Modelling Spillover Effects on Informal Carers: The Carer QALY Trap.

The provision of informal (unpaid) care can impose significant 'spillover effects' on carers, and accounting for these effects is consistent with the efficiency and equity objectives of health technology assessment (HTA). Inclusion of these effects in health economic models, particularly carer health-related quality of life (QOL), can have a substantial impact on net quality-adjusted life year (QALY) gains and the relative cost effectiveness of new technologies. Typically, consideration of spillover effects improves the value of a technology, but in some circumstances, consideration of spillover effects can lead to situations whereby life-extending treatments for patients may be considered cost ineffective due to their impact on carer QOL. In this piece we revisit the classic 'QALY trap' and introduce an analogous 'carer QALY trap' which may have practical implications for economic evaluations where the inclusion of carer QOL reduces incremental QALY gains. Such results may align with a strict QALY-maximisation rule, however we consider the extent to which this principle may be at odds with the preferences of carers themselves (and possibly society more broadly), potentially leading decision makers into the carer QALY trap as a result. We subsequently reflect on potential solutions, highlighting the important (albeit limited) role that deliberation has to play in HTA.

Time and lexicographic preferences in the valuation of EQ-5D-Y with time trade-off methodology.

In the valuation of EQ-5D-Y-3L, adult respondents are asked to complete composite time trade-off (cTTO) tasks for a 10-year-old child. Earlier work has shown that cTTO utilities elicited in such a child perspective are generally higher than when adults take their own perspective. We explore how differences in time preference in child and adult perspectives could explain this effect. Furthermore, as cTTO valuation in a child perspective involves explicit consideration of immediate death for a child, we also consider how cTTO utilities could be affected by decision-makers lexicographically avoiding death in children. We report the results of an experiment in which 219 respondents valued 5 health states in both adult and child perspectives with either a standard cTTO or a lead-time TTO only approach, in which immediate death is less focal. Time preferences were measured in both perspectives. Our results suggest that utilities were lower when lead-time TTO, rather than cTTO, was used. We find large heterogeneity in time preference in both perspectives, with predominantly negative time preference. The influence of time preferences on utilities, however, was small, and correcting for time preferences did not reduce differences between utilities elicited in both perspectives. Surprisingly, we found more evidence for differences in utilities between adult and child perspectives when lead-time TTO was used. Overall, these results suggest that time and lexicographic preferences affect time trade-off valuation in child and adult perspectives, but are not the explanation for differences between these perspectives. We discuss the implications of our findings for EQ-5D-Y-3L valuation.

Analytical Considerations When Anchoring Discrete Choice Experiment Values Using Composite Time Trade-Off Data: The Case of EQ-5D-Y-3L.

Discrete choice experiments (DCEs) are becoming increasingly used to elicit preferences for children's health states. However, DCE data need to be anchored to produce value sets, and composite time trade-off (cTTO) data are typically used in the context of EQ-5D-Y-3L valuation. The objective of this paper is to compare different anchoring methods, summarise the characteristics of the value sets they produce, and outline key considerations for analysts. Three anchoring methods were compared using data from published studies: (1) rescaling using the mean value for the worst health state; (2) linear mapping; and (3) hybrid modelling. The worst state rescaling value set had the largest range. The worst state rescaling and linear mapping value sets preserved the relative importance of the dimensions from the DCE, whereas the hybrid model value set did not. Overall, the predicted values from the hybrid model value set were more closely aligned with the cTTO values. These findings are relatively generalisable. Deciding upon which anchoring approach to use is challenging, as there are numerous considerations. Where cTTO data are collected for more than one health state, anchoring on the worst health state will arguably be suboptimal. However, the final choice of approach may require value judgements to be made. Researchers should seek input from relevant stakeholders when commencing valuation studies to help guide decisions and should clearly set out their rationale for their preferred anchoring approach in study outputs.

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

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

Valuing EQ-5D-Y-3L Health States Using a Discrete Choice Experiment: Do Adult and Adolescent Preferences Differ?

