A Methodological Study to Compare Alternative Modes of Administration With Value EQ-5D Using Preference-Elicitation Techniques.

OBJECTIVES: Time trade-off (TTO) and discrete choice experiment (DCE) preference-elicitation techniques can be administered using face-to-face interviews (F2F), unassisted online (UO) surveys, or remote-assisted (RA) interviews. The objective of this study was to explore how the mode of administration affects the quality and reliability of preference-elicitation data. METHODS: EQ-5D-5L health states were valued using composite TTO (cTTO) and DCE approaches by the UK general population. Participants were allocated to 1 of 2 study groups. Group A completed both F2F and UO surveys (n = 271), and group B completed both RA and UO surveys (n = 223). The feasibility of survey completion and the reliability and face-validity of data collected were compared across all modes of administration. RESULTS: Fewer participants reported receiving sufficient guidance on the cTTO tasks during the UO survey compared with the 2 assisted modes. Participants across all modes typically reported receiving sufficient guidance on the DCE tasks. cTTO data were less reliable from the UO survey compared with both assisted modes, but there were no differences in DCE data reliability. cTTO data from all modes demonstrated face-validity; however, the UO survey produced higher utilities for moderate and severe health states than both assisted modes. Both F2F and RA modes provided comparably reliable data. CONCLUSIONS: The reliability of DCE data is not affected by the mode of administration. Interviewer-assisted modes of administration (F2F or RA) yield more reliable cTTO data than unassisted surveys. Both F2F and RA surveys produced similar-quality data.

A time trade-off study to determine health-state utilities of transplant recipients with refractory cytomegalovirus infection with or without resistance.

BACKGROUND: Health-state utility values (HSUVs) for post-transplant refractory cytomegalovirus (CMV) infection (with or without resistance [R/R]) were determined using a time trade-off (TTO) survey completed by 1,020 members of the UK general public. METHODS: Existing literature and qualitative interviews with clinicians experienced in treating R/R CMV were used to develop initial draft vignettes of health states. The vignettes were refined to describe three clinical states of R/R CMV: clinically significant and symptomatic (CS-symptomatic CMV); clinically significant and asymptomatic (CS-asymptomatic CMV); and non-clinically significant (non-CS CMV). Each clinical state was valued independently and combined with three events of interest: graft-versus-host disease; kidney graft loss; and lung graft loss to generate twelve vignettes. The final vignettes were evaluated by a sample of the UK general public using an online TTO survey. Exclusion criteria were applied to the final data to ensure that responses included in the analysis met pre-defined quality control criteria. RESULTS: Overall, 738 participants met the inclusion criteria and were included in the analysis. The sample was representative of the UK general population in terms of age and sex. Non-CS CMV had the highest mean HSUV (95% confidence interval) (0.815 [0.791, 0.839]), followed by CS-asymptomatic CMV (0.635 [0.602, 0.669]), and CS-symptomatic CMV (0.443 [0.404, 0.482]). CS-symptomatic CMV with lung graft loss had the lowest mean HSUV (0.289), with none of the health states considered on average worse than dead. CONCLUSIONS: Post transplant R/R CMV has substantial impact on the health-related quality of life of patients. The utility values obtained in this study may be used to support economic evaluations of therapies for R/R CMV infection.

Population norms for the EQ-5D-3L and EQ-5D-5L in Romania.

BACKGROUND: The majority of patient reported outcome measures (PROMs) don't have population norms in Romania. This is the case with the EQ-5D as well. Therefore, we aimed to estimate population norms for the Romanian versions of the EQ-5D-5L, EQ-5D-3L, their indexes, and the EQ-VAS. METHODS: A cross-sectional survey was conducted in all regions of Romania from November 2018 to November 2019. A three-stage probability sampling procedure stratified by region and settlement size was used to select a representative sample. Interviews were computer-assisted and conducted in respondents' homes by trained interviewers. Health status was assessed with the EQ-5D-5L, the EQ-5D-3L and the EQ VAS. Descriptive statistics were used to estimate population norms by age groups and sex for the EQ-5D-5L, the EQ-5D-3L, their indexes and the EQ VAS. Population norms were weighted using survey weights. Indexes for the EQ-5D questionnaires were estimated using the recently developed Romanian value sets. RESULTS: Data from 1,649 interviews was analysed in the present study. Survey weights were used so that sex and place of residence ratios for the weighted sample matched the Romanian general population distribution. Participants' mean age was 47.4 years (SE = 1.157) and 50.3% of them reported being in good health. The dimension for which people reported the highest number of problems for both questionnaires was the pain/discomfort dimension. Men aged 35 plus reported fewer problems with pain/discomfort than women for both the EQ-5D-5L and EQ-5D-3L. Health decreased with age as shown by the decrease from age group 18-24 to age group 75 plus in the indexes of both questionnaires: from 0.977 (SE = 0.005) to 0.765 (SE = 0.017) for EQ-5D-5L and from 0.981 (SE = 0.005) to 0.784 (SE = 0.019) for EQ-5D-3L. There was 29.9 points drop in the EQ VAS score between the youngest and oldest group. CONCLUSIONS: Population norms for the Romanian versions of the EQ-5D-5L, EQ-5D-3L, their indexes, and the EQ VAS are now available. These can now be used as reference values by healthcare professionals, researchers and decision-makers leading to a further development of health-related quality of life research in Romania.

