From Health to Wellbeing: Toward a Monetary Valuation of a Wellbeing-Adjusted Life-Year.

OBJECTIVES: Economic evaluations using broader measures to capture benefits beyond improved health can inform policy making, but only if the monetary value of gains measured using these instruments is understood. This study explored contingent valuation as a method to estimate the monetary value of a wellbeing-adjusted life-year (WALY) as measured by ICEpop Capability Measure for Adults (ICECAP-A). METHODS: In a large online survey of representative samples from 7 European countries, participants valued a change in the ICECAP-A from their current health state to a randomly assigned hypothetical state. Participants were instructed that an unspecified treatment could avoid a loss or produce a gain in wellbeing and were asked for their willingness to pay (WTP) for this treatment. WTP per WALY was calculated using an aggregated approach that used ICECAP-A tariffs from the United Kingdom. RESULTS: We analyzed a sample of 7428 observations, focusing on avoided losses (n = 6002) because the results for gains were not theoretically valid. Different cutoff points for a marginal change were explored. Depending on the definition of a marginal change, WTP per WALY averaged between €13 323.28 and €61 375.63 for avoided losses between [0, 0.5] and [0, 0.1], respectively, for 1 month. Mean WTP per WALY varied across the countries as follows: Denmark (€17 867.93-€88 634.14), France (€10 278.35-€45 581.28), Germany (€12 119.39-€54 566.56), Italy (€11 753.69-€52 161.25), The Netherlands (€14 612.88-€58 951.74), Spain (€11 904.12-€57 909.17), and United Kingdom (€13 133.75-€68 455.85). CONCLUSION: Despite the inherent limitations of our study, it offers valuable insights into methods for eliciting the WTP for changes in capability wellbeing as measured with ICECAP-A.

Construct Validity, Reliability, and Responsiveness of the 10-Item Well-being Instrument for Use in Economic Evaluation Studies.

OBJECTIVES: Economic evaluations of interventions in health and social care require outcome measures that capture their full benefits, including those beyond health. This study aimed to assess construct validity, test-retest reliability, and responsiveness of the newly developed 10-item Well-being instrument (WiX). METHODS: Data were gathered via an online survey in a representative sample of the adult general population in The Netherlands (N = 1045). Construct validity was assessed by inspecting convergent, structural, and discriminant validity, following the COnsensus-based Standards for the selection of health status Measurement INstruments methodology. Regression analyses of the WiX and its items on other validated measures of well-being were performed to assess the convergent validity of the instrument and the relevance of its items. Dimensionality of the WiX was assessed using exploratory factor analysis. To assess discriminant validity, several hypotheses in terms of well-being differences were assessed. Finally, a second survey was sent out 2 weeks after the initial survey (n = 563; 53.9% response rate) to assess the test-retest reliability and responsiveness of the WiX. RESULTS: The WiX showed to be correlated with alternative well-being measures as expected and able to sufficiently differentiate between relevant subgroups in the population. Moreover, the dimensionality analysis indicated that the WiX captures a broad array of elements relevant to well-being, including physical and mental health. The test-retest reliability was good, with an intraclass correlation coefficient of 0.82. CONCLUSIONS: The results regarding the WiX are favorable and indicate that this new instrument may be a promising alternative for existing measures of well-being for evaluating interventions in health and social care.

