Validation and Application of Thresholds to Define Meaningful Change in Vasomotor Symptoms Frequency: Analysis of Pooled SKYLIGHT 1 and 2 Data.

INTRODUCTION: Vasomotor symptoms (VMS), the characteristic symptoms of menopausal transition, are often the primary reason women seek treatment. Current treatment options for VMS include fezolinetant, a nonhormonal, selective neurokinin 3 receptor antagonist. This study aimed to define a clinically meaningful threshold for reduction of moderate-to-severe VMS in postmenopausal women treated with fezolinetant and then apply it in a responder analysis of the pooled trial data. METHODS: This analysis pooled data from two identical phase 3, double-blind, placebo-controlled studies that randomized women with moderate-to-severe VMS to once-daily fezolinetant 30 mg, 45 mg, or placebo (SKYLIGHT 1 and 2). The frequency of VMS was collected daily using an electronic diary. Patients completed the Patient Global Impression of Change in VMS (PGI-C VMS) instrument, which assessed changes in hot flushes/night sweats at weeks 4 and 12 compared with baseline using a seven-point Likert scale. VMS frequency data were anchored to PGI-C VMS data; the anchor level for meaningful within-patient change in PGI-C VMS was "moderately better." RESULTS: In the pooled population (N = 1022), the mean (standard deviation) estimated thresholds for a meaningful within-patient change in moderate-to-severe VMS frequency were - 5.73 (3.47) at week 4 and - 6.20 (5.18) at week 12. Applying the thresholds for meaningful within-patient change to responder analyses ("missing as non-responder" imputation method) indicated a favorable clinical benefit: greater proportions of responders were observed in the fezolinetant 30-mg and 45-mg groups compared with placebo at week 4 (odds ratio range 2.48-2.91; P < 0.001) and week 12 (odds ratio range 1.908-2.68; P < 0.001). CONCLUSION: PGI-C VMS is sensitive to change and correlates with VMS frequency: a reduction of approximately six VMS episodes per day from baseline to week 12 was meaningful at the individual patient level. Fezolinetant provides a meaningful clinical benefit for women with moderate-to-severe VMS associated with menopause and represents an important nonhormonal treatment option. TRIAL REGISTRATION NUMBER: NCT04003155 and NCT04003142.

Remote-Use Applications of the ALSFRS-R Clinical Outcome Assessment Tool: A Scoping Review.

OBJECTIVES: In 2021, the U.S. Congress passed the ACT for ALS Act. The law encourages development of "tools, methods, and processes" to improve clinical trial efficiency for neurodegenerative diseases. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is an outcome measure administered during in-person clinic visits and used to support investigational studies for persons living with Amyotrophic Lateral Sclerosis (PALS). Availability of a standardized, remote-use version of the ALSFRS-R may promote more inclusive, decentralized clinical trials. A scoping literature review was conducted to identify existing remote-use ALSFRS-R tools, synthesize feasibility and comparability of administration modes, and summarize barriers and facilitators to inform development of a standardized remote-use ALSFRS-R tool. METHODS: Included studies reported comparisons between remote and in-person, clinician-reported, ALSFRS-R administration and were published in English (2002-2022). References were identified by searching peer-reviewed and gray literature. Twelve studies met inclusion criteria and were analyzed to compare findings within and across modes of administration. RESULTS: Remote modes of ALSFRS-R administration were categorized into four non-mutually exclusive categories: telephone (n = 6), videoconferencing (n = 3), computer or online platforms (n = 3), mobile-apps and wearables (n = 2), and one unspecified telemedicine modality (n = 1). Studies comparing in-person to telephone or videoconferencing administration reported high ALSFRS-R rating correlations and nonsignificant between- mode differences. CONCLUSION: There is insufficient information in the ALSFRS-R literature to support remote clinician administration for collecting high quality data. Future research should engage PALS, care partners and providers to develop a standardized remote-use ALSFRS-R version.

Psychometric Evaluation of the Diary for Irritable Bowel Syndrome Symptoms-Constipation in a Prospective Observational Study.