Measuring Weight-Specific Quality of Life in Adolescents: An Examination of the Concurrent Validity and Test-Retest Reliability of the WAItE.

OBJECTIVES: To examine the concurrent validity of the Weight-specific Adolescent Instrument for Economic evaluation (WAItE) as compared with the generic, preference-based Child Health Utility 9D (CHU-9D) and the weight-specific Youth Quality of Life-Weight (YQOL-W) and also to examine the test-retest reliability of the WAItE. METHODS: An online survey was used to administer the 3 instruments on a sample of adolescents (aged 11-18 years). Individual responses were converted into either utility scores (CHU-9D) or health-related quality-of-life scores (WAItE and YQOL-W). A 10% subsample of the respondents also completed the WAItE 1 week after completion to assess test-retest reliability. RESULTS: One thousand adolescents completed the online survey. There was a strong correlation between the WAItE and both the CHU-9D (0.731; P<.001) and the YQOL-W (0.747; P<.001). All 3 instruments were able to discriminate according to different weight status categories and a measure of self-assessed health. Unlike the CHU-9D or the YQOL-W, the WAItE did not show a substantial ceiling effect. The WAItE also showed acceptable levels of test-retest reliability. CONCLUSIONS: The study results are encouraging, and illustrate that the WAItE can be used to reliably and accurately measure weight-specific outcomes in the younger population. The WAItE can also be used to assess outcomes in cost-effectiveness analysis of weight management interventions for young people, given the instrument is less likely to display ceiling effects and may thus be more sensitive in measuring change that results from interventions developed for this population.

Estimating CHU-9D Utility Scores from the WAItE: A Mapping Algorithm for Economic Evaluation.

BACKGROUND: The Weight-Specific Adolescent Instrument for Economic Evaluation (WAItE) is a new condition-specific patient reported outcome measure that incorporates the views of adolescents in assessing the impact of above healthy weight status on key aspects of their lives. Presently it is not possible to use the WAItE to calculate quality adjusted life years (QALYs) for cost-utility analysis (CUA), given that utility scores are not available for health states described by the WAItE. OBJECTIVE: This paper examines different regression models for estimating Child Health Utility 9 Dimension (CHU-9D) utility scores from the WAItE for the purpose of calculating QALYs to inform CUA. METHODS: The WAItE and CHU-9D were completed by a sample of 975 adolescents. Nine regression models were estimated: ordinary least squares, Tobit, censored least absolute deviations, two-part, generalized linear model, robust MM-estimator, beta-binomial, finite mixture models, and ordered logistic regression. The mean absolute error (MAE) and mean squared error (MSE) were used to assess the predictive ability of the models. RESULTS: The robust MM-estimator with stepwise-selected WAItE item scores as explanatory variables had the best predictive accuracy. CONCLUSIONS: Condition-specific tools have been shown to be more sensitive to changes that are important to the population for which they have been developed for. The mapping algorithm developed in this study facilitates the estimation of health-state utilities necessary for undertaking CUA within clinical studies that have only collected the WAItE.

The weight-specific adolescent instrument for economic evaluation (WAItE): psychometric evaluation using a Rasch model approach.

