(60 days)
This enzyme-linked immunosorbent assay (ELISA) is indicated for the detection and measurement of circulating IgG antibodies to ß2 Glycoprotein in human serum. The presence of these antibodies, in combination with clinical observations and other serological tests, can aid in the diagnosis of Primary and Secondary Antiphospholipid Syndrome.
An enzyme-linked immunosorbent assay (ELISA) designed for the detection and measurement of IgG antibodies to ß, Glycoprotein I in human serum. The ELISA methodology is commonly used for serum antibody evaluations. Purified human B, glycoprotein has been attached to the inner surfaces of the microwell plate. During the initial incubation step, specific antibodies in patient serum will bind to the antigen and are immobilized on the surface. After incubation and a wash step, a peroxidase labeled anti human IgG (gamma chain specific) second antibody is added to the wells to react with the immobilized anti beta 2 GP1 antibodies. After incubation and another wash step, the substrate is added. In the wells where the specific antigenantibody-HRP complex remains bound, the peroxidase enzyme catalyzes a color change in the substrate. After the enzymatic reaction is stopped, the colored product is read in an EIA plate reader at a specified wavelength.
Here is an analysis of the provided FDA 510(k) summary for the VIRGO® ß₂ Glycoprotein I IgG Antibody Kit, detailing acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for this device are not explicitly stated as numerical thresholds (e.g., "sensitivity must be > X%", "specificity must be > Y%"). Instead, the document focuses on demonstrating the device's ability to effectively detect IgG antibodies to ß₂ Glycoprotein I in human serum, showing differentiation between positive and negative samples, and agreement with an existing commercial assay.
The reported device performance is presented in tables within the document. Since specific acceptance criteria (numerical targets) are not provided, the table below presents the demonstrated performance metrics as reported. The primary performance metrics are related to diagnostic accuracy (sensitivity, specificity) and precision.
| Performance Metric | Acceptance Criteria (Implicit/Demonstrated) | Reported Device Performance |
|---|---|---|
| Diagnostic Accuracy | Implicit: The device should show clinical utility in detecting IgG antibodies to ß₂ Glycoprotein I in patients with APS and differentiating them from healthy individuals and those with other autoimmune/infectious diseases. It should also show reasonable agreement, sensitivity, and specificity when compared to a commercially available anti-cardiolipin IgG EIA assay. | |
| Initial Clinical Panel | Distinction between patient groups (APS, SLE+APS) and control groups (Rheumatoid Arthritis, SLE (No APS), Scl-70 (No APS), Infectious, Normals). | APS: 74.4% positive (43 samples) |
| SLE + APS: 85.7% positive (7 samples) | ||
| Rheumatoid Arthritis: 2.5% positive (40 samples) | ||
| SLE (No APS): 10.0% positive (20 samples) | ||
| Scl-70 (No APS): 0% positive (20 samples) | ||
| Infectious: 5.0% positive (40 samples) | ||
| Normals: 0.8% positive (120 samples) | ||
| Relative Sensitivity | Implicit: Reasonable sensitivity when compared to a predicate/comparator anti-cardiolipin IgG EIA assay. | 72.7% (95% CI: 60.3% to 82.3%) |
| Relative Specificity | Implicit: Reasonable specificity when compared to a predicate/comparator anti-cardiolipin IgG EIA assay. | 92.6% (95% CI: 83.1% to 97.0%) |
| Relative Agreement | Implicit: Reasonable overall agreement with a predicate/comparator anti-cardiolipin IgG EIA assay. | 81.7% (95% CI: 70.2% to 89.5%) |
| Precision | Implicit: Consistent and reproducible results for inter-assay and intra-assay measurements across various sample types (low, medium, high concentrations, controls, calibrators). Lower % C.V. (Coefficient of Variation) indicates better precision. | |
| Inter Assay % C.V. | No explicit numerical criterion. | Range from 1.7% to 14.6% for samples and controls, 1.7% to 7.5% for calibrator dilutions. |
| Intra Assay % C.V. | No explicit numerical criterion. | Range from 6.1% to 11.6% for samples. |
2. Sample Sizes Used for the Test Set and Data Provenance
-
Initial Clinical Panel:
- Primary APS: 43 samples
- SLE + APS: 7 samples
- Rheumatoid Arthritis: 40 samples
- SLE (No APS): 20 samples
- Scl-70 (No APS): 20 samples
- Infectious: 40 samples
- Normals: 120 samples
- Total for initial clinical panel: 290 samples.
- Data Provenance: The document states "clinically characterized serum specimens" and "characterized serum specimens from individuals diagnosed with Primary APS and other diseases." It does not specify the country of origin. The study appears to be retrospective, as samples were "characterized" (diagnosed) prior to being tested with the device.
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Comparison with aCL IgG:
- Clinically characterized serum samples: 37 samples (subset of the above panel or overlapping)
- Apparently healthy donors: 23 samples
- Total for comparison with aCL IgG: 60 samples.
- Data Provenance: Same as above, likely retrospective based on prior characterization. No country of origin specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document states that the samples were "clinically characterized serum specimens" or "from individuals diagnosed with Primary APS and other diseases." This implies that diagnoses were made by clinicians using standard diagnostic criteria. However, no specific number of experts, their names, or detailed qualifications (e.g., "radiologist with 10 years of experience") are provided for establishing the ground truth for the test set.
4. Adjudication Method for the Test Set
The document does not describe an explicit adjudication method (e.g., 2+1, 3+1) for the diagnoses of the "clinically characterized serum specimens." The implication is that these were established clinical diagnoses.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not done. This device is an in-vitro diagnostic (IVD) assay designed to directly detect antibodies, not to assist human readers in interpreting images or other data. The comparative study was between the new assay and a predicate/commercial antibody assay (anti-cardiolipin IgG EIA assay), not human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this was a standalone performance study of the device (assay kit) itself. The device (VIRGO® ß₂ Glycoprotein I IgG Antibody Kit) is an ELISA-based diagnostic test that provides a quantitative or qualitative (positive/negative based on cutoff) result for ß₂ Glycoprotein I IgG antibodies. Its performance characteristics (precision, diagnostic accuracy) were evaluated directly, without human interpretation as part of the primary output, other than reading the EIA plate reader results to determine the optical density.
7. The Type of Ground Truth Used
The ground truth used for the diagnostic accuracy studies was clinical diagnosis. Samples were obtained from individuals who had already been "diagnosed with Primary APS and other diseases." For the "Normals" group, the ground truth was "apparently healthy donors."
8. The Sample Size for the Training Set
The document does not explicitly describe a separate training set or its sample size. The performance data presented appears to be from a single evaluation study using "clinically characterized serum specimens." For IVD kits like this, the "development" or "training" often involves internal optimization of reagents, cutoff determination, and calibration, which typically uses various characterized panels internally, but these are not usually detailed in the same way as a machine learning training set for software. The "Calibrator" samples mentioned in the precision section are for daily assay standardization, not a machine learning training set.
9. How the Ground Truth for the Training Set Was Established
As no explicit training set is described in the provided summary, there is no information on how its ground truth was established. For the overall development of such diagnostics, ground truth would typically be based on established clinical diagnoses and/or reference laboratory results.
§ 866.5660 Multiple autoantibodies immunological test system.
(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).