eprintid: 10175670 rev_number: 6 eprint_status: archive userid: 699 dir: disk0/10/17/56/70 datestamp: 2023-08-24 13:08:11 lastmod: 2023-08-24 13:08:11 status_changed: 2023-08-24 13:08:11 type: article metadata_visibility: show sword_depositor: 699 creators_name: Riley, Richard D creators_name: Ensor, Joie creators_name: Hattle, Miriam creators_name: Papadimitropoulou, Katerina creators_name: Morris, Tim P title: Two-stage or not two-stage? That is the question for IPD meta-analysis projects ispublished: inpress divisions: UCL divisions: B02 divisions: D65 divisions: J38 keywords: individual participant data (IPD), meta-analysis, one-stage approach, two-stage approach note: © 2023 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). abstract: Individual participant data meta-analysis (IPDMA) projects obtain, check, harmonise and synthesise raw data from multiple studies. When undertaking the meta-analysis, researchers must decide between a two-stage or a one-stage approach. In a two-stage approach, the IPD are first analysed separately within each study to obtain aggregate data (e.g., treatment effect estimates and standard errors); then, in the second stage, these aggregate data are combined in a standard meta-analysis model (e.g., common-effect or random-effects). In a one-stage approach, the IPD from all studies are analysed in a single step using an appropriate model that accounts for clustering of participants within studies and, potentially, between-study heterogeneity (e.g., a general or generalised linear mixed model). The best approach to take is debated in the literature, and so here we provide clearer guidance for a broad audience. Both approaches are important tools for IPDMA researchers and neither are a panacea. If most studies in the IPDMA are small (few participants or events), a one-stage approach is recommended due to using a more exact likelihood. However, in other situations, researchers can choose either approach, carefully following best practice. Some previous claims recommending to always use a one-stage approach are misleading, and the two-stage approach will often suffice for most researchers. When differences do arise between the two approaches, often it is caused by researchers using different modelling assumptions or estimation methods, rather than using one or two stages per se. date: 2023-08-22 date_type: published publisher: Wiley official_url: https://doi.org/10.1002/jrsm.1661 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2046642 doi: 10.1002/jrsm.1661 lyricists_name: Morris, Timothy lyricists_id: TNMOR17 actors_name: Morris, Timothy actors_id: TNMOR17 actors_role: owner funding_acknowledgements: MR/V038168/1 [Medical Research Council & National Institute for Health and Care Research]; [National Institute for Health and Care Research Birmingham Biomedical Research Centre]; MC_UU_00004/07 [UKRI Medical Research Council]; MC_UU_00004/06 [UKRI Medical Research Council] full_text_status: public publication: Research Synthesis Methods event_location: England citation: Riley, Richard D; Ensor, Joie; Hattle, Miriam; Papadimitropoulou, Katerina; Morris, Tim P; (2023) Two-stage or not two-stage? That is the question for IPD meta-analysis projects. Research Synthesis Methods 10.1002/jrsm.1661 <https://doi.org/10.1002/jrsm.1661>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10175670/1/2023%20-%20Riley%20-%20two%20stage%20or%20not%20two%20stage%20-%20research%20syn%20meth.pdf