A core domain set for pyoderma gangrenosum trial outcomes: an international eDelphi and consensus study from the UPGRADE initiative
Authors: Jacobson Michael E , Rick Jonathan W , Gerbens Louise A A , Baghoomian Wenelia , Gould Lisa J , Marzano Angelo V , Chen Diana M , Oakes Debbie L , Dissemond Joachim , Yamamoto Toshiyuki , Shinkai Kanade , Nolan Barbara , Lobato Dan , Thomas Kim S , Ortega-Loayza Alex G ,   UPGRADE, Rick Jonathan , Gould Lisa J , Marzano Angelo V , Garg Amit , Chen Diana M , Oakes Debbie L , Dissemond Joachim , Herfarth Hans , Friedman Marcia A , Alavi Afsaneh , Yamamoto Toshiyuki , Gerbens Louise A A , Thomas Kim S , Ortega-Loayza Alex G , Jacobson Michael E , Baghoomian Wenelia , Rick Jonathan , Gerbens Louise A A , Thomas Kim S , Ortega-Loayza Alex G , Imre Mihaly , Rick Jonathan , Hampton Philip , Thomas Kim , Kolios Antonios , Bolognia Jean , Borradori Luca , Moelleken Maurice , Jacobson Michael , Gray Ashley , Maronese Carlo Alberto , Wallach Daniel , Croitoru David , Kaffenberger Ben , Marzano Angelo Valerio , Gould Lisa Jeanne , Williams Pete , Korman Neil , Chen Diana , Amber Kyle , Tolkachjov Stan N , Purvis Caitlin , Benskin Linda , Shinkai Kanade , Ortega-Loayza Alex G 
Published: November 2023

Abstract

Background
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.

Objectives
To identify and reach a 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 clinical trials in PG.

Methods
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 &lt; 15% of participants voting ‘not important’), followed by an international meeting to reach consensus on the core domain set (consensus: &lt; 30% disagreement). Item-generation discussions and consensus meetings were hosted via online videoconferences. The eDelphi exercise and consensus voting were performed using Qualtrics survey software. Participants were adults with PG, healthcare professionals, researchers and industry representatives.

Results
Collaborative discussions and systematic reviews yielded 115 items, which were distilled into 15 prospective domains. The eDelphi exercise removed the 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% of participants voted ‘no’). Refinement of this domain definition will be required and presented for consideration at future consensus meetings.

Conclusions
The UPGRADE core domain set for clinical trials in PG has been agreed by international multistakeholder consensus. Future work will develop and/or select outcome measurement instruments for these domains to establish a COS.