Major Shifts in Acid Suppression Drug Utilization After the 2019 Ranitidine Recalls in Canada and United States.

BACKGROUND: Drug shortages are a complex global challenge, and few studies have analyzed quantitative data on their impacts. In September 2019, detection of a nitrosamine impurity in ranitidine led to recalls and shortages. AIMS: We investigated the extent of the ranitidine shortage and its impacts on acid suppression drug utilization in Canada and the United States (US). METHODS: We conducted an interrupted time series analysis of acid suppression drug purchases in Canada and the US from 2016 through 2021 using IQVIA's MIDAS database. We used autoregressive integrated moving average models to determine the impact of the shortage on purchasing rates for ranitidine, other histamine-2 receptor antagonists (H2RAs), and proton pump inhibitors (PPIs). RESULTS: Prior to the recalls, 20,439,915 ranitidine units were purchased monthly in Canada and 189,038,496 in the US on average. After the recalls started in September 2019, purchasing rates decreased for ranitidine (Canada p = 0.0048, US p < 0.0001) and increased for non-ranitidine H2RAs (Canada p = 0.0192, US p = 0.0534). One month into the recalls, purchasing rates dropped by 99% (Canada) and 53% (US) for ranitidine and increased by 128.3% (Canada) and 37.3% (US) for non-ranitidine H2RAs. PPI purchasing rates did not change significantly in either country. CONCLUSIONS: The ranitidine shortage led to immediate and sustained shifts in H2RA utilization in both countries, potentially affecting hundreds of thousands of patients. Our results emphasize the need for future studies of the clinical and financial implications of the shortage, and the importance of ongoing work to mitigate and prevent drug shortages.

International trends in prescription opioid sales among developed and developing economies, and the impact of the COVID-19 pandemic: A cross-sectional analysis of 66 countries.

PURPOSE: We sought to compare trends in opioid purchasing between developed and developing economies to understand patterns of opioid consumption, and how they were impacted by the COVID-19 pandemic. METHODS: We conducted a retrospective cross-sectional study of retail pharmacy opioid sales from 66 jurisdictions between July 2014 and August 2020. We measured monthly population-adjusted rate of opioid units purchased, stratified by development group and country, and used interventional time series analysis to assess the impact of the COVID-19 pandemic on rates of opioid purchasing among developed and developing economies separately. RESULTS: Rates of opioid purchasing were generally higher among developed economies, although trends differed considerably by development group. Rates of opioid purchasing declined 23.8% (95% confidence interval [CI] -34.7% to 3.6%) in the 5 years prior to the pandemic in developed economies, but rose 15.2% (95% CI 4.6%-35.6%) among developing economies. In March 2020 there was a short-term increase in the rate of opioid purchases in both developing (10.9 units/1000 population increase; p < 0.0001) and developed (145.5 units/1000 population; p < 0.0001) economies, which was followed immediately by reduced opioid purchasing of a similar scale in April-May 2020 (-14.8 and -171.8 units/1000 population in developing and developed economies, respectively; p < 0.0001). CONCLUSION: The COVID-19 pandemic led to disruptions in opioid purchasing around the world; although the specific impacts varied both between and among developed and developing economies. With global variation in opioid use, there is a need to monitor these trajectories to ensure the safety of opioid use, and adequate access to pain management globally.

The global impact of COVID-19 on drug purchases: A cross-sectional time series analysis.

BACKGROUND: The drug supply chain is global and at risk of disruption and subsequent drug shortages, especially during unanticipated events. OBJECTIVE: Our objective was to determine the impact of coronavirus disease 2019 (COVID-19) on drug purchases overall, by class, and for specific countries. METHODS: A cross-sectional time series analysis of country-level drug purchase data from August 2014 to August 2020 from IQVIA MIDAS was conducted. Standardized units per 100 population and percentage increase in units purchased were assessed from 68 countries and jurisdictions in March 2020 (when the World Health Organization declared COVID-19 a pandemic). Analyses were compared by United Nations development status and drug class. Autoregressive integrated moving average models tested the significance of changes in purchasing trends. RESULTS: Before COVID-19, standardized medication units per 100 population ranged from 3990 to 4760 monthly. In March 2020, there was a global 15% increase in units of drugs purchased to 5309.3 units per 100 population compared with the previous year; the increase was greater in developed countries (18.5%; P < 0.001) than in developing countries (12.8%; P < 0.0001). After the increase in March 2020, there was a correction in the global purchase rate decreasing by 4.7% (April to August 2020 rate, 21,334.6/100 population; P < 0.001). Globally, we observed high purchasing rates and large changes for respiratory medicines such as inhalers and systemic adrenergic drugs (March 2020 rate, 892.7/100 population; change from 2019, 28.5%; P < 0.001). Purchases for topical dermatologic products also increased substantially (42.2%), although at lower absolute rates (610.0/100 population in March 2020; P < 0.0001). Interestingly, purchases for systemic anti-infective agents (including antiviral drugs) increased in developing countries (11.3%; P < 0.001), but decreased in developed countries (1.0%; P = 0.06). CONCLUSION: We observed evidence of global drug stockpiling in the early months of the COVID-19 pandemic, especially among developed countries. Actions toward equitable distribution of medicines through a resilient drug supply chain should be taken to increase global response to future unanticipated events, such as pandemics.

Early observations of Tier-3 drug shortages on purchasing trends across Canada: A cross-sectional analysis of 3 case-example drugs.

BACKGROUND: To curb the growing impact of drug shortages, Health Canada developed the Tiered Notification and Communication Framework which assigns potential shortages a corresponding tiered status. Tier-3 is assigned to shortages with the greatest potential impact on the healthcare system. This study aims to describe drug purchasing trends in response to Tier-3 shortages using three case-examples. METHODS: We conducted a time-series analysis of monthly purchasing data for three out of 17 Tier-3 drug shortages (hydralazine, sarilumab, and medroxyprogesterone acetate) with publicly available reports in July 2021 and available IQVIA MIDAS data from January 2016 to December 2021. We assessed percent changes in purchasing at 1-, 3-, and 6-months after the onset of each Tier-3 drug shortage and interventional ARIMA modelling was used to assess the statistical significance. RESULTS: Medroxyprogesterone acetate experienced a significant shift (p = 0.0370) in purchasing following its shortage, and the 1-, 3-, and 6-month percent changes were +14.9%, +6.8% and -3.1%, respectively. Hydralazine and sarilumab did not show a significant shift. The 1-, 3-, and 6-month percent changes for hydralazine were +15.5%, +10.2%, and +9.6% respectively and +25.2%, +45.1% and +39.2 for sarilumab. CONCLUSIONS: These results indicate that drugs assigned a Tier-3 status may not show declines in purchasing in the months following status assignment, which may be due to policy responses following the assignment. However, more insight is needed into the mechanisms through which these policy measures impact shortages and whether they are functioning as intended.