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Original research
Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis
  1. Hemalkumar B Mehta1,2,
  2. Stephan Ehrhardt1,
  3. Thomas J Moore3,
  4. Jodi B Segal1,2,4,
  5. G Caleb Alexander1,2
  1. 1Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
  2. 2Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
  3. 3Institute for Safe Medication Practices, Alexandria, Virginia, USA
  4. 4Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public health, Baltimore, Maryland, USA
  1. Correspondence to Dr G Caleb Alexander; galexan9{at}jhmi.edu

Abstract

Objectives The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19.

Design, setting and participants Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO’s International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers.

Main outcome(s) Trial intervention, sponsorship, critical design elements and specified outcomes

Results Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020.

Conclusions While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.

  • epidemiology
  • public health
  • infectious diseases
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors HM and GCA conceived the study idea. All authors contributed to the study design. HM performed the data collection and analysis. SE and TJM contributed to the data collection. HM and GCA drafted the first version of the manuscript. All authors critically reviewed the manuscript and approved the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests GCA is past Chair of Food and Drug Administration’s Peripheral and Central Nervous System Advisory Committee; has served as a paid advisor to IQVIA; is a cofounding principal and equity holder in Monument Analytics, a health carehealthcare consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation; and is a member of OptumRx’s National P&T Committee. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies.

  • Patient consent for publication Not required.

  • Ethics approval The study was considered non-human subject research by the Johns Hopkins University Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. Data are stored in an open-access Google Sheet document: https://docs.google.com/spreadsheets/d/1p_229olyi7ft6MCLYXdS4-dkKszjnAiSnLRVO68OLk8/edit%23gid=0.

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