(122 days)
Binax NOW® Flu A Test is an in vitro rapid immunochromatographic assay for the qualitative detection of influenza A nucleoprotein antigen in nasal wash and nasopharyngeal swab specimens from symptomatic patients. It is intended to aid in the rapid diagnosis of influenza A infections. Negative test results should be confirmed by cell culture.
The Binax NOW® Flu A Test is an immunochromatographic membrane assay used to detect influenza A nucleoprotein antigen in nasal wash and nasopharyngeal swab specimens. A test strip, containing goldconjugated and immobilized anti-influenza A antibodies, is mounted on the right side of a cardboard, book-shaped hinged test device. Swab specimens require a sample preparation step, in which the sample is eluted off the swab into a saline solution. The nasal wash sample does not require any preparation. The sample to be tested is added to a pad at the top of the test strip, and the test device is closed. Influenza A antigen present in the sample reacts to bind anti-influenza A conjugated antibody. The resulting antigenconjugate complexes are captured by immobilized anti-influenza A antibody, forming the Sample Line. Immobilized Control Line antibody, which appears as a blue line in an untested device, captures a visualizing conjugate, forming a pink Control Line. The sample is contained, and results are available within 15 minutes.
Here's an analysis of the provided text regarding the Binax NOW® Flu A Test, structured to address your specific questions:
Binax NOW® Flu A Test Study Analysis
1. Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria (e.g., "The device must achieve sensitivity of X% and specificity of Y%"). Instead, it presents the device's performance characteristics. The acceptance of the device is implicitly based on its substantial equivalence to the predicate device (Quidel QuickVue® Influenza Test) and the presented clinical performance data.
| Performance Metric | Acceptance Criteria (Not explicitly stated, interpreted as "demonstrated performance") | Reported Device Performance (Binax NOW® Flu A Test) |
|---|---|---|
| Nasal Wash Specimens | - | Sensitivity: 82% (69% - 90% CI) |
| - | Specificity: 94% (89% - 97% CI) | |
| - | Overall Accuracy: 91% (86% - 94% CI) | |
| Nasopharyngeal Swab Specimens | - | Sensitivity: 78% (62% - 88% CI) |
| - | Specificity: 92% (86% - 95% CI) | |
| - | Overall Accuracy: 89% (84% - 93% CI) | |
| Analytic Reactivity | Detects all influenza A strains | 100% positive for 6 ATCC traceable influenza A strains |
| Analytic Specificity (Cross-Reactivity) | No cross-reactivity with common respiratory bacteria and viruses | No cross-reactivity with 42 potential cross-reactants |
| Reproducibility | Consistent results across sites and days | 100% correctly interpreted across 3 sites, 3 days |
| Interfering Substances | No interference from common nasal/nasopharyngeal substances | No interference with 19 substances, even when spiked with LOD virus |
| Quality Control | Procedural control indicates test failure | 100% correct interpretation (positive, negative, invalid) with 9 defective devices |
2. Sample Size and Data Provenance
- Test Set Sample Size:
- 191 nasal wash specimens
- 182 nasopharyngeal swab specimens
- Data Provenance: Prospective clinical studies, multi-site. The country of origin is not explicitly stated, but the submission is to the U.S. FDA, suggesting U.S.-based or internationally accepted clinical trials.
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 for the Test Set
The document does not mention an adjudication method for the test set.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This study evaluated the performance of the device against a laboratory reference standard (viral cell culture), not human readers with or without AI assistance.
6. Standalone Performance (Algorithm Only)
Yes, a standalone performance study was done. The reported sensitivity, specificity, and accuracy values are for the Binax NOW® Flu A Test device on its own when compared to viral cell culture. There is no human-in-the-loop component described in these performance metrics.
7. Type of Ground Truth Used
The primary ground truth used for the clinical sensitivity and specificity evaluation was viral cell culture. This is a recognized laboratory standard for confirming influenza infections.
8. Sample Size for the Training Set
The document does not specify a training set sample size. This type of rapid diagnostic test typically does not involve a "training set" in the context of machine learning algorithms. The device's performance is established through its design, antibody selection, and validation against known positive and negative samples, rather than an iterative learning process on a large dataset.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the machine learning sense, this question is not directly applicable. However, the device's design and analytical performance (reactivity, specificity) would have been developed and validated using characterized influenza A strains (e.g., ATCC traceable strains) and various potential cross-reactants, for which the ground truth (presence/absence of target, identity of organism) would be established by standard microbiological and virological methods.
§ 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.