Effectiveness of Seizure Dogs for People With Severe Refractory Epilepsy: Results From the EPISODE Study.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate whether people living with severe medically refractory epilepsy (PSRE) benefit from a seizure dog. METHODS: An individual-level stepped-wedge randomized controlled trial was conducted. The study was conducted in the Netherlands among adults with daily to weekly seizures. All participants were included simultaneously (on June 1, 2019) while receiving usual care. Then, during the 36-month follow-up, they received a seizure dog in a randomized sequence. Participants kept a seizure diary and completed 3-monthly surveys. Seizure frequency was the primary outcome. Secondary outcomes included seizure-free days, seizure severity, health-related quality of life (HRQoL), and well-being. Data were analyzed using generalized linear mixed modeling (GLMM). The models assumed a delayed intervention effect, starting when the seizure dog reached an advanced stage of training. Effects were calculated as changes per 28-day period with the intervention. RESULTS: Data were collected from 25 participants, of whom 20 crossed over to the intervention condition. The median follow-up was 19 months with usual care and 12 months with the intervention. On average, participants experienced 115 (SD 164) seizures per 28-day period in the usual care condition and 73 (SD 131) seizures in the intervention condition. Seven participants achieved a reduction of 50% or more at the end of follow-up. GLMM indicated a 3.1% decrease in seizure frequency for each consecutive 28-day period with the intervention (0.969, 95% CI 0.960-0.977). Furthermore, an increase in the number of seizure-free days was observed (1.012, 95% CI 1.009, 1.015), but no effect on seizure severity measured with the NHS3. Generic HRQoL scores improved, as reflected in the decrease in EQ-5D-5L utility decrement (0.975, 95% CI 0.954-0.997). Smaller improvements were observed on overall self-rated HRQoL, epilepsy-specific HRQoL, and well-being, measured with the EQ VAS, QOLIE-31-P, and ICECAP-A, respectively. DISCUSSION: Seizure dogs reduce seizure frequency, increase the number of seizure-free days, and improve the quality of life of PSRE. The magnitude of the effect on generic HRQoL indicates that seizure dogs benefit PSRE beyond the impact on seizure frequency alone. Early discontinuation of seizure dog partnerships suggests that this intervention is not suitable for all PSRE and requires further study. TRIAL REGISTRATION INFORMATION: This study was registered in the Dutch Trial Register (NL6682) on November 28, 2017. Participants were enrolled on June 1, 2019. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that seizure dogs are associated with a decrease in seizure frequency in adult patients with medically refractory epilepsy.

The role of budget impact and its relationship with cost-effectiveness in reimbursement decisions on health technologies in the Netherlands.

Health authorities using cost-effectiveness analysis (CEA) for informing reimbursement decisions on health technologies increasingly require economic evaluations encompassing both CEA and budget impact analysis (BIA). Good Research Practices advocate that the economic and clinical assumptions underlying these analyses are aligned and consistently applied. Nonetheless, CEAs and BIAs often are stand-alone analyses used in different stages of the decision-making process. This article used policy reports and Ministerial correspondence to discuss and elucidate the role of budget impact and its relationship with cost-effectiveness in reimbursement decisions in the Netherlands. The results indicate that CEAs and BIAs are both considered important for informing these decisions. While the requirements regarding CEAs-and application of the associated decision rule-are consistent across the different stages, the same does not hold for BIAs. Importantly, the definition of and evidence on budget impact differs between stages. Some important aspects (e.g. substitution and saving effects) typically are considered in the assessment and appraisal stages but are seemingly not considered in price negotiations and the final reimbursement decision. Further research is warranted to better understand why BIAs are not aligned with CEAs (e.g. in terms of underlying assumptions), vary in form and importance between stages, and do not have a clear relationship with the results of CEAs in the decision-making framework. Improving the understanding of the circumstances under which decision-makers attach a relatively larger or smaller weight to (different aspects of) budget impact may contribute to increasing the transparency, consistency, and optimality of reimbursement decisions in the Netherlands.

On spillovers in economic evaluations: definition, mapping review and research agenda.

