Half of Pediatric Trials Go Unfinished or Unpublished

Marcia Frellick

August 08, 2016

Nearly half (49%) of pediatric clinical trials are either discontinued or unpublished, resulting in tens of thousands of children each year being exposed to interventions that do not result in usable information, a study of registered trials finds.

Natalie Pica, MD, PhD, and Florence Bourgeois, MD, MPH, from the Department of Pediatrics at Harvard Medical School and Boston Children's Hospital, both in Massachusetts, published their findings online August 4 in Pediatrics.

The researchers completed a retrospective, cross-sectional study of pediatric randomized controlled trials registered in ClinicalTrials.gov from 2008 to 2010 and compared them with identified publications. They confirmed final status (completed or discontinued) by the end of 2012. When the investigators found no publication, they queried investigators and sponsors.

Inability to recruit enough patients (36.5%) was the most common reason for trial discontinuation. Pediatric trials have added difficulties in recruiting and consenting study participants working with their parents or caretakers. The authors also note there are heightened considerations surrounding interventions with children, and typically less funding for research in pediatric populations than adult populations.

Researchers were less likely to halt trials if they were funded by industry compared with academic institutions (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.27 - 0.77; P = .004).

"This may be related to additional financial and human resources available in industry-funded trials, such as research coordinators to manage patient recruitment or technical infrastructure to facilitate trial conduct," the authors write.

One in Five Trials Were Discontinued

Of the 559 trials studied, 104 (19%) were stopped early. Two thirds of these had already enrolled children. Of those trials stopped early, 39.4% were industry-sponsored and 54.8% were sponsored by academic institutions. The rest were funded by other sources, including governmental agencies.

Of the 455 completed trials, 136 (29.8%) were unpublished an average of 58 months after completion.

Industry-funded trials were more than twice as likely to result in nonpublication at 24 and 36 months (OR, 2.21 [95% CI, 1.35 - 3.64; P = .002] and OR, 3.12 [95% CI, 1.60 - 6.08; P < .001], respectively) and had a longer average time to publication compared with academia-sponsored trials (33 vs 24 months; P < .001).

Findings Raise Scientific and Ethical Concerns

Uncompleted or unpublished trials raise scientific and ethical concerns. The problem has been well-documented with similar results among adults, the authors write, but had not been thoroughly studied in children.

Study results published earlier this year in Medscape Medical News found that "just 29% of completed trials at 51 major research centers had been published 2 years after completion, and a mere 13% had submitted their results to ClinicalTrials.gov."

"This is the first study to look systematically at discontinuation and nonpublication of interventional pediatric clinical trials," Dr Bourgeois said in a statement. "A number of legislative initiatives have been implemented to increase the study of interventions in children. Now we need to make sure that the proper resources are in place to ensure that information gleaned from these studies reaches the scientific community."

The authors note that some trials stopped early may be informative and prevent waste down the road, but they suggest much more can be done to make better use of resources.

One suggestion they highlight is the Restoring Invisible and Abandoned Trials initiative, backed by some high-profile journals.

"This proposal invites researchers with unpublished trials to signal their intent to publish the trial within a year or else provide public access to their trial results and offer the opportunity to independent investigators to become 'restorative authors,' " they write.

"It's hard to reanalyze others' data," Dr Pica said in a statement, "but this may be a useful mechanism to make sure that findings from completed trials are disseminated in the medical literature."

One coauthor received support from the National Institute of Child Health and Human Development. One coauthor received support from the Fred Lovejoy House-Staff Research and Education Fund at Boston Children's Hospital. The authors have disclosed no relevant financial relationships.

Pediatrics. Published online August 4, 2016. Abstract

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