The effectiveness and safety of antifibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis

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.

Download Full-text

The effectiveness and safety of antifibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis

Wellcome Open Research ◽

10.12688/wellcomeopenres.13262.1 ◽

2017 ◽

Vol 2 ◽

pp. 120 ◽

Cited By ~ 4

Author(s):

Katharine Ker ◽

David Prieto-Merino ◽

Nikola Sprigg ◽

Abda Mahmood ◽

Philip Bath ◽

...

Keyword(s):

Statistical Analysis ◽

Intracranial Haemorrhage ◽

Individual Patient Data ◽

Meta Analysis ◽

Statistical Analysis Plan ◽

Patient Data ◽

Time To Treatment ◽

Logistic Regression Models ◽

Secondary Outcomes

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 at end of trial follow-up, and 2) death in hospital or dependency at end of trial follow-up. 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.

Download Full-text

The effectiveness and safety of anti-fibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis

Wellcome Open Research ◽

10.12688/wellcomeopenres.13262.3 ◽

2019 ◽

Vol 2 ◽

pp. 120

Author(s):

Katharine Ker ◽

David Prieto-Merino ◽

Nikola Sprigg ◽

Abda Mahmood ◽

Philip Bath ◽

...

Keyword(s):

Statistical Analysis ◽

Head Injury ◽

Intracranial Haemorrhage ◽

Individual Patient Data ◽

Meta Analysis ◽

Statistical Analysis Plan ◽

Patient Data ◽

Time To Treatment ◽

Logistic Regression Models ◽

Secondary Outcomes

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.

Download Full-text

Re–evaluation of the effects of high PEEP with recruitment manoeuvres versus low PEEP without recruitment manoeuvres during general anaesthesia for surgery – Protocol and statistical analysis plan for an individual patient data meta–analysis of PROVHILO, iPROVE and PROBESE

Revista Española de Anestesiología y Reanimación (English Edition) ◽

10.1016/j.redare.2019.08.003 ◽

2020 ◽

Vol 67 (2) ◽

pp. 76-89

Author(s):

N.S. Campos ◽

T. Bluth ◽

S.N.T. Hemmes ◽

J. Librero ◽

N. Pozo ◽

...

Keyword(s):

Statistical Analysis ◽

General Anaesthesia ◽

Individual Patient Data ◽

Meta Analysis ◽

Statistical Analysis Plan ◽

Patient Data ◽

High Peep

Download Full-text

A collaborative sequential meta-analysis of individual patient data from randomized trials of endovascular therapy and tPA vs. tPA alone for acute ischemic stroke: ThRombEctomy And tPA (TREAT) analysis: statistical analysis plan for a sequential meta-analysis performed within the VISTA-Endovascular collaboration

International Journal of Stroke ◽

10.1111/ijs.12622 ◽

2015 ◽

Vol 10 (SA100) ◽

pp. 136-144 ◽

Cited By ~ 9

Author(s):

Rachael L. Macisaac ◽

Pooja Khatri ◽

Martin Bendszus ◽

Serge Bracard ◽

Joseph Broderick ◽

...

Keyword(s):

Ischemic Stroke ◽

Statistical Analysis ◽

Acute Ischemic Stroke ◽

Endovascular Therapy ◽

Randomized Trials ◽

Individual Patient Data ◽

Meta Analysis ◽

Statistical Analysis Plan ◽

Patient Data ◽

Treat Analysis

Download Full-text

INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and Statistical Analysis Plan for an investigator-initiated international meta-trial of randomised studies

10.22541/au.160841507.73902506/v1 ◽

2020 ◽

Author(s):

Frank van Haren ◽

Alice Richardson ◽

Jin Yoon ◽

Antonio Artigas ◽

John Laffey ◽

...

Keyword(s):

Unfractionated Heparin ◽

Mammalian Cells ◽

Individual Patient Data ◽

Therapeutic Potential ◽

Statistical Analysis Plan ◽

Patient Data ◽

Intention To Treat ◽

Institutional Review ◽

Hospitalised Patients ◽

Randomised Controlled

Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus’ entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anti-coagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. Methods and intervention The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) meta-trial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the meta-trial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes. Analysis We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. Trial registration, ethics and dissemination The meta-trial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board.

Download Full-text