Rationale, conceptual issues, and resultant protocol for a mixed methods Person Trade Off (PTO) and qualitative study to estimate and understand the relative value of gains in health for children and young people compared to adults.

BACKGROUND: Economic evaluation of healthcare typically assumes that an identical health gain to different patients has the same social value. There is some evidence that the public may give greater value to gains for children and young people, although this evidence is not always consistent. We present a mixed methods study protocol where we aim to explore public preferences regarding health gains to children and young people relative to adults, in an Australian setting. METHODS: This study is a Person Trade Off (PTO) choice experiment that incorporates qualitative components. Within the PTO questions, respondents will be asked to choose between treating different groups of patients that may differ in terms of patient characteristics and group size. PTO questions will be included in an online survey to explore respondent views on the relative value of health gains to different age groups in terms of extending life and improving different aspects of quality of life. The survey will also contain attitudinal questions to help understand the impact of question style upon reported preferences. Additionally, the study will test the impact of forcing respondents to express a preference between two groups compared with allowing them to report that the two groups are equivalent. One-to-one 'think aloud', semi-structured interviews will be conducted to explore a sub-sample of respondents' motivations and views in more detail. Focus groups will be conducted with members of the public to discuss the study findings and explore their views on the role of public preferences in health care prioritisation based on patient age. DISCUSSION: Our planned study will provide valuable information to healthcare decision makers in Australia who may need to decide whether to pay more for health gains for children and young people compared with adults. Additionally, the methodological test of forcing respondent choice or allowing them to express equivalence will contribute towards developing best practice methods in PTO studies. The rationale for and advantages of the study approach and potential limitations are discussed in the protocol.

Using Patient Preferences in Health Technology Assessment: Evaluating Quality-Adjusted Survival Equivalents (QASE) for the Quantification of Non-health Benefits.

Interest in using patient preference (PP) data alongside traditional economic models in health technology assessment (HTA) is growing, including using PP data to quantify non-health benefits. However, this is limited by a lack of standardised methods. In this article, we describe a method for using discrete choice experiment (DCE) data to estimate the value of non-health benefits in terms of quality-adjusted survival equivalence (QASE), which is consistent with the concept of value prevalent among HTA agencies. We describe how PP data can be used to estimate QASE, assess the ability to test the face-validity of QASE estimates of changes in mode of administration calculated from five published DCE oncology studies and review the methodological and normative considerations associated with using QASE to support HTA. We conclude that QASE may have some methodological advantages over alternative methods, but this requires DCEs to estimate second-order effects between length and quality of life. In addition, empirical work has yet to be undertaken to substantiate this advantage and demonstrate the validity of QASE. Further work is also required to align QASE with normative objectives of HTA agencies. Estimating QASE would also have implications for the conduct of DCEs, including standardising and defining more clear attribute definitions.

Recommendations for Emerging Good Practice and Future Research in Relation to Family and Caregiver Health Spillovers in Health Economic Evaluations: A Report of the SHEER Task Force.

BACKGROUND: Omission of family and caregiver health spillovers from the economic evaluation of healthcare interventions remains common practice. When reported, a high degree of methodological inconsistency in incorporating spillovers has been observed. AIM: To promote emerging good practice, this paper from the Spillovers in Health Economic Evaluation and Research (SHEER) task force aims to provide guidance on the incorporation of family and caregiver health spillovers in cost-effectiveness and cost-utility analysis. SHEER also seeks to inform the basis for a spillover research agenda and future practice. METHODS: A modified nominal group technique was used to reach consensus on a set of recommendations, representative of the views of participating subject-matter experts. Through the structured discussions of the group, as well as on the basis of evidence identified during a review process, recommendations were proposed and voted upon, with voting being held over two rounds. RESULTS: This report describes 11 consensus recommendations for emerging good practice. SHEER advocates for the incorporation of health spillovers into analyses conducted from a healthcare/health payer perspective, and more generally inclusive perspectives such as a societal perspective. Where possible, spillovers related to displaced/foregone activities should be considered, as should the distributional consequences of inclusion. Time horizons ought to be sufficient to capture all relevant impacts. Currently, the collection of primary spillover data is preferred and clear justification should be provided when using secondary data. Transparency and consistency when reporting on the incorporation of health spillovers are crucial. In addition, given that the evidence base relating to health spillovers remains limited and requires much development, 12 avenues for future research are proposed. CONCLUSIONS: Consideration of health spillovers in economic evaluations has been called for by researchers and policymakers alike. Accordingly, it is hoped that the consensus recommendations of SHEER will motivate more widespread incorporation of health spillovers into analyses. The developing nature of spillover research necessitates that this guidance be viewed as an initial roadmap, rather than a strict checklist. Moreover, there is a need for balance between consistency in approach, where valuable in a decision making context, and variation in application, to reflect differing decision maker perspectives and to support innovation.

