(255 days)
An enzyme-linked immunoassay (ELISA) for the detection of IgG antibodies to complexes formed by oxidized low-density lipoprotein (oxLDL) with ß2-glycoprotein I (ß2GPI) in individuals with systemic lupus erythematosus (SLE) and lupus-like disorders (antiphospholipid syndrome).
The IgG Anti-AtherOx Test Kit is an indirect ELISA detecting IgG anti-oxLDL/B2GPI antibodies. Diluted serum samples, calibrator(s), and controls are incubated in microwells coated with the oxLDL-ß2GPI complex. Incubation allows the IgG anti-oxLDL-B2GPI antibody present in the samples to react with the immobilized antigen complex. After the removal of unbound serum proteins by washing, anti-human IgG antibodies, labeled with horseradish peroxidase (HRP), are added forming complexes with the bound IgG anti-oxLDL-B2GPI antibody. Following another washing step, the bound enzyme-antibody conjugate is assayed by the addition of a solution containing tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2) as the chromogenic substrate. Color develops in the wells at an intensity proportional to the serum concentration of IgG anti-oxLDL-B2GPI antibody. Results are obtained by reading the OD (optical density or absorbance) of each well in a spectrophotometer. Calibrator sera are provided, with the IgG anti-oxLDL-B2GPI antibody concentration expressed in G Units. A log-log regression analysis is performed with calibrator values plotted against calibrator mean ODs. Controls and patient results are determined from the calibration curve.
Here's an analysis of the provided 510(k) summary regarding acceptance criteria and the study that proves the device meets those criteria:
The document provided does not contain explicit "acceptance criteria" for clinical performance in the typical sense of metrics like sensitivity, specificity, or agreement thresholds against an established reference standard. Instead, the clinical testing section focuses on demonstrating agreement with a legally marketed predicate device (REAADS IgG Anti-Cardiolipin Test Kit) across various patient populations. Therefore, the "acceptance criteria" are implied by the observed agreement rates with the predicate, rather than set a-priori.
Acceptance Criteria and Reported Device Performance
Given the nature of the submission (demonstrating substantial equivalence to a predicate device), the primary "acceptance criterion" appears to be sufficient agreement with the predicate device across different patient populations.
| Performance Metric (Implied Acceptance) | Reported Device Performance |
|---|---|
| Agreement with Predicate Device (Overall) | 90.2% (404/448) |
| Agreement for Healthy Controls | |
| Positive Percent Agreement | N/A (0 cases) |
| Negative Percent Agreement | 97.1% (95% CI = 94.8-99.4%) |
| Overall % Agreement | 97% (95% CI = 94.8-99.4%) |
| Agreement for Rheumatoid Arthritis | |
| Positive Percent Agreement | 100% (1 case) |
| Negative Percent Agreement | 82.7% (95% CI = 75.2-90.2%) |
| Overall % Agreement | 82.8% (95% CI = 75.4-90.3%) |
| Agreement for Systemic Lupus Erythematosus (SLE) | |
| Positive Percent Agreement | 76.0% (95% CI = 59.3-92.7%) |
| Negative Percent Agreement | 86.4% (80.3-92.6%) |
| Overall % Agreement | 84.6% (95% CI = 78.7-90.5%) |
| Agreement for Secondary Anti-Phospholipid Syndrome | |
| Positive Percent Agreement | 73.9% (95% C1 = 56.0-91.9%) |
| Negative Percent Agreement | 88.7% (95% CI = 81.4-96.1%) |
| Overall % Agreement | 85.1% (95% CI = 77.9-92.3%) |
| Agreement for Pregnancy Morbidity (Subgroup) | |
| Positive Percent Agreement | 0% (0 cases) |
| Negative Percent Agreement | 92.3% (77.8-100%) |
| Overall % Agreement | 80.0% (95% CI = 59.8-100%) |
| Agreement for Arterial Thrombosis (Subgroup) | |
| Positive Percent Agreement | 78.6% (95% CI = 57.1-100%) |
| Negative Percent Agreement | 96.4% (95% CI = 89.6-100%) |
| Overall % Agreement | 90.5% (95% CI = 84.7-100%) |
| Agreement for Venous Thrombosis (Subgroup) | |
| Positive Percent Agreement | 85.7% (95% CI = 59.8-100%) |
| Negative Percent Agreement | 80.0% (95% CI = 65.7-94.3%) |
| Overall % Agreement | 81.1% (95% CI = 68.5-93.7%) |
Study Information:
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Sample Size used for the test set and the data provenance:
- Test Set Sample Size: A total of 448 serum samples were tested:
- 205 from healthy control patients.
- 99 from patients with rheumatoid arthritis.
- 143 from patients with systemic lupus erythematosus (SLE).
- Data Provenance: Not explicitly stated (e.g., country of origin). The study appears to be retrospective as it uses "serum samples from" patients, implying they were collected prior to the study for testing.
- Test Set Sample Size: A total of 448 serum samples were tested:
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not state that experts were used to establish a "ground truth" for the test set. Instead, the device's performance is compared to a legally marketed predicate device (REAADS IgG Anti-Cardiolipin Test Kit). The predicate device itself serves as the reference for comparison, not an independent expert consensus.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- There is no mention of an adjudication method in the context of expert review or ground truth establishment. The comparison is directly between the new device and the predicate device.
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If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- This is an in vitro diagnostic (IVD) device (ELISA test kit) for detecting antibodies in serum. It is not an AI-powered diagnostic imaging device or a device involving human readers/interpreters in the presented study. Therefore, an MRMC study or evaluation of human reader improvement with AI assistance is not applicable to this submission.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- This is an IVD test kit. The "standalone" performance is essentially what is presented in the study: the direct comparison of the assay's results against the predicate device. There is no human-in-the-loop component in the interpretation of the test results described here beyond the laboratory technician performing the assay and reading the ODs.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" (or reference standard for comparison) in this 510(k) submission is the performance of the REAADS IgG Anti-Cardiolipin Test Kit, a legally marketed predicate device. The clinical diagnoses of the patients (healthy controls, RA, SLE, APS) serve as classification for the samples, but the direct comparison is test-vs-test.
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The sample size for the training set:
- The document does not explicitly mention a "training set" for the purpose of machine learning or algorithm development. This is a traditional ELISA assay kit. The provided clinical study data (448 samples) represent the "test set" for performance evaluation, not a training set. Development and optimization of the assay would typically involve internal validation, but those details are not part of this summary in terms of a "training set" as understood in AI/ML contexts.
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How the ground truth for the training set was established:
- As there's no mention of a "training set" in the context of algorithm development, this question is not applicable. The development of the assay itself would have involved establishing specific assay parameters, but the mechanism for doing so isn't detailed as "ground truth establishment" for a training set.
§ 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).