OBJECTIVES: To evaluate the psychometric properties of the Diary for Irritable Bowel Syndrome Symptoms-Constipation (DIBSS-C), which was developed to support primary and secondary endpoints in irritable bowel syndrome (IBS) with predominant constipation (IBS-C) clinical trials. METHODS: Observational data were collected from 108 adults with IBS-C using a smartphone-type device for 17 days. DIBSS-C data regarding bowel movements (BMs) were collected for each event (along with the Bristol Stool Form Scale); abdominal symptoms were rated each evening. Global status items and the Gastrointestinal Symptom Rating Scale-IBS were completed on day 10 and day 17 and the IBS-Symptom Severity Scale on day 17. Item-level performance, internal consistency reliability, test-retest reliability, and construct validity were evaluated. RESULTS: The Abdominal Symptoms Domain score demonstrated high internal consistency reliability (Cronbach's alpha week 1 = 0.98; week 2 = 0.96) and test-retest reliability (intraclass correlation coefficient [ICC] = 0.93). Test-retest reliability was stronger for abdominal symptoms (ICC = 0.91-0.94) than for the frequency-based BM-related outcomes (ICC = 0.54-0.66). Key construct validity hypotheses were supported by moderate to strong correlations with the corresponding Gastrointestinal Symptom Rating Scale-IBS, IBS-Symptom Severity Scale, and Bristol Stool Form Scale items. All known-groups comparisons were statistically significant for the abdominal symptom items and domain score; evidence for known-groups validity of BM-related outcomes was supportive when based on constipation severity. CONCLUSIONS: The results of this study provided key psychometric evidence for the DIBSS-C, ultimately contributing to its qualification by the US Food and Drug Administration for use in IBS-C clinical trials.

Comparison of anchor-based methods for estimating thresholds of meaningful within-patient change using simulated PROMIS PF 20a data under various joint distribution characteristic conditions.

PURPOSE: To compare the performance of anchor-based methods for estimating thresholds of meaningful within-patient change (i.e., individual change) of clinical outcome assessments in conditions reflecting data characteristics of small- to medium-sized clinical trials. METHODS: Datasets were generated from the joint distributions of the PROMIS PF 20a T-score changes and a seven-point global change anchor measure. The 108 simulation conditions (1000 replications per condition) included combinations of three marginal distributions of T-score changes, three improvement percentages in the anchor measure, four levels of responsiveness correlations, and three sample sizes. Threshold estimation methods included mean change, median change, ROC curve, predictive modeling, half SD, and SEM. Relative bias, precision, accuracy, and measurement significance of the estimates were evaluated based on comparison with true thresholds and IRT-based individual reliable changes of PROMIS scores. Quantile regression models were applied to select and interpret effects of simulation conditions on estimation bias. RESULTS: When PROMIS T-score changes were distributed normally, the predictive modeling method performed best with 50% or more responders identified by the anchor; the mean and median methods were preferred with 30% responders. For skewed distributions, the median method and ROC method gained more advantages. Among the evaluated study conditions, the improvement percentage condition had the most obvious effects on estimation bias. CONCLUSION: To establish accurate and precise thresholds, clinical researchers are recommended to prioritize study designs with at least 50% anchor-defined responders and strongly responsive target endpoints with highly reliable scoring calibration and to select optimal anchor-based methods given the data characteristics.

Is IQWiG's 15% Threshold Universally Applicable in Assessing the Clinical Relevance of Patient-Reported Outcomes Changes? An ISPOR Special Interest Group Report.

This article discusses a recent methodological change to assess the additional benefit of drug intervention by the German Federal Joint Committee (Gemeinsamer Bundesausschuss), a key stakeholder in EUnetHTA21 (European Network for Health Technology Assessment joint consortium for future EU HTA regulation), methodological workstream. The German Federal Joint Committee (Gemeinsamer Bundesausschuss) set a universal individual response threshold at ≥ 15% of the scale range of the measurement instrument, for all patient-reported outcomes, to achieve an additional benefit rating for a given pharmaceutical intervention. This approach is originally based on a corresponding recommendation from the Institute for Quality and Efficiency in Health Care. The merits of this approach are reviewed from various perspectives, including the evidence basis, statistical and psychometric considerations, and regulatory perspectives by the ISPOR Clinical Outcomes Assessment Special Interest Group's multistakeholder group of authors (academia, contract research organizations, and industry). Particular focus is placed on the patient perspective within the Institute for Quality and Efficiency in Health Care approach. The article development incorporated feedback from ISPOR members during well-attended ISPOR US and European conference presentations and 2 formal rounds of written review. The authors concluded that the ≥ 15% response threshold is incongruent with previously defined and scientifically established thresholds and is not well-suited for universal implementation. Further scientific evidence and discussion among all stakeholders are needed, especially should this universal rule be considered in the context of future joint clinical assessments of health technologies in the European Union scheduled from 2025 onward.

