Publication of important phase 3 clinical trial results often delayed by year or more
An analysis of potentially important phase 3 oncology trials showed considerable time elapsed between analysis completion and publication of trial results.
Median publication delays approached 1 year. Such delays could hinder research and advances in clinical care, researchers wrote.
“Even among the most important clinical trials in oncology, there is a considerable delay in the release of comprehensive findings from the time they are presumably known to the study sponsor,” Lindor Qunaj, BSc, medical student at Warren Alpert Medical School of Brown University, told HemOnc Today. “These delays force physicians to treat patients without the latest available information, which may mean not recommending therapies that have just shown promise in a new indication or avoiding treatments with recently uncovered toxicities.
“[Delays] may also result in duplicative research efforts, as companies and academics plan their clinical trial agendas with incomplete data,” Qunaj added. “These inefficiencies lead to unnecessary spending, slow the pace of scientific discovery, and result in patients enrolling in studies that put them at risk [for] drug-related adverse events with little chance of making novel contributions to the field.”
Clinical trial results often are not publicly shared quickly or consistently. For example, 36% of clinical trials performed at academic medical centers have published results within 2 years of completion. In addition, only 57% of trials relevant to FDA drug approvals in 2012 had been registered, and only 56% had published results within 13 months after approval, according to study background.
Another study showed nearly two-thirds (62%) of abstracts presented at an ASCO annual meeting had not been published in a peer-reviewed journal within 2 years of presentation, and nearly one-quarter (23%) had not been published within 5 years of presentation.
Pharmaceutical companies often issue press releases about trial results when they anticipate they will lead to practice patterns related to their product.
Qunaj and colleagues — including Peter B. Bach, MD, MAAP, director of Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center — evaluated delays in publication of phase 3 oncology trial results that sponsors deemed important enough to detail in a press release.
Investigators measured time between the press release issue date — the earliest possible time at which they could be confident the results were available to the trial sponsor — and the time when results were available via ClinicalTrials.gov, or published in a peer-reviewed biomedical journal accessible via PubMed or Google Scholar.
Researchers evaluated 745 oncology-related press releases that eight pharmaceutical companies issued between January 2011 and June 2016.
Investigators excluded press releases that contained announcements for the following:
- A regulatory step;
- Presentation scheduled for an upcoming conference;
- Results from preclinical, phase 1 or phase 2 clinical trials;
- Long-term analyses of phase 3 clinical trials;
- Retrospective or subgroup analyses;
- Studies of supportive care therapies; and
- Studies that investigated various infusion methods of the same therapies.
Researchers only analyzed the first press release for each clinical trial.
The final analysis included 100 press releases, 70% of which reported positive results.
Thirty-one press releases (31%) included quantitative estimates of effect size. Those that included these estimations tended to contain positive findings. Press releases about preapproved drugs appeared less likely to include quantitative reports of effect sizes (P = .04 for positive vs. negative findings).
The median time from issuance of a press release announcing trial results until publication in a peer-reviewed journal or posting on ClinicalTrials.gov was 300 days (95% CI, 263-348).
Ninety-nine percent of press releases had an associated peer-reviewed publication, complete data posting to ClinicalTrials.gov or both through the end of follow-up (mean, 4.2 years).
Median time to publication appeared shorter for trials with positive findings (272 days; 95% CI, 211-318) than those with negative findings (407 days; 95% CI, 298-705).
Of all studies with negative results announced in press releases, only 70% had published or posted results within 2 years of press release issuance.
Multivariate Cox analysis indicated reporting of positive results was a predictor of shorter time to public release even when controlling for the company (P < .001).
Researchers observed no difference in median delay between trials that studied approved drugs and those that studied unapproved drugs. However, they observed significant difference in delays between the eight pharmaceutical companies evaluated.
“We understand that no one stakeholder is exclusively responsible for these delays,” Qunaj told HemOnc Today. “For that reason, we advocate for collaboration across pharmaceutical companies, publishers, regulatory bodies and academic researchers to develop mechanisms that allow for faster sharing of clinical trial findings without being onerous for any involved party.”
The researchers proposed several possible strategies for mitigating delays in publication or posting. They included preprinting — the practice of publishing “draft” findings prior to or in conjunction with peer review — or the possibility that regulatory agencies, medical journals or medical meeting program committees could require study results be posted to ClinicalTrials.gov at the time results are shared in a press release or other public announcement.
In addition, publishers should consider innovative strategies to further reduce the time between manuscript acceptance and data availability, as well as give similar consideration to reports of positive and negative results, Qunaj and colleagues wrote.
“We do foresee possible objections from pharmaceutical companies, scientific journals and medical societies,” the researchers wrote. “Embargoed, timed data releases are a potent tool for marketing study findings and drawing traffic to the journal or meeting where the results are presented. However, these interests are narrow, [whereas] the needs of science more generally — and the patients with the conditions that these companies have studied — matter more.” – by Melinda Stevens
For more information:
Lindor Qunaj, BSc, can be reached at Lindor_Qunaj@brown.edu.
Disclosures: Qunaj reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.