Core outcome domain sets for clinical trials in epidermolysis bullosa — a COSEB protocol to achieve consensus on “what” to measure

Abstract

Background: Epidermolysis bullosa (EB) comprises a heterogeneous group of rare, genetic blistering diseases. The wide variety in EB trial outcomes limits the comparability of outcomes and, consequently, the implementation of the best available treatment options. A core outcome set (COS) is a minimum set of outcomes that should be measured in all clinical trials, comprising what should be measured (i.e., outcome domains) and how it should be measured (i.e., outcome measurement instruments). This enables standardization of outcome measurement aiming at improving the comparability and quality of research. Methods: The Core Outcome Set for Epidermolysis Bullosa (COSEB) initiative aims to develop COSs for use in clinical trials for the four major EB types: EB simplex, junctional EB, dystrophic EB, and Kindler EB. This protocol focuses on the development of core outcome domain sets — outlining what should be measured in EB clinical trials. Involved stakeholders are patients and patient representatives, clinicians, researchers, methodologists, industry representatives, regulators, health technology assessors, and payers. In the initial part, working groups are formed to define long lists of candidate outcome domains for the four major EB types. Potentially relevant outcome domains will be identified based on scoping literature reviews and qualitative studies. Following consultations with a stakeholder advisory panel, a short list of candidate outcome domains will be subject to voting in Delphi consensus procedures. Finally, the definitive core outcome domain sets for the four major EB types and, if indicated, any overarching core outcome domain sets, will be confirmed in consensus meetings. The project Has been prospectively registered in the COMET registry for COSs on 23 October 2017 (registration number 1033). Discussion: This protocol provides guidance to ensure a systematic, transparent, and comprehensible approach of COSEB. The final core outcome domain sets are supposed to serve as the minimum sets of what to measure in future EB trials. This will provide the basis for the subsequent outcome measurement instrument selection. Particularly in this rare disease with inherently small-sized study cohorts, this will facilitate the incorporation of meaningful outcomes and pooling of data, ultimately enhancing optimal treatment for EB. Trial registration: This study Has been prospectively registered in the COMET database on 23 October 2017 and updated on 24 January 2022 (registration number 1033 https://www.comet-initiative.org/studies/details/1033).