Assessment of craving in opioid use disorder: Psychometric evaluation and predictive validity of the opioid craving VAS.

BACKGROUND: This work evaluated the psychometric properties of the single-item Opioid Craving Visual Analog Scale (OC-VAS) for opioid use disorder (OUD). METHODS: Psychometric evaluation of the OC-VAS (range: 0-100 mm) was supported by Subjective Opiate Withdrawal Scale (SOWS) item 16 and total score, Clinical Opiate Withdrawal Scale (COWS) scores, and the 36-Item Short-Form Health Survey, using data from phase 3 study (NCT02357901; N = 487) participants who received randomized treatment and completed the OC-VAS at screening. Descriptive properties, test-retest reliability, construct validity, known-groups validity, and responsiveness were assessed. Interpretation of meaningful change and predictive validity were also explored. RESULTS: Descriptive properties for the OC-VAS at screening did not provide evidence of problematic floor/ceiling effects or missingness. The test-retest reliability was established by weekly intraclass correlations >0.70. At the screening and end of the study, the strong positive correlations between OC-VAS and SOWS Total/Item 16 score and the significant OC-VAS differences among COWS severity groups supported construct validity and known-groups (discriminating ability) validity, respectively. The associations between the changes in OC-VAS and in supporting measures/opioid use from screening to the end of the study demonstrated responsiveness and the ability to detect change in clinical status. During the induction and randomization treatment periods, significant relationships were identified between OC-VAS score and subsequent opioid use. CONCLUSIONS: This psychometric evaluation of the OC-VAS performed on a large OUD patient population provides evidence to support its use to measure the severity of opioid craving and its ability to predict opioid use.

Psychometric validation of the Hypoparathyroidism Patient Experience Scales (HPES).

BACKGROUND: Hypoparathyroidism (HP) is a rare endocrine disorder characterized by absent or inappropriately low levels of circulating parathyroid hormone with associated significant physical and cognitive symptoms. This study evaluated the psychometric properties of the Hypoparathyroidism Patient Experience Scales (HPES), which were developed as disease-specific, patient-reported outcome (PRO) measures to assess the symptoms and impacts associated with HP in adults. METHODS: Data from a non-interventional, observational study (N = 300) and a Phase 2 clinical trial (N = 59) were used in the psychometric evaluation. Observational and trial assessments included: an online validation battery (baseline or screening) and retest (approximately 2 weeks after baseline or screening). In the trial, the primary efficacy endpoint was assessed at week 4 through re-administration of the HPES and validation battery subset. The observational study's larger sample size allowed for evaluation of the HPES descriptive properties, scoring algorithm, test-retest reliability, and construct validity. The trial data examined responsiveness, meaningful within-patient change estimates, and treatment impact on HPES scores. RESULTS: Demographic and self-reported medical characteristics results were similar across the 2 studies. Factor analysis confirmed domains in the HPES-Symptom (n = 2) and HPES-Impact (n = 4). For both measures, total and domain scores demonstrated acceptable reliability and validity for both the observational and trial samples. Internal consistency evidence was strong. Test-retest reliability estimates generally approached the recommended 0.70 threshold. The construct validity correlations with other PRO measures were mainly as hypothesized, thus supporting the HPES scores and constructs. Mean scores for both measures also differed as anticipated and significantly across known-groups, thus providing evidence for the scores discriminating between meaningful groups. Trial results supported both HPES total and domain scores' ability to detect change. The difference in mean total and domain scores for both measures demonstrated statistically significant improvements for TransCon PTH compared to placebo treated subjects despite the small sample and a short 4-week duration on fixed, non-optimized doses. CONCLUSIONS: The HPES were found to be conceptually sound with adequate evidence supporting their reliability and validity. Incorporation of the HPES into clinical and research settings will help to further elucidate and assess the patient experience of living with HP and identify treatment differences.

Psychometric evaluation of the DAILY EATS questionnaire in individuals living with obesity.

