Background:
Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit,or futility. Other RCTs are discontinued early because of insufficient recruitment. Trialdiscontinuation has ethical implications, because participants consent on the premise ofcontributing to new medical knowledge, Research Ethics Committees (RECs) spendconsiderable effort reviewing study protocols, and limited resources for conducting researchare wasted. Currently, little is known regarding the frequency and characteristics ofdiscontinued RCTs.
Methods:
Our aims are, first, to determine the prevalence of RCT discontinuation for any reason;second, to determine whether the risk of RCT discontinuation for specific reasons differsbetween investigator- and industry-initiated RCTs; third, to identify risk factors for RCTdiscontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs arediscontinued; and fifth, to examine the publication history of discontinued RCTs.We are currently assembling a multicenter cohort of RCTs based on protocols approvedbetween 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We areextracting data on RCT characteristics and planned recruitment for all included protocols.Completion and publication status is determined using information from correspondencebetween investigators and RECs, publications identified through literature searches, or bycontacting the investigators. We will use multivariable regression models to identify riskfactors for trial discontinuation due to insufficient recruitment. We aim to include over 1000RCTs of which an anticipated 150 will have been discontinued due to insufficientrecruitment.DiscussionOur study will provide insights into the prevalence and characteristics of RCTs that werediscontinued. Effective recruitment strategies and the anticipation of problems are key issuesin the planning and evaluation of trials by investigators, Clinical Trial Units, RECs andfunding agencies. Identification and modification of barriers to successful study completionat an early stage could help to reduce the risk of trial discontinuation, save limited resources,and enable RCTs to better meet their ethical requirements.