PURPOSE: The Weight-specific Adolescent Instrument for Economic evaluation (WAItE) is a 7-item condition-specific tool assessing the impact of weight status on seven dimensions of quality of life. The content of the WAItE was developed with both treatment-seeking and non-treatment-seeking adolescents aged 11-18 years. The aim of this study was to assess the psychometric properties of the WAItE in adolescent and adult populations. METHODS: Treatment-seeking adolescents with obesity (females n = 155; males n = 123; mean age = 13.3; 13.1 years, respectively) completed the WAItE twice. An adult general population sample completed the WAItE via an online survey (females n = 236; males n = 231; mean age = 41.2; 44.3 years, respectively). The Partial Credit Model was applied to the data and item fit evaluated against published criteria. RESULTS: The WAItE had a unidimensional structure both for adolescents and adults. There was no item misfit observed for either participant samples and no differential item functioning (DIF) was present by age or gender for the adolescents. Some DIF was observed across age groups for the adult sample. For the adolescent sample, stable item locations were observed over time. CONCLUSIONS: The aim of the WAItE is to assess the impact of weight status on the lives of adolescents in cost-effectiveness evaluation of weight management programmes. The results of this study demonstrated that the WAItE has reliable psychometric properties. The instrument may therefore be used to aid informed decision around the identification of cost-effective weight management programmes in both adolescent and adult populations.

Development and refinement of the WAItE: a new obesity-specific quality of life measure for adolescents.

BACKGROUND: Few weight-specific outcome measures, developed specifically for obese and overweight adolescents, exist and none are suitable for the elicitation of utility values used in the assessment of cost effectiveness. OBJECTIVES: The development of a descriptive system for a new weight-specific measure. METHODS: Qualitative interviews were conducted with 31 treatment-seeking (above normal weight status) and non-treatment-seeking (school sample) adolescents aged 11-18 years, to identify a draft item pool and associated response options. 315 eligible consenting adolescents, aged 11-18 years, enrolled in weight management services and recruited via an online panel, completed two version of a long-list 29-item descriptive system (consisting of frequency and severity response scales). Psychometric assessments and Rasch analysis were applied to the draft 29-item instrument to identify a brief tool containing the best performing items and associated response options. RESULTS: Seven items were selected, for the final item set; all displayed internal consistency, moderate floor effects and the ability to discriminate between weight categories. The assessment of unidimensionality was supported (t test statistic of 0.024, less than the 0.05 threshold value). CONCLUSIONS: The Weight-specific Adolescent Instrument for Economic-evaluation focuses on aspects of life affected by weight that are important to adolescents. It has the potential for adding key information to the assessment of weight management interventions aimed at the younger population.

Valuing selected WAItE health states using the Time Trade-Off methodology: findings from an online interviewer-assisted remote survey.

PURPOSE: The Weight-Specific Adolescent Instrument for Economic Evaluation (WAItE) is a physical weight-specific patient reported outcome measure for use in adolescence. The purpose of this study was to use the Time Trade-Off (TTO) methodology, administered using an online interviewer-assisted remote survey, to obtain utility values for several health states from the WAItE descriptive system from a sample of the UK adult general population. METHODS: The adult sample was gathered using a market research company and a sample of local residents. All participants completed the same interviewer-assisted remote survey, which included rating WAItE states of varying impairment using the TTO. RESULTS: 42 adults completed the survey. Utility values were gathered for four health states, ranging from low impairment to the most severe health from the WAItE descriptive system (the Pits state). Consistent orderings of the WAItE health states were observed; the health state with the lowest level of impairment was valued highest and the Pits state was valued lowest. Several respondents (n = 7, 17%) considered the Pits state to be worse than death; however, the mean value of this health state was 0.23. CONCLUSIONS: The utility value of the Pits state relative to death generated from this study will be used to anchor latent values for WAItE health states generated from a Discrete Choice Experiment onto the 0 = death, 1 = full health Quality Adjusted Life Year (QALY) scale as part of a valuation study for the WAItE in the UK population. This study also provides further evidence that interviewer-assisted digital studies are feasible for collecting TTO data.

Effectiveness of septoplasty compared to medical management in adults with obstruction associated with a deviated nasal septum: the NAIROS RCT.

