Informing Clinical Guideline Development With Real-World Data During the COVID-19 Pandemic: Complementing Clinical Trials Real-Time

Author(s)

Chandak A1, Mozaffari E2, Read S3, Casciano R4, Khachatryan A5, Gottlieb RL6
1Certara Inc., NEW YORK, NY, USA, 2Gilead Sciences, Foster City, CA, USA, 3Certara Inc. Evidence & Access, Edinburgh, Midlothian, UK, 4Certara Inc., NEW YORK, Poland, 5Certara Inc. Evidence & Access, London, London, UK, 6Baylor Scott and White Research Institute, Dallas, TX, USA

Problem Statement: There was an urgent need to identify life-saving therapeutics following the emergence of COVID-19. Findings from clinical trials were limited and evidence from real-world data (RWD) sources offered the opportunity to better characterize the effectiveness and public health value of treatments in specific populations and inform the development of clinical guidelines and support clinical decision-making. However, the rapidly evolving nature of the pandemic posed considerable challenges in the conduct of RWD studies.

Description: To address real-world evidence needs, we emulated a target trial (ACTT-1 trial) using RWD from a large hospital discharge database to examine the comparative effectiveness of remdesivir in reducing mortality among hospitalized COVID-19 patients. Using rigorous methodology accounting for regional and temporal variations in treatment practices and case-mix, differences in baseline oxygenation and variations in hospital practices, we observed significant mortality reduction in patients treated with remdesivir compared to those not treated with remdesivir. This study was published in October 2021 and was cited in the clinical guidelines of the European Society of Clinical Microbiology and Infectious Disease, World Health Organization and the Infectious Diseases Working Party guideline of the German Society for Hematology and Medical Oncology. Important updates are currently underway to address outstanding evidence gaps such as remdesivir effectiveness in vulnerable populations (e.g., immunocompromised patients).

Lessons Learned: Scientifically and methodologically rigorous RWD research offered an essential means to assess and validate the public health value of available treatments during the COVID-19 pandemic. The importance of rigor was especially acute when considering the poor research designs and flawed conclusions widely encountered throughout the pandemic. Our research demonstrated that target trial emulation within RWD employing robust matching techniques and multivariate modeling can enhance validity and acceptance of real-world evidence and ultimately offer useful real-time insights to drive guidelines and consequent clinical practice.

Stakeholder perspective: Industry