Randomized controlled trials in pediatric patients had higher completion rates than adult trials: a cross-sectional study

Abstract

Objective

Conduct of clinical trials is perceived to be more challenging in children than in adults. This study aimed to evaluate the impact of the age of participants on completion rates of randomized controlled trials (RCTs).

Study Design and Setting

A cross-sectional study on RCTs registered in the ClinicalTrials.gov database. All RCTs registered up to December 31, 2016, were extracted and were classified according to their recruitment status: active, completed, or discontinued and according to the age of participants: children (<17 years), adults (≥18 years), and mixed-age population. A logistic regression model was applied to assess the impact of participant's age category on trial completion while controlling for other relevant trial features.

Results

A total of 65,095 registered RCTs were identified. Among pediatric trials, 49.9% were completed and 8.5% were discontinued. Among adult and mixed age RCTs, respectively, 49.7% and 47.9% were completed whereas, 10.2% and 9.4% were discontinued. Overall, pediatric and mixed age RCTs were more likely to be registered as completed than adult RCTs (odds ratio: 1.16, 95% CI: 1.02–1.30; odds ratio: 1.15, 95% CI: 1.04–1.27, respectively). Also, funding source, type of intervention under evaluation, primary trial purpose, use of a blinding procedure, use of a placebo, and participants' assignment model were identified as independent predictors of RCT completion.

Conclusion

Contrary to current perceptions and despite several specific challenges, recruitment of children and adolescents is not a limiting factor to completing a RCT. Other study features such as funding source, impact completeness and should be carefully considered before initiating research.

Introduction

Reducing waste has been identified as an important challenge in clinical research [1], [2]. Specifically, premature discontinuation of randomized controlled trials (RCTs) concerns almost 25% of planned RCTs and raises both resources wasting and ethical concerns. It also contributes to creating a body of medical literature that potentially misguides clinical practice as more than half of discontinued trials remain unpublished and valuable, mostly negative information is lost [3], [4].

Reasons for premature RCT discontinuation have been studied in various medical fields in adults and overall, failure to achieve planned sample size and issues in trial design account for most cases of trial discontinuation [5], [6], [7], [8], [9], [10]. In pediatrics, completion of RCTs is perceived to be more challenging than in adults. This is mainly related to the low prevalence of pediatric diseases and therefore, the scarcity of potential participants and the need for multicenter studies but also the ethical considerations pertaining to vulnerable populations [11], [12], [13], [14]. Indeed, obtaining both parents' written informed consent while respecting the child's autonomy and the requisite implication of parents in research may eventually prevent or at least delay children's participation. Moreover, methodological challenges regarding the choice of trial design and that of comparators or study outcomes, rarely validated in children, may seriously delay the implementation of a pediatric RCT, sometimes to the point of questioning its relevance [15], [16].

Currently, there is little evidence on how these challenges impact the completion of pediatric trials, and no study has directly compared completion rates in RCTs conducted in children to the ones conducted in adults. This study aimed to evaluate the impact of participants' age on the completion rate of RCTs and to identify other associated predictive factors.