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The LIAISON PLEX® Gram‐Negative Blood Culture (BCN) Assay, performed using the automated, sample‐to‐result LIAISON PLEX® System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram‐negative pathogens and/or selected genetic determinants associated with antimicrobial resistance in positive blood culture bottles. LIAISON PLEX® BCN Assay is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system which contain gram‐negative bacteria as determined by Gram stain.

The LIAISON PLEX® BCN Assay detects and identifies the following:

Resistance Markers:

• CTX‐M (blaCTX‐M)
• IMP (blaIMP)
• KPC (blaKPC)
• NDM (blaNDM)
• OXA (blaOXA)
• VIM (blaVIM)
• MCR
• SME (blaSME)

Gram Negative Genera and Species:

• Enterobacteriaceae / Morganellaceae
• Acinetobacter baumannii
• Acinetobacter spp.
• Citrobacter spp.
• Enterobacter spp. (1)
• Escherichia coli (2)
• Haemophilus influenzae
• Klebsiella oxytoca
• Klebsiella pneumoniae
• Klebsiella variicola
• Morganella morganii
• Neisseria meningitidis
• Proteus spp.
• Pseudomonas aeruginosa
• Pseudomonas spp.
• Salmonella spp.
• Serratia marcescens
• Stenotrophomonas maltophilia

(1) Due to reclassification, Klebsiella aerogenes will be reported Enterobacter spp.
(2) LIAISON PLEX® BCN Assay will not distinguish between Escherichia coli and Shigella spp. (S. dysenteriae, S. boydii, S. flexneri and S. sonnei)

LIAISON PLEX® BCN Assay contains targets for the detection of genetic determinants associated with resistance to carbapenems (blaCTX‐M, blaIMP, blaKPC, blaNDM, blaOXA48‐like, blaVIM, blaSME) to aid in the identification of potentially antimicrobial‐resistant organisms in positive blood culture samples. In addition, the panel includes an assay for the detection of the mobilized genetic determinant MCR, an emerging marker of public health importance. The antimicrobial resistance gene or marker detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene and marker assays do not indicate susceptibility, as multiple mechanisms of resistance to ß‐lactams and colistin exist.

LIAISON PLEX® BCN Assay is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections (BSI). LIAISON PLEX® BCN Assay is not intended to monitor treatment of these infections. Sub‐culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by LIAISON PLEX® BCN Assay, to detect mixed infections that may not be detected by LIAISON PLEX® BCN Assay, for association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing.

The LIAISON PLEX® Gram‐Negative Blood Culture (BCN) Assay is an automated test for the detection and identification of nucleic acid from gram‐negative bacteria in a positive blood culture media sample. The BCN Assay is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system, and which contain gram‐negative bacteria, as determined by a Gram stain.

The LIAISON PLEX® System is a fully automated, bench‐top "sample‐to‐answer" device that performs sample preparation, polymerase chain reaction (PCR) and microarray‐based hybridization for the detection of target‐specific nucleic acids. The test reagents are supplied as a single, disposable test cartridge. PCR is not performed on the LIAISON PLEX® BCN Assay, as it is a non‐amplified, direct detection test performed on the LIAISON PLEX® System.

Here's a breakdown of the acceptance criteria and study details for the LIAISON PLEX Gram-Negative Blood Culture Assay, based on the provided FDA 510(k) clearance letter:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The reported performance for individual targets (Sensitivity/PPA and Specificity/NPA) is explicitly given for the "Combined" data set (Prospective + Pre-selected). For Resistance Markers, some N/A entries indicate insufficient positive reference cases in the clinical study.

