Trial Results Reported on ClinicalTrials.gov Often Not Published
In a random sampling of 600 randomized controlled drug trials with results posted at ClinicalTrials.gov, half had no corresponding publication in a journal. In addition, studies with both posted and published results were more completely reported on the website than in print.
“Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials,” wrote Carolina Riveros of the French health-research institute INSERM in Paris, and colleagues in their report in PLOS Medicine.
As the investigators reiterated in their paper, the US Food and Drug Administration Amendments Act of 2007 requires that results from clinical trials of FDA-approved drugs are posted on the ClinicalTrials.gov website within one year after study completion. On March 27, 2012, Riveros and team searched that website for reports of completed phase 3 and phase 4 randomized controlled trials of drugs with posted results. This yielded a random sample of 600 eligible trials, ultimately narrowed to 594.
A search of the PubMed data base showed that only 297 of those 594 trials had a matching published article, despite the fact that the median year of completion for the unpublished trials was 2009. Among 202 trials with both posted and published results, the median time between primary completion date and first public posting of results was 19 months, and the median time between primary completion date and journal publication was 21 months.
Riveros and coauthors found that some outcomes were significantly more likely to be posted on ClinicalTrials.gov than published in the article, including flow of participants through trials (completely reported in 64% of the ClinicalTrials.gov postings, compared with 48% of the corresponding publications), efficacy results (completely reported in 79% of the ClinicalTrials.gov postings and in 69% of the corresponding publications), adverse events (completely reported in 73% of the ClinicalTrials.gov postings but in only 45% of the corresponding publications), and serious adverse events (completely reported in 99% of the ClinicalTrials.gov postings compared with just 63% of the corresponding publications).
The reporting at ClinicalTrials.gov, however, is still suboptimal, according to the study group. For example, some elements, such as the number of patients assessed for eligibility, are nearly never reported on the website.
The main study limitation was that the investigators considered only the publication describing the results for the primary outcomes. Riveros and associates acknowledged that unpublished trial results could be published at a future date; some trials may be submitted for publication years after completion.
Nevertheless, their results “highlight the importance of extracting efficacy and safety data posted at ClinicalTrials.gov not only for trials whose results are not yet published, but also for those with published results, because we found that reporting was more complete at ClinicalTrials.gov,” the investigators concluded.
Riveros' group suggested that the use of templates that allow for standardized reporting of trial results in journals or that broader mandatory registration of results for all trials may help further improve transparency.