Measuring What Matters in Bullous Diseases: Patient Needs, Outcome Measurement and Drug Development

Bullous diseases encompass rare, chronic skin and mucosal disorders characterized by fragile skin and blister formation. This thesis focuses on the genetic condition epidermolysis bullosa (EB) and acquired autoimmune bullous disease (AIBD), which profoundly impact patients' and their families' daily lives. Despite growing scientific knowledge and increasing clinical trials investigating new therapies, treating these patients remains highly challenging.
This thesis comprises three components: investigating patient experiences during diagnosis and treatment, mapping outcome measurement and clinical trial design, and establishing an international consortium to advance harmonization of outcomes.
Through interviews (Chapter 2) and questionnaires (Chapter 3), we explored patient experiences in EB diagnostics and care, revealing underrecognized needs with important implications for practice and research. Literature reviews (Chapters 4-5) analyzed outcome measurement in EB and AIBD clinical trials, demonstrating heterogeneity in outcome domains (‘what’ to measure) and outcome measurement instruments (‘how’ to measure). Moreover, we found a disproportionately low representation of patient-reported outcomes. Analysis of failed trials and expert surveys (Chapter 6) identified AIBD trial failure causes and potential improvement strategies. Lastly, we established an international consortium - the ‘Core Outcome Sets for EB’ (COSEB) initiative (Chapter 7-8) – to develop minimum sets of outcomes for future EB trials. This will enhance study comparability, prevent overlooking patient-centered outcomes, and optimize data utilization, increasing individual study value and ultimately enabling better clinical recommendations.
Key conclusions of this thesis are that integrating patient perspectives is crucial for clinical research, uniform outcomes and measurement instruments are needed, and international collaboration is vital for achieving outcome harmonization. Overall, this thesis contributes to improving research and care for patients with bullous disease.