The study, which was conducted by researchers at Boston Children's Hospital, found that in all, 19% of the 599 trials in the study were discontinued early, and 30% of completed trials remained unpublished in medical literature several years later.
“Previous research has shown that discontinuation and non-publication are common amongst clinical trials performed in adults, though the prevalence of these outcomes in pediatric populations was less well-defined,” senior investigator Florence Bourgeois, MD, MPH, of Boston Children's Hospital, told Outsourcing-Pharma.com.
“Alarmingly,” Bourgeios explained the researchers found more than 69,000 children were involved in studies that were completed, but that were never published in scientific literature. “As a result, these trials fail to contribute to our scientific knowledge and to inform the clinical care we can provide to children,” he added.
Catherine Y. Spong, M.D., Acting Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) added, “Clinical trials and research in children is critically important as the information known or studied in adults does not necessarily translate to children.
“Children may respond to things differently, their physiology and adaptation are different. We cannot assume that if an intervention works in an adult it will be the same for a child,” she told us.
However, she said it’s not a matter of encouraging or discouraging the trials, but instead “fostering the research that provides the information needed to inform the care of children.”
Historically, children have been under-represented in clinical trials. To counteract this, several legislative initiatives were enacted, such as the Best Pharmaceuticals for Children Act (BPCA), passed in 2002 and the Pediatric Research Equity Act (PREA) implemented in 2003.
“These acts have been credited with increasing the number of pediatric drug trials and the number of drug labels that contain pediatric safety and efficacy information, with the overall goal of providing better care for children,” said Bourgeois.
In fact, until legislative initiatives like 1997 FDAMA, which created the six month exclusivity provision, Spong said there was no expectation of children’s inclusion in clinical trials.
This was changed with BPCA, which is a continuation of the FDAMA six-month additional exclusivity provision, and PREA, which mandates pediatric studies for a drug not yet approved, for the same indication as in adults.
No small challenge
While BPCA and PREA have helped address many barriers to initiating and conducting clinical trials in children, researchers still face several unique challenges.
“Pediatric studies are complicated, because they have to be tailored to the needs of children and their families,” said Spong. Additionally, there has been limited funding allotted to pediatric research.
According to the researchers, trial funding source was found to be a significant determinant of trial discontinuation and non-publication. Specifically, industry sponsored trials were less likely to be discontinued, compared to trials sponsored by academia, but were more likely to have a longer time to publication or remain unpublished.
“Therefore, it is imperative that industry continue to focus on the timely and complete reporting of all trials conducted in children, regardless of the trial findings,” said Natalie Pica, MD, PhD, a resident at Boston Children's, a coauthor on the study’s paper.
“Incentives for companies to develop and test medications for children are needed because the pediatric market is much smaller than the adult market,” said Spong, as children are generally healthier than adults and there is less of a financial motive to market treatments for them.
Spong added that it’s important to keep in mind why trials were unfinished: “was there a safety problem that forced study closure, were there problems locating and enrolling children who were eligible, or with monitoring the children after the treatment phase had concluded and participants had moved on,” she asked.
Title: Discontinuation and Nonpublication of Randomized Clinical Trials Conducted in Children
Authors: Natalie Pica, Florence Bourgeois
Publication: Journal of Pediatrics