As many as 29% of large clinical trials registered on the ClinicalTrials.gov database remain unpublished five years after completion, a new US analysis has found.
Of those unpublished trials, moreover, 78% had no results available on ClinicalTrials.gov after an average 60-month time lag, the researchers said.
This meant an estimated 250,000 people were exposed to the risks of trial participation without reaping the societal benefits that come from disseminating study results, the authors commented on BMJ.com.
They condemned this imbalance as violating “an ethical obligation that investigators have towards study participants” and called for additional safeguards to “ensure timely public dissemination of trial data”.
The research team was led by Christopher Jones, from the Department of Emergency Medicine, Cooper Medical School of Rowan University in New Jersey, and Tim Platts-Mills, from the Department of Emergency Medicine, University of North Carolina Chapel Hill.
By searching databases of scientific literature (PubMed, Google Scholar, and Embase), the team identified 585 trials with at least 500 participants that had been registered with ClinicalTrials.gov and completed before January 2009.
The average time between study completion and the final literature search (in November 2012) was 60 months for the unpublished trials.
Registry entries for these unpublished trials were then reviewed to determine whether results for the studies were available on ClinicalTrials.gov, as required by US legislation.
Obligation to publish
The US Food and Drug Administration Amendments Act of 2007 made publication within 12 months of a results summary on ClinicalTrials.gov mandatory for all eligible trials in the US initiated or ongoing as of September 2007, an editorial in the BMJ pointed out last year.
A review by Prayle et al, published in the same issue of the journal, found that only 22% of trials subject to mandatory reporting under the 2007 Act had results available within one year of completion.
No results available
Of the 585 registered trials reviewed by the Jones/Platts-Mills team, 171 (29%) remained unpublished at the cut-off point, the authors reported on BMJ.com. These 171 unpublished trials had an estimated total enrolment of 299,_763 participants.
In addition, 133 (78%) of the unpublished trials had no results available on the ClinicalTrials.gov database.
Non-publication was more common among clinical trials that received industry funding (32%) than among those that did not (18%), the BMJ report noted.
Of the 150 industry-funded studies that remained unpublished, 38 (25%) had results available on ClinicalTrials.gov.
None of the 11 unpublished trials funded by the US National Institutes of Health or of the 20 unpublished trials with other funding sources provided results on ClinicalTrials.gov.
From the initial group of 585 trials, 414 (71%) had published results; 38 (6%) remained unpublished as of November 2012 but had results available on ClinicalTrials.gov; and 133 (23%) had no results available either in published form or on ClinicalTrials.gov.
Fifteen (39%) of the 38 trials with results reported also provided statistical analyses for at least one primary outcome. The remaining 23 trials reported results without including statistical analyses.
Jones et al identified an estimated 250_000 trial participants for whom they were unable to find results either in the published literature or in the result database of the registry. This amounted to roughly 26% of all participants in the included trials.
The findings were “consistent with previously observed rates of non-publication among trials representing a broad spectrum of clinical topics and funding sources”, the authors observed.
“Our results add to existing work by showing that non-publication is an important problem even among large randomised trials,” they stated.