BACKGROUND: An important question in the valuation of children's health is whether the preferences of younger individuals should be captured within value sets for measures that are aimed at them. This depends on whether younger individuals can complete valuation exercises and whether their preferences differ from those of adults. This study compared the preferences of adults and adolescents for EQ-5D-Y-3L health states using latent scale values elicited from a discrete choice experiment (DCE). METHODS: An online DCE survey, comprising 15 pairwise choices, was provided to samples of UK adults and adolescents (aged 11-17 y). Adults considered the health of a 10-year-old child, whereas adolescents considered their own health. Mixed logit models were estimated, and comparisons were made using relative attribute importance (RAI) scores and a pooled model. RESULTS: In total, 1000 adults and 1005 adolescents completed the survey. For both samples, level 3 in pain/discomfort was most important, and level 2 in self-care the least important, based on the relative magnitudes of coefficients. The RAI scores (normalized on self-care) indicated that adolescents gave less weight relative to adults to usual activities (1.18 v. 1.51; P < 0.05), pain/discomfort (1.77 v. 3.12; P < 0.01), and anxiety/depression (1.64 vs. 2.65; P < 0.01). The pooled model indicated evidence of differences between the two samples in both levels in pain/discomfort and anxiety/depression. LIMITATIONS: The perspective of the DCE task differed between the 2 samples, and no data were collected to anchor the DCE data to generate value sets. CONCLUSIONS: Adolescents could complete the DCE, and their preferences differed from those of adults taking a child perspective. It is important to consider whether their preferences should be incorporated into value sets.

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.

Economic evaluation of meningococcal vaccines: considerations for the future.

In 2018, a panel of health economics and meningococcal disease experts convened to review methodologies, frameworks, and decision-making processes for economic evaluations of vaccines, with a focus on evaluation of vaccines targeting invasive meningococcal disease (IMD). The panel discussed vaccine evaluation methods across countries; IMD prevention benefits that are well quantified using current methods, not well quantified, or missing in current cost-effectiveness methodologies; and development of recommendations for future evaluation methods. Consensus was reached on a number of points and further consideration was deemed necessary for some topics. Experts agreed that the unpredictability of IMD complicates an accurate evaluation of meningococcal vaccine benefits and that vaccine cost-effectiveness evaluations should encompass indirect benefits, both for meningococcal vaccines and vaccines in general. In addition, the panel agreed that transparency in the vaccine decision-making process is beneficial and should be implemented when possible. Further discussion is required to ascertain: how enhancing consistency of frameworks for evaluating outcomes of vaccine introduction can be improved; reviews of existing tools used to capture quality of life; how indirect costs are considered within models; and whether and how the weighting of quality-adjusted life-years (QALY), application of QALY adjustment factors, or use of altered cost-effectiveness thresholds should be used in the economic evaluation of vaccines.

A new method for valuing health: directly eliciting personal utility functions.

BACKGROUND: Standard methods for eliciting the preference data upon which 'value sets' are based generally have in common an aim to 'uncover' people's preferences by asking them to evaluate a subset of health states, then using their responses to infer their preferences over all dimensions and levels. An alternative approach is to ask people directly about the relative importance to them of the dimensions, levels and interactions between them. This paper describes a new stated preference approach for directly eliciting personal utility functions (PUFs), and reports a pilot study to test its feasibility for valuing the EQ-5D. METHODS: A questionnaire was developed, designed to directly elicit PUFs from general public respondents via computer-assisted personal interviews, with a focus on helping respondents to reflect and deliberate on their preferences. The questionnaire was piloted in England. RESULTS: Seventy-six interviews were conducted in December 2015. Overall, pain/discomfort and mobility were found to be the most important of the EQ-5D dimensions. The ratings for intermediate improvements in each dimension show heterogeneity, both within and between respondents. Almost a quarter of respondents indicated that no EQ-5D health states are worse than dead. DISCUSSION: The PUF approach appears to be feasible, and has the potential to yield meaningful, well-informed preference data from respondents that can be aggregated to yield a value set for the EQ-5D. A deliberative approach to health state valuation also has the potential to complement and develop existing valuation methods. Further refinement of some elements of the approach is required.

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

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

Valuing health at the end of life: A review of stated preference studies in the social sciences literature.

