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Publication . Article . 2018

Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation

Ben Vandermeer; Ingeborg van der Tweel; Marijke C. Jansen-van der Weide; Stephanie S. Weinreich; Despina G. Contopoulos-Ioannidis; Dirk Bassler; Ricardo M. Fernandes; +5 Authors
Open Access
Published: 10 Jan 2018 Journal: BMC Medical Research Methodology, volume 18 (eissn: 1471-2288, Copyright policy )
Publisher: Springer Science and Business Media LLC
Country: Netherlands

Background: We wished to compare the nuisance parameters of pediatric vs. adult randomized-trials (RCTs) and determine if the latter can be used in sample size computations of the former.Methods: In this meta-epidemiologic empirical evaluation we examined meta-analyses from the Cochrane Database of Systematic-Reviews, with at least one pediatric-RCT and at least one adult-RCT. Within each meta-analysis of binary efficacy-outcomes, we calculated the pooled-control-group event-rate (CER) across separately all pediatric and adult-trials, using random-effect models and subsequently calculated the control-group event-rate risk-ratio (CER-RR) of the pooled-pediatric-CERs vs. adult-CERs. Within each meta-analysis with continuous outcomes we calculated the pooled-control-group effect standard deviation (CE-SD) across separately all pediatric and adult-trials and subsequently calculated the CE-SD-ratio of the pooled-pediatric-CE-SDs vs. adult-CE-SDs. We then calculated across all meta-analyses the pooled-CER-RRs and pooled-CE-SD-ratios (primary endpoints) and the pooled-magnitude of effect-sizes of CER-RRs and CE-SD-ratios using REMs. A ratio < 1 indicates that pediatric trials have smaller nuisance parameters than adult trials.Results: We analyzed 208 meta-analyses (135 for binary-outcomes, 73 for continuous-outcomes). For binary outcomes, pediatric-RCTs had on average 10% smaller CERs than adult-RCTs (summary-CE-RR: 0.90; 95% CI: 0.83, 0.98). For mortality outcomes the summary-CE-RR was 0.48 (95% CIs: 0.31, 0.74). For continuous outcomes, pediatric-RCTs had on average 26% smaller CE-SDs than adult-RCTs (summary-CE-SD-ratio: 0.74).Conclusions: Clinically relevant differences in nuisance parameters between pediatric and adult trials were detected. These differences have implications for design of future studies. Extrapolation of nuisance parameters for sample-sizes calculations from adult-trials to pediatric-trials should be cautiously done.

Subjects by Vocabulary

Microsoft Academic Graph classification: Future studies Standard deviation law.invention Randomized controlled trial law Statistics Medicine business.industry Sample size determination business Nuisance

Library of Congress Subject Headings: lcsh:R5-920 lcsh:Medicine (General)


Adult, Adult trials, Epidemiology, Extrapolation, Nuisance parameters, Health Informatics, Meta-Analysis as Topic, Outcome Assessment, Health Care, Humans, Sample size computations, Child, Pediatric trials, Randomized Controlled Trials as Topic, Sample Size, Systematic Reviews as Topic, Research Article

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Funded by
NWO| Blue Action
  • Funder: Netherlands Organisation for Scientific Research (NWO) (NWO)
  • Project Code: 16872
Global Research in Paediatrics
  • Funder: European Commission (EC)
  • Project Code: 261060
  • Funding stream: FP7 | SP1 | HEALTH
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