Adapting the EQ-5D-3L for adults with mild to moderate learning disabilities.

BACKGROUND: Approximately 1.5 million adults in the UK have a learning disability. The difference between age at death for this group and the general population is 26 years for females and 22 years for males. The NHS Long Term Plan (January 2019) recognises learning disabilities as a clinical priority area. People with a learning disability are often excluded from research by design or lack of reasonable adjustments, and self-reported health status/health-related quality of life questionnaires such as the EQ-5D are often not appropriate for this population. Here, we systematically examine the EQ-5D-3L (its wording, content, and format) using qualitative methods to inform the adaption of the measure for use with adults with mild to moderate learning disabilities. METHODS: Think-aloud interviews with carers/advocates of learning-disabled adults were undertaken to explore the difficulties with completing the EQ-5D-3L. Alternative wording, language, structure, and images were developed using focus groups, stakeholder reference groups, and an expert panel. Data analysis followed a framework method. RESULTS: The dimensions and levels within the EQ-5D-3L were deemed appropriate for adults with mild to moderate learning disabilities. Consensus on wording, structure, and images was reached through an iterative process, and an adapted version of the EQ-5D-3L was finalised. CONCLUSION: The EQ-5D-3L adapted for adults with mild to moderate intellectual/learning disabilities can facilitate measurement of self-reported health status. Research is underway to assess the potential use of the adaptation for economic evaluation.

Impact of in-hospital postoperative complications on quality of life up to 12 months after major abdominal surgery.

BACKGROUND: Postoperative complications are common, but there are limited data regarding their implications on patients' quality of life. This study aimed to address this gap in the literature by analysing the impact of postoperative complications on patients' health-related quality of life. METHODS: Data from the Perioperative Quality Improvement Programme were analysed, and included patient-level data for 19 685 adults who underwent elective major abdominal procedures in England since 2016. Postoperative complications were graded using the Clavien-Dindo classification. Quality of life was assessed by responses to the EuroQol five-dimension five-levels-of-response (EQ-5D-5L™) questionnaire before surgery, and at 6 and 12 months after operation. Ordinal logistic regression was used to estimate the association between Clavien-Dindo grades and quality of life. Tobit and ordinary least squares regression analyses were used to estimate the quality-adjusted life-year (QALY) loss resulting from postoperative complications between admission and 12 months after surgery. RESULTS: At 6 and 12 months after surgery, increasingly severe postoperative complications were significantly associated with poorer health-related quality of life. The effect of postoperative complications on quality of life was sustained until at least 12 months after operation. Between admission and 12 months after surgery, 0.012, 0.026, 0.033, and 0.086 QALYs were lost for those experiencing a grade I, II, III, or IV postoperative complication respectively. CONCLUSION: Postoperative complications have a significant and sustained effect on patients' quality of life after surgery; this effect worsens as the severity of the complications increases.

Cost-Effectiveness of Pain Management Strategies in Advanced Cancer.

OBJECTIVES: Uncontrolled pain in advanced cancer is a common problem and has significant impact on individuals' quality of life and use of healthcare resources. Interventions to help manage pain at the end of life are available, but there is limited economic evidence to support their wider implementation. We conducted a case study economic evaluation of two pain self-management interventions (PainCheck and Tackling Cancer Pain Toolkit [TCPT]) compared with usual care. METHODS: We generated a decision-analytic model to facilitate the evaluation. This modelled the survival of individuals at the end of life as they moved through pain severity categories. Intervention effectiveness was based on published meta-analyses results. The evaluation was conducted from the perspective of the U.K. health service provider and reported cost per quality-adjusted life-year (QALY). RESULTS: PainCheck and TCPT were cheaper (respective incremental costs -GBP148 [-EUR168.53] and -GBP474 [-EUR539.74]) and more effective (respective incremental QALYs of 0.010 and 0.013) than usual care. There was a 65 percent and 99.5 percent chance of cost-effectiveness for PainCheck and TCPT, respectively. Results were relatively robust to sensitivity analyses. The most important driver of cost-effectiveness was level of pain reduction (intervention effectiveness). Although cost savings were modest per patient, these were considerable when accounting for the number of potential intervention beneficiaries. CONCLUSIONS: Educational and monitoring/feedback interventions have the potential to be cost-effective. Economic evaluations based on estimates of effectiveness from published meta-analyses and using a decision modeling approach can support commissioning decisions and implementation of pain management strategies.

