Societal Preferences in Health Technology Assessments for Rare Diseases and Orphan Drugs: A Systematic Literature Review of New Analytic Approaches.

OBJECTIVES: This systematic literature review aimed to explore experiences worldwide of societal preferences integration into health technology assessments (HTAs) for rare diseases (RDs) and orphan drugs (ODs) through the implementation of multicriteria decision analysis (MCDA), discrete choice experiments (DCEs), and person trade-off (PTO) methods, among others. METHODS: A systematic search of the literature was conducted in April 2021 using PubMed, Cochrane, Embase, and Scopus databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach was used for the review phases. Finally, the Promoting Action on Research Implementation in Health Services framework was used to discuss the implementation of these instruments in the RD context. RESULTS: A total of 33 articles met the inclusion criteria. The studies measured societal preferences for RD and OD as part of HTA using MCDA (n = 17), DCE (n = 8), and PTO (n = 4), among other methods (n = 4). These found that patients and clinicians do not prioritize funding based on rarity. The public is willing to allocate funds only if the OD demonstrates effectiveness and improves the quality of life, considering as relevant factors disease severity, unmet health needs, and quality of life. Conversely, HTA agency experts preferred their current approach, placing more weight on cost-effectiveness and evidence quality, even though they expressed concern about the fairness of the drug review process. CONCLUSIONS: MCDA, PTO, and DCE are helpful and transparent methods for assessing societal preferences in HTA for RD and OD. However, their methodological limitations, such as arbitrary criteria selection, subjective scoring methods, framing effects, weighting adaptation, and value measurement models, could make implementation challenging.

Can Independently Elicited Adult- and Child-Perspective Health-State Utilities Explain Priority Setting?

OBJECTIVES: Time trade-off (TTO) utilities for EQ-5D-Y-3L health states valued by adults taking a child's perspective are generally higher than their valuations of the same state for themselves. Ceteris paribus, the use of these utilities in economic evaluation implies that children gain less from treatments returning them to full health for a specified amount of time than adults. In this study, we explore if this implication affects individuals' views of priority-setting choices between treatments for adults and children. METHODS: We elicited TTO utilities for 4 health states in online interviews, in which respondents valued states for a 10-year-old child and another adult their age. Views on priority setting were studied with person trade-off (PTO) tasks involving the same health states. We tested the ability of the subjects' TTO utilities to predict these societal choices in PTO. RESULTS: There are no significant differences between adult and child health state valuations in our study, but we do observe a substantial preference for treating children over adults in the PTO task. CONCLUSIONS: Our findings suggest that perspective-dependent health-state utilities only explain a small part of views on priority setting between adults and children. External equity weights might be useful to better explain the higher priority given to children.

Disability weights for castration-resistant prostate cancer: an empirical investigation.

Introduction: Health state valuation and diagnostic-therapeutic pathways at the junction between non-metastatic and metastatic castration-resistant prostate cancer (CRPC) are not well documented. We aimed at: (i) estimating the disability weights (DWs) for health states across a continuum of disease from asymptomatic non-metastatic (nmCRPC) to symptomatic metastatic state (mCRPC); (ii) mapping the diagnostic-therapeutic pathway of nmCRPC in Italy. Methods: Structured qualitative interviews were performed with clinical experts to gather information on nmCRPC clinical pathway. An online survey was administered to clinical experts to estimate DWs for four CRPC health states defined from interviews and literature review (i.e., nmCRPC, asymptomatic mCRPC, symptomatic mCRPC, mCRPC in progression during or after chemotherapy). Clinicians' preferences for health states were elicited using the Person-Trade-Off (PTO) and Visual Analogue Scale (VAS) methods. DWs associated with each health state, from 0 (best imaginable health state) and 1 (worst imaginable health state), were estimated. Results: We found that the management of nmCRPC is heterogeneous across Italian regions and hospitals, especially with respect to diagnostic imaging techniques. DWs for PTO ranged from 0.415 (95% confidence interval [CI] 0.208-0.623) in nmCRPC to 0.740 (95% CI 0.560-0.920) in mCRPC, in progression during or after chemotherapy. DWs for VAS ranged between 0.246 (95% CI 0.131-0.361) in nmCRPC to 0.689 (95% CI 0.583-0.795) in mCRPC, in progression during or after chemotherapy. Conclusions: Estimated DWs suggest that delaying transition to a metastatic state might ease the disease burden at both patient and societal levels.

