AS11. Diagnostics and biomarkers

EP355 - THE PERFORMANCE OF THE BV SCORE FOR DIFFERENTIATING BETWEEN BACTERIAL AND VIRAL INFECTION IS ROBUST TO METHODOLOGICAL ALTERNATIVES IN BUILDING THE REFERENCE STANDARD (ID 1054)

Abstract

Backgrounds:

A host-protein score (BV score) based on TNF-related apoptosis-induced ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was shown to accurately differentiate bacterial from viral infections. We assessed the impact of reference standard methodology on performance results.

Methods

Sub-analysis of children selected randomly from AutoPilot-Dx study. Five reference standards were generated based on two separate adjudication processes, where independent clinical experts were provided with comprehensive patient data (except BV score). Adjudicators were either ‘blinded’ or ‘unblinded’ to CRP and procalcitonin. The reference standards were built as follows: (1) Majority unblinded – ≥2/3 experts assigning same classification (bacterial or viral) with confidence >90% or all with confidence ≥70%; (2) Unanimous unblinded – all experts assigning same classification with confidence >90%; (3) Majority blinded – (1) with blinded experts; (4) Unanimous blinded – (2) with blinded experts; (5) All inclusive – indeterminate cases from majority blinded cohort were subjected to additional adjudications until majority attained. BV score performance was compared to each reference standard.

Results:

There were no changes of viral to bacterial reference standard outcomes or vice versa comparing blinded vs. non-blinded. Performance was comparable across the 5 reference standards (Table).

Table: Performance across different cohorts

All-inclusive blinded

Majority blinded

Unanimous blinded

Majority unblinded

Unanimous unblinded

n

270

224

125

231

137

Sensitivity %

90.0

(78.6-100.0)

93.3

(79.0-100.0)

100.0

(100.0-100.0)

100.0

(100.0-100.0)

100.0

(100.0-100.0)

Specificity %

82.2

(77.1-87.4)

85.8

(80.8-90.8)

91.9

(86.7-97.0)

88.0

(83.4-92.7)

94.9

(90.9-98.9)

Positive predictive value %

41.5

(29.2-53.8)

34.1

(19.0-49.3)

40.0

(11.9-68.1)

46.5

(31.0-62.0)

57.1

(27.5-86.8)

Negative predictive value %

98.3

(91.6-100.0)

99.4

(93.2-100.0)

100.0

(94.1-100.0)

100.0

(94.4-100.0)

100.0

(95.6-100.0)

Equivocal %

9.6

8.5

6.4

8.2

8.0

Conclusions/Learning Points:

BV score performance is robust to alternative reference standards.

Hide