Exploration of likely engagement with Monetary Contingency Contracts for weight loss: a questionnaire study.

Monetary Contingency Contracts (MCCs) are schemes that ask individuals to pledge money that is returned contingent on behaviour change. In relation to weight loss, this study explored likely levels of engagement with MCCs, how much individuals would be willing to pay into an MCC, and how these amounts vary under different contract conditions. Fifty-six individuals with BMI above 25 who were motivated to lose weight were recruited. The majority of participants (87.5%) indicated that they would be willing to engage with weight loss MCCs, but showed more reluctance to subscribe to pair-based MCCs which offered; (a) refunds contingent on the weight loss of a weight loss partner, and (b) 'all or nothing refunds' in which no reward is given for any weight loss below the target weight loss goal. This study provides preliminary evidence that individuals motivated to lose weight may be willing to engage with weight loss MCCs. Further research is needed to explore reasons for reluctance to subscribe to MCCs with certain conditions, to inform the design of future experimental studies testing the efficacy of MCCs as part of an intervention for weight loss.

Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial.

BACKGROUND: Early intervention and tight control of inflammation optimise outcomes in rheumatoid arthritis but these approaches have not yet been studied in psoriatic arthritis. We aimed to assess the effect of tight control on early psoriatic arthritis using a treat-to-target approach. METHODS: For this open-label multicentre randomised controlled trial, adult patients (aged ≥18 years) with early psoriatic arthritis (<24 months symptom duration), who had not previously received treatment with any disease-modifying anti-rheumatic drugs, were enrolled from eight secondary care rheumatology centres in the UK. Enrolled patients were randomly assigned in a 1:1 ratio to receive either tight control (with review every 4 weeks and with escalation of treatment if minimal disease activity criteria not met) or standard care (standard therapy according to the treating clinician, with review every 12 weeks) for 48 weeks. Randomisation was done by minimisation incorporating a random element, to ensure treatment groups were balanced for randomising centre and pattern of arthritis (oligoarticular vs polyarticular). The randomisation procedure was done through a central 24-h automated telephone system based at the Leeds Institute of Clinical Trials Research (Leeds, UK). This was an open-label study in which patients and clinicians were aware of treatment group assignment. Clinical outcomes were recorded by a masked assessor every 12 weeks. The primary outcome was the proportion of patients achieving an American College of Rheumatology (ACR) 20% (ACR20) response at 48 weeks, analysed by intention to treat with multiple imputation for missing ACR components. Cost-effectiveness was also assessed. This trial is registered with ClinicalTrials.gov, number NCT01106079, and the ISCRCTN registry, number ISCRCTN30147736. FINDINGS: Between May 28, 2008, and March 21, 2012, 206 eligible patients were enrolled and randomly assigned to receive tight control (n=101) or standard care (n=105). In the intention-to-treat patient population, the odds of achieving an ACR20 response at 48 weeks were higher in the tight control group than in the standard care group (odds ratio 1·91, 95% CI 1·03-3·55; p=0·0392). Serious adverse events were reported by 20 (10%) patients (25 events in 14 [14%] patients in the tight control group and eight events in six [6%] patients in the standard care group) during the course of the study. No unexpected serious adverse events or deaths occurred. INTERPRETATION: Tight control of psoriatic arthritis disease activity through a treat-to-target approach significantly improves joint outcomes for newly diagnosed patients, with no unexpected serious adverse events reported. FUNDING: Arthritis Research UK and Pfizer.

Testing a workplace physical activity intervention: a cluster randomized controlled trial.

