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June 06, 2023; 100 (23) Research Methods in Neurology

An Introduction to Individual Participant Data Meta-analysis

Areti Angeliki Veroniki, View ORCID ProfileGeorgios Seitidis, Georgios Tsivgoulis, Aristeidis H. Katsanos, Dimitris Mavridis
First published February 16, 2023, DOI: https://doi.org/10.1212/WNL.0000000000207078
Areti Angeliki Veroniki
From the Knowledge Translation Program (A.A.V.), Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto; Institute of Health Policy Management and Evaluation (A.A.V.), University of Toronto, Ontario, Canada; Department of Primary Education (G.S., D.M.), School of Education, University of Ioannina, Greece; Department of Neurology (G.T.), University of Tennessee Health Sciences Center, Memphis; Second Department of Neurology (G.T.), Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Division of Neurology (A.H.K.), McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada; and Faculté de Médecine (D.M.), Université Paris Descartes, France.
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Georgios Seitidis
From the Knowledge Translation Program (A.A.V.), Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto; Institute of Health Policy Management and Evaluation (A.A.V.), University of Toronto, Ontario, Canada; Department of Primary Education (G.S., D.M.), School of Education, University of Ioannina, Greece; Department of Neurology (G.T.), University of Tennessee Health Sciences Center, Memphis; Second Department of Neurology (G.T.), Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Division of Neurology (A.H.K.), McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada; and Faculté de Médecine (D.M.), Université Paris Descartes, France.
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  • ORCID record for Georgios Seitidis
Georgios Tsivgoulis
From the Knowledge Translation Program (A.A.V.), Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto; Institute of Health Policy Management and Evaluation (A.A.V.), University of Toronto, Ontario, Canada; Department of Primary Education (G.S., D.M.), School of Education, University of Ioannina, Greece; Department of Neurology (G.T.), University of Tennessee Health Sciences Center, Memphis; Second Department of Neurology (G.T.), Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Division of Neurology (A.H.K.), McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada; and Faculté de Médecine (D.M.), Université Paris Descartes, France.
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Aristeidis H. Katsanos
From the Knowledge Translation Program (A.A.V.), Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto; Institute of Health Policy Management and Evaluation (A.A.V.), University of Toronto, Ontario, Canada; Department of Primary Education (G.S., D.M.), School of Education, University of Ioannina, Greece; Department of Neurology (G.T.), University of Tennessee Health Sciences Center, Memphis; Second Department of Neurology (G.T.), Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Division of Neurology (A.H.K.), McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada; and Faculté de Médecine (D.M.), Université Paris Descartes, France.
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Dimitris Mavridis
From the Knowledge Translation Program (A.A.V.), Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto; Institute of Health Policy Management and Evaluation (A.A.V.), University of Toronto, Ontario, Canada; Department of Primary Education (G.S., D.M.), School of Education, University of Ioannina, Greece; Department of Neurology (G.T.), University of Tennessee Health Sciences Center, Memphis; Second Department of Neurology (G.T.), Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Division of Neurology (A.H.K.), McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada; and Faculté de Médecine (D.M.), Université Paris Descartes, France.
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Citation
An Introduction to Individual Participant Data Meta-analysis
Areti Angeliki Veroniki, Georgios Seitidis, Georgios Tsivgoulis, Aristeidis H. Katsanos, Dimitris Mavridis
Neurology Jun 2023, 100 (23) 1102-1110; DOI: 10.1212/WNL.0000000000207078

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Abstract

Meta-analysis using individual participant data (IPD-MA) from randomized controlled trials (RCTs) can strengthen evidence used for decision making and is considered the “gold standard” approach. In this study, we present the importance, properties, and main approaches of conducting an IPD-MA. We exemplify the main approaches of conducting an IPD-MA and how these can be used to obtain subgroup effects through estimation of interaction terms. IPD-MA has several benefits over traditional aggregate data (AD) meta-analysis. These include standardization of definitions of outcomes and/or scales, reanalysis of eligible RCTs using the same analysis model across all studies, accounting for missing outcome data, detecting outliers, using participant-level covariates to explore intervention-by-covariate interactions, and tailoring intervention effects to participant characteristics. IPD-MA can be performed in either a 2-stage or 1-stage approach. We exemplify the presented methods using 2 illustrative examples. The first real-life example includes 6 studies assessing sonothrombolysis with or without addition of microspheres against IV thrombolysis alone (i.e., control) in acute ischemic stroke participants with large vessel occlusions. The second real-life example includes 7 studies evaluating the association between blood pressure levels after endovascular thrombectomy and functional improvement of acute ischemic stroke in patients with large vessel occlusion. IPD reviews can be associated with higher quality statistical analysis and may differ from AD reviews. Unlike individual trials that lack power and AD meta-analysis results, which suffer from confounding and aggregation bias, the use of IPD allows us to explore intervention-by-covariate interactions. However, a key limitation of conducting an IPD-MA is retrieval of IPD from original RCTs. Time and resources should be carefully planned before embarking on retrieving IPD.

Glossary

AD=
aggregate data;
IPD=
individual participant data;
IPD-MA=
meta-analysis using IPD;
NIHSS=
NIH Stroke Scale;
OR=
odds ratio;
RCT=
randomized clinical trial

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Submitted and externally peer reviewed. The handling editor was Associate Editor Roy Strowd III, MD, MEd, MS.

  • Received June 23, 2022.
  • Accepted in final form January 5, 2023.
  • © 2023 American Academy of Neurology
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  • Article
    • Abstract
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    • Introduction
    • When Is an IPD-MA Useful?
    • How to Start an IPD-MA?
    • Analytic Approaches to IPD-MA
    • Illustrative Examples
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