Study citation: Prats-Uribe A, Sena AG, Lai LYH, Ahmed WU, Alghoul H, Alser O, Alshammari TM, Areia C, Carter W, Casajust P, Dawoud D, Golozar A, Jonnagaddala J, Mehta PP, Gong M, Morales DR, Nyberg F, Posada JD, Recalde M, Roel E, Shah K, Shah NH, Schilling LM, Subbian V, Vizcaya D, Zhang L, Zhang Y, Zhu H, Liu L, Cho J, Lynch KE, Matheny ME, You SC, Rijnbeek PR, Hripcsak G, Lane JC, Burn E, Reich C, Suchard MA, Duarte-Salles T, Kostka K, Ryan PB, Prieto-Alhambra D. Use of repurposed and adjuvant drugs in hospital patients with covid-19: multinational network cohort study. BMJ. 2021 May 11;373:n1038.5
Study objective: Early in the COVID-19 pandemic, there was great interest in understanding how repurposing of already available therapeutics might be useful, particularly prior to the authorization of antiviral treatments. The primary objective of this study was to understand the most common drugs being used as adjuvant treatment across multiple countries.
PICO: This multinational network cohort study focused on drug utilization, and included electronic health record and administrative claims data from 4 countries (US, South Korea, Spain, and China). Patients were identified by either a diagnosis of COVID-19 or a positive PCR test. Drugs that these patients received were studied as either adjuvant therapies for mitigation of sequelae or repurposed drugs meant to directly serve the purpose of COVID-19 treatment.
Data source: This large study used a mixture of claims and electronic health record data from 4 countries. The data were mapped to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM).
Study period: January 2020 to December 2020
Key sources of error and how they were handled: Understanding usage patterns of therapeutics throughout the time course early in the COVID-19 pandemic has important public health implications and can guide investigators toward opportunities for further real-world evidence generation related to the outcomes of these medications. This study found several interesting trends, including usage of drugs that varied widely by country as well as time. Presumably, this was due to the rapidly evolving evidence within the COVID-19 pandemic as well as local drug availability. Specifically, earlier in the study period, hydroxychloroquine was found to have been prescribed broadly, despite lack of evidence of its clinical effectiveness. Prescription of hydroxychloroquine tapered off in later months after observational studies and clinical trials found no clinical benefit in addition to a questionable safety profile.6 Conversely, dexamethasone and remdesivir experienced increases in widespread use in later months of 2020. This is another important aspect of drug utilization studies—their ability to demonstrate the impact of implementation and de-implementation of clinical guidance and detection of changes in therapeutic recommendations.
As with all studies relying on diagnosis codes to identify COVID-19, there may have been misclassification of disease, particularly for those with minor illness, who may therefore have been underrepresented.