Core Outcome Set for Epidermolysis Bullosa (COSEB)

Epidermolysis bullosa (EB) comprises a group of hereditary skin fragility disorders characterized by skin and mucosal blistering upon minor trauma with a prevalence of 2-5/100.000 inhabitants and an incidence of 10-15 per 100.000 newborns per year. Over 30 clinical subtypes are known, based on the level of separation in the skin and the clinical features. Depending on the mutation and the consequences on protein and tissue level many complications may arise, like scarring, pseudosyndactyly, contractures, esophagus strictures, cornea erosions and skin cancer. Other organs may be involved as well, like the heart and skeletal muscle. In the last thirty years, significant progress has been achieved in understanding molecular genetics and underlying pathomechanisms of EB, which form the cornerstone of the development of novel therapies. With genetic, protein and cell-based therapies in development, and repurposed drugs being explored for use in EB, it becomes of utmost importance to be able to combine, contrast and compare efficacy and safety data of these promising treatments. Therefore, we aim to develop a core outcome set for EB studies.


EB Expertise Center, University Medical Center Groningen, The Netherlands
- Marieke Bolling, MD, PhD
- Eva Korte, MD
- Barbara Horváth, MD, PhD

EB Haus, Hospital of the Paracelsus Medical University, Salzburg, Austria
- Martin Laimer, MD, PhD
- Tobias Welponer, MD
- Verena Wally, PhD

Department of Dermatology, Medical Center-University of Freiburg, Germany
- Dimitra Kiritsi, MD, PhD

Medicines Evaluation Board, Utrecht, Netherlands.
- Marjon Pasmooij, PhD

Further Study Information

Current Stage: Ongoing
Date: January 2021 - January 2026
Funding source(s): None

Health Area

Disease Category: Skin, Genetic disorders

Disease Name: Epidermolysis bullosa

Target Population

Age Range: 0 - 100

Sex: Either

Nature of Intervention: Any

Stakeholders Involved

- Clinical experts
- Consumers (patients)
- Families
- Methodologists
- Patient/ support group representatives
- Regulatory agency representatives
- Researchers

Study Type

- COS for clinical trials or clinical research
- COS for practice
- Recommendations for outcome measures (measurement/how)


- Consensus meeting
- Delphi process
- Systematic review
- Focus group(s)

A stepwise approach will be used based on the principles of the COMET handbook, HOME roadmap and COSMIN guidelines.

First we will conduct a scoping review to identify outcomes and outcome measurement instruments reported in EB research. We will organize a kick-off meeting to present the results and present the COS proposal regarding the scope of the core outcome sets. We aim to develop a COS for all main EB types separately (EBS, JEB and DEB) in working groups.

The identified outcomes from the scoping review, together with input from all relevant stakeholder groups by surveys and focus groups will be used to compile a list of possibly relevant outcomes to include in the core domain set. In order to reach international consensus on this core outcome set, we will perform three rounds of e-Delphi exercises in which all stakeholders will be involved. The final list of outcome domains for the core domain set will be discussed in a consensus meeting.

We will perform systematic reviews regarding the outcome measurement instruments suitable for these core domains, which will include the assessment of the psychometric properties (e.g. validity, reliability, responsiveness) according to the COSMIN manual. If necessary, a new instrument will be developed. Once certain instruments can be recommended, a voting procedure will decide whether this instrument will be part of the core measurement set for the specific domain.
The final core outcome set will consist of the core domain set and core measurement set for the specific EB types.