BACKGROUND: Increased physical activity levels benefit both an individuals' health and productivity at work. The purpose of the current study was to explore the impact and cost-effectiveness of a workplace physical activity intervention designed to increase physical activity levels. METHODS: A total of 1260 participants from 44 UK worksites (based within 5 organizations) were recruited to a cluster randomized controlled trial with worksites randomly allocated to an intervention or control condition. Measurement of physical activity and other variables occurred at baseline, and at 0 months, 3 months and 9 months post-intervention. Health outcomes were measured during a 30 minute health check conducted in worksites at baseline and 9 months post intervention. The intervention consisted of a 3 month tool-kit of activities targeting components of the Theory of Planned Behavior, delivered in-house by nominated facilitators. Self-reported physical activity (measured using the IPAQ short-form) and health outcomes were assessed. RESULTS AND DISCUSSION: Multilevel modelling found no significant effect of the intervention on MET minutes of activity (from the IPAQ) at any of the follow-up time points controlling for baseline activity. However, the intervention did significantly reduce systolic blood pressure (B=-1.79 mm/Hg) and resting heart rate (B=-2.08 beats) and significantly increased body mass index (B=.18 units) compared to control. The intervention was found not to be cost-effective, however the substantial variability round this estimate suggested that further research is warranted. CONCLUSIONS: The current study found mixed support for this worksite physical activity intervention. The paper discusses some of the tensions involved in conducting rigorous evaluations of large-scale randomized controlled trials in real-world settings.

Development and validation of the living with chronic obstructive pulmonary disease questionnaire.

PURPOSE: Available patient-reported outcome (PRO) measures for chronic obstructive pulmonary disease (COPD) focus primarily on impairment (symptoms) and activities (functioning). The purpose of the study was to develop a patient-based PRO measure for COPD that captures the overall everyday impact of living with COPD from the patient's perspective. METHODS: LCOPD items (Living with COPD Questionnaire) were generated from qualitative interviews in the U.K. and focus groups in the U.S.A. The draft measure was tested for face and content validity in both countries. Item reduction and testing for reproducibility and construct validity was conducted via Rasch and traditional psychometric analyses. RESULTS: The draft LCOPD was found to be relevant and acceptable to patients in the U.K. (N = 19) and U.S. (N = 16). Application of Rasch analysis to data collected in validation studies (n = 162 in the U.K. and 145 in U.S.) identified a 22-item scale that measured a single construct in both countries. Psychometric analyses indicated that this version was internally consistent and reproducible. Scores on the measure were related as expected to clinician ratings of disease severity and patient ratings of COPD severity and general health. CONCLUSIONS: The LCOPD is a new measure examining the everyday impact of living with COPD. It demonstrates good scaling properties and may prove valuable in understanding treatment benefits.

Effects of method of translation of patient-reported health outcome questionnaires: a randomized study of the translation of the Rheumatoid Arthritis Quality of Life (RAQoL) Instrument for Sweden.

AIMS: To compare two versions of a questionnaire translated using forward-backward (FB) translation and dual-panel (DP) methodologies regarding preference of wording and psychometric properties. METHODS: The Rheumatoid Arthritis Quality of Life instrument was adapted into Swedish by two independent groups using FB and DP methodologies, respectively. Seven out of thirty resulting items were identical. Nonidentical items were evaluated regarding preference of wording by 23 bilingual Swedes, 50 people with rheumatoid arthritis (RA), and 2 lay panels (n = 11). Psychometric performance was assessed from a postal survey of 200 people with RA randomly assigned to complete one version first and the other 2 weeks later. RESULTS: Preference did not differ among the 23 bilinguals (P = 0.196), whereas patients and lay people preferred DP over FB item versions (P < 0.0001). Postal survey response rates were 74% (FB) and 75% (DP). There were more missing item responses in the FB than the DP version (6.9% vs. 5.6%; P < 0.0001). Floor/ceiling effects were small (FB, 6.1/0%; DP, 4.4/0.7%) and reliability was 0.92 for both versions. Construct validity was similar for both versions. Differential item functioning by version was detected for five items but cancelled out and did not affect estimated person measures. CONCLUSIONS: The DP approach showed advantages over FB translation in terms of preference by the target population and by lay people, whereas there were no obvious psychometric differences. This suggests advantages of DP over FB translation from the patients' perspective, and does not support the commonly held view that FB translation is the "gold standard."

International development of the patient-reported outcome indices for multiple sclerosis (PRIMUS).

