(78 days)
The Quidel Molecular Influenza A+B Assay is a multiplex Real Time RT-PCR assay for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA in nasal and nasopharyngeal swabs from patients with signs and symptoms of respiratory infection. This test is intended for use as an aid in the differential diagnosis of influenza A and influenza B viral infections in humans in conjunction with clinical and epidemiological risk factors. The assay does not detect the presence of influenza C virus.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2011 and 2013 influenza seasons when influenza A/H3 and 2009 H1N1 influenza 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 assay can be performed using either the Life Technologies QuantStudio™ Dx, the Applied Biosystems® 7500 Fast Dx, or the Cepheid SmartCycler® II.
The Quidel Molecular Influenza A+B Assay detects viral nucleic acids that have been extracted from a patient sample using the NucliSENS® easyMAG® automated extraction platform. A multiplex real-time RT-PCR reaction is carried out under optimized conditions in a single tube generating amplicons for each of the target viruses present in the sample. This reaction is performed utilizing the Life Technologies QuantStudio™ Dx, the Applied Biosystems® 7500 Fast Dx, or the Cepheid SmartCycler® II platform. Identification of influenza A occurs by the use of target specific primers and a fluorescentlabeled probe that hybridizes to a conserved influenza A sequence within the matrix protein gene. Identification of influenza B occurs by the use of target specific primers and fluorescent-fabeled probes that will hybridize to a conserved influenza B sequence within the neuraminidase gene.
The Quidel Molecular Influenza A + B Assay is a multiplex Real Time RT-PCR assay for the in vitro qualitative detection and differentiation of influenza A and influenza B viral RNA in nasal and nasopharyngeal swabs from patients with signs and symptoms of respiratory infection. This device is intended to be used as an aid in the differential diagnosis of influenza A and influenza B viral infections in humans in conjunction with clinical and epidemiological risk factors.
Here's an analysis of the acceptance criteria and study as presented in the document:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the clinical performance study aiming to demonstrate substantial equivalence to an FDA-cleared RT-PCR influenza detection device. The agreement metrics (Positive Percent Agreement, Negative Percent Agreement) are the key performance indicators. The document does not explicitly state pre-defined acceptance thresholds (e.g., "PPA must be > 90%"). However, the reported performance is presented in comparison to a predicate device.
| Metric | Target/Acceptance Criteria (Implied by comparison to FDA-cleared RT-PCR) | Reported Device Performance (Quidel Molecular Influenza A + B Assay) |
|---|---|---|
| Influenza A | ||
| Positive Percent Agreement (PPA) | High agreement with predicate device | 100% (204/204) |
| Negative Percent Agreement (NPA) | High agreement with predicate device | 92.0% (382/415) |
| Influenza B | ||
| Positive Percent Agreement (PPA) | High agreement with predicate device | 99.1% (106/107) |
| Negative Percent Agreement (NPA) | High agreement with predicate device | 98.0% (502/512) |
2. Sample Size and Data Provenance for the Test Set
- Sample Size:
- Initial specimens: 631 fresh swab specimens
- Specimens remaining after exclusions for invalid results: 619
- Data Provenance: Prospective study conducted during the 2013 respiratory virus season (January to March 2013) at three sites across the United States.
3. Number of Experts and Qualifications for Ground Truth
The document does not explicitly state that experts were used to establish the ground truth for the clinical test set. Instead, a "high performance FDA-cleared Influenza A and B molecular test" was used as the comparator (reference standard) to determine agreement.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method for reconciling discordant results between the subject device and the comparator device. It simply reports the raw agreement percentages and notes the number of discordant dual infections.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. This study focuses on a standalone diagnostic device performance.
6. Standalone Performance
Yes, a standalone performance study was conducted. The "Clinical Performance" section evaluates the Quidel Molecular Influenza A + B Assay's performance (algorithm only, as it's an in vitro diagnostic test) against an FDA-cleared comparator device without human intervention in the result interpretation from the device itself.
7. Type of Ground Truth Used
The ground truth for the clinical test set was established by a "high performance FDA-cleared Influenza A and B molecular test" (a comparator device). This is a type of reference standard comparison, where the performance of the new device is measured against an established, cleared diagnostic method.
8. Sample Size for the Training Set
The document does not specify a separate training set or its sample size for the clinical performance evaluation. The clinical study described appears to be a validation/test set. For analytical performance (e.g., Limit of Detection, Analytical reactivity), quantified cultures of various influenza strains were used, but these are for analytical validation, not for training a machine learning model. This is a molecular diagnostic assay, not an AI/ML-based device in the sense of requiring a "training set" of patient data for model development.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" for an AI/ML model with associated ground truth from patient data is not applicable here because this is a molecular diagnostic assay. For the analytical studies (e.g., Limit of Detection, Inclusivity), the "ground truth" was established by using quantified cultures of known influenza A and B strains at specified concentrations (TCID50/mL). These cultures serve as the known positive and negative controls at defined viral loads.
§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.
(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.