Background: The indications for septoplasty are practice-based, rather than evidence-based. In addition, internationally accepted guidelines for the management of nasal obstruction associated with nasal septal deviation are lacking. Objective: The objective was to determine the clinical effectiveness and cost-effectiveness of septoplasty, with or without turbinate reduction, compared with medical management, in the management of nasal obstruction associated with a deviated nasal septum. Design: This was a multicentre randomised controlled trial comparing septoplasty, with or without turbinate reduction, with defined medical management; it incorporated a mixed-methods process evaluation and an economic evaluation. Setting: The trial was set in 17 NHS secondary care hospitals in the UK. Participants: A total of 378 eligible participants aged > 18 years were recruited. Interventions: Participants were randomised on a 1: 1 basis and stratified by baseline severity and gender to either (1) septoplasty, with or without turbinate surgery (n = 188) or (2) medical management with intranasal steroid spray and saline spray (n = 190). Main outcome measures: The primary outcome was the Sino-nasal Outcome Test-22 items score at 6 months (patient-reported outcome). The secondary outcomes were as follows: patient-reported outcomes - Nasal Obstruction Symptom Evaluation score at 6 and 12 months, Sino-nasal Outcome Test-22 items subscales at 12 months, Double Ordinal Airway Subjective Scale at 6 and 12 months, the Short Form questionnaire-36 items and costs; objective measurements - peak nasal inspiratory flow and rhinospirometry. The number of adverse events experienced was also recorded. A within-trial economic evaluation from an NHS and Personal Social Services perspective estimated the incremental cost per (1) improvement (of ≥ 9 points) in Sino-nasal Outcome Test-22 items score, (2) adverse event avoided and (3) quality-adjusted life-year gained at 12 months. An economic model estimated the incremental cost per quality-adjusted life-year gained at 24 and 36 months. A mixed-methods process evaluation was undertaken to understand/address recruitment issues and examine the acceptability of trial processes and treatment arms. Results: At the 6-month time point, 307 participants provided primary outcome data (septoplasty, n = 152; medical management, n = 155). An intention-to-treat analysis revealed a greater and more sustained improvement in the primary outcome measure in the surgical arm. The 6-month mean Sino-nasal Outcome Test-22 items scores were -20.0 points lower (better) for participants randomised to septoplasty than for those randomised to medical management [the score for the septoplasty arm was 19.9 and the score for the medical management arm was 39.5 (95% confidence interval -23.6 to -16.4; p < 0.0001)]. This was confirmed by sensitivity analyses and through the analysis of secondary outcomes. Outcomes were statistically significantly related to baseline severity, but not to gender or turbinate reduction. In the surgical and medical management arms, 132 and 95 adverse events occurred, respectively; 14 serious adverse events occurred in the surgical arm and nine in the medical management arm. On average, septoplasty was more costly and more effective in improving Sino-nasal Outcome Test-22 items scores and quality-adjusted life-years than medical management, but incurred a larger number of adverse events. Septoplasty had a 15% probability of being considered cost-effective at 12 months at a £20,000 willingness-to-pay threshold for an additional quality-adjusted life-year. This probability increased to 99% and 100% at 24 and 36 months, respectively. Limitations: COVID-19 had an impact on participant-facing data collection from March 2020. Conclusions: Septoplasty, with or without turbinate reduction, is more effective than medical management with a nasal steroid and saline spray. Baseline severity predicts the degree of improvement in symptoms. Septoplasty has a low probability of cost-effectiveness at 12 months, but may be considered cost-effective at 24 months. Future work should focus on developing a septoplasty patient decision aid. Trial registration: This trial is registered as ISRCTN16168569 and EudraCT 2017-000893-12. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/226/07) and is published in full in Health Technology Assessment; Vol. 28, No. 10. See the NIHR Funding and Awards website for further award information.

Septoplasty is an operation to straighten the septum, which is the partition wall between the nostrils inside the nose. Septoplasty can be used as a treatment for people who have a bent septum and symptoms of a blocked nose, such as difficulty sleeping and exercising. Medical management (a saltwater spray to clear the nose followed by a nose steroid spray) is an alternative treatment to septoplasty. The Nasal AIRway Obstruction Study (NAIROS) aimed to find out whether septoplasty or medical management is a better treatment for people with a bent septum and symptoms of a blocked nose. We recruited 378 patients with at least moderately severe nose symptoms from 17 hospitals in England, Scotland and Wales to take part in the NAIROS. Participants were randomly put into one of two groups: septoplasty or medical management. Participants' nose symptoms were measured both when they joined the study and after 6 months, using a questionnaire called the Sino-nasal Outcome Test-22 items. This questionnaire was chosen because patients reported that it included symptoms that were important to them. Other studies have shown that a 9-point change in the Sino-nasal Outcome Test-22 items score is significant. After 6 months, on average, people in the septoplasty group improved by 25 points, whereas people in the medical management group improved by 5 points. We saw improvement after septoplasty among patients with moderate symptoms, and among those with severe symptoms. Most patients who we spoke to after a septoplasty were happy with their treatment, but some would have liked more information about what to expect after their nose surgery. In the short term, septoplasty is more costly than medical management. However, over the longer term, taking into account all the costs and benefits of treatment, suggests that septoplasty would be considered good value for money for the NHS.

Evidence for a unidimensional 15-item version of the CASP-19 using a Rasch model approach.

