Discontinuation and Nonpublication of Randomized Clinical Trials Conducted in Children

• Published in: Pediatrics (Evanston) Vol. 138; no. 3; p. 1
• Main Authors: Pica, Natalie, Bourgeois, Florence
• Format: Journal Article
• Language: English
• Published: United States American Academy of Pediatrics 01-09-2016
• Subjects: Adolescent; Analysis; Child; Child health; Child, Preschool; Children; Children & youth; Clinical trials; Cross-Sectional Studies; Early Termination of Clinical Trials - economics; Early Termination of Clinical Trials - statistics & numerical data; Female; Government regulation; Health aspects; Human experimentation in medicine; Human medical experimentation; Humans; Infant; Infant, Newborn; Laws, regulations and rules; Logistic Models; Male; Pediatrics; Publishing - economics; Publishing - statistics & numerical data; Randomized Controlled Trials as Topic - economics; Randomized Controlled Trials as Topic - statistics & numerical data; Registries; Research Support as Topic - statistics & numerical data; Retrospective Studies; Self-experimentation in medicine; United States; United States
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.2016-0223

Trial discontinuation and nonpublication represent potential waste in research resources and lead to compromises in medical evidence. Pediatric trials may be particularly vulnerable to these outcomes given the challenges encountered in conducting trials in children. We aimed to determine the prevalence of discontinuation and nonpublication of randomized clinical trials (RCTs) conducted in pediatric populations.
Retrospective, cross-sectional study of pediatric RCTs registered in ClinicalTrials.gov from 2008 to 2010. Data were collected from the registry and associated publications identified (final search on September 1, 2015).
Of 559 trials, 104 (19%) were discontinued early, accounting for an estimated 8369 pediatric participants. Difficulty with patient accrual (37%) was the most commonly cited reason for discontinuation. Trials were less likely to be discontinued if they were funded by industry compared with academic institutions (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.27-0.77). Of the 455 completed trials, 136 (30%) were not published, representing 69 165 pediatric participants. Forty-two unpublished trials posted results on ClinicalTrials.gov. Trials funded by industry were more than twice as likely to result in nonpublication at 24 and 36 months (OR 2.21, 95% CI 1.35-3.64; OR 3.12, 95% CI 1.6-6.08, respectively) and had a longer mean time to publication compared with trials sponsored by academia (33 vs 24 months, P < .001).
In this sample of pediatric RCTs, discontinuation and nonpublication were common, with thousands of children exposed to interventions that did not lead to informative or published findings. Trial funding source was an important determinant of these outcomes, with both academic and industry sponsors contributing to inefficiencies.