AB1600 TIME TO PUBLICATION AND TIME-LAG PUBLICATION BIAS FOR RANDOMIZED TRIALS ON CONNECTIVE TISSUE DISEASES

Abstract

BackgroundConnective tissue diseases (CTDs) are systemic autoimmune diseases, some of which rare, characterized by a dysregulated immune response and a heterogeneous clinical picture. Similarly to nonpublication, a long time from completion to publication of randomized controlled trials (RCTs) results can indirectly harm patients by allowing inefficacious or dangerous intervention being prescribed[1], or by delaying the prescription of useful treatment. We have recently shown that one-third of CTDs-RCTs registered after 2000 never reached publication[2], but we did not estimate the extent of time-lag publication bias, neither analyzed factors associated with delayed publication.ObjectivesTo assess the time from completion to publication of randomized controlled trials (RCTs) on connective tissue diseases (CTDs), investigate the factors associated with, and explore the influence of significance of study results on time to publication (time-lag publication bias).MethodsWe included interventional, phase 2/3, 3 or 4 RCTs on CTDs registered in Clinicaltrials.gov from 2000 to 2016, whose results had been published in a peer-review journal less than 5 years after their completion. Two reviewers selected studies according to pre-specified criteria. Main trial features including the significance of primary outcome results were collected. Time to publication was the time from study primary completion to the earliest online publication date. Multivariable linear regression was used to identify association between time to publication and the significance of study results, adjusted for variables previously shown to impact this outcome, e.g. the funder, the size of the trial, the international status, the year of completion and the impact factor of the journal.ResultsWe included 62 studies, mostly phase 3 (62%) trials on pharmacologic treatments (94%), recruiting patients with systemic lupus (55%) or systemic sclerosis (23%), and planning to enroll a median of 131 [IQR 61-288] patients. Twenty-two (35%) reported at least a statistically significant primary outcome. Median time to publication was 28 months [IQR 17-36], with more than half studies (n = 34, 55%) published 2 or more year after completion (see Table 1). In multivariable analysis, time to publication progressively improved over time (faster publication in recent years, with the time to publication begin 1.3 [0.3, 2.4] months shorter every year), and was not influenced by the significance of primary outcome results, funder, impact factor of the journal, number of recruiting countries (see Figure 1).ConclusionA high proportion of CTDs-RCTs is published beyond 2 years from completion. We did not find evidence of time-lag publication bias, and time to publication improved over time.