Practicality, Validity, and Responsiveness of Using the Proxy Version of the Child Health Utility-9 Dimensions With Children Aged 2 to 5 Years.

OBJECTIVES: This study aimed to assess the practicality, validity, and responsiveness of the proxy Child Health Utility-9 Dimensions (CHU9D) in children aged 2 to 5 years. METHODS: We used data from the Barrier Enhancement for Eczema Prevention trial, a UK randomized controlled trial testing whether daily emollients in infancy could prevent eczema in high-risk infants. The main parent/carer completed the proxy CHU9D using developers' additional guidance for completion in those younger than 5 years and the Patient-Oriented Eczema Measure (POEM) at ages 2, 3, 4, and 5 years. Practicality was assessed by completion rates. Construct validity assessed whether CHU9D could discriminate between those with/without eczema and between eczema severity levels on POEM. Responsiveness was determined by ability to discriminate between 3 groups: (1) those whose POEM score deteriorated ≥3 points, (2) those whose change was not clinically important (-2.9 to 2.9 points), and (3) those whose POEM score improved ≥3 points. Analysis was conducted in Stata 17. RESULTS: Of 1394 children participating in the Barrier Enhancement for Eczema Prevention trial, study questionnaires were completed by 1212 (87%), 981 (70%), 990 (71%), and 976 (70%) at 2, 3, 4, and 5 years. Of these the CHU9D was completed by 1066 (88.0%), 685 (69.8%), 925 (93.4%), and 923 (94.6%), respectively. Mean utility at all time points was approximately 0.934 (range 0.443-1). For construct validity, very small differences in the CHU9D between known groups were observed (P < .01). A total of 801 participants had responsiveness data: 13% deteriorated, 72% had nonclinically important change, and 15% improved. Mean utility change (standardized response mean) for these groups was -0.0198 (0.21), 0.0041 (0.05), and 0.0175 (0.21) showing small change and small responsiveness. CONCLUSIONS: Proxy CHU9D in 2- to 5-year-old children shows potential but further research is needed.

Emollients for preventing atopic eczema: Cost-effectiveness analysis of the BEEP trial.

BACKGROUND: Recent discoveries have led to the suggestion that enhancing skin barrier from birth might prevent eczema and food allergy. OBJECTIVE: To determine the cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children at 2 years from a health service perspective. We also considered a 5-year time horizon as a sensitivity analysis. METHODS: A within-trial economic evaluation using data on health resource use and quality of life captured as part of the BEEP trial alongside the trial data. Parents/carers of 1394 infants born to families at high risk of atopic disease were randomised 1:1 to the emollient group, which were advised to apply emollient (Doublebase Gel or Diprobase Cream) to their child at least once daily to the whole body during the first year of life or usual care. Both groups received advice on general skin care. The main economic outcomes were incremental cost-effectiveness ratio (ICER), defined as incremental cost per percentage decrease in risk of eczema in the primary cost-effectiveness analysis. Secondary analysis, undertaken as a cost-utility analysis, reports incremental cost per Quality-Adjusted Life Year (QALY) where child utility was elicited using the proxy CHU-9D at 2 years. RESULTS: At 2 years, the adjusted incremental cost was £87.45 (95% CI -54.31, 229.27) per participant, whilst the adjusted proportion without eczema was 0.0164 (95% CI -0.0329, 0.0656). The ICER was £5337 per percentage decrease in risk of eczema. Adjusted incremental QALYs were very slightly improved in the emollient group, 0.0010 (95% CI -0.0069, 0.0089). At 5 years, adjusted incremental costs were lower for the emollient group, -£106.89 (95% CI -354.66, 140.88) and the proportion without eczema was -0.0329 (95% CI -0.0659, 0.0002). The 5-year ICER was £3201 per percentage decrease in risk of eczema. However, when inpatient costs due to wheezing were excluded, incremental costs were lower and incremental effects greater in the usual care group. CONCLUSIONS: In line with effectiveness endpoints, advice given in the BEEP trial to apply daily emollient during infancy for eczema prevention in high-risk children does not appear cost-effective.

Emollients for prevention of atopic dermatitis: 5-year findings from the BEEP randomized trial.

