Download the full-sized PDF of Drug Exposure Definition and Healthy User Bias Impacts on the Evaluation of Oral Anti Hyperglycemic TherapiesDownload the full-sized PDF



Permanent link (DOI):


Export to: EndNote  |  Zotero  |  Mendeley


This file is in the following communities:

Graduate Studies and Research, Faculty of


This file is in the following collections:

Theses and Dissertations

Drug Exposure Definition and Healthy User Bias Impacts on the Evaluation of Oral Anti Hyperglycemic Therapies Open Access


Other title
Healthy User Bias
Exposure Definition
Type of item
Degree grantor
University of Alberta
Author or creator
Eskin, Maxim
Supervisor and department
Simpson, Scot
Eurich, Dean
Examining committee member and department
Veugelers, Paul (School of Public Health)
Simpson, Scot (Faculty of Pharmacy and Pharmaceutical Sciences)
Eurich, Dean (School of Public Health)
Voaklander, Don (School of Public Health)
School of Public Health
Health Policy Research
Date accepted
Graduation date
2017-11:Fall 2017
Master of Science
Degree level
Accurate estimation of medication use is an essential component of any pharmacoepidemiological research as exposure misclassification will threaten study validity and lead to spurious associations. Many pharmacoepidemiological studies use simple definitions, such as the categorical “any versus no use” to classify oral antihyperglycemic medications exposure, which has potentially serious drawbacks. This approach has led to numerous highly publicized observational studies of metformin effect on health outcomes reporting exaggerated relationships that were later contradicted by randomized controlled trials. Although selection bias, unmeasured confounding, and many other factors contribute to the discrepancies, one critical element, which is often overlooked, is the method used to define exposure. Another factor that may provide additional explanation for the discrepancy between randomized controlled trials and observational study results of the association between metformin use and various health outcomes is the healthy user effect. Aspects of a healthy lifestyle such as following a balanced diet, exercising regularly, avoiding tobacco use, etc., are not recorded in typical administrative databases and failure to account for these factors in observational studies may introduce bias and produce spurious associations. The influence of a healthy user bias has not been fully examined when evaluating the effect of oral antihyperglycemic therapies in observational studies. It is possible that some, if not all, of the benefit, observed with metformin in observational studies may be related to analytic design and exposure definitions. Thus, our first objective is to explore the potential impact of exposure definition on estimates of the association between metformin and all-cause mortality risk, using a large administrative health database, similar to databases used in previous studies. The variety of exposure definitions tested in our analysis produced a wide range of associations between metformin and mortality risk, therefore, we recommend that pharmacoepidemiological studies should include at least two exposure definitions and sensitivity analyses of different exposure definitions. Moreover, our second objective is to explore the healthy user effect in metformin users versus non-users on various health outcomes that should not be associated with metformin use. Results of this study suggest that metformin users are more likely to initiate preventive therapies and engage in other healthy behaviors, therefore we recommend that the influence of these behaviors should be accounted for pharmacoepidemiological studies evaluating the effect of oral antihyperglycemic therapies.
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
Citation for previous publication

File Details

Date Uploaded
Date Modified
Audit Status
Audits have not yet been run on this file.
File format: pdf (PDF/A)
Mime type: application/pdf
File size: 3172158
Last modified: 2017:11:08 18:20:27-07:00
Filename: Maxim Eskin Thesis ID # 1425730(PDFA Format) 8_9_17.pdf
Original checksum: 029faedc1f250aaab0f3cdfa6eab859c
Activity of users you follow
User Activity Date