Premature Discontinuation of Prospective Clinical Studies Approved by a Research Ethics Committee - A Comparison of Randomised and Non-Randomised Studies.

Abstract

BACKGROUND: Premature discontinuation of clinical studies affects about 25% of randomised controlled trials (RCTs) which raises concerns about waste of scarce resources for research. The risk of discontinuation of non-randomised prospective studies (NPSs) is yet unclear. OBJECTIVES: To compare the proportion of discontinued studies between NPSs and RCTs that received ethical approval. METHODS: We systematically surveyed prospective longitudinal clinical studies that were approved by a single REC in Freiburg, Germany between 2000 and 2002. We collected study characteristics, identified subsequent publications, and surveyed investigators to elucidate whether a study was discontinued and, if so, why. RESULTS: Of 917 approved studies, 547 were prospective longitudinal studies (306 RCTs and 241 NPSs). NPSs were on average smaller than RCTs, more frequently single centre and pilot studies, and less frequently funded by industry. NPSs were less frequently discontinued than RCTs: 32/221 (14%) versus 78/288 (27%, p<0.001, missing data excluded). Poor recruitment was the most frequent reason for discontinuation in both NPSs (36%) and RCTs (37%). CONCLUSIONS: Compared to RCTs, NPSs were at lower risk for discontinuation. Measures to reliably predict, sustain, and stimulate recruitment could prevent discontinuation of many RCTs but also of some NPSs.