(279 days)
The Clearview Exact II Influenza A & B Test is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasal swab specimens collected from symptomatic patients. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. It is recommended that negative test results be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions.
The Clearview® Exact II Influenza A & B Test is an immunochromatographic membrane assay that uses highly sensitive monoclonal antibodies to detect influenza type A and B nucleoprotein antigens in respiratory swab specimens. These antibodies and a control protein are immobilized onto a membrane support as three distinct lines and are combined with other reagents/pads to construct a Test Strip. Nasal swab samples are added to a Coated Reaction Tube to which an extraction reagent has been added. A Clearview Exact II Influenza A & B Test Strip is then placed in the Coated Reaction Tube holding the extracted liquid sample. Test results are interpreted at 10 minutes based on the presence of pink-to-purple colored Sample Lines. The yellow Control Line tums blue in a valid test.
Here's a breakdown of the acceptance criteria and the study details for the Clearview® Exact II Influenza A & B Test, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined "acceptance criteria" in numerical terms (e.g., "Sensitivity must be > 90%"). Instead, it presents the device's performance against a gold standard (viral culture) as the evidence for substantial equivalence. The predicate device's performance often serves as an implicit benchmark for acceptance.
However, we can infer what constitutes acceptable performance from the presented results, as there's no indication that the results were unacceptable.
| Criterion (Inferred from Performance Data) | Acceptance Criteria (Implicit/Benchmark) | Reported Device Performance |
|---|---|---|
| Influenza Type A Detection | ||
| Sensitivity (vs. Viral Culture) | Likely comparable to predicate device | 94% (95% CI: 83-98%) |
| Specificity (vs. Viral Culture) | Likely comparable to predicate device | 94% (95% CI: 91-96%) |
| Positive Predictive Value (PPV) | Likely comparable to predicate device | 63% (95% CI: 52-74%) |
| Negative Predictive Value (NPV) | Likely comparable to predicate device | 99% (95% CI: 98-100%) |
| Influenza Type B Detection | ||
| Sensitivity (vs. Viral Culture) | Likely comparable to predicate device | 78% (95% CI: 68-86%) |
| Specificity (vs. Viral Culture) | Likely comparable to predicate device | 97% (95% CI: 95-98%) |
| Positive Predictive Value (PPV) | Likely comparable to predicate device | 84% (95% CI = 74-90%) |
| Negative Predictive Value (NPV) | Likely comparable to predicate device | 95% (95% CI = 93-97%) |
| Analytical Sensitivity (LOD 95%) | Likely comparable to predicate device | |
| A/HongKong/8/68 | Not explicitly stated | $2.37 \times 10^4$ TCID50/ml (97% detected) |
| A/PuertoRico/8/34 | Not explicitly stated | $3.16 \times 10^5$ TCID50/ml (88% detected) |
| B/Malaysia/2506/2004 | Not explicitly stated | $3.00 \times 10^6$ TCID50/ml (95% detected) |
| B/Lee/40 | Not explicitly stated | $4.20 \times 10^5$ TCID50/ml (95% detected) |
| Reproducibility | Likely high detection rates for positive samples, very low for negative | |
| Influenza A Moderate Positive | Not explicitly stated | 99.2% |
| Influenza A Low Positive | Not explicitly stated | 94.2% |
| Influenza A High Negative | Not explicitly stated | 9.2% |
| Influenza B Moderate Positive | Not explicitly stated | 99.2% |
| Influenza B Low Positive | Not explicitly stated | 96.7% |
| Influenza B High Negative | Not explicitly stated | 7.5% |
| Negative Samples (Overall) | Not explicitly stated | 100% (118/118) negative results |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 486 prospective specimens
- Data Provenance:
- Country of Origin: U.S. (multi-center, seven trial sites)
- Retrospective or Prospective: Prospective study, conducted during the 2008-2009 respiratory season. Specimens were collected from symptomatic patients.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly state the number or specific qualifications of experts involved in establishing the ground truth. It relies on viral culture as the ground truth. Viral culture is a laboratory method, not typically performed by "experts" in the sense of clinicians or radiologists, but by trained laboratory personnel.
4. Adjudication Method for the Test Set
The document does not mention an explicit adjudication method (e.g., 2+1, 3+1). The primary comparison is the Clearview® Exact II test result directly against the viral culture result. For discrepant results with Influenza B (19 samples positive by culture, negative by Clearview), an investigational RT-PCR assay was used as a secondary check, showing 10 of these were negative by PCR. This suggests a form of post-hoc investigation for specific discrepancies, rather than a pre-defined adjudication process, but not a consensus reading among multiple human readers.
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
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study is a standalone performance evaluation of a rapid diagnostic test against a gold standard (viral culture), not a study involving human readers or AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance study was done for the device. The Clearview® Exact II Influenza A & B Test is itself a rapid immunoassay, a "device-only" test. The "performance vs. viral culture" is the standalone performance of the diagnostic test without human interpretation of complex images or data beyond reading simple color lines.
7. The Type of Ground Truth Used
The ground truth used for the clinical study was Viral Culture. For the 19 discrepant Influenza B samples, an investigational RT-PCR assay was also used as a secondary reference.
8. The Sample Size for the Training Set
The document does not mention a separate "training set" for the clinical performance evaluation. The clinical study described is a prospective validation set. For a device like this, the "training" (development and optimization) would typically involve internal efforts during the assay development process, using laboratory-prepared samples or retrospective samples, but a dedicated "training set" for clinical evaluation is not described for this type of diagnostic device.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" for clinical performance is described, the method for establishing its ground truth is not provided. For analytical studies (e.g., analytical sensitivity, reactivity), the ground truth is typically precisely quantified viral cultures or preparations.
§ 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.