The relative value of carer and patient quality of life: A person trade-off (PTO) study.

Carer quality of life is increasingly considered alongside patient quality of life in economic evaluation. Important questions remain about how to value carer and patient quality of life effects alongside one another. In this study, we estimated the relative social value of two conceptualisations of carer quality of life (health-related and care-related) compared to patient quality of life. Relative valuations were estimated using a person trade-off (PTO) study with 990 representative members of the UK public. Participants chose between hypothetical services that improved the quality of life of carers and patients, iterating to a point of indifference. Overall 84% of participants completing the task were willing to trade patient and carer quality of life effects. Relative to a reference point of 1 for patient health-related quality of life, we estimated a social value of 0.74 for carer health-related quality of life effects and 0.69 for carer care-related quality of life effects. In conclusion, public preferences appear to support the inclusion of carer quality of life effects within economic evaluation. The results provide a means to value different carer quality of life outcomes in economic evaluation, where such values are needed and deemed appropriate.

Does the UK-public's aversion to inequalities in health differ by group-labelling and health-gain type? A choice-experiment.

Public health policy has two primary aims: promoting population health and reducing health inequalities. When these aims conflict, policy-makers must determine the relative importance to place on each in decision-making. We conducted a computer-based, face-to-face, choice-experiment to explore how the UK-public think government should act in these situations; and to explore how "inequality-aversion" may differ depending on the groups between which a health inequality exists and type of health an intervention provides. We tested three hypotheses: (1) the UK-public are more averse to inequalities in health between socioeconomic groups than they are to inequalities in health between neutrally labelled groups; (2) this difference is, at least in part, driven by the role non-health information plays in determining aversion to inequalities in health between socioeconomic groups; and (3) the UK-public are more willing to prioritise groups with lower lifetime health over groups with higher lifetime health if an intervention improves life-expectancy than if it improves quality-of-life. Eighty people participated in Sheffield and Hull in May/June 2019. Each participant completed three Person-Trade-Off exercises between interventions that would improve population health and reduce health inequalities, or improve population health by a larger amount but increase health inequalities. Participants were randomised to exercises involving scenarios with socioeconomic groups or neutrally-labelled groups, and each answered questions about three health-benefit types: increased life-expectancy; pain-relief; and mobility-improvement. Following the exercises, participants provided rationales for their selections. Respondents were (1) more averse to inequalities in health between socioeconomic groups than neutrally labelled groups. Participant rationales suggest (2) this divergence is partly motivated by factors other than health: for example, financial inequality between socioeconomic groups. The sample was also (3) more willing to prioritise neutrally labelled groups with lower lifetime health if an intervention improves life-expectancy rather than if it improves quality-of-life.

Exploring the relative value of end of life QALYs: Are the comparators important?