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.

We need to talk about values: a proposed framework for the articulation of normative reasoning in health technology assessment.

It is acknowledged that health technology assessment (HTA) is an inherently value-based activity that makes use of normative reasoning alongside empirical evidence. But the language used to conceptualise and articulate HTA's normative aspects is demonstrably unnuanced, imprecise, and inconsistently employed, undermining transparency and preventing proper scrutiny of the rationales on which decisions are based. This paper - developed through a cross-disciplinary collaboration of 24 researchers with expertise in healthcare priority-setting - seeks to address this problem by offering a clear definition of key terms and distinguishing between the types of normative commitment invoked during HTA, thus providing a novel conceptual framework for the articulation of reasoning. Through application to a hypothetical case, it is illustrated how this framework can operate as a practical tool through which HTA practitioners and policymakers can enhance the transparency and coherence of their decision-making, while enabling others to hold them more easily to account. The framework is offered as a starting point for further discussion amongst those with a desire to enhance the legitimacy and fairness of HTA by facilitating practical public reasoning, in which decisions are made on behalf of the public, in public view, through a chain of reasoning that withstands ethical scrutiny.

Estimation of Health State Utility Values in Fabry Disease Using Vignette Development and Valuation.

Background: Health state utilities are measures of health-related quality of life that reflect the value placed on improvements in patients' health status and are necessary for estimation of quality-adjusted life-years. Health state utility data on Fabry disease (FD) are limited. In this study we used vignette (scenario) construction and valuation to develop health state utilities. Objectives: The aim of this study was to use vignette construction and valuation to estimate health state utility values suitable for inclusion in economic models of FD treatments. Methods: Health state vignettes were developed from semistructured qualitative telephone interviews with patients with FD and informed by published literature and input from an expert. Each vignette was valued in an online survey by members of the United Kingdom (UK) general population using the composite time trade-off (TTO) method, which aims to determine the time the respondent would trade to live in full health compared with each impaired health state. Results: Eight adults (50% women) with FD from the UK were interviewed. They were recruited via various approaches, including patient organizations and social media. The interviewees' responses, evidence from published literature, and input from a clinical expert informed the development of 6 health state vignettes (pain, moderate clinically evident FD [CEFD], severe CEFD, end-stage renal disease [ESRD], stroke, and cardiovascular disease [CVD]) and 3 combined health states (severe CEFD + ESRD, severe CEFD + CVD, and severe CEFD + stroke). A vignette valuation survey was administered to 1222 participants from the UK general population who were members of an external surveying organization and agreed to participate in this study; 1175 surveys were successfully completed and included in the analysis. Responses to TTO questions were converted into utility values for each health state. Pain was the highest valued health state (0.465), and severe CEFD + ESRD was the lowest (0.033). Discussion: Overall, mean utility values declined as the severity of the vignettes increased, indicating that respondents were more willing to trade life-years to avoid a severe health state. Conclusions: Health state vignettes reflect the effects of FD on all major health-related quality-of-life domains and may help to support economic modeling for treatment of FD.

Environmental impact assessment in health technology assessment: principles, approaches, and challenges.

To reduce harm to the environment resulting from the production, use, and disposal of health technologies, there are different options for how health technology assessment (HTA) agencies can consider environmental information. We identified four approaches that HTA agencies can use to take environmental information into account in healthcare decision making and the challenges associated with each approach. Republishing data that is in the public domain or has been submitted to an HTA agency we term the "information conduit" approach. Analyzing and presenting environmental data separately from established health economic analyses is described as "parallel evaluation." Integrating environmental impact into HTAs by identifying or creating new methods that allow clinical, financial, and environmental information to be combined in a single quantitative analysis is "integrated evaluation." Finally, evidence synthesis and analysis of health technologies that are not expected to improve health-related outcomes but claim to have relative environmental benefits are termed "environment-focused evaluation."

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.

Incorporating environmental and sustainability considerations into health technology assessment and clinical and public health guidelines: a scoping review.

