BackgroundIdiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder that is associated with a broad range of symptoms, including constitutional, gastrointestinal, neuropsychiatric, dermatologic, respiratory, and hematologic or lymphoreticular problems. These broad symptoms can impact the daily lives of people living with iMCD, creating a high symptom burden. Despite this, no robust, disease-specific patient-reported outcome measure (PROM) for subjective iMCD symptom burden exists. This limits accurate symptom monitoring, impacts sensitive end point selection in clinical trials, and represents a regulatory gap in patient-centered evidence generation when evaluating iMCD treatments. ObjectiveThis protocol describes the international multistakeholder Idiopathic Multicentric Castleman Disease Symptom Burden Scale (ISBUS) project. The primary aim of this project is to develop and preliminarily evaluate the measurement properties of a novel PROM for capturing symptom burden (ie, perceived symptom frequency and impact on daily life) in people living with iMCD. The central objective is to produce a valid and robust PROM that can be used to assess iMCD symptom burden in research, clinical trials, and symptom monitoring in clinical practice. MethodsThe project has a mixed methods design, split into 4 sequential stages, with collaborative advisory input throughout. Stage 1 uses existing data and consultation with expert clinical and patient advisors to generate draft PROM content. Stage 2 uses qualitative cognitive debriefing interviews (n=10) to evaluate the content validity of the draft PROM content and enable meaningful revisions. Stage 3 involves a cross-sectional quantitative survey design in people living with iMCD (n≥50), allowing for psychometric analyses of structural validity (using classical test theory and/or Rasch methodology), construct validity (known-group validity and correlational methods), and internal consistency reliability (Cronbach α). Stage 4 uses a mixed methods design, including longitudinal quantitative survey evidence (n≥20) and qualitative interviews (n=10), triangulated to estimate preliminary meaningful change estimates for the new PROM. The project is international in scope, with primary data collection in 6 countries (ie, Australia, Brazil, Canada, New Zealand, the United Kingdom, and the United States). ResultsFunding for ISBUS began in June 2023 and is ongoing. As of March 2026, stage 3 had been completed, with 51 people living with iMCD completing the survey, and stage 4 was ongoing, with 32 follow-up surveys completed. Analyses for stages 1-3 were completed and are expected to be published in 2026, followed by stage 4 findings in 2027. ConclusionsThe aim of the ISBUS project is to produce a novel symptom burden PROM codeveloped with patients with iMCD to measure what matters to patients with iMCD. It is anticipated that the new PROM will be used in iMCD research, as a secondary end point in trials, and as a clinical tool to monitor symptom burden in the management of iMCD. Trial RegistrationClinicalTrials.gov NCT05995834; https://clinicaltrials.gov/study/NCT05995834 International Registered Report Identifier (IRRID)DERR1-10.2196/96022

ObjectiveWe describe physical distancing behaviors to avoid coronavirus disease 2019 (COVID-19) and their associations with health-related quality of life (HRQoL) and related outcomes, among immunocompromised adolescents (aged 13–17 years).MethodsEAGLE was a cross-sectional, observational study of immunocompromised adults, adolescents, and children in the United States and United Kingdom. Adolescents and their caregivers were enrolled between February and June 2023 and completed a web-based survey that was designed to capture the following outcomes: physical distancing behaviors in the past 4 weeks, measured using the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19®); HRQoL (Pediatric Quality of Life Inventory™ [PedsQL™] Generic Core Scales); loneliness (Direct Measure of Loneliness [DMOL] scale); health-state utility (EQ-5D-5L); mental health (Hospital Anxiety and Depression Scale; HADS®); and school and activity impairment (Work Productivity and Activity Impairment plus Classroom Impairment Questions: Specific Health Problem questionnaire; WPAI-CIQ:SHP).ResultsAmong 405 immunocompromised adolescents, the PDS-C19 mean T-score was 49.1, indicative of moderate physical distancing intensity. Most participants reported moderate (60.1%) or high/very high (16.3%) physical distancing intensity; fewer reported low (10.0%) or very low (13.7%) physical distancing intensity. The PedsQL™ Generic Core Scales mean total score was 58.0 (scale range: 0–100, where higher scores indicate better HRQoL). Most outcomes moderately correlated with PDS-C19 (|r| = 0.4–0.5), with stronger correlations (|r|>0.6) shown for WPAI-CIQ:SHP activity impairment, school presenteeism, and overall school impairment. Linear regression models adjusting for confounders showed similar associations.ConclusionsTwo years after national lockdowns ended, most immunocompromised adolescents practiced moderate-to-high intensities of physical distancing to avoid COVID-19. Higher intensities of physical distancing were associated with worse HRQoL and greater school and activity impairment, emphasizing the prolonged burden of COVID-19 avoidance in this population.

