(34 days)
The QuickVue Influenza A + B test allows for the rapid, qualitative detection of influenza type A and type B antigens directly from nasal swab, nasopharyngeal swab, nasal wash and/or nasal aspirate specimens. The test is intended for use as an aid in the rapid differential diagnosis of acute influenza type A and type B viral infections. The test is not intended to detect influenza C antigens. Negative test results should be confirmed by cell culture. The test is intended for professional and laboratory use.
The QuickVue Influenza A + B test, has two Test Line indicators - one for type A and one for type B. The two Test Line indicators allow for the separate identification of type A and type B viral antigens from the same specimen. If either Test Line turns pink-to-red, the test is positive for influenza. Nasal swabs, nasopharyngeal swabs, nasal wash and/or nasal aspirates serve as specimens for this test. The patient specimen is placed in a tube containing Extraction Reagent, during which time the virus particles in the specimen are disrupted, exposing internal viral antigens. After extraction, the Test Strip is placed in the Extraction Tube for 10 minutes. During this time, the extracted specimen will react with the reagents in the Test Strip. If the extracted specimen contains influenza Type A and/or B antigens, a pink-to-red Test Line along with a blue procedural Control Line will appear on the Test Strip. If influenza Type A and B viral antigens are not present, or present at very low levels, only a blue procedural Control Line will appear. If no blue procedural Control Line develops, the result is considered invalid.
Acceptance Criteria and Study for QuickVue® Influenza A + B Test
The QuickVue® Influenza A + B test is a rapid, qualitative lateral-flow immunoassay designed for the detection of influenza type A and type B antigens directly from nasal swab, nasopharyngeal swab, nasal wash, and/or nasal aspirate specimens.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state numerical acceptance criteria (e.g., "sensitivity must be > X%, specificity must be > Y%"). However, the summary of performance data implies that "excellent sensitivity and specificity" were the desired outcomes when compared to a reference standard.
| Performance Metric | Implied Acceptance Criteria (from text) | Reported Device Performance (from multi-center field clinical study) |
|---|---|---|
| Sensitivity | Excellent sensitivity when compared to viral culture and RT-PCR | Calculated sensitivity compared to viral culture and RT-PCR was "excellent" |
| Specificity | Excellent specificity when compared to viral culture and RT-PCR | Calculated specificity compared to viral culture and RT-PCR was "excellent" |
| Overall Accuracy | Overall accuracy when compared to viral culture and RT-PCR | Calculated overall accuracy compared to viral culture and RT-PCR |
Note: The document uses descriptive terms like "excellent sensitivity and specificity" rather than specific numerical thresholds.
2. Sample Size and Data Provenance for Test Set
- Sample Size: The document states that a "multi-center field clinical study" was conducted, but it does not specify the exact sample size used for the test set.
- Data Provenance: The document does not explicitly state the country of origin of the data. Given it's a submission to the FDA, it's highly likely that a significant portion, if not all, of the clinical data was collected in the United States. The study was a "field clinical study," implying prospective data collection.
3. Number of Experts and Qualifications for Ground Truth
The document does not specify the number or qualifications of experts used to establish the ground truth for the test set.
4. Adjudication Method
The document states that results were compared to "viral culture and discrepant results resolved by RT-PCR." This implies an adjudication method where:
- Initial Comparison: QuickVue results were compared against viral culture (the primary reference standard).
- Discrepancy Resolution: For any results where the QuickVue test and viral culture disagreed, RT-PCR was used as a tie-breaker or definitive secondary reference. This can be interpreted as a form of discrepancy resolution or "2-test" rule where viral culture is one and RT-PCR is the second for discrepant cases. It is not a typical 2+1 or 3+1 consensus method among experts on interpretations of the device results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
The document does not mention a multi-reader multi-case (MRMC) comparative effectiveness study comparing human readers with AI assistance versus without AI assistance. This device is a rapid diagnostic test, not an AI-powered diagnostic imaging tool, so such a study would not be relevant.
6. Standalone (Algorithm Only) Performance
The primary performance study described is essentially a standalone performance study of the device. The QuickVue® Influenza A + B test is a lateral-flow immunoassay, a diagnostic device itself, and its performance (sensitivity, specificity, accuracy) was evaluated without human interpretation being the primary variable. The results of the test strip are visually interpreted but the "algorithm" is inherent to the chemical reactions on the strip.
7. Type of Ground Truth Used
The ground truth used for the test set was:
- Viral Culture: This was the primary reference method.
- RT-PCR: Used to resolve discrepant results between the QuickVue test and viral culture. This is a highly sensitive and specific molecular method.
8. Sample Size for the Training Set
The document does not specify the sample size used for a "training set." As a lateral-flow immunoassay, the device itself is not an algorithm that requires a training set in the machine learning sense. Its design and reagents are developed through R&D, not through data-driven training of a model.
9. How Ground Truth for the Training Set Was Established
As stated above, this device is not an AI/ML algorithm that requires a "training set" in the conventional sense. Therefore, the concept of establishing ground truth for a training set does not apply directly to this type of diagnostic device. The development of the monoclonal antibodies and assay parameters would involve extensive laboratory testing and validation using known positive and negative samples, but these are part of the R&D process rather than a "training set" for an algorithm.
§ 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.