BACKGROUND: The effectiveness of emollients for preventing atopic dermatitis/eczema is controversial. The Barrier Enhancement for Eczema Prevention trial evaluated the effects of daily emollients during the first year of life on atopic dermatitis and atopic conditions to age 5 years. METHODS: 1394 term infants with a family history of atopic disease were randomized (1:1) to daily emollient plus standard skin-care advice (693 emollient group) or standard skin-care advice alone (701 controls). Long-term follow-up at ages 3, 4 and 5 years was via parental questionnaires. Main outcomes were parental report of a clinical diagnosis of atopic dermatitis and food allergy. RESULTS: Parents reported more frequent moisturizer application in the emollient group through to 5 years. A clinical diagnosis of atopic dermatitis between 12 and 60 months was reported for 188/608 (31%) in the emollient group and 178/631 (28%) in the control group (adjusted relative risk 1.10, 95% confidence interval 0.93 to 1.30). Although more parents in the emollient group reported food reactions in the previous year at 3 and 4 years, cumulative incidence of doctor-diagnosed food allergy by 5 years was similar between groups (92/609 [15%] emollients and 87/632 [14%] controls, adjusted relative risk 1.11, 95% confidence interval 0.84 to 1.45). Findings were similar for cumulative incidence of asthma and hay fever. CONCLUSIONS: Daily emollient application during the first year of life does not prevent atopic dermatitis, food allergy, asthma or hay fever.

'Eczema shouldn't control you; you should control eczema': qualitative process evaluation of online behavioural interventions to support young people and parents/carers of children with eczema.

BACKGROUND: There is a lack of well-conducted randomized controlled trials evaluating the effectiveness of theory-based online interventions for eczema. To address these deficiencies, we previously developed and demonstrated the effectiveness of two online behavioural interventions: Eczema Care Online for parents/carers of children with eczema, and Eczema Care Online for young people with eczema. OBJECTIVES: To explore the views and experiences of people who have used the Eczema Care Online interventions to provide insights into how the interventions worked and identify contextual factors that may impede users' engagement with the interventions. METHODS: Qualitative semistructured interviews were conducted with 17 parents/carers of children with eczema and 17 young people with eczema. Participants were purposively sampled from two randomized controlled trials of the interventions and recruited from GP surgeries in England. Transcripts were analysed using inductive thematic analysis, and intervention modifications were identified using the person-based approach table of changes method. RESULTS: Both young people and parents/carers found the interventions easy to use, relatable and trustworthy, and perceived that they helped them to manage their eczema, thus suggesting that Eczema Care Online may be acceptable to its target groups. Our analysis suggested that the interventions may reduce eczema severity by facilitating empowerment among its users, specifically through improved understanding of, and confidence in, eczema management, reduced treatment concerns, and improved treatment adherence and management of irritants/triggers. Reading about the experiences of others with eczema helped people to feel 'normal' and less alone. Some (mainly young people) expressed firmly held negative beliefs about topical corticosteroids, views that were not influenced by the intervention. Minor improvements to the design and navigation of the Eczema Care Online interventions and content changes were identified and made, ready for wider implementation. CONCLUSIONS: People with eczema and their families can benefit from reliable information, specifically information on the best and safest ways to use their eczema treatments early in their eczema journey. Together, our findings from this study and the corresponding trials suggest wider implementation of Eczema Care Online (EczemaCareOnline.org.uk) is justified.

Efficacy and safety of ciclosporin versus methotrexate in the treatment of severe atopic dermatitis in children and young people (TREAT): a multicentre parallel group assessor-blinded clinical trial.