AIMS:To develop a comprehensive, in-depth understanding of the impacts of hypoglycaemia on the quality of life of adults living with type 1 (T1D) or type 2 diabetes (T2D). METHODS:Thirty-one adults with T1D or T2D who experienced hypoglycaemia participated in semi-structured interviews. Participants were purposively sampled by age, sex and type/duration of diabetes. Informed by a health-related quality of life (HRQoL) framework and literature review, an interview guide explored hypoglycaemia-related impacts on quality of life. Interviews were audio-recorded, transcribed verbatim and analysed using Framework Analysis. RESULTS:Impacts were coded within three overall themes (physical, psychological and social) comprising 38 subthemes. Of the 11 physical subthemes, the most discussed were sleep, physiological symptoms, leisure and exercise, eating and drinking. Of the 18 psychological subthemes, the most discussed included: awareness; cognitive burden and planning; self management and coping; worry and anxiety; autonomy, independence and control. Of the nine social subthemes, the most discussed were impacts on others and relationship with partner. CONCLUSIONS:A novel HRQoL framework highlights a comprehensive range of impacts of hypoglycaemia on physical, psychological and social functioning of people living with diabetes. These findings offer insights for clinicians, researchers and other interested parties seeking to benefit person-centred outcomes, such as quality of life.

Uncontrolled hypertension (ucHTN) and treatment-resistant hypertension (trHTN) are associated with a substantial increase in the risk of cardiorenal events and mortality compared with well-controlled hypertension. Treatment strategies that can optimise blood pressure management are urgently needed to improve health outcomes in ucHTN and trHTN populations; health economic models play a key role in assessing the economic value of new and existing treatments and supporting resource allocation. This systematic literature review critically assesses the construct and quality of existing health economic modelling used in the evaluation of management approaches for ucHTN and trHTN, to inform the design and development of future health economic models. This review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist. Searches were conducted on Medline, Embase, EconLit, the Cost-effectiveness Analysis and the International HTA database. Searches were run from inception to May 2024 and re-run in February 2026. Although no date limits were placed on the electronic searches, a limit of 2005 and onwards was applied during study selection. Economic model studies were included if they assessed pharmacological or renal denervation (RDN) interventions for treatment of either ucHTN or trHTN in adult populations. Study eligibility, data extraction and quality assessment using the Drummond checklist were conducted independently by two reviewers. After deduplication, a total of 2754 records were identified. Of these, 2556 did not meet the eligibility criteria after title and abstract screening; 198 full texts were reassessed for eligibility. A total of 21 modelling studies were included: 16 economic evaluations (14 cost-utility analyses, 1 cost-effectiveness analysis and 1 cost-minimization analysis), 4 burden-of-illness studies and 1 budget impact analysis. The majority of studies focused on people with ucHTN and employed a healthcare system perspective. Economic evaluations were based on treatment effects on systolic blood pressure estimated from clinical trials. Several models predicted long-term cardiorenal events and mortality on the basis of published, validated risk equations; however, these risk equations were not developed in populations with ucHTN or trHTN. Although models were generally assessed to be of good quality, models incorporated health-related quality of life and cost data from controlled hypertensive or non-hypertensive populations, rather than those with ucHTN and trHTN. A range of economic models were identified and considered structurally relevant. These models demonstrated that treatment related improvements in blood pressure were cost-effective and robust in scenario analysis. However, important model limitations include their lack of use of population-specific health-related quality-of-life data and risk equations which may result in underestimation of treatment cost effectiveness. To reduce uncertainty and support improved economic modelling that can accurately contextualize emerging therapies for ucHTN and trHTN, future economic model analyses in ucHTN and trHTN need appropriate population health and cost data for these underserved populations.

