(148 days)
The QIAstat-Dx Respiratory Panel is a multiplexed nucleic acid test intended for use with QIAstat-Dx system for the simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) eluted in Universal Transport Media (UTM) obtained from individuals suspected of respiratory tract infections. The following organism types are identified using the QIAstat-Dx Respiratory Panel: Adenovirus, Coronavirus 229E, Coronavirus HKU1, Coronavirus NL63, Coronavirus OC43, Human Metapneumovirus A+B, Influenza A, Influenza A H1, Influenza A H1N1/pdm09, Influenza B, Parainfluenza Virus 1, Parainfluenza Virus 2, Parainfluenza Virus 4, Rhinovirus/Enterovirus, Respiratory Syncytial Virus A+B, Bordetella pertussis, Chlamydophila pneumoniae and Mycoplasma pneumoniae.
The detection and identification of specific viral and bacterial nucleic acids from individuals presenting with signs and symptoms of a respiratory infection aids in the diagnosis of respiratory infection with other clinical and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment or other management decisions. Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by the test or lower respiratory tract infection that is not detected by a nasopharyngeal swab specimen. Positive results do not rule out co-infection with other organisms: the agent(s) detected by the QIAstat-Dx Respiratory Panel may not be the definite cause of disease. Additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence and radiography) may be necessary when evaluating a patient with possible respiratory tract infection.
Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for Bordetella pertussis and Parainfluenza Virus 1 were established primarily with retrospective clinical specimens. Performance characteristics for Chlamydophila pneumoniae, Parainfluenza Virus 2, Parainfluenza Virus 4, Influenza A subtype H1 and Coronavirus 229E were established primarily using contrived clinical specimens.
Due to the genetic similarity between Human Rhinovirus and Enterovirus, the QIAstat-Dx Respiratory Panel cannot reliably differentiate them. A positive QI Respiratory Panel Rhinovirus/Enterovirus result should be followed-up using an alternate method (e.g., cell culture or sequence analysis).
Performance characteristics for Influenza A were established when Influenza A H1N1-2009 and A H3 were the predominant Influenza A viruses in circulation. Performance of detecting Influenza A may vary if other Influenza A strains are circulating or a novel Influenza A virus emerges. 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 departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
QIAstat-Dx® is based on single-test cartridges with pre-packaged reagents including both wet and dry chemistry to handle the sample preparation and detection steps for the presence of a range of selected analytes by PCR technology. After insertion of the sample, the QIAstat-Dx assay cartridge is processed by the QIAstat-Dx® Analyzer 1.0.
The QIAGEN QIAstat-Dx Respiratory Panel is a multiplexed nucleic acid test intended for the simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) eluted in Universal Transport Media (UTM). The device is intended for use with the QIAstat-Dx system to aid in the diagnosis of respiratory infections in individuals suspected of having such infections.
Acceptance Criteria and Device Performance
The acceptance criteria for the QIAstat-Dx Respiratory Panel are primarily demonstrated through its analytical performance (Limit of Detection, Analytical Reactivity, Analytical Specificity, Interference, Specimen Stability, and Reproducibility) and clinical performance (sensitivity and specificity compared to an FDA-cleared multiplexed respiratory pathogen panel). While explicit quantitative acceptance criteria for all aspects are not provided in the document (e.g., specific minimum acceptable sensitivity/specificity percentages), the data presented demonstrates the device meets acceptable performance levels for diagnostic assays.