In the UK, life extending, end-of-life (EoL) treatments are an exception to standard cost-per-quality-adjusted life year (QALY) thresholds. This implies that greater value is placed on gaining these QALYs, than QALYs gained by the majority of other patient groups treated for anything else in the health system, even for other EoL contexts (such as quality of life (QoL) improvements alone). This paper reports a Person Trade-Off (PTO) study to test whether studies that find societal support for prioritising EoL life extensions can be explained by the severity, in terms of prospective QALYs loss, of the non-terminal comparator scenarios. Eight health scenarios were designed depicting i) QoL improvements for non-EoL temporary (T-QoL) and chronic (C-QoL) health problems and ii) QoL improvements and life extensions (LEs) for EoL health problems. Preferences were elicited from a quota sample of 901 Scottish respondents in 2016 using PTO techniques via Computer Assisted Personal Interview (CAPI). Our results indicate that there is little evidence to suggest that the severity of non-EoL comparator scenarios influence preferences for EoL treatments. Respondents do not appear to have a preference for EoL over non-EoL health gains; instead there is some indication that non-EoL health gains are preferred, particularly when compared to EoL-LE health gains. Comparing between QoL and life extending EoL scenarios, our results suggest QoL improvements are preferred to life extensions. Overall, results challenge current UK EoL policy which gives additional weight to EoL health gains, particularly EoL life extensions in the case of the National Institute for Health and Care Excellence (NICE).

Equity Weights for Priority Setting in Healthcare: Severity, Age, or Both?

BACKGROUND: Priority setting in healthcare can be guided by both efficiency and equity principles. The latter principle is often explicated in terms of disease severity and, for example, defined as absolute or proportional shortfall. These severity operationalizations do not explicitly consider patients' age, even though age may be inextricably related to severity and an equity-relevant characteristic. OBJECTIVE: This study examines the relative strength of societal preferences for severity and age for informing allocation decisions in healthcare. METHODS: We elicited preferences for severity and age in a representative sample of the public in The Netherlands (N = 1025) by applying choice tasks and person-trade-off tasks in a design in which severity levels and ages varied both separately and simultaneously between patient groups. We calculated person trade-off ratios and, in addition, applied ordinary least squares regression models to aid interpretation of the ratios when both severity and age varied. RESULTS: Respondents attached a higher weight (median of ratios: 2.46-3.50) to reimbursing treatment for relatively more severely ill and younger patients when preferences for both were elicited separately. When preferences were elicited simultaneously, respondents attached a higher weight (median of ratios: 1.98 and 2.42) to reimbursing treatment for relatively younger patients, irrespective of patients' severity levels. Ratios varied depending on severity level and age and were generally higher when the difference in severity and age was larger between groups. CONCLUSIONS: Our results suggest that severity operationalizations and equity weights based on severity alone may not align with societal preferences. Adjusting decision-making frameworks to reflect age-related societal preferences should be considered.

Disability Weights for Osteoporosis and Osteoporotic Fractures in South Korea.

BACKGROUND: Korea is expected to become an ultra-aged society, in which the elderly population will account for more than 20% of the total population, after 2025. Thus, the social costs due to osteoporotic fractures are expected to increase. Therefore, this study aimed to measure disability weights (DWs) of osteoporosis and osteoporotic fractures in Korea. METHODS: The scenarios were developed to standardize the severity of 6 health statuses: osteoporosis and osteoporotic fractures including wrist, hip, post-hip, vertebral, and post-vertebral fracture. The values for these 6 health statuses were sought via a person trade-off (PTO) approach. We measured the value by PTO and we calculated it to DW of 6 health statuses. Three clinical expertise panels of 33 experts were established, and face-to-face interviews were conducted from July to December 2017. RESULTS: The distribution of DW varied by panel. DWs ranged from 0.5 (Osteoporosis) to 0.857 (Hip fracture) for Panel 1, 0.091 (Osteoporosis) to 0.5 (Hip fracture) for Panel 2, and 0.091 (Osteoporosis) to 0.726 (Hip fracture) for Panel 3. The final values for the 6 health statuses obtained by pooling all data from 3 panels ranged from 0.286 (Osteoporosis) to 0.750 (Hip fracture). There was no significant difference in rankings for the 6 health statuses among the 3 panels. CONCLUSIONS: Comparing the DW of osteoporotic fracture in this study with other diseases in previous studies, it is predicted that osteoporotic fractures, especially hip fractures, will have a considerable burden of disease.

Societal Preferences for Funding Orphan Drugs in the United Kingdom: An Application of Person Trade-Off and Discrete Choice Experiment Methods.