AIM: The aim of this study is to explore the dimensionality of the CASP-19-a quality-of-life measure for early old age-and to assess the stability of the item locations over time and changes in person measures. METHODS: The Rasch partial credit model was applied to the CASP-19 data obtained from Waves 1 and 3 (N = 9,407 and N = 7,732) of the English Longitudinal Study of Ageing to assess item fit, dimensionality and differential item functioning (DIF). RESULTS: Five items demonstrated category disordering for the last two response categories of the CASP-19 (which were collapsed), and 4 items demonstrated item misfit and were removed from the analysis. Cronbach's alpha indicated good internal consistency for both waves (0.87 for Wave 1 and 0.88 for Wave 3). There was no evidence of multidimensionality, and no significant DIF was observed for gender. When the two datasets were combined, no statistically significant differences were observed between the two sets of item locations. A statistically significant difference was found for the mean person measure [t(5,524) = 17.88, p < 0.001)], suggesting quality of life improves as people age. CONCLUSION: A 15-item unidimensional factor structure was observed for the CASP-19, which was stable over time.

The factor structure of the GHQ-12: the interaction between item phrasing, variance and levels of distress.

PURPOSE: The general health questionnaire-12 (GHQ-12) is a self-report instrument for measuring psychological morbidity. Previous work has suggested several multidimensional models for this instrument, although it has recently been proposed that these may be an artefact resulting from a response bias to negatively phrased items. The aim here was to explore the dimensionality of the GHQ-12. METHODS: Cluster analysis, exploratory factor analysis and confirmatory factor analysis were applied to waves of data from the English longitudinal study of ageing (ELSA Waves 1 and 3), in order to evaluate fit and factorial invariance over time of the GHQ-12. RESULTS: Two categories of respondents were identified: high and low scorers. Item variances were higher across all items for high scorers and higher for negatively phrased items (for both high and low scorers). The unidimensional model accounting for variance observed with negative phrasing (Hankins in Clin Pract Epidemiol Ment Health 4:10, 2008) was identified as having the best model fit across the two time points. CONCLUSIONS: Item phrasing, item variance and levels of respondents' distress affect the factor structure observed for the GHQ-12 and may perhaps explain why different factor structures of the instrument have been found in different populations.

EQ-5D-5L: a value set for Romania.

OBJECTIVE: We aimed to develop an EQ-5D-5L value set for Romania. METHODS: In line with the EuroQoL standardized valuation protocol, computer-assisted interviews were conducted face-to-face in a representative sample in Romania (November 2018-November 2019). Valuation methods included composite time trade-off and discrete choice experiment tasks. Several models were tested, including models that accounted for data censoring, panel structure of the data, heteroscedasticity, conditional logit, and hybrid models. The final model was selected based on logical consistency, theoretical considerations, and use of all available data. We compared our value set with other value sets from Central and Eastern Europe region. RESULTS: Data from 1493 respondents was used to estimate the value set. A censored hybrid model corrected for heteroscedasticity was selected to represent the value set. The highest decrements in utility were observed for the pain/discomfort dimension (0.375), followed by the mobility dimension (0.293). Health utilities ranged from 1.000 to - 0.323 and 1.3% of the values were negative. The model was corrected with survey weights to better reflect the representativeness of the sample, but the first two coefficients of the self-care dimension stopped being logically consistent. Differences were found between the Romanian, Hungarian and Polish EQ-5D-5L value sets. Good agreement was noted with the Romanian EQ-5D-3L value set, with a swap between pain/discomfort and mobility in ranking of dimensions. CONCLUSION: A value set for EQ-5D-5L is now available for Romania. This will push one-step further the development of health technology assessment and encourage more health-related quality-of-life research to be conducted locally.

Clinical effectiveness of septoplasty versus medical management for nasal airways obstruction: multicentre, open label, randomised controlled trial.