Here's a table summarizing reported performance characteristics:
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Limit of Detection (LoD) | ≥95% detection rate at specific concentrations for each pathogen | Achieved ≥95% (typically 19/20 or 20/20 positives) for all 51 pathogen strains at their determined LoD concentrations (e.g., Influenza A H1N1: 4 TCID50/ml, Coronavirus NL63: 0.01 TCID50/ml). |
| Analytical Reactivity (Inclusivity) | 100% detection rate for clinically relevant and diverse strains at tested concentrations. | 100% detection rate for all 127 tested influenza, coronavirus, parainfluenza, RSV, metapneumovirus, adenovirus, enterovirus, rhinovirus, Mycoplasma pneumoniae, Bordetella pertussis, and Chlamydophila pneumoniae strains at specified concentrations. |
| Analytical Specificity (Cross-Reactivity/Exclusivity) | No false positives due to common respiratory flora or other common pathogens, or clearly identified and disclosed cross-reactivity. | Only observed cross-reactivity with Bordetella holmesii and Bordetella bronchiseptica (off-panel Bordetella species), which was predicted by in silico analysis. No other significant cross-reactivity. |
| Interference | No inhibition or false results due to endogenous or exogenous substances (except for disclosed interferences like high concentrations of nasal influenza vaccines). | No inhibition observed except for high concentrations of nasal influenza vaccines (Fluenz Tetra and FluMist), which were predicted to be reactive and disclosed. Performance was unaffected by other substances. |
| Specimen Stability | Stable performance across specified storage conditions (RT, refrigerated, frozen). | Assay capable of processing samples stored up to 4 hours at RT, 3 days refrigerated, and 30 days frozen without impacting performance. |
| Reproducibility | Consistent detection rates across different sites, days, lots, operators, and analyzers. For concentrations near LoD (0.1x LoD), expected detection rate 85%, with many > 95%. | |
| Clinical Specificity (NPA) | High NPA against a comparator FDA-cleared multiplexed respiratory pathogen panel. | Overall NPA consistently very high, ranging from 97.9% (Rhinovirus/Enterovirus) to 100.0% for all analytes. |
| Validity Rate | High rate of valid results on first attempt. | 95.88% (1912/1994) valid results on first attempt in prospective study. 4.11% invalid/no result initially. After retesting, 72 of 82 initially failed specimens yielded valid results. |
Study Details
This device is not an AI/ML powered device, therefore some of the questions (e.g. data provenance for test set, number of experts, adjudication method and MRMC study) are not relevant. This is a traditional IVD device and the study demonstrates the analytical and clinical performance through wet-lab and clinical sample testing against a comparator method.
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A table of acceptance criteria and the reported device performance: See table above.
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Sample sized used for the test set and the data provenance:
- Analytical Performance Studies (Non-clinical):
- Limit of Detection: For each of the 51 pathogen strains, at least 20 replicates were tested. Data provenance is not explicitly stated as patient data, but rather contrived analytical samples prepared from commercial suppliers or artificial samples.
- Analytical Reactivity: 127 respiratory pathogen isolates/strains were tested in triplicates.
- Analytical Specificity: Samples were contrived by spiking off-panel organisms into simulated nasopharyngeal swab sample matrix.
- Interference: 30 potentially interfering substances were tested in contrived samples (mix of organisms at 5xLoD and negative specimens).
- Specimen Stability: 10 sample mixes (each containing multiple pathogens) were tested with 10 replicates per storage condition per target.
- Matrix Equivalency: 20 replicates for at least one strain per pathogen, prepared in true-negative clinical NPS sample matrix.
- Reproducibility: 12 sample mixes (contrived samples) were tested across 3 sites, with 20 replicates per target, concentration, and site (4 replicates/day for 5 days).
- Clinical Performance Study:
- Sample Size: A total of 2,304 residual NPS specimens were tested: 1994 prospective (1093 frozen prospective, 901 fresh prospective) and 310 archived.
- Data Provenance: The study was conducted at six (6) geographically diverse study sites, five (5) U.S. sites and one (1) international site. Specimens were collected from individuals suspected of respiratory tract infections. The study involved both prospective collection (patients meeting inclusion criteria) and archived specimens.
- Analytical Performance Studies (Non-clinical):
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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): Not applicable for this type of IVD device. The ground truth for the clinical study was established by an FDA-cleared multiplexed respiratory pathogen panel (the comparator method).
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Adjudication method (e.g. 2+1, 3+1, none) for the test set: Not applicable as the ground truth was established by a single comparator device, not through human expert adjudication of images.
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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: Not applicable. This is an IVD device, not an AI/ML-powered imaging device that assists human readers.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Yes, the device operates as a standalone diagnostic system, performing nucleic acid extraction, amplification, and detection without human interpretation beyond reading the displayed results. Its performance was directly compared to another FDA-cleared multiplexed respiratory pathogen panel.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Analytical Studies: Ground truth was established by known concentrations of pathogen strains (from commercial suppliers like ZeptoMetrix and ATCC) or artificial samples.
- Clinical Study: Ground truth was established by an FDA-cleared multiplexed respiratory pathogen panel, which served as the comparator method.
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The sample size for the training set: Not applicable. This is a traditional IVD device, not an AI/ML product that undergoes a "training" phase with a large dataset. The device's design and analytical parameters are based on scientific principles of multiplex PCR and reagent formulation.
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How the ground truth for the training set was established: Not applicable, as there is no "training set" in the context of an AI/ML model for this device.
§ 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.