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, Lisa Askie, Haroon Saloojee, Paola Baiardi, Susan S Ellenberg, Johanna H van der Lee

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)7
JournalBMC Medical Research Methodology
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 10 2018

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Pediatrics
Control Groups
Meta-Analysis
Sample Size
Odds Ratio
Databases
Mortality

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Vandermeer, B., van der Tweel, I., Jansen-van der Weide, M. C., Weinreich, S. S., Contopoulos-Ioannidis, D. G., Bassler, D., ... van der Lee, J. H. (2018). Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation. BMC Medical Research Methodology, 18(1), 7. https://doi.org/10.1186/s12874-017-0456-8

Comparison of nuisance parameters in pediatric versus adult randomized trials : a meta-epidemiologic empirical evaluation. / Vandermeer, Ben; van der Tweel, Ingeborg; Jansen-van der Weide, Marijke C; Weinreich, Stephanie S; Contopoulos-Ioannidis, Despina G; Bassler, Dirk; Fernandes, Ricardo M; Askie, Lisa; Saloojee, Haroon; Baiardi, Paola; Ellenberg, Susan S; van der Lee, Johanna H.

In: BMC Medical Research Methodology, Vol. 18, No. 1, 10.01.2018, p. 7.

Research output: Contribution to journalArticle

Vandermeer, B, van der Tweel, I, Jansen-van der Weide, MC, Weinreich, SS, Contopoulos-Ioannidis, DG, Bassler, D, Fernandes, RM, Askie, L, Saloojee, H, Baiardi, P, Ellenberg, SS & van der Lee, JH 2018, 'Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation', BMC Medical Research Methodology, vol. 18, no. 1, pp. 7. https://doi.org/10.1186/s12874-017-0456-8
Vandermeer B, van der Tweel I, Jansen-van der Weide MC, Weinreich SS, Contopoulos-Ioannidis DG, Bassler D et al. Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation. BMC Medical Research Methodology. 2018 Jan 10;18(1):7. https://doi.org/10.1186/s12874-017-0456-8
Vandermeer, Ben ; van der Tweel, Ingeborg ; Jansen-van der Weide, Marijke C ; Weinreich, Stephanie S ; Contopoulos-Ioannidis, Despina G ; Bassler, Dirk ; Fernandes, Ricardo M ; Askie, Lisa ; Saloojee, Haroon ; Baiardi, Paola ; Ellenberg, Susan S ; van der Lee, Johanna H. / Comparison of nuisance parameters in pediatric versus adult randomized trials : a meta-epidemiologic empirical evaluation. In: BMC Medical Research Methodology. 2018 ; Vol. 18, No. 1. pp. 7.
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T1 - Comparison of nuisance parameters in pediatric versus adult randomized trials

T2 - a meta-epidemiologic empirical evaluation

AU - Vandermeer, Ben

AU - van der Tweel, Ingeborg

AU - Jansen-van der Weide, Marijke C

AU - Weinreich, Stephanie S

AU - Contopoulos-Ioannidis, Despina G

AU - Bassler, Dirk

AU - Fernandes, Ricardo M

AU - Askie, Lisa

AU - Saloojee, Haroon

AU - Baiardi, Paola

AU - Ellenberg, Susan S

AU - van der Lee, Johanna H

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N2 - 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.

AB - 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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