Evaluating Demographic Representation in Clinical Trials: Use of the Adaptive Coronavirus Disease 2019 Treatment Trial (ACTT) as a Test Case

Author:

Ortega-Villa Ana M1ORCID,Hynes Noreen A2,Levine Corri B3,Yang Katherine4ORCID,Wiley Zanthia5,Jilg Nikolaus67ORCID,Wang Jing8,Whitaker Jennifer A9,Colombo Christopher J1011,Nayak Seema U12,Kim Hannah Jang1314,Iovine Nicole M15,Ince Dilek16ORCID,Cohen Stuart H17,Langer Adam J18,Wortham Jonathan M19,Atmar Robert L20,El Sahly Hana M9,Jain Mamta K21,Mehta Aneesh K2223,Wolfe Cameron R24,Gomez Carlos A25,Beresnev Tatiana12,Mularski Richard A2627,Paules Catharine I28,Kalil Andre C25ORCID,Branche Angela R29,Luetkemeyer Annie30,Zingman Barry S31,Voell Jocelyn32,Whitaker Michael19,Harkins Michelle S33,Davey Richard T32,Grossberg Robert34,George Sarah L35,Tapson Victor36,Short William R37,Ghazaryan Varduhi12,Benson Constance A38,Dodd Lori E1,Sweeney Daniel A39,Tomashek Kay M12

Affiliation:

1. Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases , Rockville, Maryland , USA

2. Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA

3. Division of Infectious Disease, Department of Internal Medicine, University of Texas Medical Branch , Galveston, Texas , USA

4. Department of Clinical Pharmacy, University of California, San Francisco , San Francisco, California , USA

5. Department of Medicine, Emory University School of Medicine , Atlanta, Georgia , USA

6. Department of Medicine, Massachusetts General Hospital , Boston, Massachusetts , USA

7. Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts , USA

8. Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research , Frederick, Maryland , USA

9. Molecular Virology and Microbiology, Baylor College of Medicine , Houston, Texas , USA

10. Department of Virtual Health and Department of Medicine, Madigan Army Medical Center , Tacoma, Washington , USA

11. Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland , USA

12. Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA

13. Department of Community Health Systems, School of Nursing, University of California, San Francisco, San Francisco, California , USA

14. National Patient Care Services, Kaiser Permanente , Oakland, California , USA

15. Division of Infectious Diseases and Global Medicine, Department of Medicine, University of Florida Health , Gainesville, Florida , USA

16. Division of Infectious Diseases, Department of Internal Medicine, University of Iowa , Iowa City, Iowa , USA

17. Division of Infectious Diseases, University of California, Davis , Sacramento, California , USA

18. COVID-19 Emergency Response Team, Centers for Disease Control and Prevention , Atlanta, Georgia , USA

19. COVID-19–Associated Hospitalization Surveillance Network, Centers for Disease Control and Prevention , Atlanta, Georgia , USA

20. Department of Medicine, Baylor College of Medicine , Houston, Texas , USA

21. Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, Texas , USA

22. Division of Infection Diseases, Emory University School of Medicine , Atlanta, Georgia , USA

23. National Emerging Special Pathogens Treatment and Education Center , Atlanta, Georgia , USA

24. Division of Infectious Diseases, Department of Medicine, Duke University Medical Center , Durham, North Carolina , USA

25. Division of Infectious Diseases, Department of Internal Medicine, University of Nebraska Medical Center , Omaha, Nebraska , USA

26. Department of Pulmonary and Critical Care Medicine, Northwest Permanente, Kaiser Permanente Northwest , Portland, Oregon , USA

27. The Center for Health Research, Kaiser Permanente Northwest , Portland, Oregon , USA

28. Division of Infectious Diseases, Penn State Health Milton S. Hershey Medical Center , Hershey, Pennsylvania , USA

29. Division of Infectious Diseases, Department of Medicine, University of Rochester Medical Center , Rochester, New York , USA

30. Department of Medicine, University of California, San Francisco , San Francisco, California , USA

31. Department of Medicine, Montefiore Medical Center, University Hospital for Albert Einstein College of Medicine , Bronx, New York , USA

32. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA

33. Division of Pulmonary and Critical Care, Department of Internal Medicine, University of New Mexico Health Sciences Center , Albuquerque, New Mexico , USA

34. Division of Infectious Diseases, Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine , Bronx, New York , USA

35. Department of Internal Medicine, Saint Louis University and St Louis Veterans Affairs Medical Center , St Louis, Missouri , USA

36. Division of Pulmonary and Critical Care, Cedars-Sinai Medical Center , Los Angeles, California , USA

37. Division of Infectious Diseases, Department of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania , USA

38. Division of Infectious Diseases and Global Public Health, University of California, San Diego , San Diego, California , USA

39. Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego , San Diego, California , USA

Abstract

Abstract Background Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. Methods We evaluated the utility of the Centers for Disease Control and Prevention’s COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. Results US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

Funder

NIAID

NIH

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Oncology

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