Patient-reported outcomes in randomized controlled trials evaluating BRAF inhibitors in patients with cutaneous melanoma: a systematic scoping review of quality of reporting and trial results.

The objective of this study was to provide an overview of the current practice of patient-reported outcome (PRO) assessments in trials investigating treatment with BRAF inhibitors in patients with advanced melanomas. In addition, we extracted information on symptomatic adverse events (AEs) reported by clinicians to inform future PRO measurement strategies. For our systematic scoping review, we investigated randomized controlled trials (RCTs) evaluating treatment with BRAF inhibitors that had a primary, secondary or exploratory PRO endpoint and were indexed on PubMed. Two independent reviewers extracted information on general RCT characteristics, clinical results (e.g. survival, treatment response and symptomatic AEs) and the PRO measurement and results. Quality of PRO reporting using the CONSORT-PRO checklist was also assessed. We identified nine RCTs meeting the inclusion criteria, in which PROs were secondary or exploratory endpoints. In all trials but one, PROs were measured with the generic EORTC QLQ-C30 questionnaire. The quality of PRO reporting showed substantial variation across the different types of information, with information on handling of missing data and on PRO hypotheses lacking most frequently. Our analysis identified 29 relevant symptomatic AEs that could be reported directly by patients. Our findings may inform the planning of the PRO component of future RCTs, in particular regarding what symptoms and AEs should be covered by PRO measures to provide a comprehensive assessment of treatment tolerability. Our results also indicate a need for improving the quality of PRO reporting, to maximize the impact of PRO findings in real-word practice.