A source of debate in the health care priority setting literature is whether to weight health gains to account for equity considerations, such as concern for those with very short life expectancy. This paper reviews the empirical evidence in the published social sciences literature relevant to the following research question: do members of the public wish to place greater weight on a unit of health gain for end-of-life patients than on that for other types of patients? An electronic search of the Social Sciences Citation Index for articles published until October 2017 was conducted, with follow-up of references to obtain additional data. Hierarchical criteria were applied to select empirical studies reporting stated preferences relating to hypothetical health care priority setting contexts. Twenty-three studies met the inclusion criteria and were included in the review. Choice exercises were the most common method used to elicit preferences; other approaches included budget allocation, person trade-off and willingness-to-pay. Some studies found that observed preferences regarding end-of-life patients are influenced by information about the patients' ages. Overall, the evidence is mixed, with eight studies that report evidence consistent with a 'premium' for end-of-life treatments and 11 studies that do not. Methodological and design aspects that appear to influence the findings of end-of-life-related preference studies are identified and discussed. The findings of the UK studies have particular relevance for assessing the legitimacy of the National Institute for Health and Care Excellence's policy for appraising life-extending end-of-life treatments.

New methods for modelling EQ-5D-5L value sets: An application to English data.

Value sets for the EQ-5D-5L are required to facilitate its use in estimating quality-adjusted life years. An international protocol has been developed to guide the collection of stated preference data for this purpose and has been used to generate EQ-5D-5L valuation data for England. The aim of this paper is report the innovative methods used for modelling those data to obtain a value set. Nine hundred and ninety-six members of the English general public completed time trade-off (TTO) and discrete choice experiment (DCE) tasks. We estimate models, with and without interactions, using DCE data only, TTO data only, and TTO/DCE data combined. TTO data are interpreted as both left and right censored. Heteroskedasticity and preference heterogeneity between individuals are accounted for. We use Bayesian methods in the econometric analysis. The final model is chosen based on the deviance information criterion (DIC). Censoring and taking account of heteroskedasticity have important effects on parameter estimation. For DCE data only, TTO data only, and DCE/TTO data combined, models with parameters for all dimensions and levels perform best, as judged by the DIC. Taking account of heterogeneity improves fit, and the multinomial model reports the lowest DIC. This paper presents approaches that suit observed characteristics of EQ-5D-5L valuation data and recognise respondents' preference heterogeneity. The methods described are potentially relevant to other value set studies.

Valuing health-related quality of life: An EQ-5D-5L value set for England.

A new version of the EQ-5D, the EQ-5D-5L, is available. The aim of this study is to produce a value set to support use of EQ-5D-5L data in decision-making. The study design followed an international research protocol. Randomly selected members of the English general public completed 10 time trade-off and 7 discrete choice experiment tasks in face-to-face interviews. A 20-parameter hybrid model was used to combine time trade-off and discrete choice experiment data to generate values for the 3,125 EQ-5D-5L health states. Valuation data are available for 996 respondents. Face validity of the data has been demonstrated, with more severe health states generally given lower values. Problems with pain/discomfort and anxiety/depression received the greatest weight. Compared to the existing EQ-5D-3L value set, there are considerably fewer "worse than dead" states (5.1%, compared with over one third), and the minimum value is higher. Values range from -0.285 (extreme problems on all dimensions) to 0.950 (for health states 11211 and 21111). Results have important implications for users of the EQ-5D-5L both in England and internationally. Quality-adjusted life year gains from interventions seeking to improve very poor health may be smaller using this value set and may previously have been overestimated.

The effect of religion on the perception of health states among adults in the United Arab Emirates: a qualitative study.

