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Industry concerned over unfinished and unreported pediatric trials

Monday, August 15, 2016

A newly published study has underscored concerns in the industry about the number of pediatric trials that go unfinished and unreported.

In an article in the August issue of Pediatrics, coauthors Natalie Pica, M.D., Ph.D., and Florence Bourgeois, M.D., MPH, of Boston Children’s Hospital and Harvard Medical School, found that of 559 randomized clinical pediatric trials, 104 (19%) were discontinued early—and of 455 completed trials, 136 (30%) were not published.

“Non-publication introduces bias into medical literature, distorting the apparent safety and efficacy of interventions and compromising the available knowledge on which to inform clinical guidelines and practice,” Pica said. “In addition, we believe that non-publication of completed clinical trials represents a waste of both human and material resources and is a breach of contract with those who enroll in clinical trials, often participating without any direct benefit to themselves.”

Difficulty with patient accrual (37%) was the most commonly cited reason for discontinuation; other obstacles include concerns about data integrity and disclosure as well as limited funding.

Despite federal laws to promote clinical research in children—such as the Best Pharmaceuticals for Children Act (BPCA), which provides incentives to conduct FDA-requested pediatric studies, and the Pediatric Research Equity Act (PREA), which requires drug companies to study their products in children under certain circumstances—observers say there is still much work to be done.

Among the challenges is the small patient population from which to draw. Children under age 18 represent less than one-third of the total population, and they are generally healthy. “When you’re looking for a specific therapeutic area or a specific disease, it’s awfully hard to find in a population that small,” said Cynthia Jackson, DO, vice president and head of the Pediatric Center of Excellence at Quintiles. “So you’re searching for a very hard-to-find needle in a very hard-to-find haystack.”

In addition, the pool of investigators who conduct pediatric clinical trials is relatively small as well. “Few sites have trained pediatricians to conduct and design clinical trials,” said Robert Ward, M.D., emeritus professor at the University of Utah and an advocate of improving clinical research in children. “It’s hard to find PIs to do these studies because they involve a different set of skills to do them safely and in accordance with FDA regulations.”

For most busy pediatric specialists, patient care takes precedence over research initiatives. “Research isn’t baked into clinical care; it’s considered an add-on,” Jackson said. “I think we can do a lot in the industry to really advocate for pediatric clinical trials as being a part of good clinical care.”

Adding to the challenges is competition in the industry for the same patient population, Jackson pointed out. “When you have two or three companies looking to fulfill their regulatory obligations by looking for the same needles in the same haystack, you can see the problem,” she said. “We have this in a number of therapeutic areas. There are dozens of different conditions for which there are multiple companies looking to perform clinical trials to fulfill their regulatory obligations.”

Organizations including the nonprofit Critical Path Institute (C-Path) and the Pediatric Trials Network, sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), are advocating for efforts to improve the conduct of pediatric studies. “Usually studies in children are completed at a slower pace,” Ward said. “The cost of doing these trials, which are now required, are more expensive than adult trials and can take twice as long to complete. We are looking at ways to make these studies much more efficient so we can enroll patients faster and complete them faster.”

Improvement efforts could involve the development of master protocols, the use of modeling and simulation and the use of different statistical methods to reduce the number of pediatric patients needed for a clinical trial, observers say.

Raising awareness and improving communication among both the general public and providers also could go a long way toward recruitment. Jackson pointed out that while the main motivation for parents to enroll a child is altruism—that it could help another child in addition to helping their own—a main reason why parents don’t enroll is because they were never asked. “I think there’s something to a global campaign to get the word out about participation in clinical research,” she said.

In the Pediatrics article, the authors cite the Declaration of Helsinki, which states that investigators are responsible for the public dissemination of trial results involving human participants regardless of the findings, and suggest the Restoring Invisible and Abandoned Trials (RIAT), a proposal that invites researchers with unpublished trials to provide public access to their results.

According to the FDA, as much as 80% of drugs are given to children off-label because of lack of research data. “Children have historically been under-represented in clinical trials,” Pica said. “While there are many obstacles to completing and publishing clinical trials, we urge the community to reduce non-informative trial discontinuation and to publish findings in a timely fashion.” 


This article was reprinted from Volume 20, Issue 32, of CWWeekly, a leading clinical research industry newsletter providing expanded analysis on breaking news, study leads, trial results and more. Subscribe »

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