(63 days)
The Thermo BioStar® RSV OLA assay is an Optical ImmunoAssay test for the rapid and qualitative detection of respiratory syncytial virus (RSV) antigens (nucleoproteins) from nasal wash and nasopharyngeal swab specimens. This test is intended for in vitro diagnostic use to aid in the diagnosis of RSV infections in symptomatic neonatal and pediatric patients under the age of five. It is recommended that all negative test results be confirmed by cell culture.
The RSV OIA test involves the qualitative extraction and detection of protein antigens unique to RSV (nucleoprotein and fusion protein). The Optical ImmunoAssay technology enables the direct visual detection of a physical change in the optical thickness of molecular thin films. This change is a result of antigen-antibody binding on an optical surface (silicon wafer). When an extracted specimen is placed directly on the optical surface, the immobilized specific antibodies capture the antigen. After washing, the substrate is added, increasing the thickness (mass enhancement) of the molecular thin film. This change in thickness alters the reflected light path and is visually perceived as a color change. Slight changes in optical thickness produce a distinct, visible color change. A positive result appears as a purple spot on the predominant gold background. When antigen is not present in the specimen, no binding takes place. Therefore, the optical thickness remains unchanged and the original gold color indicating a negative result.
Here's a breakdown of the acceptance criteria and the study details for the RSV OIA® device, 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 sensitivity and specificity thresholds that needed to be met for regulatory clearance. Instead, it presents the achieved performance characteristics and compares them to a predicate device and historical standard method (viral culture). The implicit acceptance criterion seems to be demonstrating substantial equivalence to these established methods.
| Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Nasal Wash) | Reported Device Performance (Nasopharyngeal Swab) |
|---|---|---|---|
| Sensitivity | Substantially Equivalent to Cell Culture | 86.8% | 66.7% |
| Specificity | Substantially Equivalent to Cell Culture | 83.2% | 96.4% |
| Reproducibility | High consistency across sites | 95% across all sites (151/159) | Not specified separately, assumed from overall |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: A total of 414 nasalpharyngeal specimens were included in the data analysis from a multicenter study, with 77 specimens excluded.
- Data Provenance: The data was collected from a multicenter study with "geographically diverse clinical sites," indicating it was conducted in multiple locations. The study was clinical, suggesting prospective or a mix of prospective and retrospective data collection, focused on symptomatic neonatal and pediatric patients. Specific countries are not mentioned.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document states that the RSV OIA test was compared to "commercially available cell culture, with confirmation and typing by fluorescent antibody staining." It also mentions "Secondary confirmation testing of specimens positive to OIA and negative to culture was done by specific nucleic acid detection by PCR."
This suggests that the ground truth was established by:
- Cell Culture: This is a laboratory standard, executed by trained laboratory personnel.
- Fluorescent Antibody Staining: Performed as a confirmation and typing method, also by trained laboratory personnel.
- PCR: Used for secondary confirmation, performed by trained laboratory personnel.
The document does not specify the number of individual experts who performed these ground truth assessments or their specific qualifications (e.g., "board-certified virologist with 10 years of experience"). However, the reliance on established laboratory methods implies qualified personnel.
4. Adjudication Method for the Test Set
The document describes a clear adjudication process for discrepant results:
- "Secondary confirmation testing of specimens positive to OIA and negative to culture was done by specific nucleic acid detection by PCR."
This indicates a hierarchical adjudication method where PCR was used to resolve discrepancies between the OIA test and primary cell culture results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, the document does not describe a Multi-Reader Multi-Case (MRMC) comparative effectiveness study involving human readers with and without AI assistance. The device is a diagnostic assay (OIA), not an AI-powered image analysis or decision support tool for human readers.
6. Standalone (Algorithm Only) Performance Study
Yes, the described clinical studies evaluate the standalone performance of the RSV OIA assay. The sensitivity and specificity figures (86.8% and 83.2% for nasal wash; 66.7% and 96.4% for nasopharyngeal swab) represent the performance of the device itself against the established ground truth. There is no human-in-the-loop component mentioned for the device's diagnostic output.
7. Type of Ground Truth Used
The ground truth used was a combination of:
- Laboratory Reference Standard: Commercially available cell culture.
- Confirmatory Assays: Fluorescent antibody staining and specific nucleic acid detection by PCR.
This represents a strong form of ground truth based on established scientific and diagnostic methods.
8. Sample Size for the Training Set
The document does not provide information on a specific "training set" sample size. For an Optical ImmunoAssay (OIA) like the RSV OIA, the development process typically involves optimizing reagents and protocols during product development rather than training a machine learning algorithm on a distinct dataset. Clinical studies are performed for validation and performance assessment, not for "training" in the machine learning sense.
9. How the Ground Truth for the Training Set Was Established
As there is no explicit mention of a "training set" in the context of machine learning, there is no description of how ground truth for such a set was established. Product development and optimization would rely on laboratory-based characterization against known positive and negative controls, and potentially early clinical samples, similar to the methods described for ground truth in point 7.
§ 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.