BACKGROUND: Conventional systemic drugs are used to treat children and young people (CYP) with severe atopic dermatitis (AD) worldwide, but no robust randomized controlled trial (RCT) evidence exists regarding their efficacy and safety in this population. While novel therapies have expanded therapeutic options, their high cost means traditional agents remain important, especially in lower-resource settings. OBJECTIVES: To compare the safety and efficacy of ciclosporin (CyA) with methotrexate (MTX) in CYP with severe AD in the TREatment of severe Atopic Eczema Trial (TREAT) trial. METHODS: We conducted a parallel group assessor-blinded RCT in 13 UK and Irish centres. Eligible participants aged 2-16 years and unresponsive to potent topical treatment were randomized to either oral CyA (4 mg kg-1 daily) or MTX (0.4 mg kg-1 weekly) for 36 weeks and followed-up for 24 weeks. Co-primary outcomes were change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare (relapse) after treatment cessation. Secondary outcomes included change in quality of life (QoL) from baseline to 60 weeks; number of participant-reported flares following treatment cessation; proportion of participants achieving ≥ 50% improvement in Eczema Area and Severity Index (EASI 50) and ≥ 75% improvement in EASI (EASI 75); and stratification of outcomes by filaggrin status. RESULTS: In total, 103 participants were randomized (May 2016-February 2019): 52 to CyA and 51 to MTX. CyA showed greater improvement in disease severity by 12 weeks [mean difference in o-SCORAD -5.69, 97.5% confidence interval (CI) -10.81 to -0.57 (P = 0.01)]. More participants achieved ≥ 50% improvement in o-SCORAD (o-SCORAD 50) at 12 weeks in the CyA arm vs. the MTX arm [odds ratio (OR) 2.60, 95% CI 1.23-5.49; P = 0.01]. By 60 weeks MTX was superior (OR 0.33, 95% CI 0.13-0.85; P = 0.02), a trend also seen for ≥ 75% improvement in o-SCORAD (o-SCORAD 75), EASI 50 and EASI 75. Participant-reported flares post-treatment were higher in the CyA arm (OR 3.22, 95% CI 0.42-6.01; P = 0.02). QoL improved with both treatments and was sustained after treatment cessation. Filaggrin status did not affect outcomes. The frequency of adverse events (AEs) was comparable between both treatments. Five (10%) participants on CyA and seven (14%) on MTX experienced a serious AE. CONCLUSIONS: Both CyA and MTX proved effective in CYP with severe AD over 36 weeks. Participants who received CyA showed a more rapid response to treatment, while MTX induced more sustained disease control after discontinuation.

Prescribing and using vitiligo treatments: lessons from a nested process evaluation within the HI-Light vitiligo randomized controlled trial.

BACKGROUND: The HI-Light Trial demonstrated that for active, limited vitiligo, combination treatment with potent topical corticosteroid (TCS) and handheld narrowband ultraviolet B offers a better treatment response than potent TCS alone. However, it is unclear how to implement these findings. AIM: We sought to answer three questions: (i) Can combination treatment be used safely and effectively by people with vitiligo?; (ii) Should combination treatment be made available as routine clinical care?; and (iii) Can combination treatment be integrated within current healthcare provision? METHODS: This was a mixed-methods process evaluation, including semi-structured interviews with a purposive sample of trial participants, structured interviews with commissioners, and an online survey and focus groups with trial staff. Transcripts were coded by framework analysis, with thematic development by multiple researchers. RESULTS: Participants found individual treatments easy to use, but the combination treatment was complicated and required nurse support. Both participants and site investigators felt that combination treatment should be made available, although commissioners were less certain. There was support for the development of services offering combination treatment, although this might not be prioritized above treatment for other conditions. A 'mixed economy' model was suggested, involving patients purchasing their own devices, although concerns regarding the safe use of treatments mean that training, monitoring and ongoing support are essential. The need for medical physics support may mean that a regional service is more practical. CONCLUSION: Combination treatment should be made available for people seeking treatment for vitiligo, but services require partnership with medical physics and ongoing training and support for patients.

Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial.

BACKGROUND: Skin barrier dysfunction precedes eczema development. We tested whether daily use of emollient in the first year could prevent eczema in high-risk children. METHODS: We did a multicentre, pragmatic, parallel-group, randomised controlled trial in 12 hospitals and four primary care sites across the UK. Families were approached via antenatal or postnatal services for recruitment of term infants (at least 37 weeks' gestation) at high risk of developing eczema (ie, at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma, diagnosed by a doctor). Term newborns with a family history of atopic disease were randomly assigned (1:1) to application of emollient daily (either Diprobase cream or DoubleBase gel) for the first year plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). The randomisation schedule was created using computer-generated code (stratified by recruiting centre and number of first-degree relatives with atopic disease) and participants were assigned to groups using an internet-based randomisation system. The primary outcome was eczema at age 2 years (defined by UK working party criteria) with analysis as randomised regardless of adherence to allocation for participants with outcome data collected, and adjusting for stratification variables. This trial is registered with ISRCTN, ISRCTN21528841. Data collection for long-term follow-up is ongoing, but the trial is closed to recruitment. FINDINGS: 1394 newborns were randomly assigned to study groups between Nov 19, 2014, and Nov 18, 2016; 693 were assigned to the emollient group and 701 to the control group. Adherence in the emollient group was 88% (466 of 532) at 3 months, 82% (427 of 519) at 6 months, and 74% (375 of 506) at 12 months in those with complete questionnaire data. At age 2 years, eczema was present in 139 (23%) of 598 infants with outcome data collected in the emollient group and 150 (25%) of 612 infants in the control group (adjusted relative risk 0·95 [95% CI 0·78 to 1·16], p=0·61; adjusted risk difference -1·2% [-5·9 to 3·6]). Other eczema definitions supported the results of the primary analysis. Mean number of skin infections per child in year 1 was 0·23 (SD 0·68) in the emollient group versus 0·15 (0·46) in the control group; adjusted incidence rate ratio 1·55 (95% CI 1·15 to 2·09). INTERPRETATION: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Our study shows that families with eczema, asthma, or allergic rhinitis should not use daily emollients to try and prevent eczema in their newborn. FUNDING: National Institute for Health Research Health Technology Assessment.