Introduction Immunocompromised individuals have suboptimal COVID-19 vaccine responses and may continue physically distancing to avoid COVID-19. The EAGLE Study aimed to quantify physical distancing behaviours and associations with health-related quality of life (HRQoL) and related measures in immunocompromised adults. Methods EAGLE was a cross-sectional, observational online survey study of US and UK immunocompromised adults, children and those children’s caregivers, with adult analyses reported here. Multichannel enrolment and self-reported data collection occurred from December 2022 to June 2023. Immunocompromising diagnosis confirmation using medical records was requested from a randomly selected subset. Physical distancing (in past 4 weeks) was measured using the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19). HRQoL and related measures were the 12-item Short Form Health Survey version 2 (SF-12v2) (includes Short-Form 6-Dimensions), Quality of Life Disease Impact Scale-7-item (QDIS-7), Direct Measure of Loneliness, EQ-5D-5L, Hospital Anxiety and Depression Scale and Work Productivity and Activity Impairment plus Classroom Impairment Questions: Specific Health Problem (WPAI+CIQ:SHP). Associations between PDS-C19 and HRQoL and related measures were assessed using Pearson correlation, linear regression (potential confounders-adjusted) and preliminary structural equation modelling (SEM). Results 2320 immunocompromised adults fully completed the survey. Confirmation of diagnosis was requested from 27% and confirmed for 90% of responders. 68% of participants reported moderate to high physical distancing. Physical distancing had low correlations with SF-12v2-measured HRQoL domains (range |r|=0.18 to 0.39) and medium correlations with QDIS-7 (r=0.78) and WPAI+CIQ:SHP-measured activity impairment (r=0.68) and presenteeism (r=0.51). In SEM, direct PDS-C19 relationships explained most activity correlations: QDIS, β=0.46 (SE=0.02); activity impairment, β=0.40 (0.02); presenteeism, β=0.29 (0.04). Unstandardised PDS-C19 confounder-adjusted linear regression coefficients were similar to those of SEM. Conclusions Over 3 years after COVID-19 emergence, a disproportionate number of immunocompromised adults reported substantially physically distancing to avoid COVID-19. Higher physical distancing intensities were associated with greater HRQoL impairments, suggesting such challenges coexist as ongoing concerns for immunocompromised adults.

Abstract Background Many immunocompromised individuals continue to practice physical distancing behaviors to avoid severe COVID-19 outcomes. To measure the intensity of these physical distancing behaviors, we aimed to develop and validate a standardized metric across age groups: the Physical Distancing Scale for COVID-19 Avoidance (PDS-C19©). Methodology PDS-C19 development involved content scoping, initial draft PDS-C19 design phase, and exploratory testing (via asynchronous online forums). Psychometric properties (structural validity, reliability, and construct validity) of the PDS-C19 were evaluated using a random sample of immunocompromised and non-immunocompromised participants (n = 1059) of the EAGLE Study, including adults and children aged 0.5–17 years from the US and UK. Adult caregivers of children aged ≤ 12 years completed a proxy version of the PDS-C19 on their behalf, in addition to providing self-reported responses. Results Findings from the two asynchronous forums (n = 23 and n = 22) indicated that the items identified in the scoping phase were relevant and well-understood. As part of the structural validity analysis, item-response distributions, inter-item correlations, and exploratory factor analyses supported a nine-item unidimensional intensity scale. Confirmatory factor analyses reduced the PDS-C19 to seven items (two items were dropped due to high residual correlations or differential item functioning by age). Internal consistency was high (ω = 0.97); convergent validity was good, with high correlations (r max=0.74) with clinical outcome assessments of the ability to participate in activities and with worry. The PDS-C19 had good known-groups validity, with scores distinguishable by types of activities, level of worry, and number of close contacts. Conclusion The PDS-C19 had acceptable structural and construct validity and high internal consistency, demonstrating its value as a measure of physical distancing to avoid COVID-19 in immunocompromised and non-immunocompromised individuals.

