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Premature Discontinuation of Pediatric Randomized Controlled Trials: A Retrospective Cohort Study
Stefan Schandelmaier1, Yuki Tomonaga2, Dirk Bassler3
1Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Academy of Swiss Insurance Medicine, University Hospital Basel, Basel, Switzerland.
Insights
Pediatric randomized controlled trials (RCTs) have a high discontinuation rate, primarily due to slow recruitment. However, enrolling children was not an independent risk factor for recruitment failure in these trials.
Area of Science:
- Clinical Trials
- Pediatric Research
- Research Ethics
Background:
- Pediatric randomized controlled trials (RCTs) are crucial for evidence-based child healthcare.
- Understanding factors influencing RCT success, particularly discontinuation rates, is vital for improving pediatric research.
- Previous studies have not comprehensively assessed discontinuation reasons and recruitment failure risks in pediatric versus adult RCTs.
Purpose of the Study:
- To determine the proportion of pediatric RCTs that are prematurely discontinued.
- To examine the primary reasons for discontinuation in pediatric RCTs.
- To compare the risk of recruitment failure in pediatric versus adult RCTs.
Main Methods:
- A retrospective cohort study design was employed, analyzing RCTs approved by Research Ethics Committees (RECs) in Switzerland, Germany, and Canada from 2000-2003.
- Data on trial characteristics, discontinuation status, and reasons were collected from protocols, publications, REC files, and trialist surveys.
- Multivariable logistic regression was used to identify independent risk factors for recruitment failure, adjusting for potential confounders.
Main Results:
- Of 894 RCTs (86 pediatric, 808 adult), 40% of pediatric RCTs and 29% of adult RCTs were discontinued.
- Slow recruitment was the predominant reason for discontinuation, accounting for 56% of pediatric RCTs and 43% of adult RCTs.
- Pediatric RCT enrollment was not an independent risk factor for recruitment failure (aOR, 1.22; 95% CI, 0.57-2.63). Independent risk factors included acute care setting, non-industry sponsorship, and smaller planned sample size.
Conclusions:
- Forty percent of pediatric RCTs were discontinued prematurely, mainly due to slow recruitment.
- Enrollment of children was not identified as an independent risk factor for recruitment failure in RCTs.
- Factors such as acute care setting, non-industry sponsorship, and smaller sample size independently increased the risk of recruitment failure.
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.