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The GenePOC™ Carba assay, performed on the revogene™ instrument, is a qualitative in vitro diagnostic test designed for the detection and differentiation of the blakec. blaNDM, blackA-48-like, and blamp gene sequences associated with carbapenem-nonsusceptible pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa, when grown on blood agar or MacConkey agar. The test utilizes automated real-time Polymerase Chain Reaction (PCR).

The GenePOC™ Carba assay should be used in conjunction with other laboratory tests including phenotypic antimicrobial susceptibility testing. A negative GenePOC™ Carba assay result does not preclude the presence of other resistance mechanisms.

The GenePOC™ Carba assay is intended as an aid for infection control in the detection of carbapenem-non-susceptible bacteria that colonize patients in healthcare settings. The identification of a bland, blaym or blaviM metallo-B-lactamase gene (i.e., the genes that encode the IMP, NDM and VIM metallo-ß-lactamases, respectively) may be used as an aid to clinicians in determining appropriate therapeutic strategies for patients with known or suspected carbapenem non-susceptible infections.

The GenePOC™ Carba assay is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for the qualitative detection and differentiation of the blaype, blayDM, blavin, blaoxA-48-ike, and blamp gene sequences in carbapenem-non-susceptible pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa grown on blood agar or MacConkey agar. The GenePOC™ Carba assay is designed to be performed on the revogene™ instrument. The revogene™ is an instrument that automates sample homogenization, sample dilution, cells lysis, DNA amplification, and detection of the amplified PCR products.

The GenePOC™ Carba assay kit is comprised of single-use, disposable microfluidic cartridges (PIEs), Sample Buffer Tubes (SBT), and Disposable Transfer Tools (DTT). These components are used to dilute the sample, extract, amplify, and simultaneously detect blayDM, blavin, blaoxA-48-like, and blamp DNA. A Process Control (PrC) is also incorporated into each PIE to verify sample processing and amplification steps. The PrC allows for the verification of potential inhibitor substances as well as microfluidic, instrument or reagent failure.

Each GenePOC™ Carba assay kit contains 24 individual pouches. Each pouch has components for one (1) test including one (1) Carba PIE, one (1) SBT, and one (1) DTT. The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time PCR for the detection of the blaker, blands, blaoxa-48-like, and blanyp gene sequences from isolates of pure cultures of carbapenem-non-susceptible gram-negative bacteria in approximately 70 minutes. User intervention is only required for preparing the standardized 0.5 McFarland bacterial suspension from characterized carbapenem-non-susceptible isolated colonies, inoculating the bacterial suspension into the Sample Buffer Tube (SBT), transferring the sample into the single-use disposable PIE, and loading/unloading the PIEs into the revogene™ carousel. Each PIE is a completely integrated closed device in which a sample is dispensed and processed through different microfluidic chambers and channels that allow for the sample processing and subsequent real-time PCR steps.

Upon completion of a run, the results are interpolated by the revogene™ from measured fluorescent signals and embedded calculation algorithms. The output results include positive, negative, indeterminate, and unresolved. Upon completion of a run, the user removes the used cartridges and disposes of them in normal biological waste. The results are automatically generated at the end of the process in a report that can be viewed and printed.

Here's a breakdown of the acceptance criteria and the study details for the GenePOC™ Carba assay, based on the provided FDA 510(k) summary:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the clinical study's objective: to establish the performance characteristics (sensitivity and specificity) of the GenePOC™ Carba assay compared to a Reference Method for detecting carbapenemase genes. No explicit numerical acceptance criteria (e.g., "Sensitivity >= 95%") are formally stated in the provided text as pass/fail thresholds for clearance, but the reported performance represents what was achieved and found acceptable for substantial equivalence.

Table of Acceptance Criteria (Implied) and Reported Device Performance

The summary presents performance broken down by each target gene. The "Reference Method" in the clinical study refers to an FDA-cleared Nucleic Acid Amplification Test (NAAT) whose performance was established against PCR/bidirectional sequencing.

Performance on Isolated Colonies Grown on Blood Agar Relative to Reference Method (Overall by Target)

Performance on Isolated Colonies Grown on MacConkey Agar Relative to Reference Method (Overall by Target)

Study Details

1. Sample size used for the test set and the data provenance:

   • Test Set Size: 512 fully compliant bacterial isolates.
     • 475 clinical stock isolates.
     • 57 prospectively collected fresh isolates.
   • Data Provenance: Three clinical centers (one in Canada and two in the United States of America).

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The ground truth was established by a "Reference Method" (an FDA-cleared Nucleic Acid Amplification Test) whose performance was previously established against PCR/bidirectional sequencing. The document does not specify the number or qualifications of experts involved in running or interpreting this reference method or the PCR/bidirectional sequencing, nor in the initial characterization of the clinical isolates.

3. Adjudication method for the test set:

   • Discordant analysis: For samples with discrepant results between the GenePOC™ Carba assay and the Reference Method, further testing was performed using alternative PCR for each of the five assay analytes, followed by bi-directional Sanger sequencing. The results of this discrepant testing were then used to reconcile the initial findings (effectively re-evaluating the "true" status of the sample).

4. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

   • No, an MRMC comparative effectiveness study involving human readers with/without AI assistance was not performed. This device is an automated in vitro diagnostic test, not an AI-assisted diagnostic imaging device targeting human interpretation.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • Yes, the clinical study assessed the "standalone" performance of the GenePOC™ Carba assay. The device is an automated real-time PCR platform that extracts, amplifies, and detects target DNA, and "the results are interpolated by the revogene™ from measured fluorescent signals and embedded calculation algorithms." User interaction is primarily for sample preparation and loading/unloading. The reported sensitivity and specificity values represent this standalone algorithmic performance against the defined Reference Method.

6. The type of ground truth used:

   • The ground truth for the clinical study was established by a Reference Method, which was an FDA-cleared Nucleic Acid Amplification Test (NAAT). This NAAT itself had its performance previously established in comparison to PCR/bidirectional sequencing. For discordant results, alternative PCR followed by bi-directional Sanger sequencing was used for final adjudication, indicating that molecular sequencing data served as the ultimate ground truth for discrepant cases.

7. The sample size for the training set:

   • The document describes analytical and clinical performance studies, but it does not specify a separate "training set" for the algorithm's development in the context of machine learning. For an in vitro diagnostic like this, the "training" involves assay design, optimization, and establishment of thresholds. The document states, "The assay cut-offs were determined by testing a total of 599 samples" (Section N.1.g), which could be considered part of the internal development/training phase for establishing the algorithm's decision boundaries.

8. How the ground truth for the training set was established:

   • As noted above, for the "training" (assay cut-off determination), ground truth would have been established through well-characterized samples with known presence or absence of the target genes. The analytical reactivity (inclusivity) study also contributes to this, using 58 carbapenem-non-susceptible isolates with known resistance genes and variants, determined by their collection number, geographical/temporal origin, and reported resistance gene/variant. For the 599 samples used to determine assay cut-offs, the specific method for establishing their ground truth is not detailed, but it is implied to be based on the known genetic makeup of the strains, likely through sequencing or other established molecular methods.

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