The Landscape of COVID-19 Research in the United States: a Cross-sectional Study of Randomized Trials Registered on ClinicalTrials.Gov

• Main Authors: Campbell, K.R (Author), Dougan, M. (Author), Fralick, M. (Author), Moggridge, J. (Author), North, C.M (Author), Sacks, C.A (Author), Wolf, M. (Author)
• Format: Article
• Language: English
• Published: Springer 2022
• Subjects: adult; aged; anticoagulant agent; antivirus agent; Article; artificial ventilation; chloroquine; controlled study; coronavirus disease 2019; COVID-19; Cross-Sectional Studies; cross-sectional study; dipeptidyl carboxypeptidase inhibitor; epidemiology; geographic distribution; human; Humans; hydroxychloroquine; immunomodulating agent; major clinical study; medical research; monoclonal antibody; mortality; oxygen; pandemic; Pandemics; phase 1 clinical trial (topic); phase 2 clinical trial (topic); phase 3 clinical trial (topic); phase 4 clinical trial (topic); polyclonal antibody; randomized controlled trial (topic); Randomized Controlled Trials as Topic; risk factor; risk reduction; sample size; SARS-CoV-2; treatment outcome; Treatment Outcome; United States
• Online Access: View Fulltext in Publisher

 Importance: SARS-CoV-2 has infected over 200 million people worldwide, resulting in more than 4 million deaths. Randomized controlled trials are the single best tool to identify effective treatments against this novel pathogen. Objective: To describe the characteristics of randomized controlled trials of treatments for COVID-19 in the United States launched in the first 9 months of the pandemic. Design, Setting, and Participants We conducted a cross-sectional study of all completed or actively enrolling randomized, interventional, clinical trials for the treatment of COVID-19 in the United States registered on www.clinicaltrials.gov as of August 10, 2020. We excluded trials of vaccines and other interventions intended to prevent COVID-19. Main Outcomes and Measures We used descriptive statistics to characterize the clinical trials and the statistical power for the available studies. For the late-phase trials (i.e., phase 3 and 2/3 studies), we compared the geographic distribution of the clinical trials with the geographic distribution of people diagnosed with COVID-19. Results: We identified 200 randomized controlled trials of treatments for people with COVID-19. Across all trials, 87 (43.5%) were single-center, 64 (32.0%) were unblinded, and 80 (40.0%) were sponsored by industry. The most common treatments included monoclonal antibodies (N=46 trials), small molecule immunomodulators (N=28), antiviral medications (N=24 trials), and hydroxychloroquine (N=20 trials). Of the 9 trials completed by August 2020, the median sample size was 450 (IQR 67–1113); of the 191 ongoing trials, the median planned sample size was 150 (IQR 60–400). Of the late-phase trials (N=54), the most common primary outcome was a severity scale (N=23, 42.6%), followed by a composite of mortality and ventilation (N=10, 18.5%), and mortality alone (N=6, 11.1%). Among these late-phase trials, all trials of antivirals, monoclonal antibodies, or chloroquine/hydroxychloroquine had a power of less than 25% to detect a 20% relative risk reduction in mortality. Had the individual trials for a given class of treatments instead formed a single trial, the power to detect that same reduction in mortality would have been greater than 98%. There was large variability in access to trials with the highest number of trials per capita in the Northeast and the lowest in the Midwest. Conclusions and Relevance: A large number of randomized trials were launched early in the pandemic to evaluate treatments for COVID-19. However, many trials were underpowered for important clinical endpoints and substantial geographic disparities were observed, highlighting the importance of improving national clinical trial infrastructure. © 2021, Society of General Internal Medicine.