REPEAT Study 17 - Replication of "Risk of major bleeding and stroke associated with the use of vitamin K antagonists, nonvitamin K antagonist oral anticoagulants and aspirin in patients with atrial fibrillation: a cohort study"

Date of ISAC Approval: 
30/11/2018
Lay Summary: 
Science should be replicable. The methods section in publications describe how research is conducted. This protocol is part of the REPEAT Initiative, a project that is attempting to replicate a sample of published research studies using information provided in the publications. REPEAT is focused on studies using observational healthcare data from electronic health records or administrative claims to generate scientific evidence. The goal is to better understand what information is missing in publications that prevents replication of the published results. This project will evaluate how commonly important decisions in research process design are not clearly reported as well as how lack of impacts ability to replicate study findings. Our results will inform future policies and guidelines for reporting on healthcare database research. This protocol focuses on one sampled study: "Risk of major bleeding and stroke associated with the use of vitamin K antagonists, nonvitamin K antagonist oral anticoagulants and aspirin in patients with atrial fibrillation: a cohort study" by Gieling and colleagues. The Gieling paper compared the risk of major bleeding in patients with atrial fibrillation (irregular heart rate) using different types of oral anticoagulants (drugs to prevent formation of blood clots) among the general population of the United Kingdom (UK) between 2008 and 2014. We will replicate this study based on methods reported in the publication.
Technical Summary: 
This objective of this protocol is to replicate the study: "Risk of major bleeding and stroke associated with the use of vitamin K antagonists, nonvitamin K antagonist oral anticoagulants and aspirin in patients with atrial fibrillation: a cohort study" by Gieling et al based on methods reported in the publication and appendices. We have created a checklist of specific study implementation parameters based on a comprehensive catalogue outlined in a consensus paper endorsed by the International Society of Pharmacoepidemiology and the International Society of Pharmacoeconomics and Outcomes research. We will start by reviewing the paper to identify which parameters from the catalogue are reported. We will then replicate the study population and analyses based on the study design and implementation parameters extracted during review. The Gieling paper compared the risk of major bleeding in patients with atrial fibrallation using nonvitamin K antagonist oral anticoagulants (NOACs) compared to patients with atrial fibrallation using vitamin K antagonists (VKAs) in the UK general population between 2008 and 2014. We will focus on replicating the age/sex adjusted hazard ratio comparing the risk of major bleeding in atrial fibrillation patients for current users of NOACs versus current users of VKAs over this time period. Patients will be followed until a first"ever diagnosis of major bleeding, death from any cause, or end of the study period (October 1, 2014), whichever occurred first. Comparative risk of major bleeding will be evaluated using a a Cox proportional hazards model. Descriptive statistics will be calculated for users of NOACs and users of VKAs within the cohort.
Health Outcomes to be Measured: 
Major bleeding defined as a bleeding at a critical site or organ
Collaborators: 

Dr Shirley Wang - Chief Investigator - Harvard University
Elisabetta Patorno - Collaborator - Brigham & Women's Hospital
Jessica Franklin - Collaborator - Brigham & Women's Hospital
Ms Krista Huybrechts - Collaborator - Brigham & Women's Hospital
Dr Sebastian Schneeweiss - Collaborator - Aetion, Inc