An important issue in economic evaluations is determining whether all relevant impacts are considered, given the perspective chosen for the analysis. Acknowledging that patients are not isolated individuals has important implications in this context. Increasingly, the term "spillovers" is used to label consequences of health interventions on others. However, a clear definition of spillovers is lacking, and as a result, the scope of the concept remains unclear. In this study, we aim to clarify the concept of spillovers by proposing a definition applicable in health economic evaluations. To illustrate the implications of this definition, we highlight the diversity of potential spillovers through an expanded impact inventory and conduct a mapping review that outlines the evidence base for the different types of spillovers. In the context of economic evaluations of health interventions, we define spillovers as all impacts from an intervention on all parties or entities other than the users of the intervention under evaluation. This definition encompasses a broader range of potential costs and effects, beyond informal caregivers and family members. The expanded impact inventory enables a systematic approach to identifying broader impacts of health interventions. The mapping review shows that the relevance of different types of spillovers is context-specific. Some spillovers are regularly included in economic evaluations, although not always recognised as such, while others are not. A consistent use of the term "spillovers", improved measurement of these costs and effects, and increased transparency in reporting them are still necessary. To that end, we propose a research agenda.

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.

Estimating a Preference-Based Value Set for the Mental Health Quality of Life Questionnaire (MHQoL).

BACKGROUND: Health economic evaluations using common health-related quality of life measures may fall short in adequately measuring and valuing the benefits of mental health care interventions. The Mental Health Quality of Life questionnaire (MHQoL) is a standardized, self-administered mental health-related quality of life instrument covering 7 dimensions known to be relevant across and valued highly by people with mental health problems. The aim of this study was to derive a Dutch value set for the MHQoL to facilitate its use in cost-utility analyses. METHODS: The value set was estimated using a discrete choice experiment (DCE) with duration that accommodated nonlinear time preferences. The DCE was embedded in a web-based self-complete survey and administered to a representative sample (N = 1,308) of the Dutch adult population. The matched pairwise choice tasks were created using a Bayesian heterogeneous D-efficient design. The overall DCE design comprised 10 different subdesigns, with each subdesign containing 15 matched pairwise choice tasks. Each participant was asked to complete 1 of the subdesigns to which they were randomly assigned. RESULTS: The obtained coefficients indicated that "physical health,""mood," and "relationships" were the most important dimensions. All coefficients were in the expected direction and reflected the monotonic structure of the MHQoL, except for level 2 of the dimension "future." The predicted values for the MHQoL ranged from -0.741 for the worst state to 1 for the best state. CONCLUSIONS: This study derived a Dutch value set for the recently introduced MHQoL. This value set allows for the generation of an index value for all MHQoL states on a QALY scale and may hence be used in Dutch cost-utility analyses of mental healthcare interventions. HIGHLIGHTS: A discrete choice experiment was used to derive a Dutch value set for the MHQoL.This allows the use of the MHQoL in Dutch cost-utility analyses.The dimensions physical health, mood, and relationships were the most important.The utility values range from -0.741 for the worst state to 1 for the best state.

Obtaining preference scores for an abbreviated self-completion version of the Teen-Addiction Severity Index (ASC T-ASI) to value therapy outcomes of systemic family interventions: a discrete choice experiment.

BACKGROUND: Systemic family interventions for adolescents with problems of substance use and/or delinquency are increasingly focused subject of economic evaluations. Treatment effects go beyond improvements in commonly measured health-related quality of life (HRQOL). The Teen-Addiction Severity Index (T-ASI) was identified as capable of capturing these broad outcomes. However, it lacks preference-based scores. An abbreviated self-completion version (ASC T-ASI) was created and validated, covering the T-ASI domains substance use, school, work, family, social relationships, justice, and mental health. This study aimed to obtain societal preference scores for the ASC T-ASI. METHODS: Preferences were elicited in a sample of the Dutch general adult population (n = 1500), using a web-based Discrete Choice Experiment. Choice tasks included two unlabeled alternatives with attributes and levels corresponding to the domains and levels of the ASC T-ASI. A pilot study (n = 106) informed priors, optimal presentation, and number of choice tasks applied in the main study. Data were analyzed using a mixed multinomial logit model. RESULTS: Preference scores were logically ordered, with lower scores for worse ASC T-ASI states. Scores were most influenced by reductions in problems concerning the domains substance use, mental health, justice, and family. Tariffs were calculated for each ASC T-ASI state, ranging from 0 (worst situation) to 1 (best situation). CONCLUSIONS: The tariffs enable preference-based assessments of the broad effects of systemic family interventions for adolescents with problems of substance use and/or delinquency. The outcome reflects addiction-related rather than health-related utility and can be used next to generic HRQOL instruments in relevant economic evaluations. Given the source used for the preferences, interpretations and valuation of scores require attention.

