Identifying predictors of early trial termination: A meta-epidemiologic study utilising elements of the research ethics committee evaluation.

Objectives: Early trial termination remains frequent. Research ethics committees (RECs) could play a role in reducing the probability of early termination. Their review process provides a window for both identifying trials at high risk of terminating prematurely and imposing preventive measures, such as design modifications. This study aimed to explore whether characteristics of ethics review, alongside trial characteristics, are related to subsequent early trial termination.

Study design and setting: This meta-epidemiologic cohort study assessed 198 clinical trials approved by a Dutch REC between 2015 - 2018. Data from archived trial protocols, related study documents and correspondence between the REC and investigators were analysed to identify predictors of early termination during ethics review.

Results: Of the 198 trials, 69 (34.8%) terminated early, most often due to recruitment failure (n = 31, 35.2%). Several characteristics were associated with early termination, such as multicentre design (vs. single centre, RR: 1.89, 95% CI: 1.24-3.14), number of comments raised during ethics review (per comment, RR: 1.02, 95% CI: 1.00-1.05), and specific comments regarding privacy and confidentiality (RR: 1.21, 95% CI: 1.05-1.41) and participant information sheets (RR: 1.05, 95% CI: 1.02-1.08). Investigator sponsorship, longer review durations, and comments raised regarding privacy and confidentiality and subject selection were associated with an increased likelihood of recruitment failure, specifically.

Conclusion: This exploratory study showed that various characteristics of ethics review have the potential to predict early trial termination. Further studies are needed to validate and expand upon these findings.