A core domain set for pyoderma gangrenosum trial outcomes - an international e-Delphi and consensus study from the UPGRADE initiative

Abstract

Abstract Importance Pyoderma gangrenosum (PG) is a rare ulcerative skin condition with no current standardized outcomes or outcome measures. With a rich investigational therapeutic pipeline, standardization of outcomes and improvement of data quality and interpretability will promote the appropriate and consistent evaluation of potential new therapies. Core Outcome Sets (COS) are agreed standardized sets of outcomes that represent the minimum that should be measured and reported in all clinical trials of a specific condition. Objective To identify and reach consensus on which domains (what to be measured) should be included in the Understanding Pyoderma Gangrenosum: Review and Analysis of Disease Effects (UPGRADE) Core Domain Set for PG clinical trials. Design Collaborative discussions between patients and PG experts, and a systematic review of the literature identified items and prospective domains. A three-round international eDelphi exercise was performed to prioritize the domains and refine the provisional items (consensus: ≥70% of participants rating a domain as ‘extremely important’ and <15% of participants voting ‘not important’, followed by an international meeting to reach consensus on the core domain set (consensus: <30% disagreement). Setting Item generation discussions and consensus meetings were hosted via online video conferences. Delphi exercise and consensus voting were performed using Qualtrics electronic survey software. Participants Adults with PG, healthcare professionals, researchers, and industry representatives. Findings Collaborative discussions and systematic review yielded 115 items, which were distilled into 15 prospective domains. The eDelphi exercise removed three lowest priority domains (Laboratory Tests, Treatment Costs, and Disease Impact on Family) and ranked Pain, Quality of Life, and Physical Symptoms as the highest priority prospective domains. Consensus was reached on the domains of Pain, Quality of Life, and Clinical Signs. The domain of disease course/disease progression narrowly failed to reach consensus for inclusion in the core set (32.2% of participants voted no). Refinement of this domain definition will be required and presented for consideration at future consensus meetings. Conclusions and Relevance The UPGRADE Core Domain Set for PG clinical trials has been agreed by international multi-stakeholder consensus. Future work will develop and/or select outcome measurement instruments for these domains to establish a core outcome set.