Regulatory delays in a multinational clinical stroke trial

Jeroen C de Jonge; Hendrik Reinink; Bridget Colam; Iris Alpers; Alfonso Ciccone; Laszlo Csiba; Janika Kõrv; Iwona Kurkowska-Jastrzebska; Malcolm R Macleod; George Ntaios; Götz Thomalla; Philip M Bath; H Bart van der Worp

doi:10.1177/23969873211004845

Regulatory delays in a multinational clinical stroke trial

Eur Stroke J. 2021 Jun;6(2):120-127. doi: 10.1177/23969873211004845. Epub 2021 Mar 30.

Authors

Affiliations

¹ Department of Neurology and Neurosurgery, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
² Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
³ Clinical Trial Center North GmbH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴ Department of Neurology and Stroke Unit, ASST di Mantova, Mantua, Italy.
⁵ Department of Neurology, University of Debrecen, Debrecen, Hungary.
⁶ Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
⁷ 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.
⁸ Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
⁹ Department of Neurology, Center for Clinical Neurosciences, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁰ Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK.

Abstract

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).

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.

Keywords: Stroke; randomised clinical trial; regulatory approval.