OBJECTIVES:Subjective cognitive decline (SCD) refers to self-perceived cognitive difficulties without objective impairment, and is associated with increased dementia risk, poorer mental health, and reduced quality of life. As research has largely relied on quantitative methods, little is known abouth how older adults interpret and respond to cognitive changes. f.This study explored how older adults with SCD notice, interpret, and respond to cognitive changes. METHODS:Twenty community-dwelling adults aged ≥60 were purposively sampled using the Subjective Cognitive Decline Questionnaire. Semi-structured interviews were analysed thematically. Rigour was ensured through collaborative coding, audit trails, reflexivity, and adherence to qualitative reporting standards. RESULTS:Participants described SCD as gradual and shaped by life transitions, social context, and health events. Fear and frustration were common,often contributing to social withdrawal, particularly among lonely participants. Media portrayals and ageist narratives amplified worry and stigma. Participants' metacognitive beliefs, informed by personal experiences and dementia exposure, influenced how cognitive changes were interpretedand managed. Coping strategies included peer comparison, cognitively stimulating activities, external aids, and adaptive attitudes. CONCLUSION:Self-perceived cognitive changes may influence emotional and social functioning. Findings support interventions incorporating cognitive training, memory strategies, group-based activities, and metacognitive approaches to address ageist beliefs and dementia-related fears shaped by media and personal experience.

Peanut allergy is a common allergy in children, affecting the health-related quality of life (HRQoL) of the child and other members of the family. Demonstrating health state utility values (HSUVs) for children with peanut allergy is a requirement for reimbursement of treatments in health technology assessment, yet evidence is scarce relative to eliciting dose (ED, in mg peanut protein). We aimed to estimate utility values of children with peanut allergy and their caregivers, for four distinct health states defined by ED and guided by survey results: <150mg; ≥150–<300mg; ≥300mg peanut-only allergy; and ≥300mg poly-nut allergy (300mg corresponding to roughly one large Virginia peanut). An online survey investigating the impacts of peanut allergy was conducted, and 604 participants completed the survey across two waves between 2019 and 2020. Health-state vignettes (descriptions) were generated based on survey outcomes and validated via six semi-structured interviews with caregivers of children with peanut allergy, members of patient organizations, and two clinical experts. The resulting eight vignettes were valued by 100 members of the UK general public using the time trade-off (TTO) method to derive HSUVs. The estimated HSUVs (standard deviation) generated using TTO for the <150mg, ≥150–<300mg, ≥300mg peanut-only allergy, and ≥300mg poly-nut allergy ED categories were: 0.80 (0.24), 0.86 (0.21), 0.92 (0.18) and 0.88 (0.19), respectively, for children; and 0.82 (0.27), 0.89 (0.18), 0.93 (0.16) and 0.91 (0.17), for caregivers. We successfully generated HSUVs for children with peanut allergy and their caregivers for different ED categories, which may be used to inform economic modelling and reimbursement decisions. Our study provides supportive evidence of a potential association between ED and utility, highlighting the importance of treatments focused on desensitizing children with peanut allergy and providing long-term solutions to living with peanut allergy.