BACKGROUND: The Patient-Reported Indices for Multiple Sclerosis (PRIMUS) comprises a suite of three scales for assessing symptoms, activity limitations, and quality of life in multiple sclerosis (MS). It was developed in the UK and has been shown to have excellent psychometric properties. This study describes the adaptation of eight language versions for Canadian English, Canadian French, French, German, Italian, Spanish, Swedish, and US English. METHODS: The PRIMUS was translated using the dual-panel process. Cognitive debriefing interviews conducted with MS patients assessed face and content validity. Psychometric and scaling properties were assessed via a two-administration postal survey conducted in each country involving the PRIMUS, the Nottingham Health Profile (NHP), the Unidimensional Fatigue Impact Scale (U-FIS), and demographic questions. RESULTS: Cognitive debriefing interviews demonstrated the acceptability of the new language versions. Analysis of survey data showed that the new language versions of the three PRIMUS scales were unidimensional (as indicated by fit to the Rasch model) and that they had good internal consistency and reproducibility. PRIMUS scale scores correlated as expected with those on the NHP and the U-FIS. The scales in all countries were able to discriminate between groups of patients on the basis of their self-reported MS severity, general health, and employment status. CONCLUSIONS: The PRIMUS was successfully adapted into eight new languages. Most of the tests showed the PRIMUS to have good unidimensionality and to have good internal consistency, reproducibility, and construct validity. The measure is now available for use in clinical studies and trials involving these countries and the UK. Further work is required to assess the measure's responsiveness.

International development of the Unidimensional Fatigue Impact Scale (U-FIS).

OBJECTIVE: The 22-item Unidimensional Fatigue Impact Scale (U-FIS) provides an index of the impact of fatigue on patients with multiple sclerosis (MS). The objective is to produce eight new language versions of the U-FIS: Canadian-English, Canadian-French, French, German, Italian, Spanish, Swedish, and US-English. METHODS: The U-FIS was translated via two translation panels. Cognitive debriefing interviews conducted with patients in each country assessed face and content validity. Scaling and psychometric properties were assessed via survey data with patients in each country completing the U-FIS, Nottingham Health Profile (NHP), and demographic questions. RESULTS: Cognitive debriefing interviews demonstrated U-FIS acceptability. Analysis of postal survey data showed all new language versions to be unidimensional. Reliability was high, with test-retest correlations and internal-consistency coefficients exceeding 0.85. Initial evidence of validity was provided by moderate to high correlations with NHP scales. The U-FIS was able to discriminate between groups based on employment status, perceived MS severity, and general health. CONCLUSION: The U-FIS is a practical new measure of the impact of fatigue. It was successfully adapted into eight new languages to broaden availability for researchers. Psychometric analyses indicated that the new language versions were unidimensional and reproducible with promising construct validity.

Cost-Effectiveness of Dementia Care Mapping in Care-Home Settings: Evaluation of a Randomised Controlled Trial.

BACKGROUND: Behaviours such as agitation impact on the quality of life of care-home residents with dementia and increase healthcare use. Interventions to prevent these behaviours have little evidence supporting their effectiveness or cost-effectiveness. We conducted an economic evaluation alongside a trial assessing Dementia Care Mapping™ (DCM) versus usual care for reducing agitation, and highlight methodological challenges of conducting evaluations in this population and setting. METHODS: RCT data over 16 months from English care-home residents with dementia (intervention n = 418; control n = 308) were analysed. We conducted a cost-utility analysis from the healthcare provider perspective. We gathered resource use and utility (EQ-5D-5L and DEMQoL-Proxy-U) from people living with dementia and proxy informants (staff and relatives). Data were analysed using seemingly unrelated regression, accounting for care-home clustering and bootstrapping used to capture sampling uncertainty. RESULTS: Costs were higher in the intervention arm than in the control arm (incremental = £1479) due in part to high cost outliers. There were small QALY gains (incremental = 0.024) in favour of DCM. The base-case ICER (£64,380 per QALY) suggests DCM is not cost-effective versus usual care. With the exception of analyses excluding high cost outliers, which suggested a potential for DCM to be cost-effective, sensitivity analyses corroborated the base-case findings. Bootstrapped estimates suggested DCM had a low probability (< 0.20 where λ = £20,000) of being cost-effective versus control. CONCLUSION: DCM does not appear to be a cost-effective intervention versus usual care in this group and setting. The evaluation highlighted several methodological challenges relating to validity of utility assessments, loss to follow-up and compliance. Further research is needed on handling high-cost individuals and capturing utility in this group. ISRCTN reference 82288852.

