Coronavirus (1058) The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days

31 October, 2020

Below are the citation, abstract and selected extracts. The authors conclude: 'The incredible volume and speed of trial research observed in the first 100 days of the COVID-19 pandemic should not hide the fact that in its early days the global clinical trial research agenda lacked clear coordination, efficiency and exploitation of synergies.'

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

Janiaud P et al.

F1000Res. 2020 Oct 2;9:1193. doi: 10.12688/f1000research.26707.1. eCollection 2020.

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.

SELECTED EXTRACTS

The global clinical research community has mounted a massive, unprecedented volume of research in response to the COVID-19 pandemic... Most trials are not blinded, and even if placebos may be not available in such short time, blinding of outcome collection would be preferable... Half of the trials include fewer than 118 patients and... it seems unlikely that such small trials would add meaningfully to the overall evidence. The extensive worldwide discussions about limited evidence from small trials reflect the substantial uncertainty patients and decision-makers face about the merits of popular interventions, such as hydroxychloroquine.

For hydroxychloroquine, over 100 smaller studies with over 76,000 patients were planned in the first 100 days to investigate this single therapeutic option out of many potential options. This case, possibly fueled by media attention relayed by decision-makers and politicians, highlights the urgent need for early evidence-based research and priority setting... The lack of coordination in the research response created substantial research waste, exposed many patients to unnecessary risks, and harms medical progress by creating competition among trials investigating similarly promising therapeutic alternatives... As many countries are facing restrictions of movement and lifestyle at various severity levels, affecting the physical and mental health of billions of people, it is remarkable that not a single trial was initially planned to evaluate these measures...

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Neil Pakenham-Walsh, HIFA Coordinator, neil@hifa.org www.hifa.org