BACKGROUND: Physiological and behavioral factors including hunger, satiety, food intake, and cravings are health determinants contributing to obesity. Patient-reported outcome (PRO) measures focused on eating-related factors provide insight into the relationships between food choice and quantity, weight change, and weight-loss treatment for individuals living with obesity. The DAILY EATS is a novel 5-item, patient-reported measure evaluating key eating-related factors (Worst and Average Hunger, Appetite, Cravings, and Satiety). METHODS: Psychometric analyses, consistent with regulatory standards, were conducted to evaluate the DAILY EATS using data from two randomized trials that included individuals with severe obesity without diabetes (NCT03486392) and with severe obesity and type 2 diabetes (NCT03586830). Additional measures included Patient Global Impression of Status (PGIS) and Patient Global Impression of Change items, Impact of Weight on Quality of Life-Lite, Ease of Weight Management, and Patient-Reported Outcomes Measurement Information System Physical Function Short Form 8b and 10a. The reliability, validity, and responsiveness of the DAILY EATS were assessed, and a scoring algorithm and thresholds to interpret meaningful score changes were developed. RESULTS: Item-level analyses of the DAILY EATS supported computation of an Eating Drivers Index (EDI), comprising the related items Worst Hunger, Appetite, and Cravings. Internal consistency (Cronbach's coefficient alphas ≥0.80) and test-retest reliability (coefficients > 0.7) of the EDI were robust. Construct validity correlation patterns with other PRO measures were as hypothesized, with moderate to strong significant correlations between the EDI and PGIS-Hunger (0.30 ≤ r ≤ 0.68), PGIS-Cravings (0.33 ≤ r ≤ 0.77) and PGIS-Appetite (0.52 ≤ r ≤ 0.77). Anchor- and distribution-based analyses support reductions ranging from 1.6 to 2.1 as responder thresholds for the EDI, representing meaningful within-person improvement. CONCLUSIONS: The DAILY EATS individual items and the composite EDI are reliable, sensitive, and valid in evaluating the concepts of hunger, appetite, and cravings for use in individuals with severe obesity with or without type 2 diabetes.

Evaluation of the Feasibility of a Web-Based Survey to Assess Patient-Reported Symptom Improvement and Treatment Satisfaction Among Patients with Psoriatic Arthritis Receiving Secukinumab.

BACKGROUND AND OBJECTIVE: Patient perspectives regarding treatment experience and satisfaction may be useful for clinicians when making treatment strategies. This US-based study assessed the feasibility of evaluating real-world, patient-reported narratives regarding symptom improvement and treatment satisfaction among patients with psoriatic arthritis treated with secukinumab. METHODS: A cross-sectional, web-based survey collected data on demographics, disease characteristics, symptoms before and after secukinumab use, and treatment satisfaction with secukinumab. RESULTS: Of 2755 patients screened, 200 patients with psoriatic arthritis were eligible and included in the analysis. Their mean age was 36.0 (standard deviation, 10.0) years; 55.5% were male and 75.0% were white. Most (87.5%) were biologic experienced; the primary reason for discontinuation of their previous treatment was lack of effectiveness (28.6%). Most patients (79.9%) reported overall psoriatic arthritis symptom improvement after secukinumab initiation compared with before secukinumab initiation; a similar trend was observed for all individual symptoms evaluated. Approximately half of patients reported improvement within 4 weeks after starting secukinumab treatment, and > 90% reported improvement within 6 months. Most patients (≥ 96%) expressed overall satisfaction with secukinumab regarding symptom improvement, speed of symptom improvement, frequency of administration, method of administration, ease of use, patient support services, and side effects, if any. CONCLUSIONS: Patient-reported perspectives may be feasibly collected to provide insights into treatment experience and satisfaction of secukinumab. Most patients with psoriatic arthritis in our real-world study experienced symptom improvement after initiating secukinumab; > 50% of patients reported symptom improvement within 4 weeks. Additionally, almost all patients reported satisfaction with secukinumab treatment.

State of the psychometric methods: patient-reported outcome measure development and refinement using item response theory.