2. Sample Size and Data Provenance

• Test Set (Clinical Study):
  • Prospective Samples: 381 unique specimens enrolled, 351 included in analysis (30 excluded due to duplicates or incomplete reference testing).
  • Pre-selected Samples: 231 left-over, de-identified specimens.
  • Contrived Samples: 746 specimens.
  • Total Clinical Samples (Prospective + Pre-selected): 582 specimens included in analysis.
  • Total Contrived Samples: 746 specimens included in analysis.
  • Data Provenance:
    • Prospective: Collected from four geographically diverse clinical sites within the United States between March 2024 and July 2024.
    • Pre-selected: Sourced from seven vendors in the United States and one site in Italy.
    • Contrived: Tested at four testing sites during April 2024 – August 2024.
  • Retrospective/Prospective: Prospective data was collected prospectively. Pre-selected and Contrived data were essentially retrospective/prepared, then tested blindly and randomized.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the use of "experts" in the sense of clinical specialists (e.g., radiologists) establishing ground truth for the test set. Instead, the ground truth was established by laboratory methods.

4. Adjudication Method for the Test Set

The document describes the "Reference Method Algorithm" (Table 19) where the LIAISON PLEX BCN Assay results were compared to:

• Culture followed by Automated microbiological/biochemical identification using VITEK 2 for most organism targets.
• Culture followed by Automated microbiological/biochemical identification using VITEK 2 with positive confirmation of the clinical isolate by PCR/BDS for Acinetobacter baumannii, Klebsiella oxytoca, Klebsiella pneumoniae, and Klebsiella variicola.
• PCR followed by bi-directional sequencing (BDS) for all resistance markers (CTX-M, IMP, KPC, NDM, OXA, VIM, MCR, SME).

This is a hierarchical or sequential method rather than an "adjudication" by multiple human readers for discrepancies. For pre-selected specimens, initial identification was by Standard of Care (SoC) and/or PCR followed by BDS, then confirmed.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No, this was not an MRMC comparative effectiveness study where human readers' improvement with AI vs. without AI assistance was measured. This device is an in vitro diagnostic test for direct detection of nucleic acids, not an AI software intended to assist human readers.

6. Standalone Performance (Algorithm Only)

• Yes, this was a standalone performance study. The LIAISON PLEX BCN Assay is an automated, qualitative multiplexed in vitro diagnostic test performed on the LIAISON PLEX System. The performance metrics (Sensitivity/PPA and Specificity/NPA) described in the clinical study (Table 20 and 21) represent the standalone performance of the device without human interpretation of its results.

7. Type of Ground Truth Used

The ground truth for the clinical study (test set) was established using a combination of:

• Culture followed by Automated microbiological/biochemical identification (VITEK 2).
• PCR followed by bi-directional sequencing (BDS).
• In some cases, a combination of VITEK 2 and PCR/BDS for confirmation.
• For resistance markers, ground truth was solely by PCR followed by bi-directional sequencing (BDS).

8. Sample Size for the Training Set

The document does not explicitly state the sample size used for the training set of the LIAISON PLEX BCN Assay. The provided information focuses on the analytical and clinical validation of the final device. For IVD products like this, internal development and optimization (which would involve data that could be considered a "training set" in a broad sense for assay design) are typically not detailed in the same way as machine learning model training sets in FDA submissions. The inclusivity and exclusivity studies (Analytical Reactivity and Specificity) use laboratory-tested strains and in silico analysis respectively, which are key parts of ensuring the assay's design covers the intended targets and avoids false positives.

9. How the Ground Truth for the Training Set Was Established

Since an explicit "training set" sample size isn't provided, the method for establishing its ground truth isn't detailed. However, the comprehensive Analytical Reactivity (Inclusivity) and Analytical Specificity (Exclusivity) studies describe how the assay's design was validated:

• Analytical Reactivity (Inclusivity): Laboratory testing of 246 on-panel organisms (in triplicate) and in silico analysis using sequences from GenBank and WGS databases (February to April 2024). The ground truth for these would be the known identity of the characterized strains and the genetic sequences from public databases.
• Analytical Specificity (Exclusivity): Laboratory testing of 113 off-panel species (in triplicate) and in silico exclusivity assessment against on-panel and off-panel organisms from GenBank (June 7, 2024). The ground truth here is the known identity of these off-panel organisms and their genetic sequences.

These analytical studies effectively serve as the validation of the assay's "knowledge" or "training" on what to detect and what not to detect.

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