The development of the Herpes Symptom Checklist and the Herpes Outbreak Impact Questionnaire.

OBJECTIVE: To develop measures of the day-to-day symptomatic and functional impact of recurrent genital herpes (RGH) outbreaks. The Herpes Outbreak Impact Questionnaire (HOIQ) and the Herpes Symptom Checklist (HSC) were designed to be acceptable to clinical professionals and to reflect patients' experience. METHODS: Scale content was derived via literature review and interviews with RGH patients and physicians. Questionnaires were assessed for face/content validity in the UK and the language checked for acceptability in the United States. The US measures were assessed for face/content validity with patients. Scaling/psychometric properties were determined via web survey. Participants completed the questionnaires twice during an outbreak, with 24 to 72 hours between administrations. RESULTS: Respondents found the questionnaires relevant and easy to understand and complete. Application of Rasch analysis resulted in the removal of two HOIQ items. Both scales were found to be unidimensional. Item stability testing for the HOIQ indicated that the measure is reproducible. Internal consistency was good (alpha: time 1 = 0.87, time 2 = 0.91). Discriminative validity was demonstrated by the measure's ability to distinguish between individuals who differed by self-reported severity of outbreak. The HOIQ and HSC were both responsive to change over time. CONCLUSIONS: The HSC and the HOIQ can determine the impact of a herpes outbreak effectively. They are designed to be used daily during such outbreaks and to determine the effectiveness of RGH treatment.

Further validation and responsiveness assessment of the Herpes Outbreak Impact Questionnaire and Herpes Symptom Checklist.

OBJECTIVE: The Herpes Outbreak Impact Questionnaire (HOIQ) and Herpes Symptom Checklist (HSC) are patient-completed questionnaires for assessing genital herpes outbreaks. This report describes the validation of paper-and-pencil versions of the scales and responsiveness assessments in an Australian clinical trial. METHODS: Acceptability of the language of the original UK versions was tested with Australians. The HOIQ and HSC were then field-tested with patients. The new versions were validated using patients' daily responses to the questionnaires in a famciclovir study. RESULTS: The HOIQ and HSC were readily adapted into Australian English and were acceptable to patients. Psychometric sample: N = 151; 81 (54%) male; mean age 39.9 +/- 11.6 years; mean outbreaks 5.1 +/- 3.0 per year. Internal consistency was good (alphas at outbreak 1 ranged 0.84-0.90 HOIQ and 0.73-0.87 HSC). Rasch analysis showed item stability over time. Correlations between HOIQ and HSC ranged from 0.46 to 0.60. Both scales distinguished outbreak healing presence or absence at day 6 (P = 0.001), and the HOIQ scale distinguished between symptom severity groups (P < 0.001). Scale scores declined significantly over study duration, exhibiting large effect sizes. CONCLUSIONS: The paper-and-pencil HOIQ and HSC were reliable, valid, and responsive in a clinical trial setting. These instruments are recommended for use in clinical studies.

Development and psychometric assessment of the COPD and Asthma Sleep Impact Scale (CASIS).

BACKGROUND: Patients with respiratory disease experience disturbed sleep, but there is no widely accepted measure of sleep impairment due to respiratory disease. We developed and evaluated the psychometric performance of a patient-reported measure to assess the impact on sleep due to respiratory disease, the COPD and Asthma Sleep Impact Scale (CASIS). METHODS: Identification of the items forming the CASIS was guided by patient interviews and focus groups. An observational study involving patients from the US and UK was then conducted to assess the psychometric characteristics of the measure. RESULTS: Qualitative data from 162 patients were used to develop the CASIS (n = 78 COPD; n = 84 asthma). The observational study included 311 patients with COPD and 324 patients with asthma. The final seven items used in the CASIS were identified based on factor and item response theory analyses. Internal consistency was 0.90 (COPD) and 0.92 (asthma), and test-retest reliability was 0.84 (both groups). In the COPD sample, CASIS scores were significantly correlated with the Saint George's Respiratory Questionnaire scores (all p < 0.0001) and differed significantly by patient-reported disease severity, exacerbation status, and overall health status (all p

Development and validation of a preference based measure derived from the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for use in cost utility analyses.

