Search Results

The cobas liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test is an automated rapid multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) test intended for the simultaneous qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, influenza B virus and respiratory syncytial virus (RSV) nucleic acids in anterior nasal (nasal) and nasopharyngeal swab specimens from individuals exhibiting signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory viral infection due to SARS-CoV-2, influenza and RSV can be similar. This test is intended to aid in the differential diagnosis of SARS-CoV-2, influenza A, influenza B, and RSV infections in humans and is not intended to detect influenza C virus infections.

Nucleic acids from the viral organisms identified by this test are generally detectable in nasopharyngeal and nasal swab specimens during the acute phase of infection. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory tract infection are indicative of the presence of the identified virus, and aid in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings.

The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out coinfection with other organisms. The organism(s) detected by the cobas liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test may not be the definite cause of disease. Negative results do not preclude SARS-CoV-2, influenza A virus, influenza B virus, or RSV infections.

The cobas liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test is performed on the cobas liat analyzer which automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using real-time PCR assays. The assay targets both the ORF1 a/b non-structural region and membrane protein gene that are unique to SARS-CoV-2, a well-conserved region of the matrix gene of influenza A (Flu A target), the nonstructural protein 1 (NS1) gene of influenza B (Flu B target) and the matrix gene of RSV (RSV target). An Internal Control (IC) is included to control for adequate processing of the target virus through all steps of the assay process and to monitor the presence of inhibitors in the RT-PCR processes.

The provided text describes the analytical and clinical performance evaluation of the cobas® liat SARS-CoV-2, Influenza A/B & RSV nucleic acid test, which is a real-time RT-PCR assay. The information mainly focuses on the performance characteristics required for FDA clearance (510(k)).

Here's a breakdown of the requested information based on the provided document:

Acceptance Criteria and Device Performance

The document does not explicitly present a table of "acceptance criteria" in a pass/fail format for clinical performance. Instead, it demonstrates the device's performance through various analytical studies and clinical agreement percentages relative to a comparator method. The acceptance for a 510(k) submission is typically that the device is "substantially equivalent" to a legally marketed predicate device, which implies demonstrating comparable performance characteristics.

The key performance metrics are the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) in clinical studies. While there aren't explicit numeric acceptance criteria stated, the achieved performance values are presented as evidence of substantial equivalence.

Here’s a table summarizing the reported clinical device performance based on the prospective study (Table 13) and the retrospective study (Table 15). These are the metrics by which the device's clinical performance would be "accepted" as substantially equivalent.

Table of Reported Device Performance (Clinical)

Note on "Acceptance Criteria" for Analytical Performance: The document describes detailed analytical studies (LoD, inclusivity, cross-reactivity, interference, reproducibility), and the reported hit rates and concentrations demonstrate that the device met the internal analytical performance specifications, which are implicitly the "acceptance criteria" for these aspects. For instance, for LoD, the acceptance criterion is implied to be ≥95% hit rate at the determined concentration. For inclusivity, it's detection at or near 3x LoD. For cross-reactivity and interference, the acceptance criterion is no cross-reactivity/interference observed. The document states that "none of the organisms tested cross reacted or interfered" and that "substances... did not interfere," indicating successful meeting of these criteria. For reproducibility, the agreement percentages for positive and negative samples are above 99% for most categories.

Study Details

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

   • Prospective Clinical Study (Category I):
     • NPS specimens: 1729 enrolled subjects leading to 1704 evaluable specimens for SARS-CoV-2, Flu A, Flu B, and 1705 for RSV.
     • ANS specimens: 1729 enrolled subjects leading to 1705 evaluable specimens for SARS-CoV-2, Flu B, 1703 for Flu A, and 1706 for RSV.
     • Data Provenance: Fresh specimens, prospective, collected between September 2023 and March 2024 at 14 point-of-care testing sites in the United States (US).
   • Retrospective Clinical Study (Category III):
     • Specimens: Frozen archived clinical NPS (n=223) and ANS (n=206) specimens.
     • Data Provenance: Retrospective, collected between 2019 and 2023. Distributed to 6 sites for testing. Country of origin not explicitly stated but implied to be US given the overall context of a US FDA clearance (though not definitively stated for the retrospective part).

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
   The ground truth for the clinical test set was established by comparing the results of the cobas® liat test to the "results of an FDA-cleared Nucleic Acid Amplification Test (NAAT)." The document does not specify the number of human experts, their qualifications, or their role in establishing this ground truth. The "ground truth" here is the result from the comparator NAAT, not human expert interpretation of images or clinical data.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
   The document describes a discrepant analysis for cases where the cobas® liat test results differed from the comparator NAAT. For the prospective study, the discrepancy analysis showed how many of the discrepant results (e.g., cobas® liat negative, comparator positive) were ultimately confirmed as positive or negative by further investigation (implied to be by the comparator method or potentially a third method, though not explicitly detailed beyond "discrepant NAAT results"). The details provided are:

   • SARS-CoV-2 NPS: Of 12 negative cobas® liat/positive comparator, 8 were positive and 4 negative. Of 35 positive cobas® liat/negative comparator, 12 were positive and 23 negative.
   • Similar analyses are provided for other targets and specimen types.
     This implies an adjudication method where discrepant results were further investigated, likely with repeat testing or a confirmatory reference method, but the specific "2+1" or "3+1" reader/expert adjudication model (common in imaging studies) is not applicable or described for this in vitro diagnostic (IVD) device.

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 was not done. This type of study is primarily relevant for imaging devices that assist human readers (e.g., AI for radiology). The cobas® liat test is an automated molecular diagnostic test directly detecting nucleic acids, not an AI-assisted interpretation device for human "readers."

5. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
   Yes, the performance reported (PPA, NPA, and analytical studies) represents the standalone performance of the cobas® liat device. It is an automated system where the "algorithm" (the RT-PCR assay and its interpretation software) directly produces a qualitative result (Detected/Not Detected), without human "in-the-loop" interpretation for the primary result. Human operators load samples and review results, but the analytical detection and differentiation itself is automated.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
   The ground truth for both prospective and retrospective clinical studies was based on the results of an FDA-cleared Nucleic Acid Amplification Test (NAAT), which served as the comparator method. For discrepant samples, further re-testing against the comparator or a reference method was performed for adjudication. This falls under a "reference standard" or "comparator method" type of ground truth.

7. The sample size for the training set:
   The document does not specify the sample size for a "training set." This type of molecular diagnostic device typically relies on analytical validation (LoD, inclusivity, specificity) and clinical validation through comparison to a reference method, rather than a machine learning model that requires explicit training data. The development process would involve iterative optimization of primers, probes, and assay conditions, but this is not typically referred to as a "training set" in the context of IVD submissions, especially for traditional PCR assays.

8. How the ground truth for the training set was established:
   As no explicit "training set" for a machine learning model is described, the question of how its ground truth was established is not applicable based on the provided text. The "ground truth" in the context of this traditional IVD development refers to the reliable identification of the target analytes in samples for analytical and clinical validation, often through established reference methods or characterized materials.

Ask a specific question about this device