Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals

PLoS Med. 2013 Dec;10(12):e1001566; discussion e1001566. doi: 10.1371/journal.pmed.1001566. Epub 2013 Dec 3.

Abstract

Background: The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration-approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals.

Methods and findings: We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes.

Conclusions: Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clinical Trials as Topic*
  • Databases, Factual
  • Humans
  • Publishing / statistics & numerical data*
  • Time Factors
  • United States

Grants and funding

Our team is supported by Grant No. DEQ20101221475, academic grant, program “Equipe espoir de la Recherche”, Fondation pour la Recherche Médicale (FRM), Paris, France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.