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The CareStart™ Flu A&B Plus is an in vitro rapid immunochromatographic assay for the qualitative detection of influenza virus type A and B nucleoprotein antigens directly from nasopharyngeal swab specimens of symptomatic patients.

The test is intended for use as an aid in the rapid differential diagnosis of acute influenza type A and B viral infections. This test is intended to distinguish between influenza type A and/or B virus in a single test. This test is not intended to detect influenza type C viral antigens. Negative test results are presumptive and should be confirmed by viral culture or an FDA-cleared influenza A and B molecular assay. Negative results do not preclude influenza virus infections and should not be used as the basis for treatment or other patient management decisions.

Performance characteristics for influenza A and B were established during the 2018-2019 influenza season when influenza A/H3N2, A/H1N1pdm09, and B/Victoria were the predominant influenza viruses in circulation. When other influenza viruses are emerging, performance characteristics may vary.

If infection with a novel influenza 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 the state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to received and culture specimens.

The CareStart™ Flu A&B Plus test is an immunochromatographic assay for detection of extracted influenza type A and B virus nucleoprotein antigens in nasopharyngeal specimens.

Nasopharyngeal swabs require a sample preparation step in which the sample is eluted and washed off into the extraction buffer solution. Extracted swab sample is added to the sample well of the test device to initiate the test. When the swab sample migrates in the test strip, influenza A or B viral antigens bind to anti-influenza antibodies conjugated to indicator particles in the test strip forming an immune complex. The immune complex is then captured by each test line and control line on the membrane as it migrates through the strip.

Test results are interpreted at 10 minutes. The presence of two colored lines, a purplecolored line in the control region "C" and a red-colored line in the influenza A test region "A", indicates influenza A positive. The presence of two colored lines, a purplecolored line in the control region "C" and a blue-colored line in the influenza B test region "B", indicates influenza B positive. The presence of three colored lines, a purple-colored line in the control region "C", a red-colored line in the influenza A test region "A", and a blue-colored line in the influenza B test region "B indicates, influenza A and B dual positive result. The absence of a line on both influenza A and B test regions with a purple-colored line in the control region "C" indicates negative. No appearance of purple-colored line in the control region "C" indicates invalid test.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Device Name: CareStart™ Flu A&B Plus (Influenza Virus Antigen Detection Test System)

General Acceptance Criteria (Implied by FDA 510(k) Clearance):
The primary acceptance criterion for a 510(k) submission is that the device is substantially equivalent to a legally marketed predicate device. This is demonstrated by showing that the new device has the same intended use and technological characteristics, and that its performance is at least as safe and effective as the predicate device. Specific performance criteria are established through analytical and clinical studies.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values (e.g., "PPA must be >X%"). Instead, the performance estimates are presented, and the implication is that these results demonstrate substantial equivalence to the predicate device. For the purpose of this analysis, I will treat the reported performance as the "met criteria" that led to substantial equivalence.

2. Sample Size Used for the Test Set and Data Provenance

• Clinical Test Set:

  • Prospective Clinical Study: 944 evaluable nasopharyngeal swab specimens.
    • Provenance: Collected from symptomatic patients during the 2018-2019 influenza season at 10 Point-of-Care investigational sites throughout the U.S. (prospective, U.S. origin).
  • Retrospective Study (supplemental for Influenza B): 162 swab samples prepared from archived respiratory specimens.
    • Provenance: Archived respiratory specimens from patients with influenza-like symptoms, confirmed positive or negative by an FDA-cleared molecular assay. Samples were distributed among four investigational sites (retrospective, likely U.S. origin, as it supplemental for the U.S. prospective study).

• Analytical Sensitivity (LoD): 20 replicates per virus strain (8 strains tested).

• Analytical Sensitivity (Reactivity/Inclusivity): 3 replicates per virus strain (25 strains tested).

• Analytical Specificity (Cross-Reactivity/Interference): 3 replicates per organism/virus, both with and without influenza viruses (31 bacteria, 15 non-influenza viruses, 30 interfering substances).

• Reproducibility Study: 7 sample categories tested in a blinded manner by 3 operators at 3 sites on 5 non-consecutive days (7 samples * 3 operators * 3 sites * 5 days = 315 tests, per virus type if applicable). Counted as 135/135 for each category overall.

• Lot-to-Lot Precision: 7 sample categories tested across 3 reagent lots (counted as 27/27 for each category overall).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not specify the number or qualifications of experts for establishing ground truth.

• Clinical Study Ground Truth: The ground truth for the clinical studies (prospective and retrospective) was established using an FDA-cleared influenza A and B molecular assay (comparator method). For discrepant results in the prospective study, an alternative FDA-cleared molecular assay was used for investigation. These are laboratory-based, highly sensitive and specific molecular tests for influenza, which are considered a gold standard for pathogen detection.

• Analytical Studies Ground Truth: For analytical studies (LoD, Reactivity, Cross-Reactivity, Interference, Reproducibility, Lot-to-Lot Precision), the ground truth was inherent to the carefully prepared samples (e.g., known virus concentrations, known interfering substances).

4. Adjudication Method for the Test Set

• Clinical Studies: For the prospective clinical study, discrepancies between the CareStart™ Flu A&B Plus results and the initial molecular comparator assay results were investigated using an alternative FDA-cleared molecular influenza A/B assay. The results of this secondary testing were captured in footnotes but not included in the primary calculations of the performance estimates. This suggests a form of 2+1 adjudication not directly applied to the final performance metrics but used for understanding discrepancies.

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

• Not applicable. This device is an in vitro rapid immunochromatographic assay (a rapid diagnostic test kit) and does not involve AI assistance or human readers interpreting AI outputs. The results are interpreted visually by a human or using a simple instrument (like the predicate, though the proposed device is visually interpreted). Therefore, an MRMC study related to AI assistance for human readers was not performed.

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

• Yes, in essence, the "device performance" in the clinical and analytical studies represents the standalone performance of the assay. The CareStart™ Flu A&B Plus itself is a rapid test that produces visual results. The clinical studies compare the device's output (positive/negative for Flu A/B) directly against a molecular truth, effectively testing its "standalone" diagnostic capabilities without a human interpretation model beyond reading a test line. The detection format is "Visual determination of presence or absence of colored line indicators" for the proposed device, indicating it functions as a standalone diagnostic tool without requiring an additional human interpretation step or an algorithm to read the result in a complex way.

7. The type of ground truth used

• Molecular Assay: The primary ground truth for clinical performance evaluation (prospective and retrospective studies) was an FDA-cleared influenza A and B molecular assay. An alternative FDA-cleared molecular assay was used to investigate discrepant results.
• Known Concentrations/Absence of Analytes: For analytical studies (LoD, Reactivity, Cross-Reactivity, Interference, Reproducibility, Lot-to-Lot Precision), the ground truth was based on samples with known concentrations of specific virus strains or known absence of target analytes/presence of interfering substances.

8. The sample size for the training set

The document does not explicitly describe a separate "training set" in the context of machine learning or AI. As a rapid diagnostic test, the device's development typically involves iterative design and testing using various lab-prepared and clinical samples, which implicitly serve as a development/training phase. However, there isn't a formally described training set as one might see for an AI algorithm. The performance evaluation presented focuses on the validation of the device.

9. How the ground truth for the training set was established

As there is no explicitly defined "training set" in the provided document, the method for establishing its ground truth is not described. The analytical and clinical studies described serve as validation of the final device. The ground truth for those validation studies was established through FDA-cleared molecular assays or by controlled preparation of samples with known viral content.

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