A standardized protocol using clinical adjudication to define true infection status in patients presenting to the emergency department with suspected infections and/or sepsis

• Published in: Diagnostic microbiology and infectious disease 2024-09, Vol.110 (1), p.116382, Article 116382
• Main Authors: Whitfield, Natalie N., Hogan, Catherine A., Chenoweth, James, Hansen, Jonathan, Hsu, Edbert B., Humphries, Roger, Mann, Edana, May, Larissa, Michelson, Edward A., Rothman, Richard, Self, Wesley H., Smithline, Howard A., Karita, Helen Cristina Stankiewicz, Steingrub, Jay S., Swedien, Daniel, Weissman, Alexandra, Wright, David W., Liesenfeld, Oliver, Shapiro, Nathan I.
• Format: Article
• Language: English
• Subjects: Adjudication; Bacterial; Bacterial Infections - diagnosis; Clinical; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Sepsis - diagnosis; Viral; Virus Diseases - diagnosis
• ISSN: 0732-8893; 1879-0070; 1879-0070
• DOI: 10.1016/j.diagmicrobio.2024.116382

In absence of a “gold standard”, a standardized clinical adjudication process was developed for a registrational trial of a transcriptomic host response (HR) test. Two physicians independently reviewed clinical data to adjudicate presence and source of bacterial and viral infections in emergency department patients. Discordant cases were resolved by a third physician. Agreement among 955 cases was 74.1% (708/955) for bacterial, 75.6% (722/955) for viral infections, and 71.2% (680/955) overall. Most discordances were minor (85.2%; 409/480) versus moderate (11.7%; 56/480) or complete (3.3%; 16/480). Concordance levels were lowest for bacterial skin and soft tissue infections (8.2%) and for viral respiratory tract infections (4.5%). This robust adjudication process can be used to evaluate HR tests and other diagnostics by regulatory agencies and for educating clinicians, laboratorians, and clinical researchers. Clinicaltrials.gov NCT04094818. Without a gold standard for evaluating host response tests, clinical adjudication is a robust reference standard that is essential to determine the true infection status in diagnostic registrational clinical studies.