Multiplier Effects and Compensation Mechanisms for Inclusion in Health Economic Evaluation: A Systematic Review.

BACKGROUND: Compensation mechanisms and multiplier effects may affect productivity losses due to illness, disability, or premature death of individuals. Hence, they are important in estimating productivity losses and productivity costs in the context of economic evaluations of health interventions. This paper presents a systematic literature review of papers focusing on compensation mechanisms and multiplier effects, as well as whether and how they are included in health economic evaluations. METHODS: The systematic literature search was performed covering EconLit and PubMed. A data-extraction form was developed focusing on compensation mechanisms and multiplier effects. RESULTS: A total of 26 studies were included. Of these, 15 were empirical studies, three studies were methodological studies, two studies combined methodological research with empirical research, four were critical reviews, one study was a critical review combined with methodological research, and one study was a cost-benefit analysis. No uniform definition of compensation mechanisms and multiplier effects was identified. The terminology used to describe compensation mechanisms and multiplier effects varied as well. While the included studies suggest that both multipliers as well as compensation mechanisms substantially impact productivity cost estimates, the available evidence is scarce. Moreover, the generalizability as well as validity of assumptions underlying the calculations are unclear. Available measurement methods for compensation mechanisms and multiplier effects differ in approaches and are hardly validated. CONCLUSION: While our review suggests that compensation mechanisms and multiplier effects may have a significant impact on productivity losses and costs, much remains unclear about their features, valid measurement, and correct valuation. This hampers their current inclusion in economic evaluation, and therefore, more research into both phenomena remains warranted.

Braving the waves: exploring capability well-being patterns in seven European countries during the COVID-19 pandemic.

The COVID-19 pandemic considerably impacted the lives of European citizens. This study aims to provide a nuanced picture of well-being patterns during the pandemic across Europe with a special focus on relevant socio-economic sub-groups. This observational study uses data from a repeated, cross-sectional, representative population survey with nine waves of data from seven European countries from April 2020 to January 2022. The analysis sample contains a total of 25,062 individuals providing 64,303 observations. Well-being is measured using the ICECAP-A, a multi-dimensional instrument for approximating capability well-being. Average levels of ICECAP-A index values and sub-dimension scores were calculated across waves, countries, and relevant sub-groups. In a fixed effects regression framework, associations of capability well-being with COVID-19 incidence, mortality, and the stringency of the imposed lockdown measures were estimated. Denmark, the Netherlands, and France experienced a U-shaped pattern in well-being (lowest point in winter 2020/21), while well-being in the UK, Germany, Portugal, and Italy followed an M-shape, with increases after April 2020, a drop in winter 2020, a recovery in the summer of 2021, and a decline in winter 2021. However, observed average well-being reductions were generally small. The largest declines were found in the well-being dimensions attachment and enjoyment and among individuals with a younger age, a financially unstable situation, and lower health. COVID-19 mortality was consistently negatively associated with capability well-being and its sub-dimensions, while stringency and incidence rate were generally not significantly associated with well-being. Further investigation is needed to understand underlying mechanisms of presented patterns.

Vaccine hesitancy comes in waves: Longitudinal evidence on willingness to vaccinate against COVID-19 from seven European countries.

