(137 days)
The VIDAS Rotavirus (RTV) Assay detects the presence of rotavirus antigen in stool specimens.
The VIDAS RTV Assay detects the presence of rotavirus antigen in stool specimens. Assay specificity is conferred by the use of two antibodies. The rotavirus antigen is captured on the SPR by a polyclonal anti-rotavirus VP6 antibody, and the detector antibody conjugate is composed of a mouse monoclonal anti-rotavirus VP6 antibody.
Here's an analysis of the provided text, focusing on the acceptance criteria and study details for the VIDAS Rotavirus Assay:
Acceptance Criteria and Study Details for the VIDAS Rotavirus Assay
This submission describes the VIDAS Rotavirus Assay, a diagnostic device for detecting rotavirus antigen in stool specimens. The primary study presented here is a standalone performance evaluation comparing the VIDAS RTV Assay to a commercially available EIA, with discrepancies resolved by a second EIA and electron microscopy (EM).
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Pivotal Study-Based Acceptance Criteria: | |
| Relative Specificity (compared to primary EIA with discrepancy resolution) | 95.1% |
| Relative Sensitivity (compared to primary EIA with discrepancy resolution) | 96.4% |
| Overall Agreement (compared to primary EIA with discrepancy resolution) | 96.5% |
| Overall Agreement (after EM resolution of all discrepant samples) | 94.8% |
| Number of Equivocal Results (following package insert instructions) | 4 |
| Number of Invalid Results (following package insert instructions) | 0 |
| Cross-reactivity/Interference (with approx. 50 microorganisms) | No cross-reactivity or interference observed. |
| Intra-assay Precision (Coefficient of Variation) | < 10% |
| Inter-assay Precision (Coefficient of Variation) | < 10% |
| Limit of Detection (concentration yielding positive result) | Approximately 2.3 x 10² viral particles/ml |
| Design Specifications (Implicitly met by device design): | |
| Assay Specificity (due to antibody type) | Conferred by polyclonal anti-rotavirus VP6 antibody (capture) and mouse monoclonal anti-rotavirus VP6 antibody (detector). |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- The document mentions "studies comparing the VIDAS RTV Assay to one commercially available EIA," indicating a test set was used.
- False Positive Calculation: 7 false positive samples. Given a relative specificity of 95.1%, this implies approximately 143 negative samples (7 / (1 - 0.951) ≈ 142.8).
- False Negative Calculation: 6 false negative samples. Given a relative sensitivity of 96.4%, this implies approximately 167 positive samples (6 / (1 - 0.964) ≈ 166.7).
- The overall agreement of 96.5% with 13 discrepant samples means the total sample size for the primary comparison was approximately 371 samples (13 / (1 - 0.965) ≈ 371.4).
- Therefore, the approximate test set size for the primary comparison was around 371 samples.
- 13 discrepant samples were further tested with EM.
- For cross-reactivity, "approximately 50 microorganisms" were tested.
- For Limit of Detection, "known concentrations of rotavirus antigen" were tested, but the sample size is not specified.
- Data Provenance: Not explicitly stated (e.g., country of origin, specific clinics).
- Retrospective or Prospective: Not explicitly stated, though performance studies for regulatory submissions are often prospective or use banked samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Number of Experts: Not applicable in the traditional sense of human consensus reading for ground truth.
- Qualifications of Experts: Not applicable.
4. Adjudication Method for the Test Set
- Adjudication Method: A 2+1 adjudication process was used for the primary comparison:
- The VIDAS RTV Assay was compared to a "commercially available EIA."
- Discrepancies between the VIDAS RTV Assay and the initial EIA were resolved by a "second EIA."
- Furthermore, the 13 samples that remained discrepant after the second EIA resolution were "further tested with EM (Electron Microscopy)." EM serves as the gold standard for visual confirmation of viral particles.
5. If a Multi-reader Multi-case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC comparative effectiveness study was not done. This study assesses the performance of a diagnostic device (the VIDAS RTV Assay) against a comparator method, not the impact of AI assistance on human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, a standalone performance study was done. The entire description pertains to the direct performance of the VIDAS RTV Assay (an automated immunoassay) in detecting rotavirus antigen in stool samples. There is no human-in-the-loop performance described.
7. The Type of Ground Truth Used
- The ground truth evolved through a hierarchical approach:
- Initial Ground Truth: Established by resolution with a second commercially available EIA in cases of disagreement with the primary EIA.
- Confirmatory Ground Truth (for discrepant samples): Electron Microscopy (EM). EM is considered a strong reference standard for viral detection due to its ability to visualize viral particles directly.
- For the Limit of Detection, rotavirus antigen was "quantitated via EM," indicating EM was used to determine the known concentration of rotavirus.
8. The Sample Size for the Training Set
- Not applicable. This describes the performance of an immunoassay, not a machine learning algorithm that requires a "training set." The assay's "training" is inherent in its biochemical design and reagent selection.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. See point 8.
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K965092 MAY - 5 1997
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SUMMARY: Safety and Effectiveness Information for the VIDAS Rotavirus Assay
The VIDAS Rotavirus (RTV) Assay detects the presence of rotavirus antigen in stool specimens. It is substantially equivalent to the Cambridge Biotech Rotaclone Rotavirus Diagnostic Kit. Safety and effectiveness issues for qualitative antigen detection enzyme immunoassays such as the VIDAS RTV Assay may include the following:
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- False positive results: In studies comparing the VIDAS RTV Assay to one commercially available EIA with resolution of discrepancies by a second EIA, there were 7 false positive samples. This results in a relative specificity of 95.1%, with overall agreement of 96.5%.
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- False negative results: In studies comparing the VIDAS RTV Assay to one commercially available EIA with resolution of discrepancies by a second EIA, there were 6 false negative samples. This results in a relative sensitivity of 96.4%, with overall agreement of 96.5%.
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- The 13 discrepant samples were furthur tested with EM. Of the 13 discrepant results, 4 resolved positive and 4 resolved negative in agreement with VIDAS RTV. Three specimens were VIDAS positive and EIA negative, confirmed negative. One specimen was VIDAS negative and EIA positive, confirmed positive. One discrepant result was not tested. The overall agreement of all samples is 94.8%
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- Equivocal results: In the studies done to support the VIDAS RTV Assay performance claims, there were 4 equivocal results when following package insert instructions.
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- Invalid results: In the studies done to support the VIDAS RTV Assay performance claims, there were no invalid results.
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- Cross-reactivity and interference: A panel of approximately 50 microorganisms representing normal enteric flora or common enteric pathogens was tested in the VIDAS RTV Assay. No cross-reactivity or interference was observed with the organisms tested.
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- Precision: In the studies done to support the VIDAS RTV Assay performance claims, the intra-assay precision testing showed coefficients of variation of less than 10%. The inter-assay precision testing gave coefficients of variation of less than 10%.
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- Assay specificity is conferred by the use of two antibodies. The rotavirus antigen is captured on the SPR by a polyclonal anti-rotavirus VP6 antibody, and the detector antibody conjugate is composed of a mouse monoclonal anti-rotavirus VP6 antibody .
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- Limit of detection: The limit of detection is defined as the concentration of organism vielding a test value greater than the negative threshold. The results of testing known concentrations of rotavirus antigen (quantitated via EM) in the VIDAS RTV Assay showed the limit of detection to be approximately 2.3 x 102 viral particles/ ml.
The VIDAS RTV Assay must be used according to package insert instructions when testing stool specimens for the presence of rotavirus antigen. Additional information and references may be found in the package insert.
§ 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.