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Pharmacoepidemiol Drug Saf. 2020 Feb;29(2):199-207. doi: 10.1002/pds.4926. Epub 2019 Dec 2.

Identifying sequential episodes of pharmacotherapy as a method for assessing treatment failure in comparative effectiveness research.

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Therapeutics Initiative, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Family Practice, University of British Columbia, Vancouver, British Columbia, Canada.
Lions Gate Hospital, Fraser Health Authority, Vancouver, British Columbia, Canada.



To describe and implement a novel method of measuring comparative effectiveness using sequential episodes of pharmacotherapy as a proxy for treatment failure.


Retrospective cohort study using linked deidentified data from the British Columbia Ministry of Health during a government-sponsored smoking cessation reimbursement program.Three study cohorts were created based on first use of varenicline, bupropion, or nicotine replacement therapy (NRT), for adults aged 18 or older, in the period September 30th, 2011 to March 31st, 2013. The study cohorts were analyzed for sequential episodes of pharmacotherapy, defined as re-initiating a smoking cessation pharmacotherapy after an initial episode of treatment and washout period. The statistical analysis used propensity score adjusted log-binomial regression models with one-year and two-year fixed follow-up after a 12-week washout period. A sensitivity analysis excluded the washout period. A secondary analysis investigated predictors of receiving a sequential episode of smoking cessation pharmacotherapy RESULTS: 116,442 participants of the B.C. Smoking Cessation Program were analyzed. Compared to NRT, varenicline users were 13% less likely, and bupropion users were 18% less likely, to re-start smoking cessation therapy within 1-year after an initial course of treatment.


Sequential episodes of pharmacotherapy identified treatment failures to smoking cessation therapy. Based on sequential episodes of pharmacotherapy during a drug benefit policy of smoking cessation medications, varenicline and bupropion were more effective aids to smoking cessation than NRT. The method was also used to identify patient characteristics associated with treatment effectiveness.


addiction; comparative effectiveness; health risk; nicotine dependence; observational research methods; pharmacoepidemiology; pharmacology; population health; smoking cessation; tobacco


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