BACKGROUND: This paper is part of a series comparing different psychometric approaches to evaluate patient-reported outcome (PRO) measures using the same items and dataset. We provide an overview and example application to demonstrate 1) using item response theory (IRT) to identify poor and well performing items; 2) testing if items perform differently based on demographic characteristics (differential item functioning, DIF); and 3) balancing IRT and content validity considerations to select items for short forms. METHODS: Model fit, local dependence, and DIF were examined for 51 items initially considered for the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Depression item bank. Samejima's graded response model was used to examine how well each item measured severity levels of depression and how well it distinguished between individuals with high and low levels of depression. Two short forms were constructed based on psychometric properties and consensus discussions with instrument developers, including psychometricians and content experts. Calibrations presented here are for didactic purposes and are not intended to replace official PROMIS parameters or to be used for research. RESULTS: Of the 51 depression items, 14 exhibited local dependence, 3 exhibited DIF for gender, and 9 exhibited misfit, and these items were removed from consideration for short forms. Short form 1 prioritized content, and thus items were chosen to meet DSM-V criteria rather than being discarded for lower discrimination parameters. Short form 2 prioritized well performing items, and thus fewer DSM-V criteria were satisfied. Short forms 1-2 performed similarly for model fit statistics, but short form 2 provided greater item precision. CONCLUSIONS: IRT is a family of flexible models providing item- and scale-level information, making it a powerful tool for scale construction and refinement. Strengths of IRT models include placing respondents and items on the same metric, testing DIF across demographic or clinical subgroups, and facilitating creation of targeted short forms. Limitations include large sample sizes to obtain stable item parameters, and necessary familiarity with measurement methods to interpret results. Combining psychometric data with stakeholder input (including people with lived experiences of the health condition and clinicians) is highly recommended for scale development and evaluation.

Pilot Evaluation of Aggregate Plate Waste as a Measure of Students' School Lunch Consumption.

BACKGROUND: Weighing an individual's plate waste provides reliable estimates of food intake by physically weighing individual food components to the nearest gram before and after a meal. Weighing aggregate, school-level food waste may be an inexpensive and less time-consuming alternative. However, it has not been determined whether aggregate plate waste is an accurate measure of individually weighed plate waste. OBJECTIVE: This pilot study aimed to evaluate the accuracy of aggregate plate waste for quantifying food waste in a school cafeteria setting in comparison with individually weighed plate waste. DESIGN: A pilot validation study in which aggregate plate waste was compared against individually weighed plate waste in a school cafeteria setting. PARTICIPANTS/SETTING: This study took place in an urban, low-income school district in Massachusetts in the spring of 2014. Four elementary schools with identical cafeterias and meals participated in the study. Approximately 1,700 students participated in this study. MAIN OUTCOME MEASURES: For individually weighed plate waste, the percent discarded was calculated by dividing the weight of each discarded item by the average weight of the food item served and the percent consumed was calculated as the residual. For aggregate-level measurements, waste was separated by component (entrée, vegetable, fruit, and milk), and the weight discarded was calculated based on the weight of the cumulative amount remaining and an average weight for each food item served, with the percent consumed calculated as the residual. STATISTICAL ANALYSES PERFORMED: Intraclass correlation coefficients (ICCs) were calculated to assess the agreement between aggregate plate waste and individual-level plate waste values. RESULTS: Agreement was excellent for entrées (ICC=0.90) and vegetables (ICC=0.78), but poor for milk (ICC=0.22) and fruits (ICC=0.23). The overall agreement for all four components combined was excellent (ICC=0.75). CONCLUSIONS: Results suggest that aggregate plate waste may provide a reasonable estimate of individually weighed plate waste, but additional research is warranted.

A Pilot Study to Assess the Feasibility of a Web-Based Survey to Examine Patient-Reported Symptoms and Satisfaction in Patients with Ankylosing Spondylitis Receiving Secukinumab.

PURPOSE: This real-world study evaluated the feasibility of assessing patient-reported symptom improvement and treatment satisfaction using a web-based survey among patients with ankylosing spondylitis (AS) treated with secukinumab. METHODS: This cross-sectional, web-based survey collected data on demographics, symptoms, treatment history, and treatment satisfaction from US patients with AS who were receiving secukinumab at survey participation. Patients reported AS symptoms experienced before and after secukinumab initiation, time to symptom improvement, and satisfaction with secukinumab treatment. RESULTS: Of 2755 patients screened, 200 with AS were included in the analysis. The mean (SD) age of patients was 34.4 (10.6) years; 86.5% were biologic experienced. Most (74.0%) reported overall improvement ("a little," "moderately," or "much better") in AS symptoms since secukinumab initiation compared with before secukinumab initiation; a similar trend was observed for all the individual symptoms analyzed (pain disrupting sleep, fatigue, morning stiffness, pain and stiffness in lower back or neck, sore areas other than joints, and ankle or heel pain [indicating enthesitis]). Approximately 41.9% of patients reported overall symptom improvement within 4 weeks of secukinumab treatment. Most expressed overall satisfaction ("very," "mostly," or "somewhat satisfied") with secukinumab regarding symptom improvement (99.0%), speed of symptom improvement (97.0%), frequency and method of administration (96.0% and 91.5%, respectively), ease of use (93.5%), patient support services (97.0%), and side effects, if any (93.0%). CONCLUSION: Most patients reported overall symptom improvement and satisfaction with treatment. Our study indicates that patient-reported perspectives may be feasibly collected using a web-based survey to provide insights into treatment experience and satisfaction.