BACKGROUND: Pulmonary Hypertension is a severe and incurable disease with poor prognosis. A suite of new disease-specific measures--the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) - was recently developed for use in this condition. The purpose of this study was to develop and validate a preference based measure from the CAMPHOR that could be used in cost-utility analyses. METHODS: Items were selected that covered major issues covered by the CAMPHOR QoL scale (activities, travelling, dependence and communication). These were used to create 36 health states that were valued by 249 people representative of the UK adult population, using the time trade-off (TTO) technique. Data from the TTO interviews were analysed using both aggregate and individual level modelling. Finally, the original CAMPHOR validation data were used to validate the new preference based model. RESULTS: The predicted health state values ranged from 0.962 to 0.136. The mean level model selected for analyzing the data had good explanatory power (0.936), did not systematically over- or underestimate the observed mean health state values and showed no evidence of auto correlation in the prediction errors. The value of less than 1 reflects a background level of ill health in state 1111, as judged by the respondents. Scores derived from the new measure had excellent test-retest reliability (0.85) and construct validity. The CAMPHOR utility score appears better able to distinguish between WHO functional classes (II and III) than the EQ-5D and SF-6D. CONCLUSION: The tariff derived in this study can be used to classify an individual into a health state based on their responses to the CAMPHOR. The results of this study widen the evidence base for conducting economic evaluations of interventions designed to improve QoL for patients with PH.

Adaptation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) into French-Canadian and English-Canadian.

BACKGROUND: The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific instrument for assessing patient-reported symptoms, functioning and quality of life (QoL) in pulmonary arterial hypertension (PAH). OBJECTIVES: To create and validate French-Canadian (FC) and English-Canadian (EC) language versions of the CAMPHOR. METHODS: A translation panel (for the FC version) and lay panels (for both versions) were convened to adapt the questionnaires (dual-panel methodology). Subsequently, these new questionnaires were field-tested in 15 FC PAH and 15 EC PAH patients. Finally, in a postal validation study, the new language versions of the CAMPHOR underwent psychometric evaluation in 41 FC and 52 EC PAH patients to test for reliability and validity. RESULTS: The FC and EC field-test interview participants found the questionnaires relevant, comprehensible and easy to complete. Psychometric analyses showed that the FC and EC adaptations were successful. High test-retest coefficients for the scales after controlling for change in respondent's QoL (FC: 0.92 to 0.96; EC: 0.85 to 0.99) indicated a high degree of reliability. The FC and EC CAMPHOR scales had good internal consistency (Cronbach's alpha coefficients 0.90 to 0.92 and 0.88 to 0.92, respectively). Predicted correlations with the Nottingham Health Profile provided evidence of the construct validity of the FC and EC scales. The FC and EC adaptations also showed known groups validity. CONCLUSIONS: The FC and EC adaptations of the CAMPHOR have been shown to be reliable and valid for measures of health-related QoL and QoL in PAH, and thus can be recommended for use in clinical studies and routine practice in PAH.

Evaluation of the psychometric properties of the Hungarian quality of life in depression scale.

The paper describes the adaptation and psychometric evaluation of the Hungarian version of the quality of life in depression scale. The adaptation procedure involved: bilingual translation; field-testing for face and content validity; and assessment of instrument's reliability and construct validity. The new language version was shown to be well-accepted by respondents and to have excellent psychometric properties.

Cost-Effectiveness of Tight Control of Inflammation in Early Psoriatic Arthritis: Economic Analysis of a Multicenter Randomized Controlled Trial.

