these data, but they have not been exploited in their full potential in leukaemias, specifically for the case of childhood B-cell Acute Lymphoblastic Leukaemia. In this paper, we analysed flow cytometry data that were obtained at diagnosis from 56 paediatric B-cell Acute Lymphoblastic Leukaemia patients from two local institutions. Our aim was to assess the prognostic potential of immunophenotypical marker expression intensity. We constructed classifiers that are based on the Fisher's Ratio to quantify differences between patients with relapsing and non-relapsing disease. We also correlated this with genetic information. The main result that arises from the data was the association between subexpression of marker CD38 and the probability of relapse

Dealing with the health state ‘dead’ when using discrete choice experiments to obtain values for EQ-5D-5L heath states - Springer

__Abstract__ __Objective__ : To evaluate two different methods to obtain a dead (0)—full health (1) scale for EQ-5D-5L valuation studies when using discrete choice (DC) modeling. __Method__ : The study was carried out among 400 respondents from Barcelona who were representative of the Spanish population in terms of age, sex, and level of education. The DC design included 50 pairs of health states in five blocks. Participants were forced to choose between two EQ-5D-5L states (A and B). Two extra questions concerned whether A and B were considered worse than dead. Each participant performed ten choice exercises. In addition, values were collected using lead-time trade-off (lead-time TTO), for which 100 states in ten blocks were selected. Each participant performed five lead-time TTO exercises. These consisted of DC models offering the health state ‘dead’ as one of the choices—for which all participants’ responses were used (DCdead)—and a model that included only the responses of participants who chose at least one state as worse than dead (WTD) (DCWTD). The study also estimated DC models rescaled with lead-time TTO data and a lead-time TTO linear model. __Results__ : The DCdead and DCWTD models produced relatively similar results, although the coefficients in the DCdead model were slightly lower. The DC model rescaled with lead-time TTO data produced higher utility decrements. Lead-time TTO produced the highest utility decrements. __Conclusions__: The incorporation of the state ‘dead’ in the DC models produces results in concordance with DC models that do not include ‘dead’

The Indonesian EQ-5D-5L Value Set

Background: The EQ-5D is one of the most used generic health-related quality-of-life (HRQOL) instruments worldwide. To make the EQ-5D suitable for use in economic evaluations, a societal-based value set is needed. Indonesia does not have such a value set. Objective: The aim of this study was to derive an EQ-5D-5L value set from the Indonesian general population. Methods: A representative sample aged 17 years and over was recruited from the Indonesian general population. A multi-stage stratified quota method with respect to residence, gender, age, level of education, religion and ethnicity was utilized. Two elicitation techniques, the composite time trade-off (C-TTO) and discrete choice experiments (DCE) were applied. Interviews were undertaken by trained interviewers using computer-assisted face-to-face interviews with the EuroQol Valuation Technology (EQ-VT) platform. To estimate the value set, a hybrid regression model combining C-TTO and DCE data was used. Results: A total of 1054 respondents who completed the interview formed the sample for the analysis. Their characteristics were similar to those of the Indonesian population. Most self-reported health problems were observed in the pain/discomfort dimension (39.66%) and least in the self-care dimension (1.89%). In the value set, the maximum value was 1.000 for full health (health state ‘11111’) followed by the health state ‘11112’ with value 0.921. The minimum value was −0.865 for the worst state (‘55555’). Preference values were most affected by mobility and least by pain/discomfort. Conclusions: We now have a representative EQ-5D-5L value set for Indonesia. We expect our results will promote and facilitate health economic evaluations and HRQOL research in Indonesia

An exploration of methods for obtaining 0 = dead anchors for latent scale EQ-5D-Y values

Objectives Discrete choice experiments (DCEs) can be used to obtain latent scale values for the EQ-5D-Y, but these require anchoring at 0 = dead to meet the conventions of quality-adjusted life year (QALY) estimation. The primary aim of this study is to compare four preference elicitation methods for obtaining anchors for latent scale EQ-5D-Y values. Methods Four methods were tested: visual analogue scale (VAS), DCE (with a duration attribute), lag-time time trade-off (TTO) and the location-of-dead (LOD) approach. In computer-assisted personal interviews, UK general public respondents valued EQ-5D-3L health states from an adult perspective and EQ-5D-Y health states from a 10-year-old child perspective. Respondents completed valuation tasks using all four methods, under both perspectives. Results 349 interviews were conducted. Overall, respondents gave lower values under the adult perspective compared to the child perspective, with some variation across methods. The mean TTO value for the worst health state (33333) was about equal to dead in the child perspective and worse than dead in the adult perspective. The mean VAS rescaled value for 33333 was also higher in the child perspective. The DCE produced positive child perspective values and negative adult perspective values, though the models were not consistent. The LOD median rescaled value for 33333 was negative under both perspectives and higher in the child perspective. Discussion There was broad agreement across methods. Potential criteria for selecting a preferred anchoring method are presented. We conclude by discussing the decision-making circumstances under which utilities and QALY estimates for children and adults need to be commensurate to achieve allocative efficiency

eq5d: A command to calculate index values for the EQ-5D quality-of-life instrument

The eq5d command computes an index value using the individual mobility, self care, usual activities, pain or discomfort, and anxiety or depression responses from the EuroQol EQ-5D quality-of-life instrument. The command calculates index values using value sets from eight countries: the United Kingdom, the United States, Spain, Germany, the Netherlands, Denmark, Japan, and Zimbabwe

Response mapping to translate health outcomes into the generic health-related quality-of-life instrument EQ-5D: Introducing the mrs2eq and oks2eq commands

Reliable and accurate mapping techniques that translate health-related quality-of-life data into EQ-5D index values are now in demand by researchers conducting economic evaluation of health care technologies. In this article, we present two commands (mrs2eq and oks2eq) that translate data from two widely used disease-specific instruments into EQ-5D index values and predicted probabilities of being at a particular level on each EQ-5D domain. mrs2eq conducts a response mapping approach to transform data from the stroke-specific modified Rankin scale into index values from the generic quality-of-life EQ-5D instrument. oks2eq uses a response mapping model to estimate EQ-5D index values based on patients’ responses to the Oxford Knee Score