(186 days)
The xTAG® Respiratory Viral Panel Fast (RVP FAST) is a qualitative nucleic acid multiplex test intended for the simultaneous detection and identification of multiple respiratory virus nucleic acids in nasopharyngeal swabs from individuals suspected of respiratory tract infections. The following virus types and subtypes are identified using RVP FAST: Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza B, Respiratory Syncytial Virus, Human Metapneumovirus, Rhinovirus, and Adenovirus. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection if used in conjunction with other clinical and epidemiological information.
Negative results do not preclude respiratory viral infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Positive results do not rule out bacterial infection or co-infection with other organisms. The agent detected may not be the definite cause of disease. The use of additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) and clinical presentation must be taken into consideration in order to obtain the final diagnosis of respiratory infection.
Due to the genetic similarity between human Rhinovirus and Enterovirus, the RVP FAST primers for the detection of rhinovirus cross react with enterovirus. A rhinovirus reactive result should be confirmed by an alternate method (e.g. cell culture).
Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 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 a 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.
RVP FAST is a PCR-based system for detecting the presence / absence of viral DNA / RNA in clinical specimens. The oligonucleotide primer / probe components of the RVP FAST have been designed to specifically target unique regions in the RNA / DNA of each molecular species listed in the intended use. Amplified products are then sorted and analyzed on the Luminex 100 or 200 instrument, which generates signals based on the acquisition of spectrofluorometric data. The raw signals are median fluorescence intensities (MFI) which are acquired in a Luminex Output.csv file that is subsequently analyzed by the xTAG Data Analysis Software (TDAS RVP FAST) to establish the presence of all viral types / subtypes for which a Luminex microsphere population has been dedicated.
Here's a breakdown of the acceptance criteria and the study details for the xTAG® RVP FAST device, based on the provided document:
Acceptance Criteria and Device Performance
The provided document details the performance characteristics through clinical sensitivity and specificity. While explicit quantitative "acceptance criteria" tables are not presented as separate targets, the FDA's clearance implies these performance metrics were deemed acceptable for the device's intended use. The table below summarizes the reported clinical performance.
| Virus (Analyte) | Reported Sensitivity (%) | Lower-Bound 95% CI for Sensitivity (%) | Reported Specificity (%) | Lower-Bound 95% CI for Specificity (%) |
|---|---|---|---|---|
| Human Influenza A | 94.2 | 88.8 | 95.5 | 94.0 |
| H1 | 96.3 | 87.3 | 98.2 | 97.2 |
| H3 | 96.1 | 89.0 | 97.8 | 96.8 |
| Human Influenza B | 94.3 | 84.3 | 98.8 | 98.0 |
| RSV | 90.9 | 84.3 | 97.7 | 96.6 |
| Rhinovirus | 95.6 | 84.9 | 92.5 | 90.8 |
| Adenovirus | 85.7 | 57.2 | 99.3 | 98.6 |
| Metapneumovirus (hMPV) | 97.2 | 85.5 | 98.9 | 98.2 |
| Adenovirus (Supplemented) | 97.06 (PPA) | 86.47 | N/A | N/A |
Study Details
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Sample Size used for the test set and the data provenance:
- Sample Size: 1191 prospectively collected clinical specimens (nasopharyngeal swabs).
- Data Provenance: Specimens were collected during the 2007/2008 and 2008/2009 flu seasons from enrolled clinical sites. They were a mix of "left-over, fresh and frozen." An additional 34 banked, pre-selected positive clinical specimens for Adenovirus were used to supplement the prospective set. Furthermore, 77 clinical specimens confirmed positive for Novel 2009/H1N1 (swine flu) were also tested.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number or qualifications of experts directly. Ground truth was established using comparator methods such as Direct Fluorescent Antibody Test (DFA), viral culture, and well-characterized RT-PCR amplification followed by bidirectional sequencing. These methods are laboratory-based and generally performed by trained laboratory personnel, rather than explicitly "experts" in the context of clinical interpretation.
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Adjudication method for the test set:
- The document does not describe an adjudication method in the sense of multiple human readers resolving discrepancies. The ground truth was established by laboratory-based comparator methods.
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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:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is a qualitative nucleic acid multiplex test for direct detection of viral RNA/DNA, not an imaging or diagnostic support system for human readers.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance characteristics (sensitivity and specificity) presented in Table 10 represent the standalone performance of the xTAG RVP FAST assay itself. The assay utilizes multiplex RT-PCR and Luminex technology, with data analyzed by the xTAG Data Analysis Software (TDAS RVP FAST) to provide a qualitative summary. There is no human interpretation of image data or similar involved in the reported performance.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Laboratory-based Comparator Methods:
- For Influenza B, RSV, and Adenovirus: Direct Fluorescent Antibody Test (DFA) and/or viral culture.
- For Influenza A subtyping, hMPV, and Rhinovirus: Well-characterized RT-PCR amplification followed by bidirectional sequencing.
- For the additional Adenovirus samples: Culture.
- For the Novel 2009/H1N1 samples: CDC real-time PCR test.
- Laboratory-based Comparator Methods:
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The sample size for the training set:
- The document does not explicitly state a "training set" in the context of machine learning or AI models. This device is a molecular diagnostic assay where primers and probes are designed based on known viral genetic sequences. The development and optimization process for such assays typically involves laboratory experimentation with known positive and negative controls and clinical samples, rather than a distinct "training set" in the AI sense for which performance metrics against a held-out test set would be reported for FDA submission.
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How the ground truth for the training set was established:
- As there isn't a stated "training set" for a machine learning model, the concept of establishing ground truth for it is not directly applicable in the terms usually associated with AI/ML device submissions. The assay itself is designed based on known biological targets, and its analytical and clinical performance is validated against established laboratory reference methods and clinical outcomes.
§ 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.