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Detecting Heterogeneity of Intervention Effects Using Analysis and Meta-analysis of Differences in Variance Between Trial Arms

Randomized controlled trials (RCTs) with continuous outcomes usually only examine mean differences in response between trial arms. If the intervention has heterogeneous effects, then outcome variances will also differ between arms. Power of an individual trial to assess heterogeneity is lower than t...

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Autores principales: Mills, Harriet L., Higgins, Julian P.T., Morris, Richard W., Kessler, David, Heron, Jon, Wiles, Nicola, Davey Smith, George, Tilling, Kate
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478324/
https://www.ncbi.nlm.nih.gov/pubmed/34432720
http://dx.doi.org/10.1097/EDE.0000000000001401
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author Mills, Harriet L.
Higgins, Julian P.T.
Morris, Richard W.
Kessler, David
Heron, Jon
Wiles, Nicola
Davey Smith, George
Tilling, Kate
author_facet Mills, Harriet L.
Higgins, Julian P.T.
Morris, Richard W.
Kessler, David
Heron, Jon
Wiles, Nicola
Davey Smith, George
Tilling, Kate
author_sort Mills, Harriet L.
collection PubMed
description Randomized controlled trials (RCTs) with continuous outcomes usually only examine mean differences in response between trial arms. If the intervention has heterogeneous effects, then outcome variances will also differ between arms. Power of an individual trial to assess heterogeneity is lower than the power to detect the same size of main effect. METHODS: We describe several methods for assessing differences in variance in trial arms and apply them to a single trial with individual patient data and to meta-analyses using summary data. Where individual data are available, we use regression-based methods to examine the effects of covariates on variation. We present an additional method to meta-analyze differences in variances with summary data. RESULTS: In the single trial, there was agreement between methods, and the difference in variance was largely due to differences in prevalence of depression at baseline. In two meta-analyses, most individual trials did not show strong evidence of a difference in variance between arms, with wide confidence intervals. However, both meta-analyses showed evidence of greater variance in the control arm, and in one example, this was perhaps because mean outcome in the control arm was higher. CONCLUSIONS: Using meta-analysis, we overcame low power of individual trials to examine differences in variance using meta-analysis. Evidence of differences in variance should be followed up to identify potential effect modifiers and explore other possible causes such as varying compliance.
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spelling pubmed-84783242021-10-06 Detecting Heterogeneity of Intervention Effects Using Analysis and Meta-analysis of Differences in Variance Between Trial Arms Mills, Harriet L. Higgins, Julian P.T. Morris, Richard W. Kessler, David Heron, Jon Wiles, Nicola Davey Smith, George Tilling, Kate Epidemiology Methods Randomized controlled trials (RCTs) with continuous outcomes usually only examine mean differences in response between trial arms. If the intervention has heterogeneous effects, then outcome variances will also differ between arms. Power of an individual trial to assess heterogeneity is lower than the power to detect the same size of main effect. METHODS: We describe several methods for assessing differences in variance in trial arms and apply them to a single trial with individual patient data and to meta-analyses using summary data. Where individual data are available, we use regression-based methods to examine the effects of covariates on variation. We present an additional method to meta-analyze differences in variances with summary data. RESULTS: In the single trial, there was agreement between methods, and the difference in variance was largely due to differences in prevalence of depression at baseline. In two meta-analyses, most individual trials did not show strong evidence of a difference in variance between arms, with wide confidence intervals. However, both meta-analyses showed evidence of greater variance in the control arm, and in one example, this was perhaps because mean outcome in the control arm was higher. CONCLUSIONS: Using meta-analysis, we overcame low power of individual trials to examine differences in variance using meta-analysis. Evidence of differences in variance should be followed up to identify potential effect modifiers and explore other possible causes such as varying compliance. Lippincott Williams & Wilkins 2021-08-20 2021-11 /pmc/articles/PMC8478324/ /pubmed/34432720 http://dx.doi.org/10.1097/EDE.0000000000001401 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Methods
Mills, Harriet L.
Higgins, Julian P.T.
Morris, Richard W.
Kessler, David
Heron, Jon
Wiles, Nicola
Davey Smith, George
Tilling, Kate
Detecting Heterogeneity of Intervention Effects Using Analysis and Meta-analysis of Differences in Variance Between Trial Arms
title Detecting Heterogeneity of Intervention Effects Using Analysis and Meta-analysis of Differences in Variance Between Trial Arms
title_full Detecting Heterogeneity of Intervention Effects Using Analysis and Meta-analysis of Differences in Variance Between Trial Arms
title_fullStr Detecting Heterogeneity of Intervention Effects Using Analysis and Meta-analysis of Differences in Variance Between Trial Arms
title_full_unstemmed Detecting Heterogeneity of Intervention Effects Using Analysis and Meta-analysis of Differences in Variance Between Trial Arms
title_short Detecting Heterogeneity of Intervention Effects Using Analysis and Meta-analysis of Differences in Variance Between Trial Arms
title_sort detecting heterogeneity of intervention effects using analysis and meta-analysis of differences in variance between trial arms
topic Methods
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478324/
https://www.ncbi.nlm.nih.gov/pubmed/34432720
http://dx.doi.org/10.1097/EDE.0000000000001401
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