(92 days)
The Alere™ i RSV assay performed on the Alere™ i Instrument is a rapid molecular in vitro diagnostic test utilizing an isothermal nucleic acid amplification technology for the qualitative detection of respiratory syncytial virus (RSV) viral RNA in direct nasopharyngeal swabs and nasopharyngeal swabs eluted in viral transport media from patients with signs and symptoms of respiratory infection. It is intended for use as an aid in the diagnosis of RSV in children
The Alere™ i RSV is a rapid, instrument-based test for the qualitative detection and differentiation of respiratory syncytial virus (RSV) viral RNA from direct nasopharyngeal swab (NPS) and NPS eluted in viral transport media from patients with signs and symptoms of respiratory infection. The Alere™ i RSV System utilizes isothermal nucleic acid amplification technology and is comprised of:
- Sample Receiver – single use, disposable containing the elution buffer
- . Test Base – single use, disposable comprising two sealed reaction tubes, each containing a lyophilized pellet
- . Transfer Cartridge – Single use, disposable for transfer of the eluted sample to the Test Base, and
- Alere™ i Instrument repeat use reader ●
The reaction tubes in the Test Base contain the reagents required for amplification of the target nucleic acid and an internal control. Alere™ i RSV utilizes a pair of templates (similar to primers) for the specific amplification of RNA from RSV A and B, which occur in two separate reaction tubes. Each reaction tube contains a fluorescently labeled molecular beacon designed to specifically identify the amplified RNA targets. Alere™ i RSV is performed within the confinement of the Test Base, and no other part of the Alere™ i Instrument has contact with the sample during the amplification process. This minimizes the risk of instrument contamination and sample carry-over between measurements.
To perform the assay, the Sample Receiver and Test Base are inserted into the Alere™ i Instrument and the elution buffer is automatically heated by the instrument. The sample is added to the Sample Receiver and transferred via the Transfer Cartridge to the Test Base, re-suspending the lyophilized pellets contained within the Test Base and initiating target amplification. Heating, mixing and detection by fluorescence are provided by the instrument, with results automatically reported.
Results are displayed by the Alere™ i Instrument and are also stored in an on-board archive and are assigned to a sample ID that has been entered into the Alere™ i Instrument by the operator, and the date/time the test was performed. Data can be retrieved and downloaded by the operator at any time after testing. An external Alere™ Universal Printer can be attached via USB to the Alere™ i Instrument to print test results.
Here's a summary of the acceptance criteria and study details for the Alere™ i RSV device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the clinical performance results needed for substantial equivalence, specifically the sensitivity and specificity values. The document presents the results directly after the methods.
| Acceptance Criteria | Alere™ i RSV Performance (Nasopharyngeal Swab Direct) | Alere™ i RSV Performance (Nasopharyngeal Swab Eluted in VTM) |
|---|---|---|
| Sensitivity | 98.6% (95% CI: 94.9%, 99.6%) | 98.6% (95% CI: 94.9%, 99.6%) |
| Specificity | 98.0% (95% CI: 96.0%, 99.1%) | 97.8% (95% CI: 95.7%, 98.9%) |
| Initial Invalid Rate | 4.1% (95% CI: 2.7% to 6.3%) | 2.2% (95% CI: 1.2% to 3.9%) |
| Invalid Rate (after repeat testing) | 0.8% (95% CI: 0.3% to 2.0%) | 0% (95% CI: 0.0% to 0.8%) |
Note: The document doesn't explicitly state "acceptance criteria" but presents these performance metrics as the outcome of the clinical study, implying they met the bar for substantial equivalence.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Nasopharyngeal Swab Direct: 497 evaluable specimens
- Nasopharyngeal Swab Eluted in Viral Transport Media (VTM): 501 evaluable specimens
- Data Provenance: Multi-center, prospective clinical study conducted at nine US trial sites during the 2015-2016 respiratory season. This indicates that the data is prospective and collected in the USA.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document states that the Alere™ i RSV performance was compared to "FDA-cleared PCR test" which served as the ground truth. It does not mention the use of human experts (e.g., radiologists, pathologists) to establish the ground truth for this clinical performance study. The ground truth was established by an objective laboratory test (PCR).
4. Adjudication Method for the Test Set
Not applicable. The ground truth was established by an FDA-cleared PCR test, not by human expert 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 is not an imaging device or one that involves human "readers" or AI assistance in interpretation in the way a typical MRMC study would assess. It's an in vitro diagnostic test with an automated result interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the clinical performance study reported is for the standalone algorithm (device) performance. The Alere™ i Instrument automatically reports results: "Results are displayed by the Alere™ i Instrument and are also stored in an on-board archive..." There is no mention of a human-in-the-loop component for result interpretation for the performance assessment.
7. The type of ground truth used
The ground truth used for the clinical performance study was an FDA-cleared PCR test. This is an objective laboratory reference method.
8. The sample size for the training set
The document does not specify a separate training set or its sample size. The description provided is for the clinical performance study (test set) and analytical studies. For in vitro diagnostic devices, the development and training (if applicable for machine learning components) are typically internal, and the regulated submission focuses on the validation of the final locked algorithm using a distinct clinical test set.
9. How the ground truth for the training set was established
As no specific training set is detailed, information on how its ground truth was established is not provided.
§ 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.