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Comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line ART

BACKGROUND: The 2018 World Health Organization HIV guidelines were based on the results of a network meta-analysis (NMA) of published trials. This study employed individual patient-level data (IPD) and aggregate data (AgD) and meta-regression methods to assess the evidence supporting the WHO recomme...

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Autores principales: Kanters, Steve, Karim, Mohammad Ehsanul, Thorlund, Kristian, Anis, Aslam H., Zoratti, Michael, Bansback, Nick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008675/
https://www.ncbi.nlm.nih.gov/pubmed/33784981
http://dx.doi.org/10.1186/s12874-021-01254-5
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author Kanters, Steve
Karim, Mohammad Ehsanul
Thorlund, Kristian
Anis, Aslam H.
Zoratti, Michael
Bansback, Nick
author_facet Kanters, Steve
Karim, Mohammad Ehsanul
Thorlund, Kristian
Anis, Aslam H.
Zoratti, Michael
Bansback, Nick
author_sort Kanters, Steve
collection PubMed
description BACKGROUND: The 2018 World Health Organization HIV guidelines were based on the results of a network meta-analysis (NMA) of published trials. This study employed individual patient-level data (IPD) and aggregate data (AgD) and meta-regression methods to assess the evidence supporting the WHO recommendations and whether they needed any refinements. METHODS: Access to IPD from three trials was granted through ClinicalStudyDataRequest.com (CSDR). Seven modelling approaches were applied and compared: 1) Unadjusted AgD network meta-analysis (NMA) – the original analysis; 2) AgD-NMA with meta-regression; 3) Two-stage IPD-AgD NMA; 4) Unadjusted one-stage IPD-AgD NMA; 5) One-stage IPD-AgD NMA with meta-regression (one-stage approach); 6) Two-stage IPD-AgD NMA with empirical-priors (empirical-priors approach); 7) Hierarchical meta-regression IPD-AgD NMA (HMR approach). The first two were the models used previously. Models were compared with respect to effect estimates, changes in the effect estimates, coefficient estimates, DIC and model fit, rankings and between-study heterogeneity. RESULTS: IPD were available for 2160 patients, representing 6.5% of the evidence base and 3 of 24 edges. The aspect of the model affected by the choice of modeling appeared to differ across outcomes. HMR consistently generated larger intervals, often with credible intervals (CrI) containing the null value. Discontinuations due to adverse events and viral suppression at 96 weeks were the only two outcomes for which the unadjusted AgD NMA would not be selected. For the first, the selected model shifted the principal comparison of interest from an odds ratio of 0.28 (95% CrI: 10.17, 0.44) to 0.37 (95% CrI: 0.23, 0.58). Throughout all outcomes, the regression estimates differed substantially between AgD and IPD methods, with the latter being more often larger in magnitude and statistically significant. CONCLUSIONS: Overall, the use of IPD often impacted the coefficient estimates, but not sufficiently as to necessitate altering the final recommendations of the 2018 WHO Guidelines. Future work should examine the features of a network where adjustments will have an impact, such as how much IPD is required in a given size of network. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12874-021-01254-5.
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spelling pubmed-80086752021-03-31 Comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line ART Kanters, Steve Karim, Mohammad Ehsanul Thorlund, Kristian Anis, Aslam H. Zoratti, Michael Bansback, Nick BMC Med Res Methodol Research Article BACKGROUND: The 2018 World Health Organization HIV guidelines were based on the results of a network meta-analysis (NMA) of published trials. This study employed individual patient-level data (IPD) and aggregate data (AgD) and meta-regression methods to assess the evidence supporting the WHO recommendations and whether they needed any refinements. METHODS: Access to IPD from three trials was granted through ClinicalStudyDataRequest.com (CSDR). Seven modelling approaches were applied and compared: 1) Unadjusted AgD network meta-analysis (NMA) – the original analysis; 2) AgD-NMA with meta-regression; 3) Two-stage IPD-AgD NMA; 4) Unadjusted one-stage IPD-AgD NMA; 5) One-stage IPD-AgD NMA with meta-regression (one-stage approach); 6) Two-stage IPD-AgD NMA with empirical-priors (empirical-priors approach); 7) Hierarchical meta-regression IPD-AgD NMA (HMR approach). The first two were the models used previously. Models were compared with respect to effect estimates, changes in the effect estimates, coefficient estimates, DIC and model fit, rankings and between-study heterogeneity. RESULTS: IPD were available for 2160 patients, representing 6.5% of the evidence base and 3 of 24 edges. The aspect of the model affected by the choice of modeling appeared to differ across outcomes. HMR consistently generated larger intervals, often with credible intervals (CrI) containing the null value. Discontinuations due to adverse events and viral suppression at 96 weeks were the only two outcomes for which the unadjusted AgD NMA would not be selected. For the first, the selected model shifted the principal comparison of interest from an odds ratio of 0.28 (95% CrI: 10.17, 0.44) to 0.37 (95% CrI: 0.23, 0.58). Throughout all outcomes, the regression estimates differed substantially between AgD and IPD methods, with the latter being more often larger in magnitude and statistically significant. CONCLUSIONS: Overall, the use of IPD often impacted the coefficient estimates, but not sufficiently as to necessitate altering the final recommendations of the 2018 WHO Guidelines. Future work should examine the features of a network where adjustments will have an impact, such as how much IPD is required in a given size of network. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12874-021-01254-5. BioMed Central 2021-03-30 /pmc/articles/PMC8008675/ /pubmed/33784981 http://dx.doi.org/10.1186/s12874-021-01254-5 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Kanters, Steve
Karim, Mohammad Ehsanul
Thorlund, Kristian
Anis, Aslam H.
Zoratti, Michael
Bansback, Nick
Comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line ART
title Comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line ART
title_full Comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line ART
title_fullStr Comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line ART
title_full_unstemmed Comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line ART
title_short Comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line ART
title_sort comparing the use of aggregate data and various methods of integrating individual patient data to network meta-analysis and its application to first-line art
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008675/
https://www.ncbi.nlm.nih.gov/pubmed/33784981
http://dx.doi.org/10.1186/s12874-021-01254-5
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