The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days

Abstract

Background: Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic. Methods: Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing any intervention to treat or prevent COVID-19, systematically identified in trial registries, preprint servers, and literature databases. A survey was conducted of all trials to assess their recruitment status up to July 6, 2020. Results: Most of the 689 trials (overall target sample size 396,366) were small (median sample size 120; interquartile range [IQR] 60-300) but randomized (75.8%; n=522) and were often conducted in China (51.1%; n=352) or the USA (11%; n=76). 525 trials (76.2%) planned to include 155,571 hospitalized patients, and 25 (3.6%) planned to include 96,821 health-care workers. Treatments were evaluated in 607 trials (88.1%), frequently antivirals (n=144) or antimalarials (n=112); 78 trials (11.3%) focused on prevention, including 14 vaccine trials. No trial investigated social distancing. Interventions tested in 11 trials with >5,000 participants were also tested in 169 smaller trials (median sample size 273; IQR 90-700). Hydroxychloroquine alone was investigated in 110 trials. While 414 trials (60.0%) expected completion in 2020, only 35 trials (4.1%; 3,071 participants) were completed by July 6. Of 112 trials with detailed recruitment information, 55 had recruited <20% of the targeted sample; 27 between 20-50%; and 30 over 50% (median 14.8% [IQR 2.0-62.0%]). Conclusions: The size and speed of the COVID-19 clinical trials agenda is unprecedented. However, most trials were small investigating a small fraction of treatment options. The feasibility of this research agenda is questionable, and many trials may end in futility, wasting research resources. Much better coordination is needed to respond to global health threats.

Recruitment and Results Reporting of COVID-19 Randomized Clinical Trials Registered in the First 100 Days of the Pandemic

“…These trials had been previously identified in a systematic assessment. 1 Between October 5 and 15, 2020, using contact information provided in the registries, we sent emails to all trial groups, requesting information on recruitment and enrollment status, reasons for trial termination or discontinuation, and any results reporting. We assessed whether trials recruited 75% or more of their target sample size, stopped before 75% recruitment, or were continuing to recruit (on schedule or delayed) but not yet 75% recruited.…”

“…The coronavirus disease 2019 (COVID-19) pandemic caused an unprecedented drive to launch clinical trials. 1 We assessed the recruitment and results reporting of randomized clinical trials (RCTs) to treat or prevent COVID-19 registered within 100 days of the first case reported to the World Health Organization. 1 …”

Challenges and Lessons Learned From COVID-19 Trials: Should We Be Doing Clinical Trials Differently?

“…Effective treatments, vaccines, and other measures were important to develop, test, and implement as quickly as possible. An unprecedent number of randomized controlled trials (RCTs) assessing therapeutics for COVID-19 were initiated, and to a lesser extent for preventive measures, in particular vaccines ( 1 , 2 ). For many other influential decisions, e.g.…”

Clinical Trials in COVID-19 Management & Prevention: A Meta-epidemiological Study examining methodological quality

“…3 Several recent reports have described the design characteristics of registered trials of Covid-19 therapies. [3][4][5][6][7][8] These reports, however, are based on registered trials, many of which will not proceed to completion and will therefore not impact clinical knowledge or practice. In addition, the appraisal of trial quality from registries does not include assessment of trial conduct as well as analysis.…”