Eligibility Criteria for Active Ulcerative Pyoderma Gangrenosum in Clinical Trials: A Delphi Consensus on Behalf of the UPGRADE (Understanding Pyoderma Gangrenosum: Review and Assessment of Disease Effects) Group.

At present, there are no standardized guidelines for determining patient eligibility for pyoderma gangrenosum (PG) clinical trials. Thus, we aim to determine which clinical features, histopathological features, or laboratory features should be included in active ulcerative PG clinical trial eligibility criteria for treatment-naïve patients and patients already treated with immunomodulating medications (treatment-exposed patients). This study employed 4 rounds of the Delphi technique. Electronic surveys were administered to 21 international board-certified dermatologists and plastic surgeon PG experts (June 2022-December 2022). Our results demonstrated that for a patient to be eligible for a PG trial, they must meet the following criteria: (i) presence of ulcer(s) with erythematous/violaceous undermining wound borders, (ii) presence of a painful or tender ulcer, (iii) history/presence of rapidly progressing disease, (iv) exclusion of infection and other causes of cutaneous ulceration, (v) biopsy for H&E staining, and (vi) a presence/history of pathergy. These criteria vary in importance for treatment-naïve versus treatment-exposed patients. Given the international cohort, we were unable to facilitate live discussions between rounds. This Delphi consensus study provides a set of specific, standardized eligibility criteria for PG clinical trials, thus addressing one of the main issues hampering progress toward Food and Drug Administration approval of medications for PG.

Minimum data set for treatment effectiveness in pyoderma gangrenosum (MIDSTEP): an international protocol of an e-Delphi study to develop a clinical physician-driven treatment effectiveness registry on behalf of the UPGRADE initiative.

Pyoderma gangrenosum (PG) is a rare inflammatory condition with an immense disease burden that remains understudied. With limited approved treatments and low-quality clinical evidence, PG continues to have poor patient outcomes. Unfortunately, improvement in PG treatments and patient care is based on additional research endeavors that can only be developed from existing high-quality data. The following protocol outlines the development of the Minimum Data Set for Treatment Effectiveness in Pyoderma gangrenosum (MIDSTEP), a core set of domains and domain items for the Pyoderma Gangrenosum Treatment Effectiveness (PyGaTE) international registry. The outcomes and benefits are focused on providing real-world data for physicians to improve their clinical decisions on PG treatment and inform clinical trial design, promoting clinical research among the international scientific community. MIDSTEP is a multi-phase project. The first phase will produce a domain item list from a literature review to take into the second phase which would finalize the core data set by an e-Delphi exercise. There will be a single stakeholder group participating together in the e-Delphi consisting of PG experts (healthcare providers, researchers, methodologists, industry representatives, and regulators), ulcerative PG patients, and PG patient advocates. The methodology outlined in the protocol is a systematic method based on several guidelines through COMET and established dermatologic registries and outcome sets with systematic methodologies of their own. The third phase will identify the instruments for the items, the 'when to measure' the items, and the platform for the registry. The last phase is the implementation and continued maintenance of the international registry PyGaTE. By solidifying a consensus on standardized outcomes and collecting information on PG treatment effectiveness in a centralized database, existing treatments can be compared more systematically and analyzed with increased evidence. MIDSTEP and the PyGaTE international registry will have the ambitious goal to generate and disseminate real-world data that can be used by all stakeholders to improve health outcomes for PG patients. Future potential for the outcome of this project includes the development of a gold-standard PG treatment.