OBJECTIVES: Investigate how religion may affect the perception of health states among adults in the United Arab Emirates and the implications for research on self-reported health and quality of life and the use of values in cost-effectiveness analysis. DESIGN: Qualitative analysis of short-structured interviews with adult Emiratis carried out by a market research agency.The COREQ criteria have been used where appropriate to guide the reporting of our findings. SETTING: Participants were recruited from shopping malls and other public places in the cities of Al Ain and Abu Dhabi. PARTICIPANTS: Two hundred adult Emiratis broadly representative of the Emirati population in terms of age and gender. RESULTS: Eighty one per cent of participants said that their perception of health states was influenced by their spiritual or religious beliefs. The two overarching themes that seemed to explain or classify these influences were 'fatalism' and 'preservation of life'. Subthemes included powerlessness to change what is preordained by God, fear of disability (particularly diminished mobility) and appreciation of health and life and the requirement to look after one's health. A final theme was that of acceptance, with respondents expressing a willingness to endure suffering and disability with patience in the expectation of rewards in the hereafter. CONCLUSIONS: Our results emphasise the need for further work to establish locally relevant value sets for Muslim majority countries in the Middle East and elsewhere for use in health technology assessment decision-making, rather than relying on value sets from other regions.

An Investigation of the Feasibility and Cultural Appropriateness of Stated Preference Methods to Generate Health State Values in the United Arab Emirates.

BACKGROUND: No five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) value sets are currently available in the Middle East to inform decision making in the region's health care systems. OBJECTIVES: To test the feasibility of eliciting EQ-5D-5L values from a general public sample in the United Arab Emirates (UAE) using the EuroQol Group's standardized valuation protocol. METHODS: Values were elicited in face-to-face computer-assisted personal interviews. Adult Emiratis were recruited in public places. Respondents completed 10 time trade-off tasks and 7 discrete choice experiment tasks, followed by debriefing questions about their experience of completing the valuation tasks. Descriptive analyses were used to assess the face validity of the data. RESULTS: Two hundred respondents were interviewed in December 2013. The face validity of the data appears to be reasonably high. Mean time trade-off values ranged from 0.81 for the mildest health state (21111) to 0.19 for the worst health state in the EQ-5D-5L descriptive system (55555). Health states were rarely valued as being worse than dead (6.2% of all observations; 10% of all valuations of 55555). In a rationality check discrete choice experiment task whereby a health state (55554) was compared with another that logically dominated it (55211), 99.5% of the respondents chose the dominant option. Most of the respondents stated that their religious beliefs influenced their responses to the valuation tasks. CONCLUSIONS: Our results suggest that it is feasible to generate meaningful health-state values in the UAE, though some adaptation of the methods may be required to improve their acceptability in the UAE (and other countries with predominantly Arab and/or Muslim populations).

Valuing health at the end of life: a stated preference discrete choice experiment.

A source of debate in the field of health care priority setting is whether health gains should be weighted differently for different groups of patients. The debate has recently focused on the relative value of life extensions for patients with short life expectancy. However, few studies have examined empirically whether society is prepared to fund life-extending end-of-life treatments that would not meet the reimbursement criteria used for other treatments. A web-based discrete choice experiment was conducted in 2012 using a sample of 3969 members of the general public in England and Wales. The study design was informed by the National Institute for Health and Care Excellence's supplementary policy for the appraisal of life-extending end-of-life treatments. The choice tasks involved asking respondents which of two hypothetical patients they would prefer to treat, assuming that the health service has enough funds to treat only one of them. Conditional logit regressions were used for modelling. Choices about which patient to treat were influenced more by the sizes of treatment gains than by patients' life expectancy without treatment. Some respondents appear to support a health-maximisation type objective throughout, whilst a small minority always seek to treat those who are worse off without treatment. The majority of respondents, however, seem to advocate a mixture of the two approaches. Overall, we find little evidence that members of the general public prefer to give higher priority to life-extending end-of-life treatments than to other types of treatment. When asked to make decisions about the treatment of hypothetical patients with relatively short life expectancies, most people's choices are driven by the size of the health gains offered by treatment.

Multinational evidence of the applicability and robustness of discrete choice modeling for deriving EQ-5D-5L health-state values.