Healthcare systems account for a substantial proportion of global carbon emissions and contribute to wider environmental degradation. This scoping review aimed to summarize the evidence currently available on incorporation of environmental and sustainability considerations into health technology assessments (HTAs) and guidelines to support the National In stitute for Health and Care Excellence and analogous bodies in other jurisdictions developing theirown methods and processes. Overall, 7,653 articles were identified, of which 24 were included in this review and split into three key areas - HTA (10 studies), healthcare guidelines (4 studies), and food and dietary guidelines (10 studies). Methodological reviews discussed the pros and cons of different approaches to integrate environmental considerations into HTAs, including adjustments to conventional cost-utility analysis (CUA), cost-benefit analysis, and multicriteria decision analysis. The case studies illustrated the challenges of putting this into practice, such as lack of disaggregated data to evaluate the impact of single technologies and difficulty in conducting thorough life cycle assessments that consider the full environmental effects. Evidence was scant on the incorporation of environmental impacts in clinical practice and public health guidelines. Food and dietary guidelines used adapted CUA based on life cycle assessments, simulation modeling, and qualitative judgments made by expert panels. There is uncertainty on how HTA and guideline committees will handle trade-offs between health and environment, especially when balancing environmental harms that fall largely on society with health benefits for individuals. Further research is warranted to enable integration of environmental considerations into HTA and clinical and public health guidelines.

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.

Spotlight environmental sustainability: a strategic priority for NICE.

This article provides the context for the ambition outlined in the the National Institute for Health and Care Excellence (NICE) 2021-2026 strategy to 'lead globally on the potential to include environmental impact data in its guidance to reduce the carbon footprint of health and care'. Anthropogenic environmental changes pose a catastrophic risk to human health, with potential to widen national and global health inequalities. Recognising the fact that NICE guidance influences the way health and care is delivered and its consequent environmental impact, NICE has included environmental sustainability among its strategic priorities. This article outlines the work underway to meet this sustainability agenda at NICE.

Assessing the comparative feasibility, acceptability and equivalence of videoconference interviews and face-to-face interviews using the time trade-off technique.

This study examines the comparative equivalence, feasibility and acceptability of video and in-person interviews in generating time trade-off (TTO) values. Sample participants in England were recruited using a blended approach of different methods and sampled based on age, gender, ethnicity, and index of multiple deprivation. Participants were randomly allocated to be interviewed either via video or in-person. Participants completed TTO tasks for the same block of 10 EQ-5D-5L health states using the EQ-VTv2 software. Feasibility, acceptability and equivalence was assessed across mode using: sample representativeness; participant understanding, engagement and feedback; participant preferred mode of interview; data quality; mean utility and distribution of values for each health state; and regression analyses assessing the impact of mode whilst controlling for participant characteristics. The video and in-person samples had statistically significant differences in ethnicity and income but were otherwise broadly similar. Video interviews generated marginally lower quality data across some criteria. Participant understanding and feedback was positive and similar across modes. TTO values were similar across modes; whilst mean in-person TTO values were lower for the more severe states, mode was insignificant in most regression analyses. There was no clear preference of mode across all participants, though the characteristics of participants preferring to be interviewed in-person or by video differs. Video and in-person TTO interviews were feasible, acceptable and generated good-quality data, though video interviews had lower quality data across some criteria. Whilst TTO values differed across modes for the more severe states, mode does not appear to be the cause. The study found that the characteristics of people preferring each mode differed, and this should be taken into account in future valuation studies since sample representativeness for some characteristics, and therefore potentially TTO values, could be affected by the choice of mode.

Criteria for developing, assessing and selecting candidate EQ-5D bolt-ons.

PURPOSE: 'Bolt-on' dimensions are additional items added to multi-attribute utility instruments (MAUIs) such as EQ-5D that measure constructs not included in the core descriptive system. The use of bolt-ons has been proposed to improve the content validity and responsiveness of the descriptive system in certain settings and health conditions. EQ-5D bolt-ons serve a particular purpose and thus satisfy a certain set of criteria. The aim of this paper is to propose a set of criteria to guide the development, assessment and selection of candidate bolt-on descriptors. METHODS: Criteria were developed using an iterative approach. First, existing criteria were identified from the literature including those used to guide the development of MAUIs, the COSMIN checklist and reviews of existing bolt-ons. Second, processes used to develop bolt-ons based on qualitative and quantitative approaches were considered. The information from these two stages was formalised into draft development and selection criteria. These were reviewed by the project team and iteratively refined. RESULTS: Overall, 23 criteria for the development, assessment and selection of candidate bolt-ons were formulated. Development criteria focused on issues relating to i) structure, ii) language, and iii) consistency with the existing EQ-5D dimension structure. Assessment and selection criteria focused on face and content validity and classical psychometric indicators. CONCLUSION: The criteria generated can be used to guide the development of bolt-ons across different health areas. They can also be used to assess existing bolt-ons, and inform their inclusion in studies and patient groups where the EQ-5D may lack content validity.

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

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

Exploration of the Reasons Why Health State Valuation Differs for Children Compared With Adults: A Mixed Methods Approach.

