Placebo-controlled trials (PCT) are the gold standard for testing efficacy and safety in novel treatments for inflammatory skin diseases such as atopic dermatitis (AD). However, this trial design also poses many concerns that must be balanced, including ethics, methodology, regulatory requirements, and real-world needs, according to a study recently published in The Journal of the European Academy of Dermatology and Venereology. By addressing these concerns, the authors developed a framework for applying PCT in AD systemic therapy development.
A subgroup at the International Eczema Council (IEC) developed and disseminated a survey to other IEC members to determine the essential considerations for designing and implementing PCT in AD, focusing on trials with systemic medications. The survey contains 27 statements with a 5-point Likert response scale (“strongly agree” to “strongly disagree”) and 2 statements with multiple-check response options. Investigators considered <30% disagreement (either “strongly disagree” or “disagree”) as a consensus.
The response rate was 43/82 (52%). The surveyed group reached consensus on 24/27 statements and on 3/11 options from multiple-selection statements, including: “performing monotherapy studies in proof-of-concept phases,” “avoiding concomitant topical corticosteroids or calcineurin inhibitors until a predefined timepoint as rescue” (borderline consensus), “selection of sites and assessors with recognized expertise in AD clinical trials,” “clear definition and identification of baseline disease severity,” “minimizing time and proportion of patients on placebo,” “using daily emollients with several options provided,” “instigating open-label extension studies for enrollment after a predefined timepoint,” and “including outcomes which set a higher bar for disease clearance.”
Limitations of the study include the low response rate, the comparative lack of research on the predictors of the placebo response in AD, and the surveyed population’s dedication to research and treatment of AD.
Designing PCT in AD systemic medication trials requires balancing many often-opposing principles. Research coordinators should be aware of this balancing act when planning clinical trials and should refer to the IEC’s framework for designing effective PCT for AD.
Disclosure: Multiple authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.
Leshem YA, Bissonnette R, Paul C, et al. Optimization of placebo use in clinical trials with systemic treatments for atopic dermatitis: an International Eczema Council survey-based position statement [published online March 12, 2019]. J Eur Acad Dermatol Venereol. doi: 10.1111/jdv.15480