Assessing test-retest reliability of patient-reported outcome measures using intraclass correlation coefficients: recommendations for selecting and documenting the analytical formula.

PURPOSE: The US Food and Drug Administration (FDA) 2009 guidance for industry on patient-reported outcome (PRO) measures describes how the Agency evaluates the psychometric properties of measures intended to support medical product labeling claims. An important psychometric property is test-retest reliability. The guidance lists intraclass correlation coefficients (ICCs) and the assessment time period as key considerations for test-retest reliability evaluations. However, the guidance does not provide recommendations regarding ICC computation, nor is there consensus within the measurement literature regarding the most appropriate ICC formula for test-retest reliability assessment. This absence of consensus emerged as an issue within Critical Path Institute's PRO Consortium. The purpose of this project was to generate thoughtful and informed recommendations regarding the most appropriate ICC formula for assessing a PRO measure's test-retest reliability. METHODS: Literature was reviewed and a preferred ICC formula was proposed. Feedback on the chosen formula was solicited from psychometricians, biostatisticians, regulators, and other scientists who have collaborated on PRO Consortium initiatives. RESULTS AND CONCLUSIONS: Feedback was carefully considered and, after further deliberation, the proposed ICC formula was confirmed. In conclusion, to assess test-retest reliability for PRO measures, the two-way mixed-effect analysis of variance model with interaction for the absolute agreement between single scores is recommended.

Longitudinal Modeling Approaches to Assess the Association Between Changes in 2 Clinical Outcome Assessments.

BACKGROUND: Understanding how one clinical outcome assessment (COA) (eg, a patient-reported outcome [PRO]) relates to a second COA (eg, a clinician-reported outcome [ClinRO]) may provide insights into disease burden or treatment efficacy. We aimed to briefly review commonly used cross-sectional methods to evaluate the association between a PRO and a ClinRO and to demonstrate the advantages of longitudinal modeling approaches, particularly a joint mixed model for repeated measures (MMRM), to evaluate this association. METHODS: We generated an example longitudinal data set that included a PRO measured on an 11-point numeric rating scale and a binary ClinRO. The association between change in PRO score and ClinRO response at each time point was examined using 2 cross-sectional analyses: point biserial correlation and logistic regression. We conducted longitudinal analyses of the association between the 2 COAs across time points using MMRM and joint MMRM approaches. RESULTS: Point-biserial correlation and logistic regression analyses correctly captured the "built in" associations between the 2 COAs that strengthened over time, but each association was applicable only for a single time point. The MMRM approach provided correlations over time but only for a single outcome variable. The joint MMRM approach modeled the relationship between both outcome variables simultaneously, allowing for evaluation of the correlations both within and between the variables over time. CONCLUSION: Each analysis demonstrated the relationship between PRO score changes and ClinRO response. Longitudinal analysis methods, particularly the joint MMRM, allow for a more thorough examination of the correlations among the 2 outcomes than cross-sectional analysis methods.

Comparison of Urticaria Activity Score Over 7 Days (UAS7) Values Obtained from Once-Daily and Twice-Daily Versions: Results from the ASSURE-CSU Study.