OBJECTIVES: Evidence comparing utilities for adults and children consistently report higher utility values for child health states. This study investigates the reasons why child health states are valued differently. METHODS: A total of 80 respondents (United Kingdom, Belgium, The Netherlands) participated in 1.5-hour face-to-face interviews. Respondents valued 4 health states from 2 perspectives (8-year-old child, 40-year-old adult) using visual analog scale and time trade-off. A total of 32 respondents participated in think-aloud interviews. Audio recordings were analyzed by 2 independent coders using NVIVO software. Statements, nodes, and themes were reviewed cyclically until consensus was reached. RESULTS: Qualitative results: a total of 5 themes were identified in the data regarding child and adult valuation-intergenerational responsibility and dependency (childhood is crucial for forming life skills based on new experiences; adulthood is an important time to take care of the family), staying alive is important (life is worth living even with impaired health-related quality of life (HRQoL), for children and adults), awareness of poor HRQoL and ability to make decisions (children have difficulties comprehending poor HRQoL and their parents make their healthcare decision; adults can assess their own HRQoL and decide for themselves), coping ability (children are flexible and resilient; adults have experience with dealing with difficulties), and practical organization of care (children are cared for by their parents; adults are able to organize and pay for care). Mixed methods: comparing qualitative statements with respondents' higher utilities for child health states confirmed concordance between results. CONCLUSIONS: Quality-adjusted life-years are interpreted differently for children and adults. Child-specific value sets are needed to reflect society's preferences and to adequately conduct health technology assessment of pediatric treatments.

Development and validation of Gaucher disease type 1 (GD1)-specific patient-reported outcome measures (PROMs) for clinical monitoring and for clinical trials.

BACKGROUND: Disease-specific patient-reported outcome measures (PROMs) are fundamental to understanding the impact on, and expectations of, patients with genetic disorders, and can facilitate constructive and educated conversations about treatments and outcomes. However, generic PROMs may fail to capture disease-specific concerns. Here we report the development and validation of a Gaucher disease (GD)-specific PROM for patients with type 1 Gaucher disease (GD1) a lysosomal storage disorder characterized by hepatosplenomegaly, thrombocytopenia, anemia, bruising, bone disease, and fatigue. RESULTS AND DISCUSSION: The questionnaire was initially developed with input from 85 patients or parents of patients with GD1 or GD3 in Israel. Owing to few participating patients with GD3, content validity was assessed for patients with GD1 only. Content validity of the revised questionnaire was assessed in 33 patients in the US, France, and Israel according to US Food and Drug Administration standards, with input from a panel of six GD experts and one patient advocate representative. Concept elicitation interviews explored patient experience of symptoms and treatments, and a cognitive debriefing exercise explored patients' understanding and relevance of instructions, items, response scales, and recall period. Two versions of the questionnaire were subsequently developed: a 24-item version for routine monitoring in clinical practice (rmGD1-PROM), and a 17-item version for use in clinical trials (ctGD1-PROM). Psychometric validation of the ctGD1-PROM was assessed in 46 adult patients with GD1 and re-administered two weeks later to examine test-retest reliability. Findings from the psychometric validation study revealed excellent internal consistency and strong evidence of convergent validity of the ctGD1-PROM based on correlations with the 36-item Short Form Health Survey. Most items were found to show moderate, good, or excellent test-retest reliability. CONCLUSIONS: Development of the ctGD1-PROM represents an important step forward for researchers measuring the impact of GD and its respective treatment.

EQ-5D-5L Health-State Values for the Mexican Population.

OBJECTIVE: To generate a value set for the Mexican adult general population to support and facilitate the inclusion of quality-adjusted life years (QALYs) into the health technology assessment process of the Mexican healthcare authorities. METHODS: A representative sample of the Mexican adult population stratified by age, sex and socio-economic status was used. Following version 2.0 of the EuroQol EQ-5D-5L valuation protocol, trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete-choice experiment (DCE) tasks included in the EQ-VT software. Generalized least squares, Tobit and Bayesian models were used for cTTO data. The choice of value set model was based on criteria that included: theoretical considerations, parsimony, logical ordering of coefficients, and statistical significance. RESULTS: Based on quality control criteria and interviewer judgment, 1000 out of 1032 participants provided useable responses. Participants' demographic characteristics were similar to the 2010 Mexican Population Census and followed the socioeconomic structure defined by the Mexican Association of Marketing Research and Public Opinion Agencies (AMAI). The predicted index values in the final cTTO model (a heteroscedastic censored model with Bayesian estimation) ranged from - 0.5960 to 1, with 19.7% of all predicted health state scores less than 0 (i.e., worse than dead). CONCLUSION: This study has generated the first value set representing the stated preferences of the Mexican adult population for use in estimating QALYs. The resulting EQ-5D-5L value set is technically robust and will facilitate health economic analyses as well as quality-of-life studies.