The effectiveness and safety of anti-fibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis [version 3; peer review: 2 approved]

Ker, Katharine; Prieto-Merino, David; Sprigg, Nikola; Mahmood, Abda; Bath, Philip; Kang Law, Zhe; Flaherty, Katie; Roberts, Ian

Abstract

Introduction: The Anti-fibrinolytics Trialists Collaboration aims to increase knowledge about the effectiveness and safety of anti-fibrinolytic treatment by conducting individual patient data (IPD) meta-analyses of randomised trials. This article presents the statistical analysis plan for an IPD meta-analysis of the effects of anti-fibrinolytics for acute intracranial haemorrhage.
Methods: The protocol for the IPD meta-analysis has been registered with PROSPERO (CRD42019128260). We will conduct an individual patient data meta-analysis of randomised controlled trials with 500 patients or more assessing the effects of anti-fibrinolytics in acute intracranial haemorrhage. The primary outcomes will be 1) death from stroke or head injury within 30 days of randomisation, and 2) death from stroke or head injury, or dependency within 90 days of randomisation. The primary outcomes will be limited to patients treated within three hours of injury or stroke onset. We will report treatment effects using odds ratios and 95% confidence intervals. We use logistic regression models to examine how the effect of anti-fibrinolytics vary by time to treatment, severity of intracranial bleeding, and age. We will also examine the effect of anti-fibrinolytics on secondary outcomes including death, dependency, vascular occlusive events, seizures, and neurological outcomes. Secondary outcomes will be assessed in all patients irrespective of time of treatment. All analyses will be conducted on an intention-to-treat basis.
Conclusions: This IPD meta-analysis will examine important clinical questions about the effects of anti-fibrinolytic treatment in patients with intracranial haemorrhage that cannot be answered using aggregate data. With IPD we can examine how effects vary by time to treatment, bleeding severity, and age, to gain better understanding of the balance of benefit and harms on which to base recommendations for practice.

• Journal Article Type: Article
• Acceptance Date: Jun 21, 2021
• Online Publication Date: Jun 11, 2019
• Publication Date: Jun 11, 2019
• Deposit Date: Sep 28, 2021
• Journal: Wellcome Open Research
• Electronic ISSN: 2398-502X
• Publisher: F1000Research
• Peer Reviewed: Peer Reviewed
• Article Number: 120
• DOI: https://doi.org/10.12688/wellcomeopenres.13262.3
• Public URL: https://nottingham-repository.worktribe.com/output/4930122
• Publisher URL: https://wellcomeopenresearch.org/articles/2-120/v3
• Additional Information: Referee status: Indexed; Referee Report: 10.21956/wellcomeopenres.16442.r31010, Peter A. G. Sandercock, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK, 12 Jun 2019, version 3, indexed; Referee Report: 10.21956/wellcomeopenres.14388.r29217, Jonathan Emberson, Nuffield Department of Population Health, University of Oxford, Oxford, UK, 24 Jan 2018, version 1, indexed; Grant Information: This work was supported by Wellcome [105439]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Copyright: This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.