The “Understanding Pyoderma Gangrenosum, Review and Assessment of Disease Effects (UPGRADE)” Project: a protocol for the development of the core outcome domain set for trials in pyoderma gangrenosum

Introduction: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that affects approximately 0.3–6 out of every 100,000 people worldwide. Clinical trials are scarce but there is growing interest in using newer and more targeted therapeutics to achieve disease remission. However, there are no standardized instruments to measure outcomes in PG and, therefore, future clinical trials are hampered by the absence of established and accurate means of assessment and comparison. Therefore, we aim to produce an internationally accepted core outcome set (COS) that will overcome this obstacle. This protocol outlines our intended approach to achieve the first part of this process, establishing a core outcome domain set. Methods: An international team of PG stakeholders, consisting of physicians, wound care nurses, patients, scientists and industry representatives, has been assembled for the purpose of building a comprehensive and universally established set of core outcome domains. During the first step, we will generate items of relevance using a nominal process from all stakeholders. Items will be distilled and collapsed into potential domains and subdomains. A systematic review of current methods for reporting PG has already been published and domains identified in this work will be considered in the generation of the core domains set. During the second step, after the potential domains and subdomains are identified, stakeholders will participate in an e-Delphi exercise to rate the importance of (sub)domains. A final consensus meeting will be organized with the goal of establishing a core domain set. Conclusion: Pyoderma gangrenosum lacks an established COS and previously published clinical trials have used inconsistent measures established from similarly inconsistent domains. As a first step this study seeks to create a core domain set within the COS, to build the foundation for future core outcome work for PG

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

ImportancePyoderma 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.ObjectiveTo 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.DesignCollaborative 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).SettingItem generation discussions and consensus meetings were hosted via online video conferences. Delphi exercise and consensus voting were performed using Qualtrics electronic survey software.ParticipantsAdults with PG, healthcare professionals, researchers, and industry representatives.FindingsCollaborative 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 RelevanceThe 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