(12 days)
The QuickVue Influenza A+B Test allows for the rapid, qualitative detection of influenza type A and type B antigens directly in nasal swab and nasopharyngeal swab specimens from symptomatic patients. The test is intended for use as an aid in the rapid differential diagnosis of acute influenza type B viral infections. The test is not intended to detect influenza C antigens. A negative test is presumptive, and it is recommended these results 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 sole basis for treatment or other patient management decisions. The test is intended for professional and laboratory use.
Performance characteristics for influenza A were established during the 2017/2018 influenza A/ H3N2 and A/H1N1 pandemic were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.
If infection with a novel influenza A 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 state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
The QuickVue Influenza A+B Test involves the extraction of influenza A and B viral antigens. The patient specimen is placed in the Extraction Reagent Tube, during which time the virus particles in the specimen are disrupted, exposing internal viral nucleoproteins. After extraction, the Test Strip is placed in the Extraction Reagent Tube where nucleoproteins in the specimen will react with the reagents in the Test Strip.
If the extracted specimen contains influenza A or B antigens, a pink-to-red Test Line along with a blue procedural Control Line will appear on the Test Strip indicating a positive result. The Test Line for influenza A or B will develop at separate specified locations on the same Test Strip. If influenza A or B antigens are not present, or are present at very low levels, only the blue procedural Control Line will appear.
The provided text describes the QuickVue Influenza A+B Test, an influenza virus antigen detection test system, and a study conducted to demonstrate its performance and substantial equivalence to a predicate device.
Here's an analysis of the acceptance criteria and study information, formatted as requested:
Acceptance Criteria and Device Performance
The acceptance criteria are not explicitly stated in a quantitative table within the provided text. However, the document indicates that the study was performed "to confirm the device meets the performance characteristics detailed in 21 CFR 866.3328 for Class II influenza virus antigen detection test systems" and that the device "meets the performance requirements according to FDA's reclassification of rapid Influenza assays."
While specific numerical targets are not given in this document, the implication is that the accuracy (sensitivity and specificity) of the QuickVue Influenza A+B Test must be sufficient to meet the regulatory requirements for a Class II influenza virus antigen detection test system.
Table 1: Implied Acceptance Criteria and Study Conclusion
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Meets performance characteristics detailed in 21 CFR 866.3328 for Class II influenza virus antigen detection test systems. | "The results of this study demonstrate that the QuickVue Influenza A+B Test meets the performance requirements according to FDA's reclassification of rapid Influenza assays." |
| Substantially equivalent to predicate device (Sofia Influenza A+B FIA). | "The QuickVue Influenza A+B test is substantially equivalent with the predicate device, Sofia Influenza A+B FIA." (This implies comparable performance characteristics, though specific numbers for the QuickVue device are not reported in this summary). The document also mentions that performance characteristics for influenza A were established during the 2017/2018 influenza seasons when influenza A/H3N2 and A/H1N1 pandemic were the predominant influenza A viruses in circulation. This indirectly suggests the device performed adequately against these prevalent strains to meet regulatory requirements. |
Study Details
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Sample size used for the test set and the data provenance:
- Sample Size: Not explicitly stated in the provided text. The document mentions "Additional Clinical Studies were performed."
- Data Provenance: Not explicitly stated. The performance characteristics for influenza A were established during the 2017/2018 influenza seasons when influenza A/H3N2 and A/H1N1 pandemic were the predominant influenza A viruses in circulation. This suggests prospective collection during a relevant influenza season, but the specific country/region is not mentioned.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not specified in the provided text.
- Ground truth confirmation is mentioned as "viral culture or an FDA-cleared influenza A and B molecular assay." This implies laboratory methods rather than expert consensus on initial interpretation for ground truth.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not specified in the provided text. The use of "viral culture or an FDA-cleared influenza A and B molecular assay" for confirmation suggests a definitive laboratory reference method, which might negate the need for a subjective adjudication process by multiple readers for the ground truth.
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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:
- This is not applicable to the QuickVue Influenza A+B Test. This device is described as a rapid, qualitative antigen detection test read "visually" (for the proposed device) or by a "Reader" (for the predicate device, Sofia Influenza A+B FIA, which is an immunofluorescence assay implying an instrument reader). The technology described does not involve AI or human-in-the-loop performance improvement with AI.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- This is not applicable as the QuickVue Influenza A+B Test is a manual, visual assay. While the Sofia predicate device uses an instrument "Reader," this is a read-out of the immunofluorescence signal, not an AI algorithm performing diagnostic interpretation.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for negative test results is recommended to be confirmed by viral culture or an FDA-cleared influenza A and B molecular assay. This indicates a high-standard laboratory reference method is used for establishing ground truth.
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The sample size for the training set:
- Not specified. The document refers to "Additional Clinical Studies." It does not directly mention a 'training set' in the context of machine learning, as this is a traditional in-vitro diagnostic device.
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How the ground truth for the training set was established:
- Not applicable in the context of a machine learning training set for this type of device. The performance characteristics were established during clinical studies, with negative results confirmed by viral culture or an FDA-cleared molecular assay.
§ 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.