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

Wellcome Open Research. 2018;2 DOI 10.12688/wellcomeopenres.13262.2

 

Journal Homepage

Journal Title: Wellcome Open Research

ISSN: 2398-502X (Online)

Publisher: Wellcome

LCC Subject Category: Medicine | Science

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML, XML

 

AUTHORS


Katharine Ker (Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK)

David Prieto-Merino (Catholic University of Murcia, Campus de los Jeronimos, Murcia, Spain)

Nikola Sprigg (Faculty of Medicine & Health Sciences, Clinical Sciences Building, Nottingham City Hospital, Nottingham, UK)

Abda Mahmood (Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK)

Philip Bath (Faculty of Medicine & Health Sciences, Clinical Sciences Building, Nottingham City Hospital, Nottingham, UK)

Zhe Kang Law (Faculty of Medicine & Health Sciences, Clinical Sciences Building, Nottingham City Hospital, Nottingham, UK)

Katie Flaherty (Faculty of Medicine & Health Sciences, Clinical Sciences Building, Nottingham City Hospital, Nottingham, UK)

Ian Roberts (Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK)

EDITORIAL INFORMATION

Open peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 1 weeks

 

Abstract | Full Text

Introduction: The Antifibrinolytic Trialists Collaboration aims to increase knowledge about the effectiveness and safety of antifibrinolytic 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 antifibrinolytics for acute intracranial haemorrhage. Methods: The protocol for the IPD meta-analysis has been registered with PROSPERO (CRD42016052155). We will conduct an individual patient data meta-analysis of randomised controlled trials with 1000 patients or more assessing the effects of antifibrinolytics in acute intracranial haemorrhage. We will assess the effect on two co-primary outcomes: 1) Death in hospital within 30 days of randomisation, and 2) Death  or dependency at final follow-up within 90 days of randomisation. The co-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 antifibrinolytics vary by time to treatment, severity of intracranial bleeding, and age. We will also examine the effect of antifibrinolytics 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 antifibrinolytic 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.