AIM: This paper investigates the prevalence and determinants of three main states of people's willingness to be vaccinated (WTBV) against COVID-19 - willing, unwilling and hesitant - and the occurrence and predictors of shifts between these states over time. Understanding the dynamics of vaccine intentions is crucial for developing targeted campaigns to increase uptake and emergency response preparedness. STUDY DESIGN: A panel survey consisting of 9 quarterly waves of data collected between April 2020 and January 2022. Baseline data included 24 952 adults from Germany, UK, Denmark, the Netherlands, France, Portugal, and Italy recruited from online panels to construct census-matched nationally representative samples. METHODS AND MEASURES: Self-reported COVID-19 vaccine intention was the main outcome. Multinomial logit random effects models were used to analyze the relationships of interest. All results reported as relative risk ratios (RRR). RESULTS: Hesitancy to get vaccinated was the most unstable vaccine intention, with on average 42% of ever hesitant respondents remaining in this state through future waves, followed by the 'unwilling' (53%) and 'willing (82%). Following COVID-19 news, trust in information from the government, GPs and the WHO, risk preferences, risk perceptions, and confidence in vaccines (or lack thereof) predicted vaccination intention reversals. Risk preferences acted both as an impediment and as a facilitator for the vaccine uptake depending on the initial vaccine intention. CONCLUSIONS AND RELEVANCE: This study revealed the dynamic nature of COVID-19 vaccine intentions and its predictors in 7 European countries. The findings provide insights to policymakers for designing more effective communication strategies, particularly targeted at hesitant and unwilling to vaccinate population groups, to increase vaccine uptake for future public health emergencies.

Adaptation in life satisfaction and self-assessed health to disability - Evidence from the UK.

Experiencing deteriorating health has implications for your quality of life. The theory of adaptation suggests that with time spend living in a health state individuals can adapt, resulting in observed quality of life levels to revert or stagnate despite persistently decreased health. Adaptation has implications for the use of subjective quality of life indicators when quantifying the impact of health changes or the benefits from new medical technologies. As both the impact from ill health and the benefit from new interventions might be disease- or subgroup-specific adaptation further raises ethical concerns but empirical evidence on its existence, magnitude, and heterogeneity remains inconclusive. This paper uses a general population sample of 9,543 individuals that participate in the UK Understanding Society survey and experience the onset of a long-standing illness or disability to provide evidence on these questions. Using ordered-response fixed effects models we explore longitudinal changes in self-assessed health and life satisfaction around the onset of disability. Our results indicate that disability onset is associated with large decreases in subjective health and well-being. Over time this initial decrease in subjective quality of life indicators attenuates, especially in life satisfaction and to a lesser extent for self-assessed health. While the relative difference in adaptation across these two measures remains persistent, we find that across demographic and severity groups the initial impact of disability onset and adaptation differs considerably in its magnitude. These results have important implications for studies aiming to quantify the impact of health conditions on quality of life outcomes, especially when using observational datasets.

Jumping the Queue:Willingness to Pay for Faster Access to COVID-19 Vaccines in Seven European Countries.

INTRODUCTION: Given the initial shortage of vaccines to protect against coronavirus disease 2019 (COVID-19), many countries set up priority lists, implying that large parts of the population had to wait. We therefore elicited the willingness to pay (WTP) for access to two hypothetical COVID-19 vaccines. METHODS: Respondents were asked how much they would be willing to pay to get an immediate COVID-19 vaccination rather than waiting for one through the public system. We report data collected in January/February 2021 from the European COVID Survey (ECOS) comprising representative samples of the population in Denmark, France, Germany, Italy, Portugal, the Netherlands, and the UK (N = 7068). RESULTS: In total, 73% (68.5%) of respondents were willing to pay for immediate access to a 100% (60%) effective vaccine, ranging from 66.4% (59.4%) in the Netherlands to 83.3% (81.1%) in Portugal. We found a mean WTP of 54.36 euros (median 37 euros) for immediate access to the 100% effective COVID-19 vaccine and 43.83 euros (median 31 euros) for the 60% effective vaccine. The vaccines' effectiveness, respondents' age, country of residence, income, health state and well-being were significant determinants of WTP. Willingness to be vaccinated (WTV) was also strongly associated with WTP, with lower WTV being associated with lower WTP. A higher perceived risk of infection, higher health risk, more trust in the safety of vaccines, and higher expected waiting time for the free vaccination were all associated with a higher WTP. CONCLUSION: We find that most respondents would have been willing to pay for faster access to COVID vaccines (jumping the queue), suggesting welfare gains from quicker access to these vaccines. This is an important result in light of potential future outbreaks and vaccines.

