(25 days)
The Panther Fusion® AdV/hMPV/RV assay is a multiplex real-time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and differentiation of Adenovirus (AdV), human Metapneumovirus (hMPV), and Rhinovirus (RV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection.
This assay is intended to aid in the differential diagnosis of Adenovirus, human Metapneumovirus, and Rhinovirus infections in humans. Negative results do not preclude Adenovirus, human Metapneumovirus, and Rhinovirus infections and should not be used as the sole basis for treatment or other management decisions. This assay is designed for use on the Panther Fusion system.
The Panther Fusion AdV/hMPV/RV assay is a multiplex real-time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and differentiation of Adenovirus (AdV) human Metapneumovirus (RV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection.
Prior to processing and testing on the Panther Fusion system, specimen Lysis Tube containing specimen transport media (STM) that lyses the cells, releases target nucleic acid and protects them from degradation during storage. The Internal Control-S (IC-S) is added to each test specimen and controls via the working Panther Fusion Capture Reagent-S (wFCR-S). The lC-S in the reagent monitors specimen processing, and detection. Capture oligonucleotides hybridize to nucleic acid in the test specimen. Hybridized nucleic acid is then specimen in a magnetic field. Wash steps remove extraneous components from the reaction tube. The elution step elutes acid. During the nucleic acid capture and elution step, total nucleic acid is isolated from specimens.
During the elution transfer step, eluted nucleic acid is transferred to a Panther Fusion tube already containing oil and reconstituted masternix. For RV, hMPV, and internal control targets, amplification occurs via RT-PCR. A reverse transcriptase step qenerates DNA copies of the target sequence. For AdV, target amplification occurs via PCR. For all targets, specific forward and reverse primers and probes amplify targets while simultaneously detecting and discriminating multiplex PCR. The Panther Fusion system compares the fluorescence signal to a predece a qualitative result for the presence or absence of the analyte. The assay analytes (Adenovirus, human Metapheumovirus, and Internal Control) through specific gene targets (Hexon, Nucleocapsid, 5' UTR, and n/a, respectively) are detected in different channels of the Panther Fusion system (HEX, ROX, FAM, and RED677, respectively).
The provided text describes a 510(k) premarket notification for the "Panther Fusion AdV/hMPV/RV Assay," an in vitro diagnostic test. The notification details the device, its intended use, and a comparison to a predicate device. Crucially, it highlights that the subject device incorporates "software algorithm changes" to improve hMPV specificity, specifically to decrease false positives, without significantly altering clinical results or assay claims.
However, the document states: "All analytical and clinical data used to support the predicate device intended use and performance was re-analyzed with the updated software. All pre-determined acceptance criteria from the original protocols were met." It does not provide the specific acceptance criteria or the detailed results of this re-analysis, nor does it describe a new study conducted to prove the device meets acceptance criteria. It only affirms that the previous data, when re-analyzed with the new software, continued to meet the original acceptance criteria.
Because the document only states that original acceptance criteria were met by re-analysis of existing data, and does not outline specific acceptance criteria or an independently designed study for the new software, I can only infer information from what is provided.
Here's an attempt to answer your questions based on the limited information that can be extracted or reasonably inferred from the provided text:
1. A table of acceptance criteria and the reported device performance
The document does not provide a specific table of acceptance criteria or reported device performance for the new software. It only states: "All pre-determined acceptance criteria from the original protocols were met." Without the original protocols, the exact acceptance criteria and the specific performance metrics (e.g., sensitivity, specificity, accuracy) are not available in this document. The focus of the changes is on improving hMPV specificity, implying that this was a key performance area.
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
The document states: "All analytical and clinical data used to support the predicate device intended use and performance was re-analyzed with the updated software." This indicates that the same test set (both analytical and clinical data) used for the predicate device was re-used for the updated software. The sample size and data provenance are therefore not detailed in this document, as it refers to pre-existing data. It doesn't specify if the original data was retrospective or prospective, nor its country of origin.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This information is not provided in the document. The study described is a re-analysis of previously established analytical and clinical data for an in-vitro diagnostic test. Establishing "ground truth" for clinical samples in an IVD context typically involves clinical diagnosis or other validated laboratory methods, rather than expert radiology reads as might be the case for imaging AI.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This information is not provided in the document. As an IVD device, the "adjudication method" in the context of clinical studies for diagnostic accuracy would typically refer to how the true status of a specimen (positive/negative for a pathogen) was determined.
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, an MRMC comparative effectiveness study was not done or described. This device is an in-vitro diagnostic test (a laboratory assay), not an AI imaging analysis tool that assists human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply here.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
The device is an in-vitro diagnostic test that operates on a "Panther Fusion system." The "software algorithm changes" affect how the assay results are processed and interpreted by the system itself. This is essentially a "standalone" or "algorithm only" performance, as the algorithm's output directly determines the qualitative detection and differentiation of the viruses. Human intervention likely involves sample preparation and loading, and subsequent interpretation of the system's output. The re-analysis was of the system's performance with the new software.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The document relates to an In Vitro Diagnostic (IVD) test for nucleic acid detection. For such assays, "ground truth" for the test set would typically be established by:
- Reference laboratory methods: Such as highly sensitive and specific PCR methods, sequencing, or culture that are considered gold standard.
- Clinical diagnosis: Based on a physician's assessment, symptoms, and other diagnostic tests.
- Composite reference standard: A combination of clinical and laboratory findings.
The exact type of ground truth used for the original predicate device data (which was re-analyzed) is not specified in this document.
8. The sample size for the training set
The document states that "All analytical and clinical data used to support the predicate device intended use and performance was re-analyzed with the updated software." This implies that the software updates likely occurred after the initial assay development. It's not explicitly stated that a new training set was used for the "software algorithm changes." The changes are presumably based on internal development and validation, potentially informed by performance issues (like the hMPV false positives). Details about any specific training set for the software algorithm are not provided.
9. How the ground truth for the training set was established
As there is no specific mention of a separate training set for the new algorithm within this document, the method for establishing its ground truth is also not provided. If the algorithm was developed iteratively based on observed performance issues (e.g., false positives), the "ground truth" for its development would be based on the established true status of the samples that generated those observed issues, similar to how the ground truth is established for the test set (reference methods or clinical diagnosis).
§ 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.