OBJECTIVE: To assess the clinical effectiveness of septoplasty. DESIGN: Multicentre, randomised controlled trial. SETTING: 17 otolaryngology clinics in the UK's National Health Service. PARTICIPANTS: 378 adults (≥18 years, 67% men) newly referred with symptoms of nasal obstruction associated with septal deviation and at least moderate symptoms of nasal obstruction (score >30 on the Nasal Obstruction and Symptom Evaluation (NOSE) scale). INTERVENTIONS: Participants were randomised 1:1 to receive either septoplasty (n=188) or defined medical management (n=190, nasal steroid and saline spray for six months), stratified by baseline symptom severity and sex. MAIN OUTCOME MEASURES: The primary outcome measure was patient reported score on the Sino-Nasal Outcome Test-22 (SNOT-22) at six months, with 9 points defined as the minimal clinically important difference. Secondary outcomes included quality of life and objective nasal airflow measures. RESULTS: Mean SNOT-22 scores at six months were 19.9 (95% confidence interval 17.0 to 22.7) in the septoplasty arm (n=152, intention-to-treat population) and 39.5 (36.1 to 42.9) in the medical management arm (n=155); an estimated 20.0 points lower (better) for participants randomised to receive septoplasty (95% confidence interval 16.4 to 23.6, P<0.001, adjusted for baseline continuous SNOT-22 score and the stratification variables sex and baseline NOSE severity categories). Greater improvement in SNOT-22 scores was predicted by higher baseline symptom severity scores. Quality of life outcomes and nasal airflow measures (including peak nasal inspiratory flow and absolute inhalational nasal partitioning ratio) improved more in participants in the septoplasty group. Readmission to hospital with bleeding after septoplasty occurred in seven participants (4% of 174 who had septoplasty), and a further 20 participants (12%) required antibiotics for infections. CONCLUSIONS: Septoplasty is a more effective intervention than a defined medical management regimen with a nasal steroid and saline spray in adults with nasal obstruction associated with a deviated nasal septum. TRIAL REGISTRATION: ISRCTN Registry ISRCTN16168569.

Differences in health-related quality of life between the Roma community and the general population in Romania.

BACKGROUND: Previous research has shown that Roma people report worse health outcomes than the general population and suffer from a myriad of economic and social disadvantages. The objective of this study was to assess the differences in the health-related quality of life (HRQoL) between the Roma people and the Romanian general population. METHODS: Two cross-sectional surveys were conducted face-to-face in 2018 and 2019 in two nationally representative samples of both the general population and Roma communities, recruited from all regions of Romania. Both samples completed the EQ-5D-5L and EQ-VAS questionnaires, as well as a range of sociodemographic questions. Coarsened Exact Matching and several different regression models were used to assess the differences in HRQoL between the two groups. RESULTS: 2308 respondents were included in the matched sample: 1,621 general population individuals; 687 Roma people. Roma people had more problems with self-care, pain/discomfort, and anxiety/depression than the general population. They also reported a lower overall level of HRQoL than the general population of Romania, as reflected by the lower EQ-5D-5L and EQ-VAS scores. Our sensitivity analysis between Coarsened Exact Matching and other matching procedures showed consistent results across all regression models. CONCLUSIONS: In Romania, the Roma community has a lower level of HRQoL than the general population. Understanding the underlying causes of this inequality should be the focus of future research. Policies aimed at reducing the level of health inequality between the Roma and the general populations should be promoted locally.

Safety and impact of eculizumab withdrawal in patients with atypical haemolytic uraemic syndrome: protocol for a multicentre, open-label, prospective, single-arm study.

INTRODUCTION: Atypical haemolytic uraemic syndrome (aHUS) is a rare, life-threatening disease caused by excessive activation of part of the immune system called complement. Eculizumab is an effective treatment, controlling aHUS in 90% of patients. Due to the risk of relapse, lifelong treatment is currently recommended. Eculizumab treatment is not without problems, foremost being the risk of severe meningococcal infection, the burden of biweekly intravenous injections and the high cost.This paper describes the design of the Stopping Eculizumab Treatment Safely in aHUS trial that aims to establish whether a safety monitoring protocol, including the reintroduction of eculizumab for those who relapse, could be a safe, alternative treatment strategy for patients with aHUS. METHODS AND ANALYSIS: This is a multicentre, non-randomised, open-label study of eculizumab withdrawal with continuous monitoring of thrombotic microangiopathy-related serious adverse events using the Bayes factor single-arm design. 30 patients will be recruited to withdraw from eculizumab and have regular blood and urine tests for 24 months, to monitor for disease activity. If relapse occurs, treatment will be restarted within 24 hours of presentation. 20 patients will remain on treatment and complete health economic questionnaires only. An embedded qualitative study will explore the views of participants. ETHICS AND DISSEMINATION: A favourable ethical opinion and approval was obtained from the North East-Tyne & Wear South Research Ethics Committee. Outcomes will be disseminated via peer-reviewed articles and conference presentations. TRIAL REGISTRATION NUMBER: EudraCT number: 2017-003916-37 and ISRCTN number: ISRCTN17503205.

Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT.

