Regulatory delays in a multinational clinical stroke trial

Introduction The initiation and conduct of randomised clinical trials are complicated by multiple barriers, including delays in obtaining regulatory approvals. Quantitative data on the extent of the delays due to national or local review in randomised clinical trials is scarce. Materials and methods We assessed the times needed to obtain regulatory approval and to initiate a trial site for an academic, EU-funded, phase III, randomised clinical trial of pharmacological prevention of complications in patients with acute stroke in over 80 sites in nine European countries. The primary outcome was the time from the first submission to a regulatory authority to initiation of a trial site. Secondary outcomes included time needed to complete each individual preparatory requirement and the number of patients recruited by each site in the first 6 and 12 months. Results The median time from the first submission to a regulatory authority to initiation of a trial site was 784 days (IQR: 586–1102). The single most time-consuming step was the conclusion of a clinical trial agreement between the national coordinator and the trial site, which took a median of 194 days (IQR: 93–293). A longer time to site initiation was associated with a lower patient recruitment rate in the first six months after initiation (B = –0.002; p = 0.02). Discussion Conclusion In this EU-funded clinical trial, approximately 26 months were needed to initiate a trial site for patient recruitment. The conclusion of a contract with a trial site was the most time-consuming activity. To simplify and speed up the process, we suggest that the level of detail of contracts for academic trials should be proportional to the risks and commercial interests of these trials.

Abstract P151: Remote Enrollment Practices for Acute Stroke Clinical Research Trials During a Pandemic

Introduction: Many clinical trials have suffered poor enrollment or have been placed on hold due to the COVID-19 pandemic. Limitations on in-person interaction with patients, legally authorized representatives, coordinators, and physician investigators disrupt research processes including screening, consent, randomization, and study interventions. Remote enrollment practices incorporating telemedicine and electronic consent may address these enrollment limitations. Methods: We retrospectively reviewed clinical trial enrollments in two pivotal phase-III acute stroke trials (NCT03735979, NCT03785678) at two high-volume stroke centers that routinely use remote enrollments in clinical research. Individual elements of acute clinical stroke trial enrollment, including: screening, consent, randomization, and intervention were reviewed. For each research phase, we compared the rate of successful completion and research protocol violations for in-person vs remote research via Fisher’s exact test. Results: Forty patients were reviewed (median age 72 [IQR 63-84], 50% female, median NIHSS 13 [IQR 7.5-19.5]; 35 patient were enrolled and 5 were screened and consented, but found ineligible on qualifying imaging. All research phases were completed successfully with the exception of one in-person study intervention. Fisher’s exact test revealed no differences in protocol violations between research elements conducted remotely (predominantly via telemedicine) versus in-person (see Table). Conclusion: Our study revealed no difference in successful completion of acute clinical trial research elements when conducted remotely or in-person. Incorporation of remote research, especially telemedicine, may enable stroke clinical trial enrollments both during the COVID 19 pandemic and beyond.