Content of Health Economics Analysis Plans (HEAPs) for Trial-Based Economic Evaluations: Expert Delphi Consensus Survey.

OBJECTIVES: Health economics analysis plans (HEAPs) currently lack consistency, with uncertainty surrounding appropriate content. We aimed to develop a list of essential items that should be included in HEAPs for economic evaluations conducted alongside randomized trials. METHODS: A list of potential items for inclusion was developed by examining existing HEAPs. An electronic Delphi survey was conducted among professional health economists. Respondents were asked to rate potential items from 1 (least important) to 9 (most important), suggest additional items, and comment on proposed items (round 1). A second survey (round 2) was emailed to participants, including the participant's own scores from round 1 along with summary results from the whole panel; participants were asked to rerate each item. Consensus criteria for inclusion in the final list were predefined as >70% of participants rating an item 7-9 and <15% rating it 1-3 after round 2. A final item selection meeting was held to scrutinize the results and adjudicate on items lacking consensus. RESULTS: 62 participants completed round 1 of the survey. The initial list included 72 potential items; all 72 were carried forward to round 2, and no new items were added. 48 round 1 respondents (77.4%) completed round 2 and reached consensus on 53 items. At the final meeting, the expert panel (n = 9) agreed that 58 items should be included in the essential list, moved 9 items to an optional list, and dropped 5 items. CONCLUSIONS: Via expert consensus opinion, this study identified 58 items that are considered essential in a HEAP.

The construct validity and responsiveness of the EQ-5D-5L, AQL-5D and a bespoke TTO in acute asthmatics.

PURPOSE: Measuring quality of life in acute asthmatics is challenging, especially when asthma attacks can occur sporadically. Several questionnaires can be used to measure quality of life in this patient group; however, psychometric testing is limited on questionnaires that can be used to estimate Quality Adjusted Life years. The objective of this study is to assess the construct validity (convergent and discriminative validity) and responsiveness of the EuroQol-5-Dimensions 5-Level (EQ-5D-5L), Asthma Quality of Life Utility Index-5 Dimensions (AQL-5D) and Time Trade-Off (TTO) in acute asthma patients. METHODS: Data from a prospective cohort study were used to test the validity and responsiveness of the EQ-5D-5L, AQL-5D and TTO in asthma patients who were recruited from UK accident & emergency departments or hospital wards. The spearman's rank correlation coefficient, the Kruskal-Wallis test statistic and the standardized response mean were used to test for convergent validity, discriminative validity and responsiveness, respectively. RESULTS: One hundred and twenty-one participants were included in the available case analysis. The EQ-5D-5L and AQL-5D showed moderate to strong correlations for convergent validity at baseline, week 4 and week 8. The AQL-5D and TTO showed moderate correlations at week 4 and week 8. No statistical significance was observed for discriminative validity at baseline. Both the EQ-5D-5L and the AQL-5D also showed that they were sensitive to change for the recovery responses. CONCLUSIONS: The EQ-5D-5L and AQL-5D showed stronger construct validity and responsiveness compared to the TTO. Therefore, both the EQ-5D-5L and AQL-5D should be considered for use in future economic evaluations.

Barriers and Facilitators to Model Replication Within Health Economics.

