(28 days)
The Alere BinaxNOW® Influenza A & B Card is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasopharyngeal (NP) swab, nasal swab, and nasal wash/aspirate specimens. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. Negative test results are presumptive and should be confirmed by cell culture or an FDA-cleared influenza A and B molecular assay. Negative test results do not preclude influenza viral infection and should not be used as the sole basis for treatment or other patient management decisions.
Caution: Assay sensitivity for nasal wash/aspirate samples was determined primarily using archived specimens. Users may wish to establish the sensitivity of these specimens on fresh samples.
The Alere BinaxNOW® Influenza A & B Card is an immunochromatographic membrane assay that uses highly sensitive monoclonal antibodies to detect influenza type A and B nucleoprotein antigens in respiratory specimens. These antibodies and a control antibody are immobilized onto a membrane support as three distinct lines and combined with other reagents/pads to construct a test strip. This test strip is mounted inside a cardboard, book-shaped hinged test card.
Swab specimens require a sample preparation step, in which the sample is eluted off the swab into elution solution, saline or transport media. Nasal wash/aspirate samples require no preparation. Sample is added to the top of the test strip and the test card is closed. Test results are interpreted at 15 minutes based on the presence or absence of pink-to-purple colored Sample Lines. The blue Control Line turns pink in a valid assay.
Here's a breakdown of the acceptance criteria and the studies that prove the device meets them, based on the provided text:
Device: Alere BinaxNOW® Influenza A & B Card
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a structured table format with specific thresholds. However, the performance summary provides quantitative results against a reference standard (Cell Culture/DFA), which implicitly serve as the criteria the device aims to meet. The implicit acceptance criteria would be for the sensitivity and specificity values to be within acceptable ranges for a rapid diagnostic test, generally aiming for high specificity to minimize false positives and reasonable sensitivity. The study results demonstrate these performance characteristics for the device.
Here's a table summarizing the reported device performance for the clinical studies, which can be interpreted as demonstrating the device meets implicit acceptance criteria for sensitivity and specificity:
Implicit Acceptance Criteria (Demonstrated Performance)
| Performance Metric | Influenza A (Prospective Study) | Influenza B (Prospective Study) | Influenza A (Retrospective Study) | Influenza B (Retrospective Study) |
|---|---|---|---|---|
| Overall Sensitivity | 81% (95% CI: 74-86%) | 65% (95% CI: 39-85%) | 83% (95% CI: 73-90%) | 53% (95% CI: 27-78%) |
| Overall Specificity | 97% (95% CI: 96-98%) | 100% (95% CI: 99-100%) | 93% (95% CI: 88-96%) | 92-98% (CI not fully legible for B) |
2. Sample Sizes Used for the Test Set and Data Provenance
Prospective Study:
- Sample Size: 846 specimens (nasopharyngeal and nasal swabs).
- Data Provenance: Multi-center clinical studies conducted at a central testing laboratory outside the US during the 2004 respiratory season and at three US trial sites during the 2005-2006 respiratory season.
Retrospective Study:
- Sample Size: 293 frozen clinical samples.
- Data Provenance: Clinical samples collected from symptomatic patients at multiple physician offices, clinics, and hospitals located in the Southern, Northeastern, and Midwestern regions of the United States and from one hospital in Sweden.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document refers to "Cell Culture / DFA" (Direct Fluorescent Antibody) as the comparative method for establishing ground truth. This indicates that the ground truth was established by laboratory testing using established and validated methods, rather than clinical expert consensus. Therefore, the concept of "number of experts" or their "qualifications" in the traditional sense of clinical adjudication by physicians is not directly applicable here. The experts would be the laboratory personnel performing and interpreting the cell culture and DFA, who are presumed to be qualified in these laboratory techniques.
4. Adjudication Method (for the test set)
The adjudication method used for the comparison was against Cell Culture / DFA. This means that discrepancies between the device's results and the Cell Culture / DFA results would be evaluated against the "gold standard" of Cell Culture / DFA without a specified clinical adjudication process detailed in the submission. The text does not mention a 2+1, 3+1, or similar expert adjudication process for discordant results.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, the provided document does not describe an MRMC comparative effectiveness study where human readers' performance with and without AI assistance is evaluated. The study focuses on the standalone performance of the Alere BinaxNOW® Influenza A & B Card compared to laboratory reference methods.
6. If a Standalone Study (algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are standalone performance studies of the Alere BinaxNOW® Influenza A & B Card. The results show the performance of the device itself (immunochromatographic assay) in detecting influenza antigens, without human interpretation being the primary variable of interest. While human operators interpret the results (presence/absence of pink-to-purple lines), the study assesses the diagnostic accuracy of the test product against the reference standard. The "Reproducibility Study" involved multiple operators interpreting cards, indicating that human interpretation is part of the device's use, but the primary clinical performance studies (sensitivity/specificity vs. Cell Culture/DFA) evaluate the device's diagnostic capability. The "Analytical Sensitivity" section involved 12 different operators interpreting cards, further indicating that the interpretation by human users is part of the device's intended use and evaluation.
7. The type of Ground Truth Used
The primary ground truth used for both prospective and retrospective clinical studies was Cell Culture / DFA (Direct Fluorescent Antibody). This is a widely accepted and established laboratory method for influenza virus detection.
8. The Sample Size for the Training Set
The document does not specify a separate "training set" or its sample size. This is common for rapid diagnostic devices like the Alere BinaxNOW® Influenza A & B Card, which are developed based on established immunological principles and optimized through R&D, rather than being "trained" in the machine learning sense on a distinct dataset. The clinical studies described are validation studies for the finalized device.
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, there is no explicit "training set" mentioned in the context of machine learning. Therefore, the establishment of ground truth for a training set is not applicable here. The device's performance was evaluated against the gold standard of Cell Culture/DFA in clinical validation studies.
§ 866.3330 Influenza virus serological reagents.
(a)
Identification. Influenza virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to influenza in serum. The identification aids in the diagnosis of influenza (flu) and provides epidemiological information on influenza. Influenza is an acute respiratory tract disease, which is often epidemic.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.