(114 days)
The Focus Diagnostics Simplexa™ Flu A/B & RSV assay is intended for use on the 3M Integrated Cycler instrument for the in vitro qualitative detection and discrimination of influenza A virus, influenza B virus, and respiratory syncytial virus (RSV) RNA in nasopharyngeal swabs (NPS) from human patients with signs and symptoms of respiratory tract infection in conjunction with clinical and epidemiological risk factors. This test is intended for use as an aid in the differential diagnosis of influenza A, influenza B, and RSV viral infections in humans and is not intended to detect influenza C.
Negative results do not preclude influenza virus or RSV infection and should not be used as the sole basis for treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2010 influenza season when 2009 H1N1 influenza was the predominant influenza A virus 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 test is a real-time RT-PCR amplification system that utilizes a bi-functional fluorescent probe-primer for the detection and differentiation of human influenza A virus RNA, human influenza B virus RNA and respiratory syncytial virus RNA in nasopharyngeal swabs (NPS). The assay is composed of two principal steps: (1) extraction of RNA from patient specimens, (2) A bi-functional fluorescent probe-primer is used together with a reverse primer to amplify a specific target (for each analyte and the RNA internal control). The assay provides three results; conserved regions of influenza A viruses (matrix gene), influenza B viruses (matrix gene) and RSV (M gene) are targeted to identify these viruses in the specimen. An RNA internal control is used to monitor the extraction process and to detect RT-PCR inhibition.
The 3M Integrated Cycler is a rapid real-time Polymerase Chain Reaction thermocycler used for the identification of nucleic acid from prepared biological samples. The instrument utilizes disk media to contain and to process samples. The instrument uses real time flourometric detection to identify targets within the sample wells. The instrument is controlled by an external computer running the Integrated Cycler Studio Software.
The Focus Diagnostics Simplexa™ Flu A/B & RSV assay is intended for the qualitative detection and discrimination of influenza A virus, influenza B virus, and respiratory syncytial virus (RSV) RNA in nasopharyngeal swabs (NPS).
Here's an analysis of the provided information:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" as distinct numerical thresholds for PPA/NPA. Instead, it provides the clinical agreement percentages, which are implicitly the performance targets for demonstrating substantial equivalence. The table below summarizes the reported clinical agreement from the clinical agreement study for both prospective and retrospective samples.
| Category | Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance | Comments |
|---|---|---|---|---|
| Influenza A | ||||
| - Prospective Samples | % Agreement (Detected) | High | 100% (25/25) | For Influenza A, Simplexa™ showed perfect agreement with the high-performance NAT for detected cases in prospective samples. |
| % Agreement (Not Detected) | High | 99.8% (527/528) | Very high agreement for not detected cases, with one discordant result. | |
| - Retrospective Samples | % Agreement (Detected) | High | 100% (79/79) | For Influenza A, Simplexa™ showed perfect agreement with the high-performance NAT for detected cases in retrospective samples. |
| % Agreement (Not Detected) | High | 99% (97/98) | High agreement for not detected cases, with one discordant result. | |
| Influenza B | ||||
| - Prospective Samples | % Agreement (Detected) | High | 50% (1/2) | Note: This is a very low agreement, but based on a very small sample size (only 2 detected samples by reference method). This would be a concern if not for the very small sample size and the fact the sample was "retested" and confirmed as a false negative. |
| % Agreement (Not Detected) | High | 99.8% (550/551) | Very high agreement for not detected cases, with one discordant result. | |
| - Retrospective Samples | % Agreement (Detected) | High | 100% (50/50) | For Influenza B, Simplexa™ showed perfect agreement with the high-performance NAT for detected cases in retrospective samples. |
| % Agreement (Not Detected) | High | 100% (127/127) | Perfect agreement for not detected cases. | |
| RSV | ||||
| - Prospective Samples | % Agreement (Detected) | High | 99.1% (110/111) | High agreement for detected cases. |
| % Agreement (Not Detected) | High | 99.5% (440/442) | High agreement for not detected cases. | |
| - Retrospective Samples | % Agreement (Detected) | High | 100% (22/22) | For RSV, Simplexa™ showed perfect agreement with NAT for detected cases in retrospective samples. |
| % Agreement (Not Detected) | High | 99.4% (154/155) | High agreement for not detected cases. |
2. Sample size used for the test set and the data provenance:
- Total Sample Size: 735 nasopharyngeal swabs (NPS).
- Provenance:
- Prospective Samples: 558 specimens, collected from patients with signs and symptoms of viral respiratory tract infection.
- Retrospective Samples: An unspecified number (the document mentions "banked specimens with signs and symptoms of viral respiratory tract infection," and the individual category summaries provide the counts for retrospective testing: 177 for Influenza A, 177 for Influenza B, and 177 for RSV). The combined numbers in the tables (e.g., 553 for prospective Flu A, 553 for prospective Flu B, etc.) indicate how the 558 prospective samples were distributed across the different analytes, and similarly for retrospective samples from the total of 735.
- Country of Origin: Not explicitly stated, but typically for FDA submissions, these studies are conducted in the US.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided in the document. The ground truth was established by laboratory methods, not expert visual assessment.
4. Adjudication method for the test set:
This information is not applicable as the ground truth was established by reference laboratory methods (high-performance NAT and culture/DFA), not by human interpretation requiring adjudication.
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:
Not applicable. This study is for an in vitro diagnostic device (RT-PCR assay), not an imaging-based AI diagnostic that typically involves human readers. Therefore, an MRMC study and analysis of human reader improvement with AI assistance were not performed.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, this was effectively a standalone study. The Simplexa™ Flu A/B & RSV assay is an automated RT-PCR system. Its performance was compared directly against reference methods (high-performance NAT and culture/DFA) without human interpretation steps that would integrate with the device's output. The device itself is the "standalone algorithm/system."
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Influenza A Virus: High performance FDA cleared nucleic acid test (NAT).
- Influenza B Virus: High performance FDA cleared nucleic acid test (NAT).
- Respiratory Syncytial Virus (RSV): Culture/DFA (Direct Fluorescent Antibody).
8. The sample size for the training set:
The document does not explicitly mention a "training set" in the context of device development. This is typical for in vitro diagnostic assays like RT-PCR, where analytical performance (e.g., Limit of Detection, analytical reactivity, cross-reactivity) is established using characterized strains and then clinical performance is validated on clinical samples, rather than a machine learning training/validation split.
9. How the ground truth for the training set was established:
As no explicit "training set" or machine learning approach is described for the device, this information is not applicable. The analytical characteristics are determined using known concentrations of viral strains and the clinical performance is compared against established reference methods.
§ 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.