BACKGROUND: Model replication is important because it enables researchers to check research integrity and transparency and, potentially, to inform the model conceptualization process when developing a new or updated model. OBJECTIVE: The aim of this study was to evaluate the replicability of published decision analytic models and to identify the barriers and facilitators to replication. METHODS: Replication attempts of 5 published economic modeling studies were made. The replications were conducted using only publicly available information within the manuscripts and supplementary materials. The replicator attempted to reproduce the key results detailed in the paper, for example, the total cost, total outcomes, and if applicable, incremental cost-effectiveness ratio reported. Although a replication attempt was not explicitly defined as a success or failure, the replicated results were compared for percentage difference to the original results. RESULTS: In conducting the replication attempts, common barriers and facilitators emerged. For most case studies, the replicator needed to make additional assumptions when recreating the model. This was often exacerbated by conflicting information being presented in the text and the tables. Across the case studies, the variation between original and replicated results ranged from -4.54% to 108.00% for costs and -3.81% to 0.40% for outcomes. CONCLUSION: This study demonstrates that although models may appear to be comprehensively reported, it is often not enough to facilitate a precise replication. Further work is needed to understand how to improve model transparency and in turn increase the chances of replication, thus ensuring future usability.

Estimating loss in quality of life associated with asthma-related crisis events (ESQUARE): a cohort, observational study.

BACKGROUND: Evidence of quality of life implications of asthma attacks are limited, particularly when measured on a utility scale, which enables calculating Quality-Adjusted Life-Years (QALYs) and comparisons with other health conditions and services. Therefore, this study sought to estimate the utility loss associated with an asthma-related crisis event (accident and emergency (A&E) attendance or hospital admission). METHODS: Participants were recruited in a cohort study from A&E and hospital admissions at three UK hospitals. They completed the EuroQol-5 Dimensions 5-Level (EQ-5D-5 L), Asthma Quality of Life Questionnaire (AQLQ), Time trade-off (TTO), and peak flow and symptom diary over 8 weeks, where three different methods (EQ-5D-5 L, AQLQ, and TTO), were used to estimate utilities. The mean difference between two time points were estimated using the Wilcoxon signed rank test. RESULTS: From baseline to week 8, mean increases (95% CI) were estimated to be 0.086 (0.019-0.153), 0.154 (0.112-0.196) and 0.132 (0.063-0.201) for EQ-5D-5 L, AQL-5D (preference-based measure derived from AQLQ), and TTO respectively over 8 weeks (p < 0.01). CONCLUSION: Asthma crisis events are estimated to be associated with a mean utility loss of between 0.086 and 0.132. The utility decrement can be used to assign values to asthma-related crisis events, which can enhance economic evaluations. TRIAL REGISTRATION: NCT02771678 . Registered 13 May 2016.

Silk garments plus standard care compared with standard care for treating eczema in children: A randomised, controlled, observer-blind, pragmatic trial (CLOTHES Trial).

BACKGROUND: The role of clothing in the management of eczema (also called atopic dermatitis or atopic eczema) is poorly understood. This trial evaluated the effectiveness and cost-effectiveness of silk garments (in addition to standard care) for the management of eczema in children with moderate to severe disease. METHODS AND FINDINGS: This was a parallel-group, randomised, controlled, observer-blind trial. Children aged 1 to 15 y with moderate to severe eczema were recruited from secondary care and the community at five UK medical centres. Participants were allocated using online randomisation (1:1) to standard care or to standard care plus silk garments, stratified by age and recruiting centre. Silk garments were worn for 6 mo. Primary outcome (eczema severity) was assessed at baseline, 2, 4, and 6 mo, by nurses blinded to treatment allocation, using the Eczema Area and Severity Index (EASI), which was log-transformed for analysis (intention-to-treat analysis). A safety outcome was number of skin infections. Three hundred children were randomised (26 November 2013 to 5 May 2015): 42% girls, 79% white, mean age 5 y. Primary analysis included 282/300 (94%) children (n = 141 in each group). The garments were worn more often at night than in the day (median of 81% of nights [25th to 75th centile 57% to 96%] and 34% of days [25th to 75th centile 10% to 76%]). Geometric mean EASI scores at baseline, 2, 4, and 6 mo were, respectively, 9.2, 6.4, 5.8, and 5.4 for silk clothing and 8.4, 6.6, 6.0, and 5.4 for standard care. There was no evidence of any difference between the groups in EASI score averaged over all follow-up visits adjusted for baseline EASI score, age, and centre: adjusted ratio of geometric means 0.95, 95% CI 0.85 to 1.07, (p = 0.43). This confidence interval is equivalent to a difference of -1.5 to 0.5 in the original EASI units, which is not clinically important. Skin infections occurred in 36/142 (25%) and 39/141 (28%) of children in the silk clothing and standard care groups, respectively. Even if the small observed treatment effect was genuine, the incremental cost per quality-adjusted life year was £56,811 in the base case analysis from a National Health Service perspective, suggesting that silk garments are unlikely to be cost-effective using currently accepted thresholds. The main limitation of the study is that use of an objective primary outcome, whilst minimising detection bias, may have underestimated treatment effects. CONCLUSIONS: Silk clothing is unlikely to provide additional benefit over standard care in children with moderate to severe eczema. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77261365.

