Reporting Rates of Opioid-Related Adverse Events Since 1965 in Canada: A Descriptive Retrospective Study.

BACKGROUND: Patients with chronic or acute/postoperative pain frequently use opioids. However, opioids may cause considerable adverse reactions (ARs), such as respiratory depression, which could be lethal. Unfortunately, only 5% of drug-related ARs (including those to opioids) are reported to health authorities. Therefore, little is known regarding the occurrence of opioid-related ARs at the population level. OBJECTIVE: The aim of this study was to investigate how the rates of reported opioid-related ARs have changed in Canada since 1965. METHODS: Our retrospective study examined trends of reported opioid-related ARs occurring in hospitalized and outpatients. Data on opioid-related ARs and mortality between 1965 and 2019 were obtained from the Canada Vigilance and Statistics Canada databases. Descriptive and Joinpoint regression analyses were performed. RESULTS: Oxycodone and normethadone were the most and least involved opioid agents, respectively, among the 18,407 reported ARs. The highest rate of reported opioid ARs (3.8 per 100,000 person-years) was recorded in 2012, whereas the lowest was recorded in 1965 (0.1 per 100,000 person-years). Between 1965 and 2019, annual rates climbed by 4.2% (95% confidence interval [CI] 3.1-5.2), and many fluctuations were observed: 1965-1974: +22.3% (95% CI 12.0-33.6); 1974-2000: - 4.1% (95% CI - 5.3 to - 2.9); 2000-2008: +30.3% (95% CI 22.6-38.4); 2008-2014: +4.1% (95% CI - 1.5 to 10.1); 2014-2017: -26.0% (95% CI - 44.7 to - 0.9); and, finally, 2017-2019: +35.4% (95% CI 3.8-76.7). CONCLUSION: Reported opioid-related ARs have increased since 1965, although fluctuations were observed in recent decades. The absolute number of opioid-related ARs might be seriously underestimated. Future studies should look into how to close this gap.

Using Data from the Canadian Post-marketing Spontaneous Pharmacovigilance System for Drug Safety Research: A Feasibility Study.

INTRODUCTION: Post-marketing studies involve the detection and interpretation of potential problems associated with the use of a given drug. Post-marketing spontaneous pharmacovigilance systems, such as the Canada Vigilance program, may constitute a gold mine of free data for drug safety research. However, the quantity and the quality of data remain to be demonstrated. OBJECTIVE: To assess the feasibility to use the Canada Vigilance database for academic drug safety research, and to document the characteristics of data that are extractable. METHODS: This is a descriptive retrospective analysis study design. The beta-blocker and anticoagulant adverse reactions (AR) in Canada were analyzed. Tests for data extraction from the Canada Vigilance database were performed in October 2019; data were then available from January 1, 1966 to June 30, 2019. RESULTS: There were 41 variables with extractable data. For anticoagulants, data were extracted in Excel and.pdf file format, while it was only plain text.pdf files for beta-blockers. Overall, there were 4707 reported ARs with the use of anticoagulants and 6332 cases reported for beta-blockers. The trend of ARs related to anticoagulants steadily increased in the study period, with a notable increase in 2009 while direct oral anticoagulants were marketed. The proportion of missing data varied from 0 to 98%, but most important variables were all available. It was not possible to distinguish brand names and generic drugs in the database. CONCLUSION: It seems feasible to use data from the Canadian Post-marketing Spontaneous Pharmacovigilance System for academic drug safety research. Upcoming studies should validate the quality of reports compared to actual medical charts.

Are Generic Drugs Used in Cardiology as Effective and Safe as their Brand-name Counterparts? A Systematic Review and Meta-analysis.

BACKGROUND: Previous systematic reviews (2008; 2016) concluded similarity in outcomes between brand-name and generic drugs in cardiology, but they included ≥ 50% comparative bioavailability studies, not designed or powered to detect a difference in efficacy or safety between drug types. We aimed to summarise best-evidence regarding the effectiveness and safety of generic versus brand-name drugs used in cardiology. METHODS: For this systematic review of the literature, scientific databases (MEDLINE and EMBASE) were searched from January 1984 to October 2018. Original research reports comparing the clinical impact of brand-name versus generic cardiovascular drugs on humans treated in a real-life setting, were selected. Meta-analyses and subgroup analyses were performed. Heterogeneity (I2) and risk of bias were tested. RESULTS: Among the 3148 screened abstracts, 72 met the inclusion criteria (n ≥ 1,000,000 patients, mean age 65 ± 10 years; 42% women). A total of 60% of studies showed no difference between drug types, while 26% concluded that the brand-name drug was more effective or safe, 13% were inconclusive and only 1% concluded that generics did better. The overall crude risk ratio of all-cause hospital visits for generic versus brand-name drug was 1.14 (95% confidence interval: 1.06-1.23; I2: 98%), while it was 1.05 (0.98-1.14; I2: 68%) for cardiovascular hospital visits. The crude risk ratio was not statistically significant for randomised controlled trials only (n = 4; 0.92 [0.63-1.34], I2: 35%). CONCLUSION: The crude risk of hospital visits was higher for patients exposed to generic compared to brand-name cardiovascular drugs. However, the evidence is insufficient and too heterogeneous to draw any firm conclusion regarding the effectiveness and safety of generic drugs in cardiology.