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

Natalie N Whitfield; Catherine A Hogan; James Chenoweth; Jonathan Hansen; Edbert B Hsu; Roger Humphries; Edana Mann; Larissa May; Edward A Michelson; Richard Rothman; Wesley H Self; Howard A Smithline; Helen Cristina Stankiewicz Karita; Jay S Steingrub; Daniel Swedien; Alexandra Weissman; David W Wright; Oliver Liesenfeld; Nathan I Shapiro

doi:10.1016/j.diagmicrobio.2024.116382

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

Diagn Microbiol Infect Dis. 2024 Sep;110(1):116382. doi: 10.1016/j.diagmicrobio.2024.116382. Epub 2024 May 31.

Authors

Natalie N Whitfield¹, Catherine A Hogan², James Chenoweth³, Jonathan Hansen⁴, Edbert B Hsu⁴, Roger Humphries⁵, Edana Mann⁴, Larissa May³, Edward A Michelson⁶, Richard Rothman⁴, Wesley H Self⁷, Howard A Smithline⁸, Helen Cristina Stankiewicz Karita⁹, Jay S Steingrub¹⁰, Daniel Swedien⁴, Alexandra Weissman¹¹, David W Wright¹², Oliver Liesenfeld², Nathan I Shapiro¹³

Affiliations

¹ Inflammatix, Inc., Sunnyvale, California, USA. Electronic address: [email protected].
² Inflammatix, Inc., Sunnyvale, California, USA.
³ Department of Emergency Medicine, University of California-Davis School of Medicine, Sacramento, California, USA.
⁴ Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁵ Department of Emergency Medicine, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
⁶ Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, Department of Emergency Medicine, El Paso, Texas, USA.
⁷ Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
⁸ Department of Emergency Medicine, University of Massachusetts Chan Medical School - Baystate, Springfield, Massachusetts, USA.
⁹ Department of Medicine, University of California, San Francisco.
¹⁰ Department of Critical Care Medicine, University of Massachusetts Chan Medical School - Baystate, Springfield, Massachusetts, USA.
¹¹ Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
¹² Department of Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia.
¹³ Beth Israel Deaconess Medical Center, Emergency Medicine, Boston, Massachusetts, USA.

PMID: 38850687
DOI: 10.1016/j.diagmicrobio.2024.116382

Abstract

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. SUMMARY: 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.

Keywords: Adjudication; Bacterial; Clinical; Viral.

MeSH terms

Bacterial Infections* / diagnosis
Emergency Service, Hospital*
Female
Humans
Male
Middle Aged
Sepsis* / diagnosis
Virus Diseases / diagnosis

Associated data

ClinicalTrials.gov/NCT04094818