Premature termination of clinical trials in Spain: reasons, characteristics, and opportunities to improve

Abstract

Purpose: The aim of this study is to determine the rate of prematurely terminated clinical trials (CTs) and describe primary reasons and characteristics, and suggest strategies to improve.

Methods: We performed a retrospective, observational, cross-sectional study including all CTs registered in the Spanish Registry of Clinical Studies (REec) from January 1, 2013 to November 31, 2021. A descriptive analysis of reasons for premature termination was made. To assess characteristics associated with a premature termination, the relative risks (RR) with a 95% confidence interval were calculated.

Results: In total, 21% (718) of CT were prematurely terminated. Reasons for premature termination included patient recruitment issues in 25% (179) of cases, efficacy or futility problems in 18% (132), and commercial or strategic decisions from the sponsor in 12% (87). Characteristics significantly associated with an increased risk of premature termination included the following: presence of placebo (RR 2.08); multiple study sites (RR 1.32); pediatric and geriatric populations (RR 1.29 children; RR 1.47 preschoolers; RR 1.92 newborns; RR 1.27 > 64 years of age). In addition, circumstances such as investigations in phase II (RR 1.21), of cancer (RR 1.37), and of digestive pathology (RR 1.65) were also associated with increased risk of premature termination.

Conclusion: Recruitment of the study subjects in a CT must be meticulous and account for age of participants. In addition, CT study sites should be evaluated to ensure they have appropriate resources and the desired patient population. Based on intermediate analyses, CT protocols should describe the criteria to terminate a study due to futility. These approaches are essential to avoid harm to participants, ensure internal validity of studies, and improve the use of resources in CT development.

Keywords: Clinical trial; Database; Futility; Premature termination; Recruitment issues.