Reproducible Evidence: Practices to Enhance and Achieve Transparency (REPEAT): Study 11 - Replication of "Co-administration of statins with cytochrome P450 3A4 inhibitors in a UK primary care population"

Date of ISAC Approval: 
30/05/2018
Lay Summary: 
This protocol is part of the REPEAT Initiative, a project which samples published research studies conducted using large healthcare data (such as electronic health record or administrative claims) and replicates them by applying the publically reported methods to the same data source as the original authors. Scientific evidence should be replicable. When methods are not reported with enough clarity and detail for independent investigators to replicate the evidence, it is difficult to evaluate the validity of the science. The goal is to better understand what information is missing from public reporting that prevents replication of the published results. This project will evaluate how commonly a set of specific design and analysis decisions are reported in publications as well as how lack of clarity in one or more decisions 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: "Co-administration of statins with cytochrome P450 3A4 inhibitors in a UK primary care population" by Bakhai and colleagues. The Bakhai paper measures the frequency of exposure to statin medications (drugs to lower cholesterol) with medications that potentially interact with them in the general population of the United Kingdom (UK) between 2007 and 2008. We will replicate this study based on methods reported in the publication.
Technical Summary: 
This objective of this protocol is to replicate the study: "Co-administration of statins with cytochrome P450 3A4 inhibitors in a UK primary care population" by Bakhai 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 Bakhai paper measures the frequency of concomitant exposure of patients to CYP3A4-metabolised statins and CYP3A4 inhibitors in the general population of the United Kingdom (UK) between 2007 and 2008. We will focus on replicating the outcome of frequency of co-prescription of CYP3A4-metabolised statins and CYP3A4 inhibitors over this time period. Concomitant exposure was defined as exposure to a statin and a CYP3A4 inhibitor on the same day. For each statin, patient demographics, duration of statin use, duration of CYP3A4 inhibitor use, duration of concomitant statin and CYP3A4 inhibitor use and proportion of patients with concomitant use of statin and CYP3A4 inhibitor will be reported.
Health Outcomes to be Measured: 
- Frequency of co-prescription of CYP3A4-metabolised statins and CYP3A4 inhibitors
Collaborators: 

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