Measuring health-related quality of life (HRQoL) in the very young (i.e., infants and toddlers, aged 0–47 months) presents unique conceptual and methodological challenges. As infants and toddlers cannot reliably self-report their HRQoL, observer inference is necessary. This raises questions about which concepts should be included; how to manage proxy reporting; and how to capture genuine variations in HRQoL, not changes in development or assessment. This commentary outlines six key challenges in measuring infant and toddler HRQoL and details eight proposed recommendations for HRQoL researchers. The piece draws on insights from the EuroQol Toddler and Infant Populations (EQ-TIPS) project, aimed to develop a generic preference-weighted measure (PWM) of HRQoL for infants and children, but has broader applicability to HRQoL measurement in the very young. Key issues addressed include: (i) what concepts to measure; (ii) how to identify which concepts matter to very young children; (iii) managing proxy reporting and reducing bias; (iv) accounting for rapid developmental changes; (v) managing continuity across life-course instruments; and (vi) separating child HRQoL from family spillover effects. Proposed recommendations include greater consensus on a core HRQoL model; prioritising primary caregiver perspectives; justifying and operationalising observable aspects of subjective HRQoL; careful design to capture genuine HRQoL, not developmental change or caregiver spillover; and developing measurement systems to prioritise age-based sensitivity or comparability across time. These recommendations offer a foundation for future consensus-building and research to refine and harmonise best practices in infant and toddler HRQoL measurement, particularly for use in health technology assessment.

Objectives: Hypoglycemia affects the health-related quality of life (HRQoL) of people living with diabetes (PwD), and existing preference-weighted measures do not capture all important aspects. The study aimed to generate a preference-weighted measure capturing the HRQoL Methods: Items for the health-state classification system were selected from the hypoglycemiaspecific Hypo-RESOLVE QoL measure using relevance in cognitive interviews, translatability, suitability for valuation, endorsement by patient advisors and experts, and psychometric performance in a large survey of PwD. Second, an online valuation survey using discrete choice experiment (DCE) with survival attribute was conducted with members of the UK public. DCE data were modeled using conditional logit analysis and results scaled to produce preference weights for the classification system on a scale in which 1 is equivalent to full health, 0 is equivalent to dead, and below 0 is worse than dead. Results: The health-state classification system consists of 8 items reflecting the factors of the HypoRESOLVE QoL (psychological, social, and physical aspects). The valuation survey was completed by 1000 members of the UK public, representative for age and sex. Good understanding of DCE tasks was demonstrated. The item "do what I want to do in my life" had the largest preference weight, and "find it hard to stop thinking about my glucose levels" had the smallest. Conclusions: This study generated Hypo-RESOLVE QoL-8D, a preference-weighted measure capturing the HRQoL impact of hypoglycemia in PwD, with UK general public preference weights. The measure can be generated from Hypo-RESOLVE QoL data.

The inclusion of health-related quality of life (HRQoL) impacts on informal carers in health technology assessments (HTAs) is lacking due, primarily, to a deficiency in evidence and methodological issues on how informal carer HRQoL is captured and incorporated into economic models. These issues are magnified in areas of significant burden, such as caring for children and adolescents with rare, progressive, life-limiting conditions. In this commentary we outline key challenges in measuring, and incorporating in HTA submissions, informal carer HRQoL data in rare, progressive, paediatric, life-limiting conditions and identify future research priorities in this space. We argue that: (i) a generic model of carer HRQoL is likely inadequate to characterise the HRQoL impacts in this population; (ii) the underlying evidence-base is underdeveloped, including understanding commonalities across conditions, impact beyond the primary carer, and differences over time; and (iii) methodological challenges in modelling informal carer HRQoL in cost-effectiveness analysis are inhibiting progress. A research agenda is proposed that addresses these challenges by focusing first on in-depth qualitative research to develop an appropriate, content valid 'disease-group-specific' model for understanding informal carer HRQoL in rare, progressive, paediatric, life-limiting conditions. This model can be used to inform the appropriate measurement of carer HRQoL in this population, which, alongside methodological research on addressing modelling challenges, can help to facilitate the recommended inclusion of informal carer HRQoL data in HTA submissions for children and adolescents living with rare, progressive, life-limiting conditions.