The Community In-reach Rehabilitation and Care Transition (CIRACT) clinical and cost-effectiveness randomisation controlled trial in older people admitted to hospital as an acute medical emergency.

Objective: To compare the clinical and cost-effectiveness of a Community In-reach Rehabilitation and Care Transition (CIRACT) service with the traditional hospital-based rehabilitation (THB-Rehab) service. Design: Pragmatic randomised controlled trial with an integral health economic study. Settings: Large UK teaching hospital, with community follow-up. Subjects: Frail older people aged 70 years and older admitted to hospital as an acute medical emergency. Measurements: Primary outcome: hospital length of stay; secondary outcomes: readmission, day 91-super spell bed days, functional ability, co-morbidity and health-related quality of life; cost-effectiveness analysis. Results: A total of 250 participants were randomised. There was no significant difference in length of stay between the CIRACT and THB-Rehab service (median 8 versus 9 days; geometric mean 7.8 versus 8.7 days, mean ratio 0.90, 95% confidence interval (CI) 0.74­1.10). Of the participants who were discharged from hospital, 17% and 13% were readmitted within 28 days from the CIRACT and THB-Rehab services, respectively (risk difference 3.8%, 95% CI −5.8% to 13.4%). There were no other significant differences in any of the other secondary outcomes between the two groups. The mean costs (including NHS and personal social service) of the CIRACT and THB-Rehab service were £3,744 and £3,603, respectively (mean cost difference £144; 95% CI −1,645 to 1,934). Conclusion: The CIRACT service does not reduce major hospital length of stay nor reduce short-term readmission rates, compared to the standard THB-Rehab service; however, a modest (<2.3 days) effect cannot be excluded. Further studies are necessary powered with larger sample sizes and cluster randomisation. Trial registration: ISRCTN 94393315, 25th April 2013

PRIORITIES FOR HEALTH ECONOMIC METHODOLOGICAL RESEARCH: RESULTS OF AN EXPERT CONSULTATION.

BACKGROUND: The importance of economic evaluation in decision making is growing with increasing budgetary pressures on health systems. Diverse economic evidence is available for a range of interventions across national contexts within Europe, but little attention has been given to identifying evidence gaps that, if filled, could contribute to more efficient allocation of resources. One objective of the Research Agenda for Health Economic Evaluation project is to determine the most important methodological evidence gaps for the ten highest burden conditions in the European Union (EU), and to suggest ways of filling these gaps. METHODS: The highest burden conditions in the EU by Disability Adjusted Life Years were determined using the Global Burden of Disease study. Clinical interventions were identified for each condition based on published guidelines, and economic evaluations indexed in MEDLINE were mapped to each intervention. A panel of public health and health economics experts discussed the evidence during a workshop and identified evidence gaps. RESULTS: The literature analysis contributed to identifying cross-cutting methodological and technical issues, which were considered by the expert panel to derive methodological research priorities. CONCLUSIONS: The panel suggests a research agenda for health economics which incorporates the use of real-world evidence in the assessment of new and existing interventions; increased understanding of cost-effectiveness according to patient characteristics beyond the "-omics" approach to inform both investment and disinvestment decisions; methods for assessment of complex interventions; improved cross-talk between economic evaluations from health and other sectors; early health technology assessment; and standardized, transferable approaches to economic modeling.

REFINE (REducing Falls in In-patieNt Elderly) using bed and bedside chair pressure sensors linked to radio-pagers in acute hospital care: a randomised controlled trial.

