(173 days)
The QuickLab RSV™ Test is intended for the qualitative detection of Respiratory Syncytial Virus antigens (fusion protein) directly from nasopharyngeal swab, and nasal aspirate specimens in children less than 6 years and adults over the age of 60. The QuickLab RSV test is intended for use as an aid in the rapid laboratory diagnosis of acute respiratory syncytial virus infection in patients with symptoms consistent with an RSV infection. It is recommended that negative results be confirmed by cell culture.
The QuickLab RSV is a lateral flow immunogold assay for the direct visual detection of RVS protein F in clinical samples. The basis for protein F detection is in the use of a red - colored gold labeled mouse monoclonal anti-RSV protein F antibody that after addition of extracted sample travels laterally along the strip test device membrane. This lateral flow carries the mixture of sample and qold-labeled anti- RSV protein F through a membrane adsorbed monoclonal anti-RSV protein F Test Line (T) and then through a membrane adsorbed goat anti-mouse immunoglobulin Control Line (C). When RSV protein F is present in clinical samples, the fluid phase mouse anti-RSV protein F binds this antigen and this formation of antigen - antibody complex is then in turn bound at the Test Line (T). The unbound or excess mouse anti - RSV protein F passes through the Test Line (T) and is bound at the Control Line (C) by goat antimouse immunoalobulin. Therefore, in the presence of RSV protein F antigen, 2 red lines become visible: one at the Test Line (T) and a second at the Control Line (C). But when RSV antigen is absent only one red line appears at the Control Line (C).
Here's a breakdown of the acceptance criteria and the study that proves the device meets the criteria, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined "acceptance criteria" in terms of specific thresholds for sensitivity and specificity that the device must meet. Instead, it presents the device's performance against reference methods as data to support substantial equivalence. We can infer the "acceptance" is based on demonstrating comparable performance to the predicate device and other FDA-cleared devices.
However, based on the clinical performance study, we can extract the reported performance:
| Metric | Acceptance Criteria (Inferred from reported performance) | Reported Device Performance |
|---|---|---|
| Overall Positive Agreement | High agreement with reference methods for positive RSV cases (specific threshold not stated, but >90% would generally be considered good for rapid diagnostic tests). | 93.9% (95% C.I. = 85.4 - 97.6%) |
| Overall Negative Agreement | High agreement with reference methods for negative RSV cases (specific threshold not stated, but >90% would generally be considered good for rapid diagnostic tests). | 97.7% (95% C.I. = 93.5 - 99.2%) |
| Positive Agreement (US Data vs. DFA) | High agreement with DFA for positive cases. | 93.3% (95% C.I. = 80.7 - 98.6%) |
| Negative Agreement (US Data vs. DFA) | High agreement with DFA for negative cases. | 96.6% (95% C.I. = 88.3 - 99.6%) |
| Sensitivity (Canada Data vs. Tissue Culture) | High sensitivity (detection of true positives). | 100% (95% C.I. = 69.2 - 100%) |
| Specificity (Canada Data vs. Tissue Culture) | High specificity (detection of true negatives). | 87.8% (95% C.I. = 80.7 - 94.9%) |
| Positive Agreement (Canada Data vs. EIA) | High agreement with EIA for positive cases. | 95.2% (95% C.I. = 76.2 - 99.9%) |
| Negative Agreement (Canada Data vs. EIA) | High agreement with EIA for negative cases. | 96.6% (95% C.I. = 92.5 - 99.9%) |
2. Sample Size Used for the Test Set and Data Provenance
- Total Sample Size for Clinical Performance Study (Test Set): 197 samples
- 104 samples from the United States
- 93 samples from Canada
- Data Provenance:
- Country of Origin: Midwest United States and Ontario, Canada.
- Retrospective or Prospective: Prospective multi-center field clinical study during the 2002 flu season.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not specify the number of experts used or their qualifications for establishing the ground truth. It refers to "Tissue Culture, EIA and Direct Fluorescent Antibody (DFA)" as reference methods, implying laboratory test results rather than expert consensus.
4. Adjudication Method for the Test Set
The document explicitly states that "All samples were split to allow testing of the same sample by QuickLab and the reference method." This indicates a direct comparison where each sample was tested by both the QuickLab RSV and the respective reference method. There is no mention of an adjudication method for conflicting results between the QuickLab test and the reference methods. The reference methods (DFA, Tissue Culture, EIA) were treated as the established ground truth.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. The study focuses on the standalone performance of the QuickLab RSV test against established laboratory reference methods, not on comparing human reader performance with and without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The provided study is a standalone (algorithm only) performance study for the QuickLab RSV test. As a point-of-care, lateral flow immunogold assay producing a visual readout (red lines), its "algorithm" is the biochemical reaction sequence and visual interpretation, which is designed to be performed without direct human-in-the-loop assistance influencing the result once the sample is applied. The test result (presence or absence of lines) is directly read, not interpreted or modified by a human expert in a way that would classify it as human-in-the-loop performance influencing the accuracy of the device's reading.
7. The Type of Ground Truth Used
The ground truth used for the clinical performance study was established by established laboratory reference methods:
- Direct Fluorescent Antibody (DFA) in the United States sites.
- Tissue Culture and EIA (Enzyme Immunoassay) at the Canadian site.
These are considered confirmatory diagnostic tests for RSV.
8. The Sample Size for the Training Set
The document does not provide information about a specific "training set" sample size. This is a rapid diagnostic test, not a machine learning algorithm in the modern sense that typically involves distinct training/validation/test sets. The analytical and reproducibility studies would involve testing known samples, but these are not explicitly termed a "training set."
9. How the Ground Truth for the Training Set Was Established
Similarly, since a distinct "training set" as understood in modern AI/ML contexts is not mentioned, information on how its ground truth was established is not provided. The analytical sensitivity and specificity studies would have used characterized known positive and negative samples, but these are for analytical validation, not for "training" an algorithm.
§ 866.3480 Respiratory syncytial virus serological reagents.
(a)
Identification. Respiratory syncytial virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to respiratory syncytial virus in serum. Additionally, some of these reagents consist of respiratory syncytial virus antisera conjugated with a fluorescent dye (immunofluorescent reagents) and used to identify respiratory syncytial viruses from clinical specimens or from tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of respiratory syncytial virus infections and provides epidemiological information on diseases caused by these viruses. Respiratory syncytial viruses cause a number of respiratory tract infections, including the common cold, pharyngitis, and infantile bronchopneumonia.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.