Unpublished clinical trials of common rheumatic diseases

Abstract

Objectives Randomized controlled trials (RCTs) provide high-quality evidence for treatment efficacy, but many RCTs remain unpublished. The objective of this study was to describe the proportion of unpublished RCTs in 5 rheumatic diseases and to identify factors associated with publication. Methods Registered RCTs for 5 rheumatic diseases (systemic lupus erythematosus, vasculitis, spondyloarthritis, Sjögren’s syndrome, and psoriatic arthritis) with over 30 months since study completion were identified using ClinicalTrials.gov. Index publications were identified by NCT ID numbers and structured text searches of publication databases. The results of unpublished studies were identified in abstracts and press releases; reasons for non-publication were assessed by surveying corresponding authors. Results Out of 203 studies that met eligibility criteria, 17.2% remained unpublished, representing data from 4,281 trial participants. Higher proportions of published trials were phase 3 RCTs (57.1% vs 28.6% unpublished, p< 0.05) or had a positive primary outcome measure (64.9% vs 25.7% unpublished, p < 0.001). In a multivariable cox proportional hazards model, a positive outcome was independently associated with publication (HR 1.55, CI 1.09–2.22). Corresponding authors of 10 unpublished trials cited ongoing preparation of the manuscript (50.0%), sponsor/funder issues (40.0%), and unimportant/negative result (20.0%) as reasons for lack of publication. Conclusions Nearly one in five RCTs in rheumatology remain unpublished two years after trial completion, and publication is associated with positive primary outcome measures. Efforts to encourage universal publication of rheumatology RCTs and reanalysis of previously unpublished trials should be undertaken.

Time to Publication and Time‐Lag Publication Bias for Randomized Trials on Connective Tissue Diseases

“…Preparation and submission of the manuscript, peer‐review process, multiple resubmissions, quality of the reporting, and study methodology all contribute to the time needed for a paper to be published ( 3 ). Additionally, it has been shown that publication and time from study completion to publication is often associated with the tendency from investigators, study sponsors, or journal editors to favor a more rapid dissemination of results that are statistically significant ( 4 , 5 ) or have a relatively large treatment effect (time‐lag publication bias) ( 6 ). This practice undermines the validity of the overall knowledge on a given topic skewing evidence toward positive findings and is therefore as deleterious as nonpublication of study results.…”