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By identifying 22 key parameters in study designs, investigators hope to establish a standardized approach for analyzing moderate-to-severe atopic dermatitis trial results.
A team of investigators identified 22 key parameters and trial design factors of contemporary clinical trials in moderate-to-severe atopic dermatitis and detailed how they influenced study outcomes.
The 5 most important design factors according to study authors included study comparators, the rules of rescue treatment, washout periods, inclusion criteria, and the length of the screening period.
In their recent paper, investigators led by Jonathan I. Silverberg, MD, PhD, MPH, Department of Dermatology, The George Washington School of Medicine and Health Sciences, noted how these key study parameters could potentially impact efficacy outcomes of clinical trials conducted in participants with moderate-to-severe atopic dermatitis.
They also intended to provide guidance in the interpretation of randomized controlled trials and raise awareness about the “harmonization” of study design elements.
In the beginning of the study, Silverberg and colleagues held 2 moderated meeting in December 2020, which included all 6 authors. The meeting was followed by an initial free-form survey that determined eligible items for the study.
The survey responses, along with findings from a recent review of the literature and trial protocols for phase 3 moderate-to-severe atopic dermatitis trials, were used to identify 22 initial trial parameters.
These parameters were subsequently ranked by importance and their potential impact on efficacy outcomes.
Silverberg and colleagues detailed several clinical trial parameters as well as how they influenced efficacy outcomes.
Among them were inclusion/exclusion criteria, washout duration, comparators, use of rescue treatment, the nature of the efficacy analysis set, and missing/censored data.
Certain aspects, such as inclusion/exclusion criteria and washout duration, pertained to the use of specific treatments prior to a study. Regarding the latter, the length of a washout period was suggested to have “cascading consequences” on various stages of a trial, such as greater disease severity as a result of longer periods.
Other factors such as rescue treatments had been offered to ensure that the disease was adequately controlled in participants. However, such treatments vary substantially across clinical trials and can drive differences in trial outcomes.
Additionally, investigators noted that different trials may also provide degrees of patient instruction regarding rescue treatment use.
Regarding missing data, investigators reported that the handling of missing data had become more standardized in recent years. However, such standards have yet to be broadly implemented.
In their concluding remarks, Silverberg and colleagues addressed the myriad ongoing clinical trials for the treatment of moderate-to-severe atopic dermatitis, and how their methodological differences challenge the need to comparatively interpret trial data.
The differences in trials, the team suggested, could have notable effect on trial outcomes and efficacy.
“This raises a need for caution towards trial comparisons and substantiates the need to harmonize study procedures in moderate-to-severe AD trials and establish a standardized approach for analyzing trial results,” the team wrote. “We welcome further research investigating the impact of these differences, as well as efforts to harmonize AD trials.”
The study,“Expert Perspectives on Key Parameters that Impact Interpretation of Randomized Clinical Trials in Moderate-to-Severe Atopic Dermatitis,” was published online in the American Journal of Clinical Dermatology.