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

Journal of Pediatrics
May 2017 Volume 184, p1-246

Original Articles
Premature Discontinuation of Pediatric Randomized Controlled Trials: A Retrospective Cohort Study
Stefan Schandelmaier, Yuki Tomonaga, Dirk Bassler, Joerg J. Meerpohl, Erik von Elm, John J. You, Anette Bluemle, Francois Lamontagne, Ramon Saccilotto, Alain Amstutz, Theresa Bengough, Mihaela Stegert, Kelechi K. Olu, Kari A.O. Tikkinen, Ignacio Neumann, Alonso Carrasco-Labra, Markus Faulhaber, Sohail M. Mulla, Dominik Mertz, Elie A. Akl, Xin Sun, Jason W. Busse, Ignacio Ferreira-González, Alain Nordmann, Viktoria Gloy, Heike Raatz, Lorenzo Moja, Rachel Rosenthal, Shanil Ebrahim, Per O. Vandvik, Bradley C. Johnston, Martin A. Walter, Bernard Burnand, Matthias Schwenkglenks, Lars G. Hemkens, Gordon Guyatt, Heiner C. Bucher, Benjamin Kasenda, Matthias Briel
Published online: March 4, 2017
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.
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).
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.