Document Detail


Replicated studies of two randomized trials of angiotensin-converting enzyme inhibitors: further empiric validation of the 'prior event rate ratio' to adjust for unmeasured confounding by indication.
MedLine Citation:
PMID:  18327852     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Using data from the United Kingdom General Practice Research Database (GPRD) randomized controlled trials (RCTs) were replicated to determine whether identifiable study characteristics and/or analytic methods influence the validity of observational studies. METHODS: This study reports GPRD replications of 2 RCTs that investigated whether angiotensin-converting enzyme inhibitors (ACEIs) improve cardiovascular outcomes in patients without congestive heart failure at high risk for cardiovascular disease (heart outcomes prevention evaluation (HOPE) and EUROPA). The GPRD studies replicated to the extent feasible all aspects of these RCTs except for randomization. RESULTS: With adjustment for confounders using conventional biostatistical techniques, both GPRD studies exhibited results divergent from the RCTs. Myocardial infarction, stroke, congestive heart failure, and coronary revascularization were increased in the Exposed group of both GPRD studies; whereas these outcomes either were decreased or unchanged by ACEI therapy in both RCTs. The results also were analyzed with a new method that appears to adjust for both identified and unmeasured confounders. With this methodology that employs the ratio of event rates between the Exposed and Unexposed cohorts prior to study start time to adjust the study hazard ratio (HR), the GPRD results for myocardial infarction, stroke, and coronary revascularization were largely similar to those found in the two RCTs. CONCLUSIONS: This study provides additional empiric evidence suggesting that this new analytic methodology, 'prior events rate ratio (PERR)' adjustment, is a promising solution for the vexing problem of 'unmeasured confounding' in observational studies. Additional statistical simulations are needed to fully appreciate the applicability and limitations of this method.
Authors:
Richard L Tannen; Mark G Weiner; Dawei Xie
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Validation Studies    
Journal Detail:
Title:  Pharmacoepidemiology and drug safety     Volume:  17     ISSN:  1099-1557     ISO Abbreviation:  Pharmacoepidemiol Drug Saf     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-16     Completed Date:  2008-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208369     Medline TA:  Pharmacoepidemiol Drug Saf     Country:  England    
Other Details:
Languages:  eng     Pagination:  671-85     Citation Subset:  IM    
Copyright Information:
Copyright 2008 John Wiley & Sons, Ltd.
Affiliation:
University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. tannen@mail.med.upenn.edu
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MeSH Terms
Descriptor/Qualifier:
Aged
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Cardiovascular Diseases / drug therapy*
Computer Simulation
Confounding Factors (Epidemiology)*
Data Interpretation, Statistical
Databases, Factual
Female
Great Britain
Humans
Male
Middle Aged
Proportional Hazards Models
Randomized Controlled Trials as Topic*
Grant Support
ID/Acronym/Agency:
R01-HL 073911/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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