BACKGROUND: falls in hospitals are a major problem and contribute to substantial healthcare burden. Advances in sensor technology afford innovative approaches to reducing falls in acute hospital care. However, whether these are clinically effective and cost effective in the UK setting has not been evaluated. METHODS: pragmatic, parallel-arm, individual randomised controlled trial of bed and bedside chair pressure sensors using radio-pagers (intervention group) compared with standard care (control group) in elderly patients admitted to acute, general medical wards, in a large UK teaching hospital. Primary outcome measure number of in-patient bedside falls per 1,000 bed days. RESULTS: 1,839 participants were randomised (918 to the intervention group and 921 to the control group). There were 85 bedside falls (65 fallers) in the intervention group, falls rate 8.71 per 1,000 bed days compared with 83 bedside falls (64 fallers) in the control group, falls rate 9.84 per 1,000 bed days (adjusted incidence rate ratio, 0.90; 95% confidence interval [CI], 0.66-1.22; P = 0.51). There was no significant difference between the two groups with respect to time to first bedside fall (adjusted hazard ratio (HR), 0.95; 95% CI: 0.67-1.34; P= 0.12). The mean cost per patient in the intervention group was £7199 compared with £6400 in the control group, mean difference in QALYs per patient, 0.0001 (95% CI: -0.0006-0.0004, P= 0.67). CONCLUSIONS: bed and bedside chair pressure sensors as a single intervention strategy do not reduce in-patient bedside falls, time to first bedside fall and are not cost-effective in elderly patients in acute, general medical wards in the UK. TRIAL REGISTRATION: isrctn.org identifier: ISRCTN44972300.

Clinical and cost-effectiveness of spironolactone in treating persistent facial acne in women: SAFA double-blinded RCT.

Background: Acne is common, can cause significant impact on quality of life and is a frequent reason for long-term antibiotic use. Spironolactone has been prescribed for acne in women for many years, but robust evidence is lacking. Objective: To evaluate whether spironolactone is clinically effective and cost-effective in treating acne in women. Design: Pragmatic, parallel, double-blind, randomised superiority trial. Setting: Primary and secondary healthcare and community settings (community and social media advertising). Participants: Women aged 18 years and older with facial acne persisting for at least 6 months, judged to potentially warrant oral antibiotic treatment. Interventions: Participants were randomised 1 : 1, using an independent web-based procedure, to either 50 mg/day spironolactone or matched placebo until week 6, increasing to 100 mg/day spironolactone or matched placebo until week 24. Participants continued usual topical treatment. Main outcome measures: Primary outcome was the adjusted mean difference in Acne-Specific Quality of Life symptom subscale score at 12 weeks. Secondary outcomes included Acne-Specific Quality of Life total and subscales; participant self-assessed improvement; Investigator's Global Assessment; Participant's Global Assessment; satisfaction; adverse effects and cost-effectiveness. Results: Of 1267 women assessed for eligibility, 410 were randomised (201 intervention, 209 control), 342 in the primary analysis (176 intervention, 166 control). Mean age was 29.2 years (standard deviation 7.2) and 7.9% (28/356) were from non-white backgrounds. At baseline, Investigator's Global Assessment classified acne as mild in 46%, moderate in 40% and severe in 13%. At baseline, 82.9% were using topical treatments. Over 95% of participants in both groups tolerated the treatment and increased their dose. Mean baseline Acne-Specific Quality of Life symptom subscale was 13.0 (standard deviation 4.7) across both groups. Mean scores at week 12 were 19.2 (standard deviation 6.1) for spironolactone and 17.8 (standard deviation 5.6) for placebo [difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46) adjusting for baseline variables]. Mean scores at week 24 were 21.2 (standard deviation 5.9) in spironolactone group and 17.4 (standard deviation 5.8) in placebo group [adjusted difference 3.77 (95% confidence interval 2.50 to 5.03) adjusted]. Secondary outcomes also favoured spironolactone at 12 weeks with greater differences at 24 weeks. Participants taking spironolactone were more likely than those taking placebo to report overall acne improvement at 12 weeks {72.2% vs. 67.9% [adjusted odds ratio 1.16 (95% confidence interval 0.70 to 1.91)]} and at 24 weeks {81.9% vs. 63.3% [adjusted odds ratio 2.72 (95% confidence interval 1.50 to 4.93)]}. Investigator's Global Assessment was judged successful at week 12 for 31/201 (18.5%) taking spironolactone and 9/209 (5.6%) taking placebo [adjusted odds ratio 5.18 (95% confidence interval 2.18 to 12.28)]. Satisfaction with treatment improved in 70.6% of participants taking spironolactone compared with 43.1% taking placebo [adjusted odds ratio 3.12 (95% confidence interval 1.80 to 5.41)]. Adverse reactions were similar between groups, but headaches were reported more commonly on spironolactone (20.4% vs. 12.0%). No serious adverse reactions were reported. Taking account for missing data through multiple imputation gave an incremental cost per quality-adjusted life-year of £27,879 (adjusted) compared to placebo or £2683 per quality-adjusted life-year compared to oral antibiotics. Conclusions: Spironolactone resulted in better participant-reported and investigator-reported outcomes than placebo, with greater differences at week 24 than week 12. Trial registration: This trial is registered as ISRCTN12892056 and EudraCT (2018-003630-33). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/13/02) and is published in full in Health Technology Assessment; Vol. 28, No. 56. See the NIHR Funding and Awards website for further award information.

