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Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation
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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
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 M. Askie; Haroon Saloojee; Paola Baiardi; Susan S. Ellenberg; Johanna H. van der Lee;
Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation
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.
Netherlands, Switzerland
- University of the Witwatersrand South Africa
- UNIVERSIDADE DE LISBOA Portugal
- University of Alberta Canada
- University of Lisbon Portugal
- UNIVERSIDADE DE LISBOA Portugal
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, 610 Medicine & health, Nuisance parameters, Health Informatics, Meta-Analysis as Topic, Outcome Assessment, Health Care, Humans, Sample size computations, Child, Pediatric trials, 2718 Health Informatics, Randomized Controlled Trials as Topic, 10027 Clinic for Neonatology, Sample Size, 2713 Epidemiology, Systematic Reviews as Topic, Research Article
Adult, Adult trials, Epidemiology, Extrapolation, 610 Medicine & health, Nuisance parameters, Health Informatics, Meta-Analysis as Topic, Outcome Assessment, Health Care, Humans, Sample size computations, Child, Pediatric trials, 2718 Health Informatics, Randomized Controlled Trials as Topic, 10027 Clinic for Neonatology, Sample Size, 2713 Epidemiology, Systematic Reviews as Topic, Research Article
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)
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).3 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Average views 23 downloads 51 citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).3 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Average - 23views51downloads
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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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- University of the Witwatersrand South Africa
- UNIVERSIDADE DE LISBOA Portugal
- University of Alberta Canada
- University of Lisbon Portugal
- UNIVERSIDADE DE LISBOA Portugal
- Stanford University United States
- University of Sydney Australia
- ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Netherlands
- Universidade de Lisboa Portugal
- Universidade de Lisboa Portugal
- University of Lisbon Portugal
- Academic Medical Center Netherlands
- Hospital de Santa Maria Portugal
- UNIVERSIDADE DE LISBOA Portugal
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- Universtity of Sydney Australia
- Universitiy of Pennsylvania United States
- UNIVERSIDADE DE LISBOA Portugal
- Universidade de Lisboa Portugal
- UNIVERSIDADE DE LISBOA Portugal
- University of Pennsylvania United States
- Academisch Medisch Centrum bij de Universiteit van Amsterdam Netherlands
- Stanford University School of Medicine United States
- University Malaya Medical Centre Malaysia
- University of Zurich Switzerland
- University Hospital and Clinics United States
- Zurich University of the Arts Switzerland
- UNIVERSIDADE DE LISBOA Portugal
- Amsterdam UMC - Vrije Universiteit Amsterdam Netherlands
- Universidade de Lisboa Portugal
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.