Using Real World Evidence to Inform Treatment Guidelines

Real-world evidence (RWE) has become increasingly valuable in informing the development of treatment guidelines for severe COVID-19 given its ability to provide evidence-based data on treatment patterns and outcomes derived from clinical practice to complement clinical development in real-time. RWE can help determine the most effective treatments for large patient populations while considering individual variations and differences. Furthermore, RWE could provide information on long-term manifestations of a disease which has limited natural history information.

Challenge

Using RWE to inform the treatment of severe COVID-19 is becoming increasingly important. However, the generation of reliable RWE presents many challenges. First, there is the issue of data availability. Reliable data sets may be scarce or difficult to access. Second, there is the question of ensuring that data sources are comprehensive and accurate enough to draw meaningful conclusions. Third, observational data sources have biases that need to be addressed through appropriate epidemiological and statistical methodologies.

Figure 1. Comparing 14/28-day mortality for adult COVID-19 inpatients treated with remdesivir within the first two days of hospitalization vs. those who did not receive RDV.

Solution

Certara was contracted by Gilead Sciences to generate high-quality RWE for the use of remdesivir to treat COVID-19 infection in hospitalized patients. A real-world comparative effectiveness study was designed and implemented using one of the largest, geographically representative hospital discharge databases in the United States.

Using robust, data-driven methods, the effectiveness of remdesivir at reducing COVID-19 mortality was compared with the standard-of-care. The study compared 14/28-day mortality for adult COVID-19 inpatients treated with remdesivir (RDV) within the first two days of hospitalization vs. those who did not receive RDV.¹

図 1. Comparing 14/28-day mortality for adult COVID-19 inpatients treated with remdesivir within the first two days of hospitalization vs. those who did not receive RDV.

利点

The study showed that patients who were treated with RDV early during their hospital admission had improved survival rates compared to those who were not treated with RDV. The findings of the study were published in Clinical Infectious Diseases.¹ The manuscript was subsequently cited in The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) treatment guidelines,² WHO guidelines³ as well as Infectious Diseases Working Party (AGIHO) guideline of the German Society for Hematology and Medical Oncology (DGHO).^4,2

参照文献

Mozaffari E, Chandak A, Zhang Z, Liang S, Thrun M, Gottlieb RL, et al., Remdesivir Treatment in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19): A Comparative Analysis of In-hospital All-cause Mortality in a Large Multicenter Observational Cohort, Clinical Infectious Diseases, Volume 75, Issue 1, 1 July 2022, Pages e450–e458, https://academic.oup.com/cid/article/75/1/e450/6378778. Accessed on 21 December 2022.
Bartoletti, M., Azap, O., Barac, A., Bussini, L., Ergonul, O., Krause, R., & Rodríguez-Baño, J. (2022). ESCMID COVID-19 living guidelines: drug treatment and clinical management. Clinical microbiology and infection, 28(2), 222-238, available at https://doi.org/10.1016/j.cmi.2021.11.007%20
WHO Solidarity Trial Consortium. (2022)。Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. The Lancet, 399(10339), 1941-1953.
Giesen N, Busch E, Schalk E, Beutel G, Rüthrich MM, Hentrich M, Hertenstein B, Hirsch HH, Karthaus M, Khodamoradi Y, Koehler P, Krüger W, Koldehoff M, Krause R, Mellinghoff SC, Penack O, Sandherr M, Seggewiss-Bernhardt R, Spiekermann K, Sprute R, Stemler J, Weissinger F, Wörmann B, Wolf HH, Cornely OA, Rieger CT, von Lilienfeld-Toal M. AGIHO guideline on evidence-based management of COVID-19 in cancer patients: 2022 update on vaccination, pharmacological prophylaxis and therapy in light of the omicron variants. Eur J Cancer. 2022 Dec 10;181:102-118. doi: 10.1016/j.ejca.2022.11.030. Epub ahead of print. PMID: 36652889; PMCID: PMC9737523.

Certara CS Using PBPK Models to Predict Effects 4

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