The Value of Health in a Cost-Effectiveness Analysis: Theory Versus Practice.

A cost-effectiveness analysis has become an important method to inform allocation decisions and reimbursement of new technologies in healthcare. A cost-effectiveness analysis requires a threshold to which the cost effectiveness of a new intervention can be compared. In principle, the threshold ought to reflect opportunity costs of reimbursing a new technology. In this paper, we contrast the practical use of this threshold within a CEA with its theoretical underpinnings. We argue that several assumptions behind the theoretical models underlying this threshold are violated in practice. This implies that a simple application of the decision rules of CEA using a single estimate of the threshold does not necessarily improve population health or societal welfare. Conceptual differences regarding the interpretation of the threshold, widely varying estimates of its value, and an inconsistent use within and outside the healthcare sector are important challenges in informing policy makers on optimal reimbursement decision and setting appropriate healthcare budgets.

Production Losses due to Absenteeism and Presenteeism: The Influence of Compensation Mechanisms and Multiplier Effects.

BACKGROUND: Productivity costs can form a large and influential component of total costs in an economic evaluation taking a societal perspective. In calculating productivity costs, estimating productivity losses is a central element. Compensation mechanisms and multiplier effects may influence these losses but remain understudied. Compensation mechanisms could reduce productivity losses while multiplier effects may increase them. METHODS: Data on productivity losses were collected in 2015 using an online survey among a sample of persons aged 15-65 years in The Netherlands who worked at least 12 h per week and reported to have experienced absenteeism and/or presenteeism during the past 4 weeks. A total of 877 respondents completed the survey that contained questions on productivity losses, compensation mechanisms, and multiplier effects. RESULTS: We found that 45.5% of the respondents reported absenteeism (average 6.5 days) during the past 4 weeks, losing on average 48.7 working hours, while presenteeism was experienced by 75.9% of respondents, with an average loss of 10.7 working hours. Compensation mechanisms were reported by 76.9% of respondents, compensating almost 80% of their lost production, while multiplier effects were reported by 23.6% of respondents, reducing the productivity of 4.2 colleagues by 27.8% on average, implying a multiplier of 2.1 in that subgroup. CONCLUSIONS: This study highlights that compensation mechanisms and multiplier effects are common and may substantially affect production losses. Investigating these mechanisms and effects further, as well as their interactions, remains important. Translating these findings into productivity cost calculations in economic evaluations is not straightforward and requires attention, especially since compensation mechanisms may not be costless and, for multiplier effects, the value of hours of colleagues may not be similar to that of the person experiencing health problems.

An accelerated access pathway for innovative high-risk medical devices under the new European Union Medical Devices and health technology assessment regulations? Analysis and recommendations.

