Nonregistration, Discontinuation, and Nonpublication of Randomized Trials: A Systematic Review

Area of Science:

• Clinical Trials Research
• Medical Research Ethics
• Health Outcomes Research

Background:

• Previous studies indicate 25-30% of randomized clinical trials (RCTs) are discontinued prematurely, often due to insufficient participant recruitment.
• Minimizing research waste necessitates mandatory RCT registration and public availability of results.

Purpose of the Study:

• To evaluate the status of RCTs approved in 2016 regarding registration, discontinuation, and publication.
• To identify RCT characteristics associated with discontinuation due to poor recruitment and nonpublication.

Main Methods:

• Systematic review of 347 RCT protocols approved in 2016 by ethics committees in the UK, Switzerland, Germany, and Canada.
• Data extraction on key trial characteristics from protocols; systematic searches for trial registrations and results publications.
• Contacting ethics committees or principal investigators for clarification when status was unclear.

Main Results:

• Of 347 RCTs, 5.8% were unregistered, 31.1% were discontinued (45.4% due to poor recruitment), and 79.5% published results.
• Industry-sponsored trials showed higher results availability (92.3%) compared to non-industry trials (66.3%), largely due to registry reporting.
• Industry-sponsored trials were less likely to be discontinued due to poor recruitment (aOR=0.32).

Conclusions:

• Nonregistration, discontinuation due to poor recruitment, and nonpublication remain significant issues, particularly for non-industry-sponsored RCTs.
• Enhanced requirements by funders and ethics committees, considering legal obligations, are needed to address these challenges.