Changes in dispensing of medicines proposed for re-purposing in the first year of the COVID-19 pandemic in Australia

  1. Andrea L Schaffer
  2. David Henry
  3. Helga Zoega
  4. Julian H Elliott
  5. Sallie-Anne Pearson

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Abstract

Objective

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, a country with relatively low COVID-19 incidence in the first year of the pandemic.

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 subsidised medicines proposed for re-purposing: hydroxychloroquine, azithromycin, ivermectin, colchicine, corticosteroids, and calcitriol (Vitamin D analogue). We quantified changes in monthly dispensing and initiation trends during COVID-19 (March-November 2020) using autoregressive integrated moving average models (ARIMA) 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 (of which approximately 22% attributable to new use), and a 199% increase (95%CI 184%-213%) in initiation, with a shift towards prescribing by general practitioners (42% in 2020 vs 25% in 2019) rather than specialists. These increases subsided following regulatory restrictions on prescribing to relevant specialties. There was a small but sustained increase in ivermectin dispensing over multiple months, with a 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 increases in initiation of calcitriol or colchicine during COVID-19. Dispensing of corticosteroids and azithromycin remained lower than expected in 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 did observed increases in initiation of hydroxychloroquine and ivermectin and a shift in prescribing patterns which may be related to media hype around these medicines. A quick response by regulators can help limit inappropriate repurposing to lessen the impact on medicine supply and patient harms.

Article activity feed

  1. Version published to 10.1101/2021.09.26.21264150v3 on medRxiv
  2. ScreenIT

    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

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationFor more detailed analyses, we used person-level claims for a 10% random sample of all PBS-eligible people for the same period.
    Blindingnot detected.
    Power Analysisnot 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.

    About SciScore

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  3. Version published to 10.1101/2021.09.26.21264150v2 on medRxiv
  4. Version published to 10.1101/2021.09.26.21264150v1 on medRxiv