Combining Real-World and Clinical Trial Data to Study the Effectiveness of Thrombolytics for Treating Patients with COVID-19 Associated Acute Respiratory Distress Syndrome
Author(s)
Discussion Leaders: Janice Wang, MD, FCCP, Northwell Health Department of Medicine, Port Washington, NY, USA Mitra Corral, BS, MPH, MS, Genentech, South San Francisco, CA, USA;
Discussants: Rongrong Wang, MPH, Genentech Inc., South San Francisco, CA, USA; Marquita Decker-Palmer, MD, MPH, PhD, Genentech Inc., South San Francisco, CA, USA; Daniel Sheinson, PhD, Evidence for Access, US Medical Affairs, Genentech, La Jolla, CA, USA
Presentation Documents
PURPOSE: To demonstrate the challenges of conducting randomized controlled trials to study treatments for hospitalized patients with COVID-19 during the pandemic and illustrate how real-world data (RWD) can help address these challenges and supplement clinical trial results.
DESCRIPTION: Pandemic conditions present multiple barriers to the study of investigational drugs, including challenges in site selection and recruitment, identification of suitable control arms for comparison, and ability to detect small effects in noisy clinical outcome data[1],[2],[3]. An analysis of COVID-19 clinical trials showed that the majority of trials for COVID-19 therapeutics were not designed to yield actionable information due to low randomization rates and underpowered outcome data[4]. These limitations highlight the need for RWD, which can help contextualize and provide supplementary evidence to support trial results.
In this workshop, we will describe the design, operation, and analyses of a multicenter cohort study that combined data from the Phase 2a STARS study (NCT04357730) and data from the electronic health records of patients treated outside of the trial. We will share the challenges faced including operational hurdles and patient enrollment, the collaborative effort involved in clinical operations (i.e. team science), how to integrate real-world patients into study design elements such as inclusion/exclusion criteria and primary/secondary endpoints, and methodology used to incorporate RWD into the analysis and interpretation of results.[1] Bauchner, Howard, and Phil B. Fontanarosa. "Randomized clinical trials and COVID-19: managing expectations." Jama 323.22 (2020): 2262-2263.
[2] Norrie, John David. "Remdesivir for COVID-19: challenges of underpowered studies." The Lancet 395.10236 (2020): 1525-1527.
[3] Xue, John Z., et al. "Clinical trial recovery from COVID-19 disruption." Nature Reviews Drug Discovery 19.10 (2020): 662-664.
[4] Bugin K, Woodcock J. Trends in COVID-19 therapeutic clinical trials. Nat Rev Drug Discov. 2021;20(4):254-255.
Conference/Value in Health Info
Code
235
Topic
Study Approaches