Changes in dispensing of medicines proposed for re-purposing in the first year of the COVID-19 pandemic in Australia
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Abstract
Since COVID-19 was first recognised, there has been ever-changing evidence and misinformation around effective use of medicines. Understanding how pandemics impact on medicine use can help policymakers act quickly to prevent harm. We quantified changes in dispensing of common medicines proposed for “re-purposing” due to their perceived benefits as therapeutic or preventive for COVID-19 in Australia.
Methods
We performed an interrupted time series analysis and cross-sectional study using nationwide dispensing claims data (January 2017-November 2020). We focused on six subsidized medicines proposed for re-purposing: hydroxychloroquine, azithromycin, ivermectin, colchicine, corticosteroids, and calcitriol (Vitamin D analog). We quantified changes in monthly dispensing and initiation trends during COVID-19 (March-November 2020) using autoregressive integrated moving average models and compared characteristics of initiators in 2020 and 2019.
Results
In March 2020, we observed a 99% (95%CI: 96%-103%) increase in hydroxychloroquine dispensing (approximately 22% attributable to new users), and a 199% increase (95%CI: 184%-213%) in initiation, with an increase in prescribing by general practitioners (42% in 2020 vs 25% in 2019) rather than specialists. These increases subsided following regulatory restrictions on prescribing. There was a small but sustained increase in ivermectin dispensing over multiple months, with an 80% (95%CI 42%-118%) increase in initiation in May 2020 following its first identification as potentially disease-modifying in April. Other than increases in March related to stockpiling, we observed no change in the initiation of calcitriol or colchicine during COVID-19. Dispensing of corticosteroids and azithromycin was lower than expected from April through November 2020.
Conclusions
While most increases in dispensing observed early on during COVID-19 were temporary and appear to be related to stockpiling among existing users, we observed increases in the initiation of hydroxychloroquine and ivermectin and a shift in prescribing patterns which may be related to the media hype around these medicines. A quick response by regulators can help limit inappropriate repurposing to lessen the impact on medicine supply and patient harm.
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SciScore for 10.1101/2021.09.26.21264150: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization For more detailed analyses, we used person-level claims for a 10% random sample of all PBS-eligible people for the same period. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Strengths and limitations: We had complete capture of medicine dispensing for the whole Australian population, and person-level data on a 10% …
SciScore for 10.1101/2021.09.26.21264150: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization For more detailed analyses, we used person-level claims for a 10% random sample of all PBS-eligible people for the same period. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Strengths and limitations: We had complete capture of medicine dispensing for the whole Australian population, and person-level data on a 10% sub-sample. However, we do not have data on dispensing of private prescriptions, meaning we have likely underestimated the impact on use of some medicines. Further, disruptions to medicine use during COVID-19 likely have multiple causes, including lockdown measures, changed interaction with the healthcare system, reduced circulation of respiratory and gastrointestinal infections, and fear of not being able to access medicines, and these cannot reliably be disentangled. Conclusions: We demonstrated temporary changes in dispensing of commonly used medicines that were proposed for re-purposing for the treatment and prevention of COVID-19, including a large short-lived increase in hydroxychloroquine dispensing, most of which appeared to be due to anticipatory stockpiling, and a later smaller but longer-lasting increase in ivermectin dispensing. Balanced and informed communication of the changing evidence, including up-to-date and reliable access to evidence-informed advice is necessary to minimise any negative health impacts related to re-purposing of medicines. When similar situations arise, a quick response by regulators can help limit inappropriate re-purposing, to avoid supply shortages and potential harms.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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