BACKGROUND: Oral mucositis is a debilitating and painful complication of head and neck cancer irradiation that is characterised by inflammation of the mucous membranes, erythema and ulceration. Oral mucositis affects 6000 head and neck cancer patients per year in England and Wales. Current treatments have not proven to be effective. International studies suggest that low-level laser therapy may be an effective treatment. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of low-level laser therapy in the management of oral mucositis in head and neck cancer irradiation. To identify barriers to and facilitators of implementing low-level laser therapy in routine care. DESIGN: Placebo-controlled, individually randomised, multicentre Phase III superiority trial, with an internal pilot and health economic and qualitative process evaluations. The participants, outcome assessors and therapists were blinded. SETTING: Nine NHS head and neck cancer sites in England and Wales. PARTICIPANTS: A total of 87 out of 380 participants were recruited who were aged ≥ 18 years and were undergoing head and neck cancer irradiation with ≥ 60 Gy. INTERVENTION: Random allocation (1 : 1 ratio) to either low-level laser therapy or sham low-level laser therapy three times per week for the duration of irradiation. The diode laser had the following specifications: wavelength 660 nm, power output 75 mW, beam area 1.5 cm2, irradiance 50 mW/cm2, exposure time 60 seconds and fluence 3 J/cm2. There were 20-30 spots per session. Sham low-level laser therapy was delivered in an identical manner. MAIN OUTCOME MEASURE: The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks following the start of irradiation. Higher scores indicate a worse outcome. RESULTS: A total of 231 patients were screened and, of these, 87 were randomised (low-level laser therapy arm, n = 44; sham arm, n = 43). The mean age was 59.4 years (standard deviation 8.8 years) and 69 participants (79%) were male. The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks was 33.2 (standard deviation 10) in the low-level laser therapy arm and 27.4 (standard deviation 13.8) in the sham arm. LIMITATIONS: The trial lacked statistical power because it did not meet the recruitment target. Staff and patients willingly participated in the trial and worked hard to make the LiTEFORM trial succeed. However, the task of introducing, embedding and sustaining new low-level laser therapy services into a complex care pathway proved challenging. Sites could deliver low-level laser therapy to only a small number of patients at a time. The administration of low-level laser therapy was viewed as straightforward, but also time-consuming and sometimes uncomfortable for both patients and staff, particularly those staff who were not used to working in a patient's mouth. CONCLUSIONS: This trial had a robust design but lacked power to be definitive. Low-level laser therapy is relatively inexpensive. In contrast with previous trials, some patients found low-level laser therapy sessions to be difficult. The duration of low-level laser therapy sessions is, therefore, an important consideration. Clinicians experienced in oral cavity work most readily adapt to delivering low-level laser therapy, although other allied health professionals can be trained. Blinding the clinicians delivering low-level laser therapy is feasible. There are important human resource, real estate and logistical considerations for those setting up low-level laser therapy services. FUTURE WORK: Further well-designed randomised controlled trials investigating low-level laser therapy in head and neck cancer irradiation are needed, with similar powered recruitment targets but addressing the recruitment challenges and logistical findings from this research. TRIAL REGISTRATION: This trial is registered as ISRCTN14224600. FUNDING: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 46. See the NIHR Journals Library website for further project information.

Around 9 out of 10 head and neck cancer patients undergoing treatment experience pain, swelling and sores in their mouth (oral mucositis). This can lead to weight loss, painful ulcers, difficulty talking, eating and drinking, and even hospitalisation. Current care includes helping patients to keep their mouth and teeth clean, encouraging them to have a healthy diet and prescribing mouthwashes, painkillers and mouth-coating gels. However, these treatments give limited help in preventing or treating this condition. The LiTEFORM trial looked at whether or not low-level laser therapy could be used to prevent and treat oral mucositis. Patients were allocated to one of two arms at random: active laser or fake (sham) laser. Neither the patients nor the hospital staff knew which laser was being used. Eighty-seven people joined the study during the time allowed (44 received low-level laser therapy and 43 received sham treatment); however, this was a smaller number than the planned target of 380 people. As a result, no meaningful conclusion can be drawn from the results about whether the therapy is beneficial or cost-effective. People receiving the low-level laser therapy reported slightly more soreness in their mouth than those receiving the sham laser, but this could be down to chance. The number of participants is too small to draw conclusions about whether or not the low-level laser is helpful. Some patients found the laser treatment sessions to be difficult. Setting up a new service delivering laser therapy at the same time as cancer treatments was more complicated than originally anticipated. Problems included the scheduling of appointments, finding suitable rooms and having enough trained staff with time to deliver laser therapy. However, this study has provided us with knowledge on how best to set up a laser therapy service in the NHS as part of the cancer treatment pathway and the costs involved. These findings could help future studies looking into low-level laser therapy for those with head and neck cancer.

Improving the quality of perinatal mental health: a health visitor-led protocol.