BACKGROUND: It is unclear whether UK National Health Service (NHS) policies for orphan drugs, which permit funding of non-cost-effective treatments, reflect societal preferences. METHODS: We conducted person trade-off (PTO) and discrete choice experiment (DCE) among 3950 adults selected to be representative of the UK general population. Experimental design was informed by surveys of patients affected by rare diseases, their caregivers, health care staff, and policymakers. Societal preferences were estimated in relation to treating a common disease, increases in waiting lists, or filling of vacant NHS posts. Results of the DCE were applied to recently licensed orphan drugs. RESULTS: On the basis of equal cost, the majority of respondents to the PTO (54%; 95% confidence interval [CI] 50-59) chose to allocate funds equally between patients treated for rare diseases and those treated for common diseases, with 32% (95% CI 28-36) favoring treating rare diseases over treating common diseases (14%; 95% CI 11-17), which this reduced to 23% (95% CI 20-27) when rare disease treatments were 10 times more expensive. When framed differently, more respondents prioritized not increasing waiting list size (43%; 95% CI 39-48) than to treat rare disease patients (34%; 95% CI 30-38). DISCUSSION: The DCE indicated a greater preference for treating a common disease over a rare disease. Respondents agreed with five of 12 positive appraisal recommendations for orphan drugs, even if their list price was higher, but preferred the NHS not to fund the remainder. CONCLUSIONS: The general public does not value rarity as a sufficient reason to justify special consideration for additional NHS funding of orphan drugs. This has implications regarding the appropriateness of operating higher thresholds of cost-effectiveness.

Valuing QALYs at the end of life.

The possibility of weighting QALYs differently for different groups of patients has been a source of debate. Most recently, this debate has been extended to the relative value of QALYs at the end of life (EoL). The objective of this study is to provide evidence of societal preferences in relation to this topic. Three cross-sectional surveys were conducted amongst Spanish general population (n = 813). Survey 1 compared increases in life expectancy for EoL patients with health gains from temporary health problems. Survey 2 compared health gains for temporary health problems with quality of life gains at the EoL (palliative care). Survey 3 compared increases in life expectancy with quality of life gains, both for EoL patients. Preferences were elicited using Person Trade-Off (PTO) and Willingness to pay (WTP) techniques presenting two different durations of health benefit (6 and 18 months). Health benefits, measured in QALYs, were held constant in all comparisons. In survey 1 mean WTP was higher for life extending treatments than for temporary health problems and the majority of respondents prioritised life extension over temporary health problems in response to the PTO questions. In survey 2 mean WTP was higher for palliative care than for temporary health problems and 83% prioritized palliative care (for both durations) in the PTO questions. In survey 3 WTP values were higher for palliative care than for life extending treatments and more than 60% prioritized palliative care in the PTO questions. Our results suggest that QALYs gained from EoL treatments have a higher social value than QALYs gained from treatments for temporary health problems. Further, we found that people attach greater weight to improvements in quality of life than to life extension at the end of life.

Test-retest reliability of health state valuation techniques: the time trade off and person trade off.

Economic analysis is increasingly being employed in formal resource allocation decision-making processes in health care. As a consequence, the methods employed by economic analysts are increasingly subject to close scrutiny. One such area of methodology concerns the instruments used to elicit preferences for various health states for use in the construction of quality-adjusted life years. There are a number of techniques which may be used to elicit preferences and different techniques produce different results. The objective of this study was to explore the test-retest reliability of two techniques: Time Trade Off (TTO) and Person Trade Off (PTO) valuations were collected by a general population postal survey. A total of 798 respondents returned questionnaires. The intra class correlation coefficients ranged from 0.40 to 0.88 for TTO and, -0.17 to 0.82 for PTO, with the majority of coefficients being >0.50. The reliability coefficients varied between techniques and health states, with the TTO technique tending to produce higher coefficients. While the reliability results for TTO were generally positive, the reliability results for PTO are less clear.