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The IQuum Liat™ Influenza A/B Assay performed on the Liat™ Analyzer is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of influenza A virus and influenza B virus RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of influenza A and influenza B in humans and is not intended to detect influenza C.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule-out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.

Performance characteristics for influenza A were established when influenza A/H1 and A/H3 were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.

If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

The Liat™ Influenza A/B Assay is a rapid, automated in vitro diagnostic test for the detection and differentiation of Influenza type A and type B viral RNA in nasopharyngeal swab (NPS) specimens in universal transport media (UTM) from patients signs and symptoms of respiratory infection. The assay targets a well-conserved region of the matrix gene of Influenza A viral RNA (Inf A target) and non-structural protein (NS) gene of Influenza B (Inf B target). An Internal Process Control (IPC) is also included. The IPC is present to control for adequate processing of the target viruses and to monitor the presence of inhibitors in the RT-PCR reactions.

The Liat Influenza A/B Assay is performed on the lab-in-a-tube technology platform. The system consists of a disposable Liat Influenza A/B Assay Tube and the Liat™ Analyzer. The Liat™ Tube uses a flexible tube as a sample vessel. It contains all required unit dose reagents prepacked in tube segments, separated by peelable seals, in the order of reagent use. Manipulating a Liat Tube, the Liat Analyzer performs all assay steps from raw sample and report assay result automatically, During the testing process, multiple sample processing actuators of the analyzer compress the Liat Tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction volume, temperature and time to conduct sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution and real-time RT-PCR. An embedded microprocessor controls and coordinates the actions of these sample processors to perform all required assay processes within the closed Liat Tube. Turnaround time from sample input to result is ~20 minutes.

1. Table of Acceptance Criteria and Reported Device Performance:

The document provided is a 510(k) Summary for the IQuum Liat™ Influenza A/B Assay and Liat™ Analyzer, a diagnostic device. For diagnostic devices like this, "acceptance criteria" are typically defined by performance metrics (e.g., sensitivity, specificity, accuracy) that demonstrate the new device is "substantially equivalent" to a legally marketed predicate device. While explicit numerical acceptance criteria are not always stated directly in the summary, the study's results (performance) serve to demonstrate this equivalence. The key performance indicators presented are clinical agreement (sensitivity and specificity) and analytical performance (limit of detection, reactivity, cross-reactivity, interference, precision, reproducibility).

Here's a table summarizing the reported device performance, which the FDA presumably found acceptable for clearance based on substantial equivalence.

2. Sample Sizes and Data Provenance for the Test Set:

• Clinical Test Set Sample Size: A total of 615 clinical specimens were tested.

  • Prospective Samples: 435 samples.
  • Retrospective Samples: 180 samples. (One retrospective sample was excluded from analysis due to being indeterminate by PCR/sequencing and retest, making the effective count 179 for that portion of the analysis).

• Data Provenance (Country of Origin and Retrospective/Prospective):

  • Prospective Samples: Collected from patients with signs and symptoms of influenza in the Eastern and Southwestern US from February 12, 2009, to March 26, 2009. These are prospective samples.
  • Retrospective Samples: Collected between 2008-2010, including 2009 H1N1 samples from the 2009-2010 flu season. These are retrospective samples.

3. Number of Experts and Qualifications for Ground Truth of the Test Set:

For this type of in vitro diagnostic device (IVD), ground truth is established by reference laboratory methods, not by human experts in the sense of radiologists.

• For prospective samples (435 samples): The reference method (ground truth) was Viral Culture and IFA staining. These are standard laboratory techniques for influenza detection, typically performed by trained clinical laboratory personnel. The document does not specify the number of individual experts or their specific qualifications beyond the method itself.
• For retrospective samples (179 samples): The reference method (ground truth) was PCR and bi-directional sequencing based on published methods (Ghedin et al. 2005; Ghedin et al. 2009; World Health Organization Sequencing Primers and Protocols, 2009). Again, this refers to established molecular diagnostic techniques performed by qualified laboratory personnel, rather than a panel of clinical experts adjudicating images or reports.

4. Adjudication Method for the Test Set:

The document describes discordant results investigation for the prospective samples:

• "Discordance results were investigated using PCR and bi-directional sequencing."

This implies that if the Liat™ Assay result differed from the initial Viral Culture/IFA staining result, a third, more definitive molecular method (PCR/sequencing) was used to resolve the discrepancy and establish the "true" status of the sample. This is a common practice in IVD studies and functions as an adjudication method for discordant results.

For the retrospective samples, PCR/sequencing itself served as the primary reference method.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done.

MRMC studies typically evaluate human reader performance (e.g., radiologists interpreting images) with and without the assistance of an AI algorithm. The IQuum Liat™ Influenza A/B Assay is an automated real-time RT-PCR assay performed on an analyzer. It is an in vitro diagnostic device, not an imaging AI or a decision support system for human readers. Therefore, the concept of human readers improving with AI assistance does not apply in this context.

6. If a Standalone (Algorithm Only without Human-in-the-Loop Performance) was done:

Yes, the performance presented for the Liat™ Influenza A/B Assay is essentially standalone (algorithm only without human-in-the-loop performance).

The device is an automated in vitro diagnostic test. The Liat™ Analyzer performs all assay steps from raw sample and automatically reports results. The user adds the sample, scans barcodes, and inserts the tube, but the detection, amplification, and interpretation are done by the instrument system, not by human interpretation of raw signals. The clinical agreement section evaluates the performance of this automated system directly against the reference methods (viral culture/IFA, PCR/sequencing).

7. The Type of Ground Truth Used:

The types of ground truth used were:

• Viral Culture and IFA staining: For prospective clinical samples.
• PCR and bi-directional sequencing: For retrospective clinical samples, and for resolving discrepancies in prospective samples.

These are established laboratory diagnostic methods considered to be definitive for the presence of influenza viruses.

8. The Sample Size for the Training Set:

The document does not explicitly mention a "training set" size for the Liat™ Influenza A/B Assay. This is common for IVD devices based on RT-PCR; their design is based on known genetic targets, and analytical validation (LOD, reactivity, specificity) uses characterized strains and samples. "Training" in the machine learning sense is not typically applicable or detailed in such 510(k) summaries for IVD assays. The studies described are primarily for analytical and clinical validation of the final device.

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

As no "training set" in the machine learning sense is described for the Liat™ Assay, the establishment of ground truth for such a set is not detailed. However, the ground truth for all samples used in the analytical and clinical performance studies (which would serve a similar purpose of verifying performance) was established using:

• Titered viruses: For Limit of Detection and Reactivity studies, the concentration of viral strains was precisely known (TCID50/mL).
• Characterized pathogens/microorganisms: For Cross-Reactivity and Interference studies, specific strains/species of bacteria and viruses were used at known concentrations (CFU/mL or TCID50/mL).
• Viral culture and IFA staining: For prospective human clinical samples.
• PCR and bi-directional sequencing: For retrospective human clinical samples and for resolving discordant results in prospective samples.

These are all well-established, objective laboratory methods for determining the presence and type of influenza virus or other microorganisms.

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