BACKGROUND:Health technology assessment agencies typically recommend generic measures of health to generate quality-adjusted life-years. Most agencies provide recommendations on which measure to use for adults, whereas few make recommendations for children. Two widely used preference-weighted measures of child and adolescent health that have evidence of good psychometric performance are the EQ-5D-Y-3L and the Child Health Utility 9D Index (CHU9D). The EQ-5D-5L has also been used to assess adolescent health. However, evidence on their content validity-a core measurement property-is limited. The objective of this study was to explore the content validity of the EQ-5D-5L, EQ-5D-Y-3L, and CHU9D measures, including their relevance, comprehensiveness, and comprehensibility. METHODS:We assessed the content validity of the EQ-5D-5L, EQ-5D-Y-3L, and CHU9D using online semi-structured cognitive interviews in the UK. Participants were asked to comment on the relevance, comprehensibility, and comprehensiveness of the measures, including response options, recall period, and completion instructions. Interviews were informed by a topic guide. Purposive sampling allowed for appropriate breadth in the sample, with variation in gender, and presence of health conditions, disease, or disability. Interviews were recorded and transcribed verbatim before thematic content analysis. RESULTS:In total, we conducted 49 interviews between August 2022 and June 2023: 21 children/adolescents aged 8-17 years and 28 parents/guardians of children aged 4-17 years. The mean duration of the interviews was 45 min. Relevance was broadly supported, but issues were identified. Comprehensibility was inconsistent on some items, and participants expressed difficulty with grouped items (e.g., 'anxiety/depression'). Participants had difficulty distinguishing qualitatively between some response options (e.g., 'a little bit/a bit'). Some participants noted that instrument comprehensiveness was insufficient. CONCLUSIONS:Although the content of the EQ-5D-5L, EQ-5D-Y-3L, and CHU9D was broadly supported, potential problems were identified in aspects of comprehensibility, relevance, and comprehensiveness. These present opportunities for future research and refinement to ultimately improve the content validity of these measures for assessing child and adolescent health.

Establishing the comprehensibility of patient reported outcome measures (PROMs) in quality of life research is essential. Cognitive interviews are recommended as a ‘gold standard’ for evaluating comprehensibility among adult populations but are not routinely used with young children (≤ 7 years). The current study therefore aimed to evaluate the feasibility of cognitive interviewing using traditional and adapted methods with children aged 6–7 years to evaluate PROM item comprehensibility. Fourteen children (6–7 years) with a range of diagnosed health conditions participated in individual cognitive interviews. Each child answered six mock PROM items (physical, psychological, and social health-related quality of life domains) and concurrent verbal probes were used to evaluate item comprehensibility. Interviews were audio recorded and transcribed verbatim. Transcripts were analysed using a novel Comprehensibility Continuum which coded the extent of alignment between children’s explanations of items and intended meanings. Cognitive interviews were successful; extent of comprehensibility could be determined for 83/84 (99

Recommendations suggest that children need to be ≥ 8 years-old to participate in concept elicitation (CE) and cognitive interviewing (CI) when developing patient reported outcome measures (PROMs). However, these recommendations have not been subject to thorough scrutiny and recent evidence suggests that younger children may be enabled to participate. This study audited current opinions of PROM developers regarding the feasibility of conducting CE and CI research with children. An online survey was developed to capture PROM developers’ perspectives, recruited from existing networks (UK PROMs, International Society for Quality of Life Research) and outcomes research groups from English-speaking countries between August-November 2024. Survey questions explored the ages from which developers considered it feasible to include children in CE and CI research, their previous experiences conducting CE/CI research with children, and respondents’ background experiences with children. Results were analysed descriptively, and exploratory comparisons were made based on developers’ characteristics. Fifty-eight responses were analysed. The mean youngest ages considered feasible to include children in CE and CI research were 6.66 years and 7.36 years, respectively. The mean youngest ages respondents reported involving children in CE and CI research in practice were 7.67 years and 8.13 years, respectively. Concern that children would have insufficient cognitive and/or linguistic skills was the most often endorsed reason for considering the involvement of younger children to be infeasible. Respondents who had recent parental experience with younger children tended to consider it feasible to include children from younger ages. Those who had conducted CI with children considered it feasible to include children in CI from younger ages. Opposingly, those who had conducted CE with children considered it less feasible to include younger children in CE research. In-line with established precedent, PROM developers included children from ∼ 8 years-old in CE and CI research, while in principle considering it feasible to include younger ages. Reasons for including (or not including) certain age groups in CE and CI research need critical evaluation and PROM developers may wish to consider ways in which more inclusive opportunities for younger children can be provided.

