Landmark legislation upped the number of pediatric clinical trials, as well as the number of drug labels containing pediatric information. However, up to half of pediatric clinical trials are abandoned or never published, according to a recent analysis published in the journal Pediatrics. Overall, more than 8,000 children were enrolled in discontinued trials and more than 69,000 in completed studies with unpublished results.
A lack of pediatric clinical trials spurred several legislative and regulatory actions in recent years, including the Best Pharmaceuticals for Children Act, which offers an additional 6 months of patent exclusivity for existing drugs later tested in children, and the Pediatric Research Equity Act, which requires that pharmaceutical companies conduct pediatric trials for any new drug likely to be used in children. These policy initiatives augmented the number of pediatric trials and significantly increased the number of drug labels containing pediatric information. How extensively data from the trials has been disseminated remains unclear, however.
Researchers from Harvard Medical School and Boston Children’s Hospital conducted a retrospective, cross-sectional study of 559 pediatric randomized clinical trials (RCTs) registered in ClinicalTrials.gov from 2008 to 2010 that were completed by 2012. They then searched for related publications in peer-reviewed journals through Sept. 1, 2015, following up with study investigators via email if none was identified.
The authors found that nearly one out of five trials (104) ended early, primarily because of difficulties recruiting patients (36 were withdrawn before recruitment began). The rate is similar to that seen in adult clinical trials. Industry-funded trials were about half as likely to be discontinued compared with those supported by academic institutions, possibly because of greater financial and human resources.
Of the 455 trials that were completed, a third were not published after an average of 58 months from completion. Industry-funded trials were 2.21 times as likely to go unpublished within the 2 years after the trial ended, and 3.1 times as likely at 3 years, compared with those supported by academia. The mean time to publication for all trials was 29 months, with a mean time for industry compared with academic institutions of 33 months versus 24 months, respectively.
While 42 of the 136 unpublished trials reported results through ClinicalTrials.gov, the authors found that the data was often presented without statistical analysis or clarification, making interpretation difficult.
This “represents a violation of the ethical imperative to share results of trials that involve human subjects and also introduces publication bias into the medical literature,” the authors wrote.
“We feel there is a lot of inefficiency and waste that could be addressed," senior investigator Florence Bourgeois, MD, of Boston Children's Hospital, said in a statement.