Time to next treatment or death as a candidate surrogate endpoint for overall survival in advanced melanoma patients treated with immune checkpoint inhibitors: an insight from the phase III CheckMate 067 trial.

BACKGROUND: Time to next treatment or death (TNT-D) may be a patient-relevant endpoint in patients treated with immune checkpoint inhibitors. This study investigated TNT-D as a surrogate endpoint (SE) for overall survival (OS) in previously untreated advanced melanoma patients. METHODS: Patient-level data from the 60-month results of the CheckMate 067 randomised, controlled trial were used. Analyses were carried out for nivolumab monotherapy or nivolumab with ipilimumab versus ipilimumab monotherapy. The SE 1-step validation method based on a joint frailty-copula model was used where the country of enrolment was applied to define clusters. Kendall's τ and the coefficient of determination (R2trial) were estimated for respective measurements of association at the individual and cluster levels. The surrogate threshold effect, the maximum threshold hazard ratio for TNT-D that would translate into OS benefit, was estimated. A leave-one-out cross-validation analysis was carried out to evaluate model robustness. RESULTS: Fifteen clusters of data were generated from 945 patients. For both nivolumab-containing arms, the association between TNT-D and OS was deemed acceptable at the individual level (Kendall's τ > 0.60) and strong at the cluster level, with R2trial fairly close to 1, with narrow confidence intervals. The estimated surrogate threshold effects were 0.61 for nivolumab versus ipilimumab and 0.49 for nivolimub + ipilimumab versus ipilimumab. Cross-validation results showed minimum variation of the correlation measures and satisfactory predictive accuracy for the model. CONCLUSION: Results suggest that TNT-D may be a valuable SE in previously untreated advanced melanoma patients treated with immune checkpoint inhibitors. Surrogacy analyses considering multiple randomised controlled trials are warranted for confirming these findings.

Prescription of compression stockings in France in primary care.

OBJECTIVES: Recent French data describing real-life compression stocking use are lacking. This study aimed to describe the actual situation for patients who were prescribed compression stockings by their general practitioner and to assess annual treatment costs from a societal perspective. METHODS: A retrospective analysis using Disease Analyzer database data from 6349 adults with at least one compression stocking prescription between July 2009 and June 2010. RESULTS: Mean patient age was 58 years, and 72.3% of patients were women. Seven out of 10 patients received only a single compression stocking prescription over one year. The estimated mean annual per patient cost was 152.2 ± 100.7 Euros. CONCLUSION: Most patients received only a single compression stocking prescription during one year. General practitioners prescribing compression stockings more often may have a better understanding of venous disease and may manage their patients differently. Although more expensive, this approach may be one which should be accepted more widely.

Atopic dermatitis burden scale: creation of a specific burden questionnaire for families.

BACKGROUND: The notion of individual burden, associated with a disease, has been introduced to determine the 'disability' in the broadest sense (psychological, social, economic and physical). Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases with an estimated prevalence of 5%-30% in children. OBJECTIVE: To develop and validate a specific questionnaire which assess the burden of families of children with AD: the Atopic dermatitis Burden Scale (ABS). METHODS: Items for inclusion in ABS were initially generated from a literature review and a verbatim report from parents whose child had AD. ABS was refined via item reduction according to interquestion correlations, consensus among experts and exploratory factor analysis. Internal consistency was determined by calculating the Cronbach's α, concurrent validity by calculating the correlation between ABS and the Short-Form 12 items. Discriminant validity was analysed according to the severity degrees of AD assessed by Patient-Oriented SCORing index of Atopic Dermatitis (PO-SCORAD). RESULTS: From an initial list of 29 items, ABS was reduced to a 14-item questionnaire, grouped into four dimensions based on the exploratory factor analysis. Construct validity was demonstrated and ABS showed good internal coherence (Cronbach's α: 0.78). ABS was significantly correlated to the mental dimension of Short-Form 12 (r = -0.49), but it was not correlated to the physical dimension (r = 0.04). ABS scores were significantly different according to the severity degrees of AD, with higher ABS score in parents whose child had severe AD. CONCLUSION: The ABS questionnaire is a validated tool for assessing the burden of families of children with AD. An implementation of a prospective study is planned to estimate sensitivity to change and to confirm its domain structure in larger samples.