Lumos FebriDx Mode D'emploi page 8

A composite reference-testing algorithm adjudicated by an expert physician panel served as the reference standard from
which FebriDx was compared. Each patient underwent the following reference tests: (1) throat swab bacterial culture;
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(2) combined nasopharyngeal and oropharyngeal (NP/OP) swabs for multiplex PCR using the FilmArray® Respiratory Panel
(Biomerieux, Inc.; Marcy-L'Etoile, France); (3) combined NP/OP swabs for real-time reverse transcriptase PCR for EBV, HSV,
and CMV; (4) EBV IgM serum antibody with the Immunosimplicity® IS-EBV-VCA IgM test kit (Diamedix Co; Miami Lakes,
FL, USA); (5) serum PCT concentration measurement using the BRAHMS PCT Kryptor™ (ThermoFisher Scientific; Waltham,
MA, USA); (6) WBC with band differential, and (7) MxA protein ELISA and CRP enzyme immunoassay (Biocheck; Foster City,
CA, USA). Reference testing was completed at a central laboratory and blinded to patients, treating clinicians, and study
personnel who performed FebriDx
The reference testing algorithm classified patients as having a bacterial infection if any of the following 5 criteria were
met: (1) throat culture positive for a bacteria that commonly causes pharyngitis (group A and C ß-hemolytic Streptococci,
N. gonorrhoeaea, C. diphtheriae, A. haemolyticum) plus PCT ≥0.1 ng/mL; (2) throat culture positive for any other bacteria plus
PCT ≥0.15 ng/mL; (3) NP/OP sample PCR positive for atypical bacteria (M. pneumoniae, C. pneumoniae, B. pertussis)
plus PCT ≥0.1 ng/mL; (4) PCT ≥0.25 ng/mL plus no identified pathogen; (5) PCT ≥0.15 ng/mL plus WBC ≥15,000 cells/mcl or
presence of WBC bands plus no identified pathogen.
Pharyngeal bacterial colonization was differentiated from true systemic bacterial infection if cell culture growth occurred in
the absence of an elevated PCT level (measure of host immune response). Patients with a negative FebriDx
an identified pathogen and a normal PCT (absent host immune response) were considered negative for infection.
The reference testing algorithm classified patients as having a viral infection if any of the following 3 criteria were met: (1)
NP/OP sample PCR positive for Influenza A or B, Adenovirus, RSV, Human Metapneumovirus, Parainfluenza viruses 1-4,
CMV, and HSV; (2) NP/OP sample PCR positive for EBV plus serum IgM positive for EBV; (3) PCT between 0.15 ng/mL and
0.25 ng/mL plus WBC <15,000 cells/mcl plus no WBC bands plus no identified pathogen.
Patients who did not meet the criteria for bacterial or viral infection were classified as negative by the reference testing
algorithm.
FEBRIDX PERFORMANCE DATA
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Prospective, Multi-Center Clinical Studies (FebriDx
•
ARI Cohort
16,17
•
429 ARI subjects symptomatic within 7 days and febrile within 3 days of presentation and who were ≥ 1 year were
enrolled in the outpatient setting. 425 symptomatic ARI were included in the analyses.
•
4 subjects were excluded prior to analysis (3 had insufficient reference standard testing to determine final diagnosis
and 1 had an invalid FebriDx
•
Results
•
16% (66/425) Bacterial
•
46% (196/425) Viral
•
38% (163/425) Negative
Summary of FebriDx
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Study
(Sample Size)
Shapiro
on Enrollment
(n = 121/220)
16
Shapiro
(n = 220) within 3 days
16
Self
(n = 205) within 3 days
17
PPA, Positive Percent Agreement; NPA, Negative Percent Agreement; PPV, Positive Predictive Value; NPV, Negative Predictive Value; CI, Confidence Interval
testing.
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test)
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Diagnostic Performance (Bacterial vs. Viral ARI)
Fever
(Exhibited or Diagnosis
Reported)
Exhibited
Bacterial
(55%)
Reported
Bacterial
Reported
Bacterial
Diagnostic Performance: Bacterial vs. Viral ARI)
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PPA
[95% CI] [95% CI]
95%
[77-100] [88-98]
85%
[69-95] [89-96]
80%
[59-93] [90-97]
8
NPA PPV
[95% CI]
94% 76%
[59-87]
93% 69%
[56-79]
93% 63%
[45-79]
result without
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NPV
[95% CI]
99%
[93-100]
97%
[94-99]
97%
[94-99]