AIMS: To investigate the feasibility of discrete choice experiments for valuing EQ-5D-5L states using computer-based data collection, the consistency of the estimated regression coefficients produced after modeling the preference data, and to examine the similarity of the values derived across countries. METHODS: Data were collected in Canada, England, The Netherlands, and the United States (US). Interactive software was developed to standardize the format of the choice tasks across countries, except for face-to-face interviewing in England. The choice task required respondents to choose between 2 suboptimal health states. A Bayesian design was used to generate 200 pairs of states that were randomly grouped into 20 blocks. Each respondent completed 1 block of 10 pairs. A main-effects probit model was used to estimate regression coefficients and to derive values. RESULTS: Approximately 400 respondents participated from each country. The mean time to perform 1 choice task was between 29.2 (US) and 45.2 (England) seconds. All regression coefficients were statistically significant, except level 2 for Usual Activities in The Netherlands (P=0.51). Predictions for the complete set of 3125 EQ-5D-5L health states were similar for the 4 countries. Intraclass correlation coefficients between the countries were high: from 0.80 (England vs. US) through 0.98 (Canada vs. US) CONCLUSIONS: Derivation of value sets from the general population using computer-based choice tasks for the EQ-5D-5L is feasible. Parameter estimates were generally consistent and logical, and health-state values were similar across the 4 countries.

Valuing health at the end of life: an empirical study of public preferences.

In 2009, the National Institute for Health and Clinical Excellence (NICE) issued supplementary advice to its Appraisal Committees to be taken into account when appraising life-extending, 'end-of-life' treatments. This indicated that if certain criteria are met, it may be appropriate to recommend the use of such treatments even if they would not normally be considered cost-effective. However, NICE's public consultation revealed concerns that there is little scientific evidence to support such a policy. This study examines whether there is public support for giving higher priority to life-extending, end-of-life treatments than to other types of treatment. In face-to-face interviews, respondents answered six questions asking them to choose which of two hypothetical patients they would prefer to treat, assuming that the health service has enough funds to treat one but not both of them. The various scenarios were designed so as to control for age- and time-related preferences. Fifty members of the general public in England were interviewed in July 2011. We find some evidence of support for giving priority to the patient with shorter remaining life expectancy, but note that a nontrivial minority of respondents expressed the opposite preference. Substantial preference for quality-of-life improvement over life extension was observed. Very few respondents expressed indifference or unwillingness to choose between the patients. Whilst there cannot be described to be a single 'consensus' set of preferences, we conclude that there are ways in which the results suggest that the current NICE policy may be insufficient.

One-to-one versus group setting for conducting computer-assisted TTO studies: findings from pilot studies in England and the Netherlands.

We compare two settings for administering time trade-off (TTO) tasks in computer-assisted interviews (one-to-one, interviewer-led versus group, self-complete) by examining the quality of the data generated in pilot studies undertaken in England and the Netherlands. The two studies used near-identical methods, except that in England, data were collected in one-to-one interviews with substantial amounts of interviewer assistance, whereas in the Netherlands, the computer aid was used as a self-completion tool in group interviews with lesser amounts of interviewer assistance. In total, 801 members of the general public (403 in England; 398 in the Netherlands) each completed five TTO valuations of EQ-5D-5L health states. Respondents in the Netherlands study showed a greater tendency to give 'round number' values such as 0 and 1 and to complete tasks using a minimal number of iterative steps. They also showed a greater tendency to skip the animated instructions that preceded the first task and to take into account assumptions that they were specifically asked not to take into account. When faced with a pair of health states in which one state dominated the other, respondents in the Netherlands study were more likely than those in the England study to give a higher value to the dominant health state. On the basis of these comparisons, we conclude that the one-to-one, interviewer-led setting is superior to the group, self-complete setting in terms of the quality of data generated and that the former is more suitable than the latter for TTO studies being used to value EQ-5D-5L.

NICE's social value judgements about equity in health and health care.

The National Institute for Health and Clinical Excellence (NICE) routinely publishes details of the evidence and reasoning underpinning its recommendations, including its social value judgements (SVJs). To date, however, NICE's SVJs relating to equity in the distribution of health and health care have been less specific and systematic than those relating to cost-effectiveness in the pursuit of improved total population health. NICE takes a pragmatic, case-based approach to developing its principles of SVJ, drawing on the cumulative experience of its advisory bodies in making decisions that command respect among its broad range of stakeholders. This paper aims to describe the SVJs about equity in health and health care that NICE has hitherto used to guide its decision making. To do this, we review both the general SVJs reported in NICE guidance on methodology and the case-specific SVJs reported in NICE guidance about particular health care technologies and public health interventions.