BACKGROUND: The Urticaria Activity Score summed over 7 days (UAS7) assesses the itch severity and hive count in chronic spontaneous urticaria (CSU) using once- or twice-daily diary-based documentation. OBJECTIVE: The aim of this study was to evaluate the comparability of twice-daily versus once-daily versions of the UAS and the resulting UAS7 values. METHODS: Data came from the ASSURE-CSU study. The twice-daily and once-daily UAS7 was calculated from morning and evening ratings, as well as from exact 24-h evening ratings of hive count and itch severity, respectively. Three UAS7 scores were computed: UAS7 twice daily (UAS7TD), UAS7 once daily for maximum itch (UAS7OD1MAX), and UAS7 once daily for average itch (UAS7OD2AVG). UAS7 values were assigned to five score bands (0, 1-6, 7-15, 16-27, 28-42), reflecting urticaria-free to severe disease activity. The score values and score band ratios of the UAS7TD and UAS7OD versions were compared and assessed for correlation by weighted Cohen's kappa statistics. RESULTS: Data from 614 patients were analyzed. All three versions of the UAS7 yielded very similar results, with a mean (standard deviation) UAS7TD, UAS7OD1MAX, and UAS7OD2AVG of 17.3 (10.49), 17.7 (8.90), and 16.2 (8.68), respectively. Correlation coefficients between UAS7TD and UAS7OD1MAX, UAS7TD and UAS7OD2AVG, and UAS7OD1MAX and UAS7OD2AVG were 0.94, 0.95, and 0.99, respectively, showing very high positive pairwise correlation. The weighted kappa coefficient, κ (95% confidence interval) was 0.78 (0.75-0.82) for UAS7TD versus UAS7OD1MAX, and 0.82 (0.78-0.85) for UAS7TD versus UAS7OD2AVG, demonstrating substantial agreement. CONCLUSIONS: The once- and twice-daily UAS7 scores were highly consistent, supporting the use of either version when evaluating CSU activity.

Economic burden of advanced melanoma in France, Germany and the UK: a retrospective observational study (Melanoma Burden-of-Illness Study).

The aim of this study was to estimate the cost-of-illness associated with completely resected stage IIIB/IIIC melanoma with macroscopic lymph node involvement, overall and by disease phase, in France, Germany and the UK. This retrospective observational study included patients aged older than or equal to 18 years first diagnosed with stage IIIB/IIIC cutaneous melanoma between 1 January 2009 and 31 December 2011. Data were obtained from medical records and a patient survey. Direct costs, indirect costs and patient out-of-pocket expenses were estimated in euros (€) (and British pounds, £) by collecting resource use and multiplying by country-specific unit costs. National annual costs were estimated using national disease prevalence from the European cancer registry and other published data. Forty-nine centres provided data on 558 patients (58.2% aged <65 years, 53.6% stage IIIB disease at diagnosis). The mean follow-up duration was 27 months (France), 26 months (Germany) and 22 months (UK). The mean total direct cost per patient during follow-up was €23 582 in France, €32 058 in Germany and €37 970 (£31 123) in the UK. The largest cost drivers were melanoma drugs [mean €14 004, €21 269, €29 750 (£24 385), respectively] and hospitalization/emergency treatment [mean: €6634, €6950, €3449 (£2827), respectively]. The total mean indirect costs per patient were €129 (France), €4,441 (Germany) and €1712 (£1427) (UK). Estimates for annual national direct cost were €13.1 million (France), €30.2 million (Germany) and €27.8 (£22.8) million (UK). The economic burden of stage IIIB/IIIC melanoma with macroscopic lymph node involvement was substantial in all three countries. Total direct costs were the highest during the period with distant metastasis/terminal illness.

Treatment patterns and outcomes of Stage IIIB/IIIC melanoma in France, Germany and the UK: A retrospective and prospective observational study (MELABIS).

AIM: Real-world data on treatment patterns/outcomes in patients with advanced melanoma, while scarce, are useful for health technology assessments that govern patient access in many countries. We collected retrospective data on treatment patterns among patients in France, Germany and the UK with Stage IIIB/IIIC melanoma with macroscopic lymph node involvement, whose primary melanoma and regional lymph node metastases had been completely resected. METHODS: Patients ≥18 years were diagnosed between 1 January 2009 and 31 December 2011. Data were obtained from patients' medical records and a patient survey. RESULTS: Forty-nine centres provided data on 558 patients: 53.6% had Stage IIIB disease; 58.2% were of working age (<65 years), 22.5% reported a change in employment status due to melanoma, 8% were on long-term sick leave; and 35.1% were deceased over the study period. Overall median distant metastases-free survival was 23.4 months and median disease-free survival was 13.3 months. Hospitalisation frequency increased during distant metastatic/terminal disease phases. Adjuvant therapy was received by 7.0% (14/199) of patients in France, 2.6% (5/195) in the UK, and 33.5% (55/164) in Germany. Low-dose interferon was used more frequently than other regimens. High-dose interferon was associated with discontinuation in 28.6% and dose delay/reduction in 33.3% of patients. CONCLUSIONS: Rapid disease progression combined with increased use of healthcare resources in later phases of disease result in a high burden-of-illness for patients and healthcare providers. The use of adjuvant interferon therapy varies considerably in this population in the countries studied, highlighting the need for improved treatments for melanoma.