Acne (or spots) is common and often persists into adulthood. Many people take long courses of antibiotic tablets, but concerns about antibiotic resistance mean alternatives are needed. Spironolactone is a medicine that is sometimes used for acne in women. However, we do not know whether it works. This trial aimed to answer this question. We invited women aged over 18 who had acne on their face for at least 6 months to take part via their general practitioner surgery, hospital or advertising. Women were randomly assigned to two groups: one group was given spironolactone and the other group was given identical-looking placebo ('dummy pill') daily for 24 weeks. Women in both groups could continue using acne treatments applied to the skin (gels/creams/lotions). We asked participants to rate their acne using a questionnaire called Acne-Specific Quality of Life, asked whether they felt their skin had improved and asked skin specialists to assess their skin. Four hundred and ten women took part, many of whom had had acne for a long time. Acne-Specific Quality of Life scores improved in both groups by 12 weeks but improved more in the spironolactone group at 12 and 24 weeks. When asked directly whether their skin had improved, 71% of participants in the spironolactone group said it had, compared with 43% on placebo. Skin specialists were also more likely to report that the acne had improved in the spironolactone group. Side effects were mild and similar in both groups but there were slightly more headaches on spironolactone (20% compared with 12%). Spironolactone is likely to represent value for money for the National Health Service, though this depends on a number of factors including what it is compared to. This trial suggests that spironolactone is a useful additional treatment for women with persistent acne.

The RETurn to work After stroKE (RETAKE) trial: Findings from a mixed-methods process evaluation of the Early Stroke Specialist Vocational Rehabilitation (ESSVR) intervention.

INTRODUCTION: A key goal for working age stroke survivors is to return to work, yet only around 50% achieve this at 12 months. Currently, there is limited evidence of effectiveness of early stroke-specialist vocational rehabilitation (ESSVR) interventions from randomised controlled trials. This study examined fidelity to ESSVR and explored social and structural factors which may have influenced implementation in the RETurn to work After stroKE (RETAKE) randomised controlled trial. METHODS: Mixed-methods process evaluation assessing intervention fidelity and incorporating longitudinal case-studies exploring stroke survivors' experiences of support to return to work. Normalisation Process Theory, and the Conceptual Model for Implementation Fidelity, informed data collection and analysis. RESULTS: Sixteen sites across England and Wales participated in RETAKE. Forty-eight occupational therapists (OTs), supported by 6 mentors experienced in vocational rehabilitation (VR), delivered the intervention (duration 12 months) between February 2018 and April 2022. Twenty-six participants (15 ESSVR, 11 usual care (UC)) were included in longitudinal case-studies. An additional 18 participants (8 ESSVR and 10 UC) were interviewed once. Nineteen OTs, 6 mentors and 19 service managers were interviewed. Fidelity was measured for 39 ESSVR participants; mean fidelity score was 78.8% (SD:19.2%, range 31-100%). Comparison of the experiences of ESSVR and UC participants indicated duration and type of support to return to work were perceived to be better for ESSVR participants. They received early, co-ordinated support including employer liaison and workplace adjustments where appropriate. In contrast, UC participants reported limited or no VR or return to work support from health professionals. Typically, UC support lasted 2-8 weeks, with poor communication and co-ordination between rehabilitation providers. Mentor support for OTs appeared to increase fidelity. Service managers indicated ESSVR would enhance post-stroke services. CONCLUSIONS: ESSVR was valued by participants and was delivered with fidelity; implementation appeared to be facilitated by mentor support for OTs.