Collaborative engagement with individuals invested in or affected by health research, beyond researchers themselves, is advantageous and encouraged by major funding bodies. However, the degree of collaborative engagement in health state valuation is unclear. A scoping review was conducted to (i) identify recommendations on best practice in collaborative engagement in health economics and related literature; (ii) identify examples of collaborative engagement in valuation studies; and (iii) map (ii) onto (i) to identify current practice and future recommendations. Eight databases were searched in March-May 2024, with grey literature searches in August-September 2024. For objective (i), reports or manuscripts in health economics or patient-reported outcome measure development/evaluation of any date providing recommendations for collaborative engagement were included. For objective (ii), articles published since 2019 featuring health state valuation and collaborative engagement were included. Best practice recommendations were extracted and thematically synthesised. Examples of collaborative engagement were extracted and mapped against recommendations. Twenty-two records featuring recommendations and 15 valuation studies were included. A 15-item framework of emerging best practice recommendations for collaborative engagement was synthesised. Most examples of collaborative engagement involved patients and/or experts helping inform health states for valuation. There was no evidence for 9 out of 15 synthesised recommendations having been applied in any of the valuation studies and only minimal evidence was extracted for the remaining six. Collaborative engagement in health state valuation is underdeveloped and unaligned with literature recommendations. A 15-point framework has been developed as a strategic starting point for developing guidance to improve practice in the field.

BACKGROUND:LGI1-antibody encephalitis (LGI1-Ab-E) is a common form of autoimmune encephalitis where most patients demonstrate 'good' clinician-rated outcomes. However, more targeted questionnaires reveal numerous debilitating symptoms for many years. To better quantify these persistent features, we designed the LGI1-Antibody Encephalitis Rating (LANTERN) scale, a quantified, disease-specific patient-reported outcome measure (PROM), adhering to FDA guidelines. METHODS:A participant-driven mixed-methods approach to develop a clinically valid questionnaire over three stages: (1) Item generation through semi-structured interviews; (2) Repeated cognitive debriefing rounds to advance comprehensibility, relevance and comprehensiveness; (3) Psychometric survey to condense the most sensitive and valid questions. Analyses incorporated sensitivity testing with multiple internal and external validations. RESULTS:From 73 items across six domains (Stage 1; n = 18), a questionnaire assessing the frequency and severity of 43 symptoms (80 questions), plus nine activities of daily living (ADL), was developed through cognitive debriefing (Stage 2; n = 15). This 89-question survey was completed (Stage 3; n = 66 patients and 32 relatives) and distilled, using exploratory factor analyses, to a three-factor symptom-burden questionnaire comprising 41 questions (19 symptoms and 6 ADL), separated into physical, cognitive/behavioural and ADL domains. These factors demonstrated strong internal reliability (Cronbach alpha: 0.85-0.91), correlations with relative-completed questionnaires (R = 0.73-0.85; p < 0.001), good-to-excellent intraclass re-testing correlations (0.81-0.98; n = 19) and strong associations with numerous predefined external measures. DISCUSSION:LANTERN represents a PROM for LGI1-Ab-E, with initial content, structural and construct validity and test-retest reliability. It can be used as a reliable, tailored, efficient and sensitive method to establish symptom burden in people with LGI1-Ab-E, both in clinical practice and trials.