Elsevier

The Journal of Pediatrics

Volume 184, May 2017, Pages 209-214.e1
The Journal of Pediatrics

Original Articles
Premature Discontinuation of Pediatric Randomized Controlled Trials: A Retrospective Cohort Study

https://doi.org/10.1016/j.jpeds.2017.01.071Get rights and content

Objectives

To determine the proportion of pediatric randomized controlled trials (RCTs) that are prematurely discontinued, examine the reasons for discontinuation, and compare the risk for recruitment failure in pediatric and adult RCTs.

Study design

A retrospective cohort study of RCTs approved by 1 of 6 Research Ethics Committees (RECs) in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics, trial discontinuation, and reasons for discontinuation from protocols, corresponding publications, REC files, and a survey of trialists.

Results

We included 894 RCTs, of which 86 enrolled children and 808 enrolled adults. Forty percent of the pediatric RCTs and 29% of the adult RCTs were discontinued. Slow recruitment accounted for 56% of pediatric RCT discontinuations and 43% of adult RCT discontinuations. Multivariable logistic regression analyses suggested that pediatric RCT was not an independent risk factor for recruitment failure after adjustment for other potential risk factors (aOR, 1.22; 95% CI, 0.57-2.63). Independent risk factors were acute care setting (aOR, 4.00; 95% CI, 1.72-9.31), nonindustry sponsorship (aOR, 4.45; 95% CI, 2.59-7.65), and smaller planned sample size (aOR, 1.05; 95% CI 1.01-1.09, in decrements of 100 participants).

Conclusion

Forty percent of pediatric RCTs were discontinued prematurely, owing predominately to slow recruitment. Enrollment of children was not an independent risk factor for recruitment failure.

Section snippets

Methods

Previous publications have described the rationale and design of this international cohort study,21, 23 and we have presented parts of the regression analysis previously in the context of acute care RCTs.24 In brief, we included RCTs approved between 2000 and 2003 by 6 RECs in Switzerland (Basel, Lucerne, Zurich, and Lausanne), Germany (Freiburg), and Canada (Hamilton). Each REC was responsible for human research in large university centers and hospitals in its respective catchment area. Every

Classification and Prevalence of Pediatric Trials

We included 894 RCTs, of which we classified 86 (10%) as pediatric RCTs and 808 (90%) as adult RCTs (Figure). Thirty-three trials included a mixed-age population, of which we classified 9 as pediatric because the proportion of children younger than 18 years was >50%. All 9 trials focused on conditions that typically manifest in childhood (ie, 4 on pediatric tumors, 2 on cerebral palsy, 2 on cystic fibrosis, 1 on type 1 diabetes). After excluding the 43 trials approved in Zürich, the proportion

Discussion

In an international cohort of 894 RCTs, 86 enrolled 50% or more children. Of these, 40% were discontinued prematurely. The main reason for trial discontinuation was slow recruitment. Overall, the risk for discontinuation due to slow recruitment was higher in pediatric RCTs than in adult RCTs; however, multivariable logistic regression analysis suggested that the pediatric setting is not an independent risk factor. Instead, an elevated risk for discontinuation due to slow recruitment was

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    Funded by the Swiss National Science Foundation (320030_133540/1) and the German Research Foundation (EL 544/1-2). M.B, A.N., V.G., H.R., L.H., and H.B. were supported by Santésuisse and the Gottfried and Julia Bangerter-Rhyner-Foundation. E.v.E. was supported by the Brocher Foundation. J.B. was funded by a New Investigator Award from the Canadian Institutes of Health Research and Canadian Chiropractic Research Foundation. D.M. was a recipient of a Research Early Career Award from Hamilton Health Sciences Foundation (Jack Hirsh Fellowship). K.T. was funded by unrestricted grants from the Academy of Finland, Competitive Research Funding of the Helsinki and Uusimaa Hospital District, Finnish Cultural Foundation, Finnish Medical Foundation, Jane and Aatos Erkko Foundation, and Sigrid Jusélius Foundation. J.Y. was supported by a Research Early Career Award from Hamilton Health Sciences. R.R. has been an employee of F. Hoffmann-La Roche Ltd since May 1, 2014; the present study was conducted before she joined F. Hoffmann-La Roche Ltd and has no connection to her employment by the company. The other authors declare no conflicts of interest.

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