Impact of covid related restrictions on clinical trials-insights from the sterling registry

ABSTRACT

Introduction The STERLING registry is a prospective collection of aneurysms treated with endovascular techniques. The primary intention is to assess the efficacy and safety of Galaxy and MicrusFrame coils (Cerenovus, Irvine, CA). The Covid pandemic has the potential to alter the delivery of medical care or trial enrollment. Changes to regional or hospital specific research infrastructure will likely affect trials for the worse. Methods A retrospective review of STERLING sites and patients was undertaken to better understand regional variation in adapting to the pandemic and how enrollment was affected. Results 45 global sites currently take part in the STERLING registry. 28 sites began enrolling pre-Covid. 34% of U.S. sites were required to halt research, enrollment or elective surgery, whereas only 8% of EU and none of the Japanese sites were required to significantly change their research protocols respectively. At the 10 (9 US, 1 EU) sites required to put a hold on research, rates of enrollment dropped from an average of 0.6 subjects/month in the US (0.5 in EU) to 0 in the first month and 0.1 subjects/month in the second month of Covid-related restrictions. At the time of this analysis (1/ 2021), the average rate of enrollment across those sites partially recovered to 0.2 subjects/month in the US and 0.2 in EU, although 5 of the 10 sites (all US) had not enrolled any subjects post Covid. Overall, mean actual vs. projected enrollment rates decreased more in the U.S. than in the EU and Japan. The percent of ruptured aneurysms in the per-protocol analysis increased from 23% to 40%, while the percent of unruptured aneurysms decreased from 76% to 60%. There were no significant changes to occlusion rates or adverse events pre/ post Covid. Conclusion The Covid pandemic has the potential to dramatically alter how research is conducted worldwide. U.S. sites faced tougher restrictions than their EU and Japan counterparts. Particularly within the U.S., moratoriums on research and elective surgery may be the driving factor in reducing overall enrollment and increasing the percentage of ruptured aneurysm enrollment. Fortunately, these changes did not appear to negatively affect occlusion rates or adverse events.