The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days [version 1; peer review: 2 approved]

Perrine Janiaud; Cathrine Axfors; Janneke van't Hooft; Ramon Saccilotto; Arnav Agarwal; Christian Appenzeller-Herzog; Despina G. Contopoulos-Ioannidis; Valentin Danchev; Ulrich Dirnagl; Hannah Ewald; Gerald Gartlehner; Steven N. Goodman; Noah A. Haber; Angeliki Diotima Ioannidis; John P. A. Ioannidis; Mark P. Lythgoe; Wenyan Ma; Malcolm Macleod; Mario Malički; Joerg J. Meerpohl; Yan Min; David Moher; Blin Nagavci; Florian Naudet; Christiane Pauli-Magnus; Jack W. O'Sullivan; Nico Riedel; Jan A. Roth; Mandy Sauermann; Stefan Schandelmaier; Andreas M. Schmitt; Benjamin Speich; Paula R. Williamson; Lars G. Hemkens

doi:10.12688/f1000research.26707.1

F1000Research (Oct 2020)

The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days [version 1; peer review: 2 approved]

Perrine Janiaud,
Cathrine Axfors,
Janneke van't Hooft,
Ramon Saccilotto,
Arnav Agarwal,
Christian Appenzeller-Herzog,
Despina G. Contopoulos-Ioannidis,
Valentin Danchev,
Ulrich Dirnagl,
Hannah Ewald,
Gerald Gartlehner,
Steven N. Goodman,
Noah A. Haber,
Angeliki Diotima Ioannidis,
John P. A. Ioannidis,
Mark P. Lythgoe,
Wenyan Ma,
Malcolm Macleod,
Mario Malički,
Joerg J. Meerpohl,
Yan Min,
David Moher,
Blin Nagavci,
Florian Naudet,
Christiane Pauli-Magnus,
Jack W. O'Sullivan,
Nico Riedel,
Jan A. Roth,
Mandy Sauermann,
Stefan Schandelmaier,
Andreas M. Schmitt,
Benjamin Speich,
Paula R. Williamson,
Lars G. Hemkens

Affiliations

Perrine Janiaud: Meta-Research Innovation Center at Stanford (METRICS), Stanford University,, Stanford, California, USA
Cathrine Axfors: Meta-Research Innovation Center at Stanford (METRICS), Stanford University,, Stanford, California, USA
Janneke van't Hooft: Amsterdam University Medical Center, Amsterdam University, Amsterdam, The Netherlands
Ramon Saccilotto: Meta-Research Innovation Center at Stanford (METRICS), Stanford University,, Stanford, California, USA
Arnav Agarwal: Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Christian Appenzeller-Herzog: University Medical Library, University of Basel, Basel, Switzerland
Despina G. Contopoulos-Ioannidis: Division of Infectious Diseases, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA
Valentin Danchev: Stanford Prevention Research Center, Department of Medicine,, Stanford University School of Medicine, Stanford, California, USA
Ulrich Dirnagl: QUEST Center for Transforming Biomedical Research, Berlin Institute of Health, Berlin, Germany
Hannah Ewald: University Medical Library, University of Basel, Basel, Switzerland
Gerald Gartlehner: Department for Evidence-based Medicine and Evaluation, Danube University Krems, Krems, Austria
Steven N. Goodman: Stanford University School of Medicine, Stanford University School of Medicine, Stanford, California, USA
Noah A. Haber: Meta-Research Innovation Center at Stanford (METRICS), Stanford University,, Stanford, California, USA
Angeliki Diotima Ioannidis: Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Los Angeles, California, USA
John P. A. Ioannidis: Meta-Research Innovation Center at Stanford (METRICS), Stanford University,, Stanford, California, USA
Mark P. Lythgoe: Department of Surgery & Cancer, Imperial College London, London, UK
Wenyan Ma: Department of Clinical Research, University of Basel, Basel, Switzerland
Malcolm Macleod: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
Mario Malički: Meta-Research Innovation Center at Stanford (METRICS), Stanford University,, Stanford, California, USA
Joerg J. Meerpohl: Institute for Evidence in Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
Yan Min: Stanford University School of Medicine, Stanford University School of Medicine, Stanford, California, USA
David Moher: Centre for Journalology, Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, Canada
Blin Nagavci: Institute for Evidence in Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
Florian Naudet: CHU Rennes, Inserm, CIC 1414 [(Centre d’Investigation Clinique de Rennes)],, University of Rennes 1, Rennes, France
Christiane Pauli-Magnus: Department of Clinical Research, University of Basel, Basel, Switzerland
Jack W. O'Sullivan: Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
Nico Riedel: QUEST Center for Transforming Biomedical Research, Berlin Institute of Health, Berlin, Germany
Jan A. Roth: Department of Clinical Research, University of Basel, Basel, Switzerland
Mandy Sauermann: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
Stefan Schandelmaier: Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
Andreas M. Schmitt: Department of Clinical Research, University of Basel, Basel, Switzerland
Benjamin Speich: Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
Paula R. Williamson: MRC/NIHR Trials Methodology Research Partnership, University of Liverpool, Liverpool, UK
Lars G. Hemkens: Department of Clinical Research, University of Basel, Basel, Switzerland

DOI: https://doi.org/10.12688/f1000research.26707.1
Journal volume & issue: Vol. 9

Abstract

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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.

Published in F1000Research

ISSN: 2046-1402 (Online)
Publisher: F1000 Research Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science
Website: https://f1000research.com

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