(80 days)
The BD Veritor™ System for Rapid Detection of Flu A+B is a rapid chromatographic immunoassay for the direct and qualitative detection of influenza A and B viral nucleoprotein antigens from nasopharyngeal and nasal swabs of symptomatic patients. The BD Veritor System for Rapid Detection of Flu A+B is a differentiated test, such that influenza A viral antigens can be distinguished from influenza B viral antigens from a single processed sample using a single device. The test is to be used as an aid in the diagnosis of influenza A and B viral infections. A negative test is presumptive and it is recommended that these results be confirmed by viral 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. The test is not intended to detect influenza C antigens.
The BD Flu A+B test is a chromatographic assay to qualitatively detect influenza A and B viral antigens in samples processed from respiratory specimens. The processed specimen is added to the test device where influenza A or influenza B viral anti-influenza antibodies conjugated to detector particles on the A+B test strip. The antigen-conjugate complex migrates across the test strip to the reaction area and is captured by an antibody line on the membrane. Results are interpreted by the BD Veritor™ System Reader, a portable electronic device which uses a reflectance-based measurement method to evaluate the line signal intensities on the assay test strip, and applies specific algorithms to determine the presence or absence of any target analyte(s). A liquid crystal display (LCD) on the instrument communicates the results to the operator.
Here's a summary of the acceptance criteria and the study proving the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance (Clinical Performance - All Swabs)
| Criterion (Implicit - based on study results presented) | Influenza A Reported Device Performance (PPA) | Influenza A Reported Device Performance (NPA) | Influenza B Reported Device Performance (PPA) | Influenza B Reported Device Performance (NPA) |
|---|---|---|---|---|
| Clinical PPA (United States) | 78.7% (95% C.I. 71.6%, 84.4%) | N/A | 74.3% (95% C.I. 65%, 81.8%) | N/A |
| Clinical NPA (United States) | N/A | 97.8% (95% C.I. 95.7%, 98.9%) | N/A | 99.5% (95% C.I. 98.3%, 99.9%) |
| Clinical PPA (Japan) | 94.4% (95% C.I. 86.4%-97.8%) | N/A | 91.4% (95% C.I. 82.5%-96%) | N/A |
| Clinical NPA (Japan) | N/A | 96.7% (95% C.I. 92.4%-98.6%) | N/A | 94.7% (95% C.I. 89.9%-97.3%) |
Note: The document doesn't explicitly state numerical acceptance criteria thresholds for PPA and NPA; rather, it presents the results from the clinical study as evidence of performance. The implicit acceptance is that these performance characteristics are adequate for its intended use and compare favorably to the predicate device, which is not detailed in terms of its performance here.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Clinical Performance: A total of 736 prospective specimens (515 in the U.S. and 221 in Japan).
- Data Provenance: Prospective, collected at five U.S. trial sites and eight Japan trial sites during the 2010-2011 respiratory season.
3. Number of Experts Used to Establish Ground Truth and Qualifications of Experts
- The document does not specify the number of experts used or their qualifications for establishing the ground truth. The ground truth was established by Polymerase Chain Reaction (PCR), which is a molecular assay, not an expert panel.
4. Adjudication Method for the Test Set
- The document does not describe an adjudication method for the test set in the context of human interpretation. The comparison is between the device's results and a reference PCR method. However, for discordant results (PCR positive, BD Veritor negative), a second swab specimen from the same patient (the reference method specimen) was tested with the BD Veritor assay to investigate the discrepancy. This isn't a traditional adjudication with human readers, but a re-testing mechanism.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an automated diagnostic test (an optical reader interprets the test strip), not an AI system designed to assist human readers. Thus, there is no "human readers improve with AI vs without AI assistance" effect size.
6. If a Standalone Study Was Done
- Yes, a standalone study was performed. The clinical performance data (PPA, NPA) directly reflects the algorithm's performance (the BD Veritor system's interpretation) without human intervention in the result determination once the sample is loaded.
7. The Type of Ground Truth Used
- The ground truth used was an FDA-cleared Influenza A and B molecular assay (PCR).
8. The Sample Size for the Training Set
- The document does not explicitly separate or mention a training set sample size for the device's algorithms. The clinical study samples (736 specimens) are identified as the test set for performance evaluation. For a point-of-care immunoassay with an optical reader, the algorithms are typically developed and validated internally during the device's development phase, rather than through external "training sets" in the typical machine learning sense for image analysis.
9. How the Ground Truth for the Training Set Was Established
- As a training set is not explicitly referred to in the document, how its ground truth was established is not detailed. However, for diagnostic devices, the development of algorithms would typically involve internal validation using characterized samples with known influenza status, likely determined by methods such as viral culture or validated molecular assays.
§ 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.