(82 days)
The IMDx Flu A/B and RSV for Abbott m2000 assay performed on the Abbott m2000 System is a qualitative in vitro diagnostic test designed for the detection of influenza B, and RSV RNA directly from nasopharyngeal swabs from patients with signs and symptoms of respiratory infection. The assay detects RNA from influenza A. influenza B, and RSV (A and B) using real-time, reverse transcription polymerase chain reaction (rRT-PCR) and fluorogenic target specific hybridization for unique sequences in the viral target genomes. The IMDx Flu A/B and RSV for Abbott m2000 assay is intended for use as an aid in diagnosing influenza A and/or RSV infection.
Negative results for influenza B, or RSV do not preclude influenza virus or RSV infection and should not be used as the sole basis for diagnosis, treatment, or patient management decisions. Conversely, positive results do not rule-out bacterial infection or co-infection with other viruses. The agent(s) detected may not be the definite cause of disease. The use of additional laboratory testing and clinical presentation must be considered when diagnosing respiratory viral infection.
Performance characteristics for influenza A were established during the 2011-2013 influenza seasons when Influenza A/2009 H1N1 and Influenza A/H3 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 IMDx Flu A/B and RSV for Abbott m2000 assay uses nucleic acid extraction and purification technology, performed on the Abbott m2000sp. combined with rRT-PCR. performed with the Abbott m2000rt, to generate and detect amplified products from influenza A, influenza B, and RSV RNA that is isolated from clinical specimens.
The assay targets the influenza A matrix (M) gene, influenza B non-structural protein (NS1) gene, and RSV A and RSV B fusion (F) gene. The presence of a viral RNA target sequence is indicated by the fluorescent signal generated through the use of fluorescently labeled oligonucleotide probes on the Abbott m2000rt instrument. The probes do not generate a signal unless they are specifically bound to the amplification cycle at which fluorescent signal is detected by the Abbott m2000rt is inversely proportional to the viral RNA target concentration present in the original sample.
An RNA bacteriophage species unrelated to influenza B, or RSV is introduced into each specimen during sample preparation to serve as a process control bacteriophage is lysed simultaneously with influenza A, influenza B and RSV B in the sample, and amplified in the same reaction as the viral RNA targets using rRT-PCR. The process control serves to demonstrate that the entire assay process has proceeded correctly for each sample.
Here's a breakdown of the acceptance criteria and the study details for the IMDx Flu A/B and RSV for Abbott m2000 assay:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for diagnostic devices often involve achieving a certain level of sensitivity and specificity against a defined ground truth. Based on the provided summary, the FDA cleared the device, implying that the observed performance met the agency's criteria. While explicit "acceptance criteria" are not listed as target percentages, the "Clinical Agreement Summary" tables present the device's performance metrics.
| Target Organism | Performance Metric | Acceptance Criteria (Implied by Clearance) | Reported Device Performance (95% CI) |
|---|---|---|---|
| Influenza A | Sensitivity | Met FDA clearance standards | 97.6% (94% - 99%) |
| Specificity | Met FDA clearance standards | 95.7% (94% - 97%) | |
| Influenza B | Sensitivity | Met FDA clearance standards | 97.1% (90% - 99%) |
| Specificity | Met FDA clearance standards | 97.2% (96% - 98%) | |
| RSV | Sensitivity | Met FDA clearance standards | 97.2% (92% - 99%) |
| Specificity | Met FDA clearance standards | 93.0% (91% - 95%) |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: A total of 932 nasopharyngeal swab (NPS) samples were tested and analyzed for performance across two influenza seasons (2011-2012 and 2012-2013).
- Data Provenance: The samples were prospectively collected from four (2011-2012 season) and three (2012-2013 season) geographically diverse test sites within the United States. These were nasopharyngeal swabs collected for routine influenza testing. The study period was February-April 2012 and March-April 2013.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The document does not specify the number of experts or their qualifications for establishing the ground truth. It states that the performance was assessed "compared to viral culture followed by direct fluorescent antibody (DFA) detection." This implies laboratory techniques were used as the reference standard, rather than expert clinical consensus or interpretation of images by experts.
4. Adjudication Method for the Test Set
The document mentions that "Discordant samples were tested using the Nanosphere Verigene® Respiratory Virus Plus Nucleic Acid Test (RV+) on the Verigene® System and subsequent results are documented in the footnote." This indicates that discordant results (where the IMDx assay result did not match the initial ground truth) were adjudicated using a "third-party" FDA-cleared molecular assay (the predicate device).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not conducted. This device is an in vitro diagnostic test for detecting viral RNA, not an imaging device or a tool that directly assists human readers in interpreting clinical information.
6. Standalone (Algorithm Only) Performance Study
- Yes, a standalone performance study was done. The entire study described under "Clinical Agreement" and "Analytical Performance" evaluates the algorithm's performance in detecting viral RNA without human interpretation or intervention in the diagnostic process beyond running the assay. The results presented are exclusively for the device's analytical detection capabilities.
7. Type of Ground Truth Used
- Clinical Agreement: The primary ground truth for the clinical agreement study was viral culture followed by direct fluorescent antibody (DFA) detection. For discordant samples, a FDA cleared molecular assay (Nanosphere Verigene® Respiratory Virus Plus Nucleic Acid Test) was used for adjudication.
- Analytical Performance: For analytical studies (reproducibility, analytical sensitivity, reactivity, specificity, interference), the ground truth generally refers to precisely prepared "spiked" samples with known concentrations of viral strains or challenging substances.
8. Sample Size for the Training Set
The document does not provide information regarding the sample size for a training set. This is typical for FDA 510(k) summaries for IVD assays. The development and training of such assays often involve proprietary internal validation data not typically released in a 510(k) summary, which focuses on clinical validation for market clearance.
9. How the Ground Truth for the Training Set Was Established
As with the training set sample size, the document does not provide information on how the ground truth for any potential training set was established. This information is typically considered proprietary to the manufacturer's development process and not part of the public 510(k) summary.
§ 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.