• Patricia Gilholm, Endrias Ergetu, Ben Gelbart, Sainath Raman, Marino Festa, Luregn J Schlapbach, Debbie Long, Kristen S Gibbons, and Australian and New Zealand Intensive Care Society Paediatric Study Group.
• Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
• Pediatr Crit Care Me. 2023 Sep 1; 24 (9): 738749738-749.

ObjectivesThis systematic review investigates the use of adaptive designs in randomized controlled trials (RCTs) in pediatric critical care.Data SourcesPICU RCTs, published between 1986 and 2020, stored in the www.PICUtrials.net database and MEDLINE, EMBASE, CENTRAL, and LILACS databases were searched (March 9, 2022) to identify RCTs published in 2021. PICU RCTs using adaptive designs were identified through an automated full-text screening algorithm.Study SelectionAll RCTs involving children (< 18 yr old) cared for in a PICU were included. There were no restrictions to disease cohort, intervention, or outcome. Interim monitoring by a Data and Safety Monitoring Board that was not prespecified to change the trial design or implementation of the study was not considered adaptive.Data ExtractionWe extracted the type of adaptive design, the justification for the design, and the stopping rule used. Characteristics of the trial were also extracted, and the results summarized through narrative synthesis. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2.Data SynthesisSixteen of 528 PICU RCTs (3%) used adaptive designs with two types of adaptations used; group sequential design and sample size reestimation. Of the 11 trials that used a group sequential adaptive design, seven stopped early due to futility and one stopped early due to efficacy. Of the seven trials that performed a sample size reestimation, the estimated sample size decreased in three trials and increased in one trial.ConclusionsLittle evidence of the use of adaptive designs was found, with only 3% of PICU RCTs incorporating an adaptive design and only two types of adaptations used. Identifying the barriers to adoption of more complex adaptive trial designs is needed.Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

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