(339 days)
Visuwell® Reagin II is an enzyme-linked immunosorbent assay for the in vitro qualitative detection of non-treponemal (reagin) antibodies as a screening test in syphilis serology. It is not intended for use in screening blood or plasma donors.
Visuwell® Reagin II is an enzyme-linked immunosorbent assay for the in vitro qualitative detection of non-treponemal (reagin) antibodies in syphills serology. In this device, serum is incubated with a mixture of cardiolipin, lecithin, cholesterol dried to a polystyrene solid phase. Antilipid antibodies react with the lipoidal antigen to form an immune complex. The presence of non-treponemal complexed antibodies is detected with a monoclonal anti-human lgG-peroxidase conjugate. The presence of bound conjugate is detected by the addition of enzyme substrate and subsequent development of colour. The reaction is stopped by the addition of acid and colour intensity is determined spectrophotometrically at 450 nm. Test results are interpreted relative to a floating cutoff based on the negative control. Positive and negative controls are used for establishing test validity.
Acceptance Criteria and Device Performance Study for Visuwell® Reagin II
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Acceptance Criteria (Reference Non-Treponemal Tests Performance) | Visuwell® Reagin II Reported Performance | Met Acceptance Criteria? |
|---|---|---|---|
| Specificity | 99.5% | 97.1% | Substantially equivalent |
| Sensitivity (Untreated Syphilis) | 95.8% | 92.2% | Substantially equivalent |
| Sensitivity (Treatment Status Unknown) | 82.4% | 93.2% | Substantially equivalent (Exceeded) |
| Sensitivity (Treated Syphilis) | 90.2% | 75.4% | Lower reactivity, but considered substantially equivalent for untreated syphilis detection. Suggests potential for monitoring therapy. |
| Predictive Value of Positive (STD Population) | 99.4% | 97.4% | Substantially equivalent |
| Predictive Value of Negative (All Sites) | 99.5% | 99.0% | Substantially equivalent |
| Specificity in Cross-Reactivity (Non-Syphilitic Conditions) | 91.9% | 86.8% | Substantially equivalent |
| Overall Agreement | Not explicitly stated as a single number (comparison to reference tests) | 96.5% | Substantially equivalent |
Note on "Substantially equivalent": The report explicitly states that Visuwell® Reagin II was "substantially equivalent" in performance to the reference tests despite some numerical differences. For example, for sensitivity in treated syphilis, Visuwell® Reagin II showed lower reactivity (75.4% vs 90.2%), but this was interpreted as potentially beneficial for therapy monitoring, and the device was still deemed substantially equivalent for its primary intended use of detecting non-treponemal antibody in untreated syphilis.
2. Sample Sizes Used for the Test Set and Data Provenance
- Specificity Comparison: 10,738 specimens from random, low-risk, and high-risk populations.
- Sensitivity Comparison:
- 306 patients with untreated syphilis
- 74 patients with unknown treatment status
- 325 patients with treated syphilis
- Predictive Values:
- Predictive value of positive calculated for the Sexually Transmitted Disease (STD) population.
- Predictive value of negative calculated with data from "all sites."
- Cross-Reactivity: 151 specimens from individuals with various bacterial, viral, and auto-immune disorders, including syphilis biological false-positives, pregnancy, and drug abuse.
- Overall Agreement: 11,443 total sera (presumably the aggregate of relevant specificity and sensitivity samples).
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It refers to "various populations" and "all sites," suggesting a multicenter study, but lacks specific details on geographical location or study design.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not provide information on the number of experts used or their qualifications for establishing ground truth. The comparison is made against "legally marketed reference non-treponemal tests" (VDRL, RPR, RST), implying that the results from these established tests were considered the ground truth.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method (e.g., 2+1, 3+1). The nature of the study involves comparing the Visuwell® Reagin II results directly to the results obtained from established reference non-treponemal tests. The interpretation of these reference tests (VDRL, RPR, RST) is described as "subjective... according to the presence or absence of flocculation," which implies expert interpretation of the reference test results themselves, but no explicit adjudication process for disagreements is mentioned.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was mentioned. The study focused on the performance of the Visuwell® Reagin II device compared to existing non-treponemal tests, not on human reader performance with or without AI assistance.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)
Yes, this was a standalone performance study. Visuwell® Reagin II is an "enzyme-linked immunosorbent assay," and its results are "objectively spectrophotometrically interpreted." This indicates an automated or semi-automated process where the device's output (color intensity) is directly converted into a result relative to a floating cutoff, without human-in-the-loop interpretation being the primary focus of the comparison with reference methods.
7. Type of Ground Truth Used
The ground truth was established by comparison to existing, legally marketed reference non-treponemal tests (Venereal Disease Research Laboratory (VDRL) Slide Test, Rapid Plasma Reagin (RPR) Card Test, Reagin Screen Test (RST)). These tests are implied to be the standard of care for detecting non-treponemal antibodies in syphilis serology. Clinical diagnosis of syphilis (e.g., "patients with untreated syphilis") was also used to categorize some samples for sensitivity calculations.
8. Sample Size for the Training Set
The document does not provide specific details about a dedicated "training set" or its size for the Visuwell® Reagin II device development. The information presented pertains to a performance study evaluating the final device's performance against reference methods.
9. How the Ground Truth for the Training Set Was Established
As no specific training set is described in the provided text, there is no information on how its ground truth was established. The focus of this submission is on the validation of the device, comparing its performance to established methods in various clinical populations.
§ 866.3820
Treponema pallidum nontreponemal test reagents.(a)
Identification. Treponema pallidum nontreponemal test reagents are devices that consist of antigens derived from nontreponemal sources (sources not directly associated with treponemal organisms) and control sera (standardized sera with which test results are compared) used in serological tests to identify reagin, an antibody-like agent, which is produced from the reaction of treponema microorganisms with body tissues. The identification aids in the diagnosis of syphilis caused by microorganisms belonging to the genusTreponema and provides epidemiological information on syphilis.(b)
Classification. Class II (performance standards).