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BMC Medical Research Methodology
Published in: BMC Medical Research Methodology 1/2018

Open Access 01-12-2018 | Research article

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

Authors: Ben Vandermeer, Ingeborg van der Tweel, Marijke C. Jansen-van der Weide, Stephanie S. Weinreich, Despina G. Contopoulos-Ioannidis, Dirk Bassler, Ricardo M. Fernandes, Lisa Askie, Haroon Saloojee, Paola Baiardi, Susan S. Ellenberg, Johanna H. van der Lee

Published in: BMC Medical Research Methodology | Issue 1/2018

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Abstract

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.
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Metadata
Title
Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation
Authors
Ben Vandermeer
Ingeborg van der Tweel
Marijke C. Jansen-van der Weide
Stephanie S. Weinreich
Despina G. Contopoulos-Ioannidis
Dirk Bassler
Ricardo M. Fernandes
Lisa Askie
Haroon Saloojee
Paola Baiardi
Susan S. Ellenberg
Johanna H. van der Lee
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medical Research Methodology / Issue 1/2018
Electronic ISSN: 1471-2288
DOI
https://doi.org/10.1186/s12874-017-0456-8

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