Changes to Registered and Pivotal Clinical Trials after the 2011 Tri-Societies Guidelines for Clinical Endpoints and Response Criteria in Mycosis Fungoides and Sézary Syndrome

Abstract

Guidelines for mycosis fungoides (MF) and Sézary syndrome (SS) clinical trials were published in 2011 to standardize endpoint criteria and trial design.Our retrospective cohort study of MF/SS clinical trials registered on ClinicalTrials.gov and pivotal trials supporting drug approvals and label extensions evaluates adherence to these guidelines.Sixty-three trials met our inclusion criteria. In a subpopulation of trials, mean adherence to the guidelines was approximately 60%. When comparing trials that began in the first six years following their publication with those that started after, we found no difference in mean adherence (4.12 vs. 3.41) (P = 0.15). Among the eight pivotal trials supporting new MF or SS systemic therapies from 1990-2020, systemic trials published after 2011 were more likely to randomize patients (100% vs. 0%, P = 0.036), perform superiority testing (100% vs. 0%, P = 0.036), and use an intention-to-treat analysis (100% vs. 0%, P = 0.036).The design of trials registered on Clinicaltrials.gov did not change significantly between the first six years following the publication of the guidelines versus after. This demonstrates that the guidelines are still not consistently implemented across all trials. However, registrational trials were more likely to implement the recommendations.