OBJECTIVE: Treat-to-target approaches have proved to be effective in rheumatoid arthritis, but have not been studied in psoriatic arthritis (PsA). This study was undertaken to examine the cost-effectiveness of tight control (TC) of inflammation in early PsA compared to standard care. METHODS: Cost-effectiveness analyses were undertaken alongside a UK-based, open-label, multicenter, randomized controlled trial. Taking the perspective of the health care sector, effectiveness was measured using the 3-level EuroQol 5-domain, which allows for the calculation of quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICERs) are presented, which represent the additional cost per QALY gained over a 48-week time horizon. Sensitivity analyses are presented assessing the impact of variations in the analytical approach and assumptions on the cost-effectiveness estimates. RESULTS: The mean cost and QALYs were higher in the TC group: £4,198 versus £2,000 and 0.602 versus 0.561. These values yielded an ICER of £53,948 per QALY. Bootstrapped uncertainty analysis suggests that the TC has a 0.07 probability of being cost-effective at a £20,000 threshold. Stratified analysis suggests that with certain costs being controlled, an ICER of £24,639 can be calculated for patients with a higher degree of disease severity. CONCLUSION: A tight control strategy to treat PsA is an effective intervention in the treatment pathway; however, this study does not find tight control to be cost-effective in most analyses. Lower drug prices, targeting polyarthritis patients, or reducing the frequency of rheumatology visits may improve value for money metrics in future studies.

Quality of life in infants and children with atopic dermatitis: addressing issues of differential item functioning across countries in multinational clinical trials.

BACKGROUND: A previous study had identified 45 items assessing the impact of atopic dermatitis (AD) on the whole family. From these it was intended to develop two separate scales, one assessing impact on carers and the other determining the effect on the child. METHODS: The 45 items were included in three clinical trials designed to test the efficacy of a new topical treatment (pimecrolimus, Elidel cream 1%) in the treatment of AD in infants and children and in validation studies in the UK, US, Germany, France and the Netherlands. Rasch analyses were undertaken to determine whether an internationally valid, unidimensional scale could be developed that would inform on the direct impact of AD on the child. RESULTS: Rasch analyses applied to the data from the trials indicated that the draft measure consisted of two scales, one assessing the QoL of the carer and the other (consisting of 12 items) measuring the impact of AD on the child. Three of the 12 potential items failed to fit the measurement model in Europe and five in the US. In addition, four items exhibiting differential item functioning (DIF) by country were identified. After removing the misfitting items and controlling for DIF it was possible to derive a scale; The Childhood Impact of Atopic Dermatitis (CIAD) with good item fit for each trial analysis. Analysis of the validation data from each of the different countries confirmed that the CIAD had adequate internal consistency, reproducibility and construct validity. The CIAD demonstrated the benefits of treatment with Elidel over placebo in the European trial. A similar (non-significant) trend was found for the US trials. CONCLUSION: The study represents a novel method of dealing with the problem of DIF associated with different cultures. Such problems are likely to arise in any multinational study involving patient-reported outcome measures, as items in the scales are likely to be valued differently in different cultures. However, where all items in a scale fit both a single theoretical construct and the Rasch measurement model, it is feasible to conceive of outcome measures with a different set of items in each language.

Translation and validation of non-English versions of the Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire.

BACKGROUND: The Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire is a unidimensional, disease-specific measure developed in the UK and the Netherlands. This study describes its adaptation into other languages. METHODS: The UK English ASQOL was translated into US English; Canadian French and English; French; German; Italian; Spanish; and Swedish (dual-panel methods). Cognitive debriefing interviews were conducted with AS patients. Psychometric/scaling properties were assessed using data from two Phase III studies of adalimumab. Baseline and Week-2 data were used to assess test-retest reliability. Validity was determined by correlation of ASQOL with SF-36 and BASFI and by discriminative ability of ASQOL based on disease severity. Item response theory (Rasch model) was used to test ASQOL's scaling properties. RESULTS: Cognitive debriefing showed the new ASQOL versions to be clear, relevant and comprehensive. Sample sizes varied, but were sufficient for: psychometric/scaling assessment for US English and Canadian English; psychometric but not scaling analyses for German; and preliminary evidence of these properties for the remaining languages. Test-retest reliability and Cronbach's alpha coefficients were high: US English (0.85, 0.85), Canadian English (0.87, 0.86), and German (0.77, 0.79). Correlations of ASQOL with SF-36 and BASFI for US English, Canadian English, and German measures were moderate, but ASQOL discriminated between patients based on perceived disease severities (p < 0.01). Results were comparable for the other languages. US English and Canadian English exhibited fit to the Rasch model (non-significant p-values: 0.54, 0.68), confirming unidimensionality. CONCLUSION: The ASQOL was successfully translated into all eight languages. Psychometric properties were excellent for US English, Canadian English, and German, and extremely promising for the other languages.