Randomized Controlled Trials of Rheumatoid Arthritis Registered at ClinicalTrials.gov: What Gets Published and When

Abstract

Objective To examine characteristics associated with the publication and timeliness of publication of randomized controlled trials (RCTs) of treatment of rheumatoid arthritis (RA). Methods RA RCTs (phases II–IV) registered at ClinicalTrials.gov and completed by December 31, 2009 were identified. A standardized strategy was used to determine publication status and outcome assessment. The association of RCT characteristics recorded at ClinicalTrials.gov and study outcome with publication and time to publication were assessed. Results A search conducted at least 30 months after trial completion revealed that among 143 eligible RCTs, 95 (64.4%) were published. The 48 unpublished RCTs had enrolled >10,000 patients. Efficacy outcomes could be ascertained for 127 of the RCTs. RCT publication was associated with positive outcome, with an adjusted odds ratio [OR] of 4.3 (95% confidence interval [95% CI] 1.8–10.2) (P = 0.001), and marginally with RCT registration before completion (adjusted OR 0.4 [95% CI 0.1–1.0], P = 0.06). The estimated median time to publication was 38 months. Positive outcome was associated with earlier publication (adjusted hazard ratio 1.9 [95% CI 1.2–2.9], P = 0.006). RCTs completed in 2006–2007 or 2008–2009 were likely to be published sooner than RCTs completed in or before 2005. Sensitivity analyses to assess the impact of 16 RCTs with unknown outcome did not alter these findings, except in the highly implausible scenario of all such trials being positive. Conclusion Positive study outcome was associated with publication and timeliness of publication despite registration in a publicly available registry. A substantial minority of RA RCTs remained unpublished. Efforts to improve transparency in reporting of clinical trials need to continue.