Original ArticlesPremature Discontinuation of Pediatric Randomized Controlled Trials: A Retrospective Cohort Study
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.