Completion and Publication Rates of Randomized Controlled Trials in Surgery: An Empirical Study.

OBJECTIVE: To investigate the prevalence of discontinuation and nonpublication of surgical versus medical randomized controlled trials (RCTs) and to explore risk factors for discontinuation and nonpublication of surgical RCTs. BACKGROUND: Trial discontinuation has significant scientific, ethical, and economic implications. To date, the prevalence of discontinuation of surgical RCTs is unknown. METHODS: All RCT protocols approved between 2000 and 2003 by 6 ethics committees in Canada, Germany, and Switzerland were screened. Baseline characteristics were collected and, if published, full reports retrieved. Risk factors for early discontinuation for slow recruitment and nonpublication were explored using multivariable logistic regression analyses. RESULTS: In total, 863 RCT protocols involving adult patients were identified, 127 in surgery (15%) and 736 in medicine (85%). Surgical trials were discontinued for any reason more often than medical trials [43% vs 27%, risk difference 16% (95% confidence interval [CI]: 5%-26%); P = 0.001] and more often discontinued for slow recruitment [18% vs 11%, risk difference 8% (95% CI: 0.1%-16%); P = 0.020]. The percentage of trials not published as full journal article was similar in surgical and medical trials (44% vs 40%, risk difference 4% (95% CI: -5% to 14%); P = 0.373). Discontinuation of surgical trials was a strong risk factor for nonpublication (odds ratio = 4.18, 95% CI: 1.45-12.06; P = 0.008). CONCLUSIONS: Discontinuation and nonpublication rates were substantial in surgical RCTs and trial discontinuation was strongly associated with nonpublication. These findings need to be taken into account when interpreting surgical literature. Surgical trialists should consider feasibility studies before embarking on full-scale trials.

Prevalence, characteristics, and publication of discontinued randomized trials.

IMPORTANCE The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001). CONCLUSIONS AND RELEVANCE In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.