Profiling trial burden and patients’ attitudes to improve clinical research in epidermolysis bullosa

Abstract

Background: Epidermolysis bullosa (EB) comprises inherited mechanobullous dermatoses with considerable morbidity and mortality. While current treatments are symptomatic, a growing number of innovative therapeutic compounds are evaluated in clinical trials. Clinical research in rare diseases like EB, however, faces many challenges, including sample size requirements and recruitment failures. The objective of this study was to determine attitudes of EB patients towards clinical research and trial participation as well as the assessment of contextual motivating and discouraging factors in an effort to support patient-centered RD trial designing. Methods: A 53-items questionnaire was handed over to EB patients (of all types and ages) in contact with the EB House Austria, a designated national center of expertise for EB care. Main categories included level of interest in and personal knowledge about clinical studies, pros/cons for participation and extent of individual expenses considered acceptable for participation in a clinical study. Descriptive subgroup analysis was calculated with SPSS 20.0 and Microsoft Excel. Results: Thirty-six individuals (mean age 25.7 years), diagnosed for recessive dystrophic EB (36.1%), EB simplex (33.4%), junctional EB (8.3%), dominant dystrophic EB (2.8%) and acral peeling syndrome (2.8%) participated. Motivation for participation in and the desire to increase personal knowledge about clinical trials were (outmost) high in 57.2 and 66.7%, respectively. Altruism was the major motivating factor, followed by hope that alleviation of the own symptoms can be achieved. The greatest hurdle was travel distance, followed by concerns about possible adverse reactions. Patients diagnosed for severe subgroups (RDEB, JEB) were more impaired by the extent of scheduled invasive investigations and possible adverse reactions of the study medication. Patients with generally milder EB forms and older patients were accepting more frequent outpatient study visits, blood takes, skin biopsies and inpatient admissions in association with trial participation. Conclusions: This study provides additional indications to better determine and address attitudes towards clinical research among EB patients as well as guidance to improve clinical trial protocols for patient centricity.

Translational perspectives to treat Epidermolysis bullosa—Where do we stand?

“…Clinical research in EB offers promising perspectives but also faces relevant methodological challenges, of which most are inherent to studies conducted in rare disease populations. [10][11][12] • First, intrinsically low patient numbers and recruitment failures impair sample size requirements and compromise statistical power while increasing trial duration and costs. As such, slight or moderate changes in response to treatment hardly reach statistical significance when using standard methods (limited acceptable evidence of efficacy).…”

“…Faster enrolment and improved compliance subsequently help to reduce expenses in inherently cost-sensitive rare disease research. [10,13] Properly trained clinical study teams are required to ensure in small populations. [10,14,15] In this context, natural history studies and registries of well-de- and the EB Clinical Characterization and Outcomes Database (CCOD).…”

“…Likewise, alternative clinical trial designs (such as series of n‐of‐1 trials design, response‐adaptive study design, randomized withdrawal design; factorial designs) hold some promise to increase trial acceptability, optimize randomization procedures and mitigate effects of clinical heterogeneity, as well as to decrease sample size requirements by applying statistical methods to adapt the significance level in small populations. [ 10,14,15 ] …”

“…Clinical research in EB offers promising perspectives but also faces relevant methodological challenges, of which most are inherent to studies conducted in rare disease populations. [ 10‐12 ] …”

“…Faster enrolment and improved compliance subsequently help to reduce expenses in inherently cost‐sensitive rare disease research. [ 10,13 ] …”