(154 days)
The Thermo BioStar® RSV OIA assay is an Optical ImmunoAssay (OIA) test for the qualitative, rapid detection of respiratory syncytial virus antigens (nucleoprotein) from nasal wash specimens. This test is intended for in vitro use to aid in the diagnosis of respiratory syncytial virus infections in symptomatic neonatal and pediatric patients under the age of five. It is recommended that all negative 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 antigenantibody 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 surface retains the original gold color indicating a negative result.
The provided text describes the RSV OIA® assay, a rapid test for Respiratory Syncytial Virus (RSV) antigens.
Here's an analysis of the acceptance criteria and study details:
1. Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined quantitative acceptance criteria (e.g., "The device must achieve a sensitivity of at least X%"). Instead, it presents performance metrics from the clinical studies. For the purpose of this analysis, we can infer that the reported performance was deemed acceptable for FDA clearance.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance | Comments |
|---|---|---|---|
| Reproducibility | High (e.g., minimal discordance) | 95% overall reproducibility | Based on 8 discordant and 3 invalid results out of 162 tests. |
| Clinical Sensitivity | Adequate for intended use | 86.2% | Compared to cell culture with fluorescent antibody staining. |
| Clinical Specificity | Adequate for intended use | 86.2% | Compared to cell culture with fluorescent antibody staining. |
| Overall PPV | Adequate for intended use | 67.1% | Not explicitly stated as acceptance criteria, but a reported outcome. |
| Overall NPV | Adequate for intended use | 94.1% | Not explicitly stated as acceptance criteria, but a reported outcome. |
2. Sample Size and Data Provenance
- Test set sample size:
- Reproducibility study: 162 samples (9 blinded samples tested 3 times at 6 sites).
- Clinical Sensitivity and Specificity study: 241 nasal wash specimens were included in the data analysis (out of 267 enrolled patients).
- Data provenance: Not explicitly stated, but the "two-site study in patients from emergency rooms and health clinics" and "four hospital laboratories and two physician office laboratories (POL)" suggest a prospective study design from clinical settings. The country of origin is not specified, but given the FDA submission, it's highly likely to be the USA.
3. Number of Experts and Qualifications for Ground Truth
The document does not specify the number or qualifications of experts involved in establishing the initial ground truth (cell culture with fluorescent antibody staining). It only states that the comparison was made against "commercially available cell culture, with confirmation and typing by fluorescent antibody staining."
However, for secondary confirmation testing of specimens positive to OIA and negative to culture, "specific nucleic acid detection by PCR" was used. The expertise for performing and interpreting these methods is not detailed.
4. Adjudication Method for the Test Set
The document describes secondary confirmation testing for discordant results in the sensitivity and specificity study: "Secondary confirmation testing of specimens positive to OIA and negative to culture was done by specific nucleic acid detection by PCR." This implies a form of adjudication for discordant cases, where PCR acted as a tie-breaker or a higher-tier confirmation method for a specific subset of results. There is no mention of a traditional 2+1 or 3+1 expert review panel for the entire dataset.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
There is no mention of a Multi-Reader Multi-Case (MRMC) comparative effectiveness study or any assessment of how human readers improve with or without AI assistance. The device is a diagnostic assay, not an AI-assisted diagnostic tool for human interpretation.
6. Standalone (Algorithm Only) Performance
Yes, the described performance of the RSV OIA assay is a standalone performance, as it is a diagnostic kit that provides a direct read-out (color change) and does not involve human interpretation beyond observing this change. The sensitivity and specificity figures represent the algorithm's (or assay's) performance.
7. Type of Ground Truth Used
The primary ground truth used for the clinical sensitivity and specificity study was:
- Expert Consensus/Reference Method: "Commercially available cell culture, with confirmation and typing by fluorescent antibody staining."
- Molecular Pathology (for discordant cases): "Specific nucleic acid detection by PCR" for secondary confirmation of specimens positive to OIA and negative to culture.
8. Sample Size for the Training Set
The document does not specify a separate training set or its sample size. This is typical for traditional in-vitro diagnostic (IVD) assays, where the device's design and parameters are often developed using internal R&D, and then validated with independent clinical studies. The concept of a distinct "training set" as understood in machine learning (ML) is not directly applicable or discussed here.
9. How Ground Truth for the Training Set Was Established
As no training set is explicitly mentioned, the method for establishing its ground truth is also not described. The development of the assay itself would have relied on established biological and chemical principles to detect RSV antigens, likely using purified antigens and characterized clinical samples during its optimization phase.
§ 866.3405 Poliovirus serological reagents.
(a)
Identification. Poliovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to poliovirus in serum. Additionally, some of these reagents consist of poliovirus antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identify polioviruses from clinical specimens or from tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of poliomyelitis (polio) and provides epidemiological information on this disease. Poliomyelitis is an acute infectious disease which in its serious form affects the central nervous system resulting in atrophy (wasting away) of groups of muscles, ending in contraction and permanent deformity.(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.