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Aims: There are conflicting signals in the literature about comparative safety and effectiveness of direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF). Methods: We conducted multicentre matched cohort studies with secondary meta‐analysis to assess safety and effectiveness of dabigatran, rivaroxaban and apixaban across 9 administrative healthcare databases. We included adults with NVAF initiating anticoagulation therapy (dabigatran, rivaroxaban or apixaban), and constructed 3 cohorts to compare DOACs pairwise. The primary outcome was pooled hazard ratio (pHR) of ischaemic stroke or systemic thromboembolism. Secondary outcomes included pHR of major bleeding, and a composite of stroke, major bleeding, or all‐cause mortality. We used proportional hazard Cox regressions models, and pooled estimates were obtained with random effect meta‐analyses. Results: The cohorts included 73 414 new users of dabigatran, 92 881 of rivaroxaban, and 61 284 of apixaban. After matching, the pHRs (95% confidence intervals) comparing rivaroxaban initiation to dabigatran were: 1.11 (0.93, 1.32) for ischaemic stroke or systemic thromboembolism, 1.26 (1.09, 1.46) for major bleeding, and 1.17 (1.05, 1.30) for the composite endpoint. For apixaban vs dabigatran, they were: 0.91 (0.74, 1.12) for ischaemic stroke or systemic thromboembolism, 0.89 (0.75, 1.05) for major bleeding, and 0.94 (0.78 to 1.14) for the composite endpoint. For apixaban vs rivaroxaban, they were: 0.85 (0.74, 0.99) for ischaemic stroke or systemic thromboembolism, 0.61 (0.53, 0.70) for major bleeding, and 0.82 (0.76, 0.88) for the composite endpoint. Conclusion: We found that apixaban use is associated with lower risks of stroke and bleeding compared with rivaroxaban, and similar risks compared with dabigatran. [ABSTRACT FROM AUTHOR]

Background and aims: Pharmacotherapies for smoking cessation are widely prescribed, despite substantial concerns being raised regarding the potential increased risk of cardiovascular (CV) and neuropsychiatric adverse events associated with these treatments. This study aimed to assess the relative CV and neuropsychiatric safety between varenicline and bupropion compared with nicotine replacement therapies (NRT) in adults without a recent history of depression. Design Retrospective new‐user cohort study. Setting: US administrative data from 2006 to 2016 covering more than 100 million individuals. Participants: Three study cohorts of new users, aged 18 years or older, limited to patients with no diagnosis or treatment for depression in the prior 12 months. Measurements: Propensity score adjusted log‐binomial regression models. The primary outcome was a composite of hospitalized CV events. Secondary outcomes included a composite of hospitalized neuropsychiatric events and individual components of the primary outcome. Findings A total of 618 497 participants were included in our study cohorts. Compared with NRT (n = 32 237), varenicline (n = 454 698) was associated with a 20% lower 1‐year CV risk [adjusted relative risk (RR) = 0.80, 95% confidence interval (CI) = 0.75–0.85], and bupropion (n = 131 562) was associated with a 25% lower 1‐year CV risk (RR = 0.75, 95% CI = 0.69–0.81). Varenicline was associated with a 35% lower 1‐year risk of neuropsychiatric hospitalization versus NRT (RR = 0.65, 95% CI = 0.59–0.72), and bupropion was associated with a 21% increase in 1‐year risk of neuropsychiatric hospitalization (RR = 1.21, 95% CI = 1.09–1.35). Conclusion: Varenicline compared with nicotine replacement therapy does not appear to be associated with an increased risk of cardiovascular or neuropsychiatric hospitalizations. Bupropion appears to be associated with a lower risk of cardiovascular hospitalization and a higher risk of neuropsychiatric hospitalization, compared with nicotine replacement therapy. [ABSTRACT FROM AUTHOR]

Purpose To describe a rapid monitoring plan to assess the impacts of a shift in drug coverage for biosimilar drugs in British Columbia following the introduction of a new policy on 27 May 2019. The Biosimilars Initiative requires users of originator infliximab or etanercept to switch to biosimilar versions of those drugs to maintain coverage. We propose a signal‐detection method to provide near‐real‐time information to policymakers on the impacts of the policy change. Methods: The exposure will be the Biosimilars Initiative, a policy affecting patients using originator infliximab (Remicade) and etanercept (Enbrel) for approved rheumatologic or dermatologic indications. Two policy cohorts and six historical control cohorts of patients using originator infliximab or etanercept will be assembled using linked and de‐identified data from the British Columbia Ministry of Health. Patients will be identified during the 6‐month period before the policy anniversary. Outcomes will include medication refills and switching, hospital admissions, emergency department visits, and physician visits. Summary outcome measures, such as cumulative incidence or average quantity as applicable, will be examined daily and reported monthly for 1 year. Outcomes in the policy cohorts will be compared with historical controls using likelihood ratios. Results: The results of this rapid monitoring plan will be based on analyses involving approximately 9000 patients: four infliximab cohorts of approximately 430 patients and four etanercept cohorts of approximately 1800 patients. Conclusions: Rapid monitoring results will inform ongoing policy decisions related to the Biosimilars Initiative, in terms of impacts on both patient health and health services utilization. [ABSTRACT FROM AUTHOR]