INTRODUCTION: The new European Union (EU) Regulations for medical devices (MDs) and health technology assessment (HTA) are welcome developments that should increase the quality of clinical evidence for MDs and reduce fragmentation in the EU market access process. To fully exploit anticipated benefits, their respective assessment processes should be closely coordinated, particularly for promising, highly innovative MDs. Accelerated approval is worth exploring for certain categories of high-risk MDs to keep the EU regulatory process competitive compared to accelerated MD approval programs elsewhere (e.g. US). AREAS COVERED: Problems observed in worldwide accelerated drug and MD regulatory approval programs are reviewed, including greater uncertainty in premarket clinical evidence generation and lack of oversight for post approval evidence requirements. Implications for MD approval, HTA and coverage are explored. EXPERT OPINION: Through analysis of two decades of drug and MD accelerated approval programs worldwide, recommendations for an Accelerated Access Pathway for select innovative, high-risk MDs are proposed to fit the EU context, leverage the two new regulations, increase opportunities for Expert Panels to provide timely advice regarding manufacturers' evidence generation plans along the MD lifecycle (pre, postmarket), and safely speed patient access while promoting increased collaboration among Member States on coverage decisions.

Willingness to pay for health gains from an international integrated early warning system for infectious disease outbreaks.

Recently, due to the corona virus outbreak, pandemics and their effects have been at the forefront of the research agenda. However, estimates of the perceived value of early warning systems (EWSs) for identifying, containing, and mitigating outbreaks remain scarce. This paper aims to show how potential health gains due to an international EWS might be valued. This paper reports on a study into willingness to pay (WTP) in six European countries for health gains due to an EWS. The context in which health is gained, those affected, and the reduction in risk of contracting the disease generated by the EWS are varied across seven scenarios. Using linear regression, we analyse this 'augmented' willingness to pay for a QALY (WTP-Q) for each of the scenarios, where 'augmented' refers to the possible inclusion of context specific elements of value, such as feelings of safety. An initial WTP-Q estimate for the basic scenario is €17,400. This can be interpreted as a threshold for investment per QALY into an EWS. Overall, WTP estimates move in the expected directions (e.g. higher risk reduction leads to higher WTP). However, changes in respondents' WTP for reductions in risk were not proportional to the magnitude of the change in risk reduction. This study provided estimates of the monetary value of health gains in the context of a pandemic under seven scenarios which differ in terms of outcome, risk reduction and those affected. It also highlights the importance of future research into optimal ways of eliciting thresholds for investments in public health interventions.

Burden of illness in people with medically refractory epilepsy who suffer from daily to weekly seizures: 12-month follow-up of participants in the EPISODE study.

Background: A small group of people with epilepsy suffers from frequent seizures despite the available pharmacological and non-pharmacological interventions. The impact of epilepsy on these people extends beyond health-related quality of life (HRQoL), impacting a person's broader well-being and ability to participate in society. This study describes the burden of medically refractory epilepsy in people who suffer from daily to weekly seizures, in terms of HRQoL, well-being, and societal costs. Methods: Data from the EPISODE study on (cost-) effectiveness of seizure dogs for adults with severe medically refractory epilepsy were used, collected in 25 patients during the first 12 months before they were partnered with a certified seizure dog. Data comprised seizure diaries covering 365 days and five three-monthly surveys, including the EQ-5D-5L, QOLIE-31-P, and ICECAP-A to measure HRQoL and well-being. A societal perspective was applied to estimate costs using the iMCQ and iPCQ questionnaires about healthcare use, informal care, and productivity losses. Results: Daily seizure frequency and survey data were collected in 25 patients. A minimum of 114 observations was available for each instrument included in the survey. A total of 80% of participants experienced seizures on three or more days per week, with a median ranging from 1 to 17 seizures per seizure day. The mean EQ-5D-5L utility score was 0.682 (SD 0.235), which is considerably lower than the age-adjusted general population average. The mean QOLIE-31-P and ICECAP-A scores were 55.8 (SD 14.0) and 0.746 (SD 0.172), respectively. The average annual total cost amounted to €39,956 (range €3,804-€132,64). Informal care accounted for the largest share of costs (50%); those who received informal care reported, on average, 26 h per week (SD 30). Conclusions: Severe medically refractory epilepsy is associated with a considerable burden of illness at the patient and societal level. People with this condition have significantly reduced HRQoL and well-being and are limited in their ability to work while having substantial medical costs and a strong dependency on informal care.