The mental health of mothers is of significant concern to community practitioners. This paper reports on a case study exploring the success factors of a well established, health visitor-led protocol to identify and treat women with mild to moderate depression. Data were collected through interviews with a purposive sample of 12 community practitioners, a focus group of four health visitors and observation of a multidisciplinary steering group meeting. The protocol was described as an evidence-based tool and safety net that could be used flexibly to support clinical judgments and tailored to individual needs. Success factors included frontline clinician engagement and ownership, continuity of leadership to drive development and maintain momentum, comprehensive and on-going staff training, and strategic support for the protocol as a quality indicator at a time of organisational change. Quality and clinical leadership are continuing policy priorities. The protocol enabled frontline staff to lead a service innovation, providing a standardised multiprofessional approach to women's mental health needs through effective support, advice and treatment that can be measured and quality assured.

Developing a preference-based measure for weight-specific health-related quality of life in adolescence: the WAItE UK valuation study protocol.

INTRODUCTION: Adolescent obesity is a public health problem in the UK. The Weight-Specific Adolescent Instrument for Economic Evaluation (WAItE) has been developed as the first weight-specific health-related quality of life measure appropriate for economic evaluation, but currently cannot be used to generate quality-adjusted life years (QALYs), which are the basis of cost-utility analysis. Generic measures (such as the EQ-5D-Y or CHU-9D) may be insensitive to small but important health changes in overweight or obese adolescents. This study aims to generate a preference-based scoring algorithm for the WAItE. METHODS AND ANALYSIS: A discrete choice experiment (DCE) will be administered to value health states described by the WAItE classification system. These health states will be presented to members of the adult general population of the UK via an online survey. A range of regression models will be used to produce the utility algorithm for the WAItE. The DCE-visual analogue scale and time trade-off (TTO) anchoring methods will be used anchor the value set on to the 0-1 QALY scale. ETHICS AND DISSEMINATION: The Newcastle University Medical School Ethics Committee approved the study (references 4772/2020 (DCE) and 9978/2020 (TTO)). The developed algorithm can be applied to future economic evaluations of weight management interventions and treatments for adolescents.

Implementing a weight-specific quality-of-life tool for young people in primary health care: a qualitative study.

BACKGROUND: Obesity is thought to be one of the most serious global public health challenges of the 21st century. The primary care setting is important in terms of the diagnosis, education, and management of obesity in children and young people. This study explored the views of primary care clinicians on the implementation of a quality-of-life (QoL) tool to help young people and their families identify the impact of weight on QoL. AIM: To assess the acceptability and feasibility of implementing the Weight-specific Adolescent Instrument for Economic-evaluation (WAItE) QoL tool for young people aged 11-18 years in primary care. DESIGN & SETTING: Qualitative study in Northern England, UK METHOD: One-to-one, semi-structured interviews were conducted with a purposive sample of primary healthcare clinicians working in practices located in areas of varying deprivation in Northern England, UK. Interview transcripts were coded and analysed using framework analysis in NVivo (version 10). RESULTS: Participants (n = 16 GPs; n = 4 practice nurses) found the WAItE tool acceptable for them and their patients, and believed it was feasible for use in routine clinical practice. It was important to primary care clinicians that the tool would provide an overall QoL score that would be easy for GPs and nurses to interpret, to help them identify patients most in need of specialist help. CONCLUSION: This study has developed a platform for further research around QoL in young people who are overweight and obese. A future feasibility study will focus on implementing the tool in a small number of primary healthcare practices.

Estimating an EQ-5D-3L Value Set for Romania Using Time Trade-Off.

OBJECTIVE: To provide health-related quality of life (HRQoL) data to support health technology assessment (HTA) and reimbursement decisions in Romania, by developing a country-specific value set for the EQ-5D-3L questionnaire. METHODS: We used the cTTO method to elicit health state values using a computer-assisted personal interviewing approach. Interviews were standardized following the most recent version of the EQ-VT protocol developed by the EuroQoL Foundation. Thirty EQ-5D-3L health states were randomly assigned to respondents in blocks of three. Econometric modeling was used to estimate values for all 243 states described by the EQ-5D-3L. RESULTS: Data from 1556 non-institutionalized adults aged 18 years and older, selected from a national representative sample, were used to build the value set. All tested models were logically consistent; the final model chosen to generate the value set was an interval regression model. The predicted EQ-5D-3L values ranged from 0.969 to 0.399, and the relative importance of EQ-5D-3L dimensions was in the following order: mobility, pain/discomfort, self-care, anxiety/depression, and usual activities. CONCLUSIONS: These results can support reimbursement decisions and allow regional cross-country comparisons between health technologies. This study lays a stepping stone in the development of a health technology assessment process more driven by locally relevant data in Romania.