Purpose: To describe and implement a novel method of measuring comparative effectiveness using sequential episodes of pharmacotherapy as a proxy for treatment failure. Methods: 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. Conclusions 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 [ABSTRACT FROM AUTHOR]

Purposes To assess the impact of a government‐sponsored reimbursement policy for cholinesterase inhibitors (ChEIs) on trends in physician visits with a diagnosis of Alzheimer's disease (AD). Methods: Longitudinal population‐based study using interrupted time series methods. British Columbia outpatient claims data for individuals aged 65 and older were used to compute monthly AD visit rates and examine the impact of the ChEI reimbursement policy on the coding of AD. We examined trends in the number of patients with AD visits, the number of AD visits per patient, and visits with "competing" diagnoses (mental, neurological, and cerebrovascular disorders and accidental falls). Finally, we described demographic and clinical features of diagnosed patients. Results: We analyzed 1.9 million AD visits. Faster growth in recorded AD visits was observed after the policy was implemented, from monthly growth of 7.5 visits per 100 000 person‐months before the policy (95% confidence interval [CI], 6.1‐8.9) to monthly growth of 16.5 per 100 000 person‐months after the policy (95% CI, 14.8‐18.3). After the implementation of the policy, we observed increased growth in the number of patients with recorded AD visits and the number of AD visits per patient, as well as a shift in diagnoses away from mental diseases and accidental falls to AD (diagnosis substitution). Conclusions: British Columbia's reimbursement policy for ChEIs was associated with a significant acceleration in Alzheimer's visits. Evaluations of health services utilization and clinical outcomes following drug policy changes need to consider policy‐induced influences on the reliability of the data used in the analysis. [ABSTRACT FROM AUTHOR]

Randomized pragmatic trials of drugs, physician education and drug policies are needed to improve pharmacosurveillance and cost-effectiveness of prescribing. Since 1994, we have developed and tested methods for low-cost education and policy trials to improve prescribing in primary care in Canada. We review methodology for using drug claims and other health services data to evaluate prescribing improvement programs and policies. We apply the lessons to a proposed trial of physician education tools (PET) for quality improvement of prescribing. Design issues for the trial include defining the potential programme in causal terms using counterfactuals, narrowing the denominator to the population affected, excluding noise from the numerator, calculating the prescribing preference, adjusting for baseline differences, controlling for modifiers and confounders, accounting for uncertainty when measuring impacts, and grouping practices for feedback and recognition. Data from a randomized trial of academic detailing illustrate measurement challenges. A decade of progress on methods for evaluating prescribing improvement programs with drug claims data has enabled planning of routine randomized pragmatic trials of education and policies in primary care in Canada. [ABSTRACT FROM AUTHOR]

Objective: Concerns persist about a possible association between tumor necrosis factor alpha (TNFalpha) antagonist treatment and development of cancers in patients with rheumatoid arthritis (RA). This study was undertaken to estimate the association between treatment with biologic disease-modifying antirheumatic drugs (DMARDs) and development of cancer in patients with RA., Methods: We conducted a cohort study pooling administrative databases from 2 US states and 1 Canadian province. A cohort of patients who had received a diagnosis of RA on > or =1 occasion and had been prescribed DMARDs was identified. We categorized patients with a prescription for a biologic DMARD as biologic DMARD users, and those with a prescription for methotrexate (MTX) but no biologic DMARD as MTX users. We used time-varying propensity scores to adjust for the large number of possible confounders and stratified proportional hazards regression to estimate the effects of biologic DMARDs on cancer. The primary end points were hematologic malignancies (lymphoma, multiple myeloma, and leukemia) and common solid tumors (colorectal, lung, stomach, breast, prostate, uterine, ovarian, urinary tract/bladder, and melanoma)., Results: The pooled cohort included 1,152 biologic DMARD users and 7,306 MTX users. We identified 11 hematologic malignancies and 46 solid tumors during 2,940 person-years of biologic DMARD use, and 88 hematologic malignancies and 558 solid tumors during 30,300 person-years of MTX use. Comparing biologic DMARD users with MTX users, the propensity score-adjusted pooled hazard ratio was 1.37 (95% confidence interval 0.71-2.65) for hematologic malignancies and 0.91 (95% confidence interval 0.65-1.26) for solid tumors., Conclusion: Our results indicate that users of biologic agents are unlikely to have a substantial increase in the risk of hematologic malignancies and solid tumors as compared with MTX users. Despite the use of large combined data sets, studying the effect of an infrequent exposure (biologic DMARDs) on rare diseases (hematologic malignancies) remains a challenge.