(200 days)
The Alere BinaxNOW® Influenza A & B Card 2 is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasopharyngeal (NP) swab and nasal swab 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. Alere BinaxNOW® Influenza A & B Card 2 must be read by the Alere™ Reader.
The Alere BinaxNOW® Influenza A & B Card 2 is an immunochromatographic membrane assay that detects influenza type A and B nucleoprotein antigens in respiratory specific 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. 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 Sample Lines. Alere BinaxNOW® Influenza A & B Card 2 test results must be read by the Alere™ Reader.
The Alere™ Reader is provided separately for result interpretation. The Alere™ Reader enables direct data entry of User ID, Subject ID, and retention of test results, but is interpretation only. All Alere BinaxNOW® Influenza A & B Card 2 assay steps are performed outside of the reader and the card assay is inserted at the 15 minute read time.
The Alere™ Reader is an easy to use bench top instrument that can be used near patient and in laboratory settings which will interpret, capture and transmit test results. The Alere™ Reader is a camera based instrument that detects the presence and identity of a completed Alere BinaxNOW® Influenza A & B Card 2 assay, analyzes the intensity of the sample and control line and displays the results (positive, negative or invalid) on a display screen is intended as a means of user interface informing the user how to operate the reader and to display test result, including any errors. Data can be retrieved and downloaded by the operator at any time after testing and uploaded to the hospital LIS/LIM system, if desired. Operator ID and Subject ID can be entered manually or via the provided barcode scanner. An external printer can be attached via USB to the Alere™ Reader to print test results.
Here's a summary of the acceptance criteria and study information for the Alere BinaxNOW® Influenza A & B Card 2 and Alere™ Reader, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" but rather presents a clinical performance study against a comparator method (FDA-cleared influenza real-time Polymerase Chain Reaction (RT-PCR) assay). The reported device performance metrics are sensitivity and specificity.
| Metric | Acceptance Criteria (Implied by Predicate/FDA Guidance) | Reported Device Performance (Influenza A) | Reported Device Performance (Influenza B) |
|---|---|---|---|
| Sensitivity | Not explicitly stated in document, but generally high concordance for rapid diagnostics. | 84.3% (95% CI: 77.2%, 89.5%) | 89.5% (95% CI: 78.9%, 95.1%) |
| Specificity | Not explicitly stated in document, but generally high concordance for rapid diagnostics. | 94.7% (95% CI: 92.1%, 96.4%) | 99.4% (95% CI: 98.3%, 99.8%) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 565 evaluable specimens (from an initial 585 collected).
- Data Provenance:
- Country of Origin: United States.
- Type: Prospective clinical study conducted at twelve (12) U.S. study centers during the 2015-2016 respiratory season.
- Patient Population: Patients presenting with flu-like symptoms.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of those Experts
The ground truth for the clinical study was established using an FDA-cleared influenza real-time Polymerase Chain Reaction (RT-PCR) assay as the comparator method. This is an objective laboratory test, not an expert consensus for the clinical study. Therefore, the concept of "experts" to establish ground truth in this context is not directly applicable in the same way it would be for image interpretation tasks.
4. Adjudication Method for the Test Set
Not applicable. The ground truth was established by an RT-PCR assay, which is a definitive laboratory test, not subject to human adjudication for its results.
5. 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
Not applicable. This device is an in vitro diagnostic (IVD) test read by an automated reader, not an AI-assisted human reader interpretation system. The Alere™ Reader is an automated instrument that interprets the test card; it does not assist human readers in interpreting results manually.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Yes, the clinical performance study evaluated the "Alere BinaxNOW® Influenza A & B Card 2 with results read by the Alere™ Reader." This represents the standalone performance of the combined device and reader system.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth used for the clinical performance study was an FDA-cleared influenza real-time Polymerase Chain Reaction (RT-PCR) assay. This is a molecular diagnostic method considered highly accurate for viral detection.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" for the device in the context of machine learning or AI algorithm development. The device is an immunochromatographic assay. The analytical studies (analytical sensitivity, reactivity, specificity) evaluate the inherent performance characteristics of the assay and reader, which are established through laboratory testing, not a dataset used to train an algorithm in the AI sense.
9. How the Ground Truth for the Training Set was Established
As noted in point 8, the concept of a "training set" in the context of an AI algorithm is not directly applicable here. The analytical studies involved:
- Analytical Sensitivity (LoD): Determined by evaluating different concentrations of known influenza virus strains. The "ground truth" was the known concentration of the virus producing positive results 95% of the time, verified against laboratory standards.
- Analytical Reactivity (Inclusivity): Determined by testing known influenza strains at specified concentrations, with the "ground truth" being the expected positive result for those strains.
- Analytical Specificity (Cross-Reactivity): Determined by testing various commensal and pathogenic microorganisms, with the "ground truth" being expected negative results.
- Interfering Substances: Tested with known substances at specified concentrations, with the "ground truth" being no effect on test performance.
- Reproducibility: Involved blind-coded specimens with known positive/negative status (likely derived from spiked samples or well-characterized clinical specimens) at low, moderate, and negative levels.
§ 866.3328 Influenza virus antigen detection test system.
(a)
Identification. An influenza virus antigen detection test system is a device intended for the qualitative detection of influenza viral antigens directly from clinical specimens in patients with signs and symptoms of respiratory infection. The test aids in the diagnosis of influenza infection and provides epidemiological information on influenza. Due to the propensity of the virus to mutate, new strains emerge over time which may potentially affect the performance of these devices. Because influenza is highly contagious and may lead to an acute respiratory tract infection causing severe illness and even death, the accuracy of these devices has serious public health implications.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device's sensitivity and specificity performance characteristics or positive percent agreement and negative percent agreement, for each specimen type claimed in the intended use of the device, must meet one of the following two minimum clinical performance criteria:
(i) For devices evaluated as compared to an FDA-cleared nucleic acid based-test or other currently appropriate and FDA accepted comparator method other than correctly performed viral culture method:
(A) The positive percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent.
(B) The negative percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent.
(ii) For devices evaluated as compared to correctly performed viral culture method as the comparator method:
(A) The sensitivity estimate for the device when testing for influenza A must be at the point estimate of at least 90 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 80 percent. The sensitivity estimate for the device when testing for influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent.
(B) The specificity estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent.
(2) When performing testing to demonstrate the device meets the requirements in paragraph (b)(1) of this section, a currently appropriate and FDA accepted comparator method must be used to establish assay performance in clinical studies.
(3) Annual analytical reactivity testing of the device must be performed with contemporary influenza strains. This annual analytical reactivity testing must meet the following criteria:
(i) The appropriate strains to be tested will be identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and sourced from CDC or an FDA-designated source. If the annual strains are not available from CDC, FDA will identify an alternative source for obtaining the requisite strains.
(ii) The testing must be conducted according to a standardized protocol considered and determined by FDA to be acceptable and appropriate.
(iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity testing must be included as part of the device's labeling. If a device has not been on the market long enough for 3 years of annual analytical reactivity testing to have been conducted since the device received marketing authorization from FDA, then the results of every annual analytical reactivity testing since the device received marketing authorization from FDA must be included. The results must be presented as part of the device's labeling in a tabular format, which includes the detailed information for each virus tested as described in the certificate of authentication, either by:
(A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or
(B) In the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access.
(4) If one of the actions listed at section 564(b)(1)(A)-(D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain:
(i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. The procedure and location of testing may depend on the nature of the emerging virus.
(ii) Within 60 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by:
(A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or
(B) In a section of the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access.