(104 days)
The Wielisa anti-GBM Test Kit is an Enzyme Linked Immunosorbent Assay (ELISA) for the detection and semi-quantitation of IgG antibodies in human serum to GBM (glomerular basement membrane). The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Goodpasture syndrome. FOR IN VITRO DIAGNOSTIC USE.
The Wielisa anti-GBM Test Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection and semi-quantitation of IgG antibodies to glomerular basement membrane(GBM) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Goodpasture syndrome. FOR IN VITRO DIAGNOSTIC USE. The wells of the microtiter strips are coated with purified GBM antigen. During the first incubation, specific antibodies in diluted serum, will bind to the antigen coating. The wells are then washed to remove unbound antibodies and other components. A conjugate of alkaline phosphatase-labeled antibodies to human IgG binds to the antibodies in the wells in this second incubation. After a further washing step, detection of specific antibodies is obtained by incubation with substrate solution. The amount of bound antibodies correlates to the color intensity and is measured in terms of absorbance (optical density (OD)). The absorbance is then calculated against a calibrator curve and the results are given in arbitrary units.
The Wieslab AB Ideon Research Park's Wielisa anti-GBM Test Kit is an enzyme-linked immunosorbent assay (ELISA) designed for the detection and semi-quantitation of IgG antibodies to glomerular basement membrane (GBM) in human sera. The assay aims to aid in the diagnosis of Goodpasture syndrome. The device applied for 510(k) clearance (K974169) to the FDA. The submission outlines studies demonstrating the performance characteristics of the device.
Here's a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical targets in the provided document. Instead, the performance is demonstrated through comparison with clinical characterization and existing methods. The implied acceptance is that the device demonstrates high sensitivity and specificity in diagnosing anti-GBM nephritis and distinguishing it from other conditions, as well as showing comparable results to a predicate device and an alternative ELISA.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Clinical Sensitivity (anti-GBM nephritis) | High sensitivity for detecting anti-GBM nephritis. | 100% (95% CI: 95.0-100%) |
| Clinical Specificity (Blood donors) | High specificity for healthy individuals. | 100% (95% CI: 97.5-100%) |
| Clinical Specificity (Systemic vasculitis: WG and MP) | High specificity for other autoimmune conditions (Systemic vasculitis). | 96.9% (95% CI: 90.7-100%) |
| Clinical Specificity (SLE) | High specificity for other autoimmune conditions (SLE). | 100% (95% CI: 92.6-100%) |
| Clinical Specificity (RA) | High specificity for other autoimmune conditions (RA). | 100% (95% CI: 82.7-100%) |
| Relative Sensitivity (vs. GBM IFA) | High sensitivity when compared to Immunofluorescence Assay (IFA) as an existing method. | 100.0% (95% CI: 94.6-100.0%) |
| Relative Specificity (vs. GBM IFA) | High specificity when compared to Immunofluorescence Assay (IFA) as an existing method. | 88.9% (95% CI: 67.9-100.0%) |
| Relative Accuracy (vs. GBM IFA) | High overall accuracy when compared to Immunofluorescence Assay (IFA). | 98.4% (95% CI: 95.3-100.0%) |
| Relative Sensitivity (vs. Alternate ELISA) | High sensitivity when compared to another commercial ELISA. | 92.7% (95% CI: 84.6-100%) |
| Relative Specificity (vs. Alternate ELISA) | High specificity when compared to another commercial ELISA. | 100% (95% CI: 95.9-100%) |
| Relative Accuracy (vs. Alternate ELISA) | High overall accuracy when compared to another commercial ELISA. | 97.4% (95% CI: 94.3-100%) |
| Batch to Batch Variation (CV%) | Low coefficient of variation (CV%) to demonstrate consistency across different manufacturing batches. | 3.1% - 17.7% (for samples with mean values 16-134 units) |
| Inter-assay Precision (CV%) | Low coefficient of variation (CV%) to demonstrate consistency between different assay runs. | 3.0% (for 46 units) and 7.6% (for 154 units) |
| Intra-assay Precision (CV%) | Low coefficient of variation (CV%) to demonstrate consistency within a single assay run. | 10% (for 77 units) |
| Linearity (r value) | High correlation (r value close to 1) for serial dilutions. | 0.823 - 0.994 |
2. Sample Size Used for the Test Set and Data Provenance
- Clinical Sensitivity and Specificity Study (Table 1):
- Sample Size: 272 frozen sera.
- Data Provenance: Retrospective, with clinical characterization. The country of origin is not specified, but the applicant's address is in Sweden.
- Relative Sensitivity and Specificity vs. GBM IFA (Table 2):
- Sample Size: 68 frozen retrospective sera.
- Data Provenance: Retrospective. Country of origin not specified.
- Relative Sensitivity and Specificity vs. Alternate ELISA (Table 3):
- Sample Size: 122 frozen retrospective sera.
- Data Provenance: Retrospective. Country of origin not specified.
3. Number of Experts Used to Establish Ground Truth and Qualifications
The document does not explicitly state the number of experts used or their detailed qualifications (e.g., radiologist with 10 years of experience).
- For Table 1 (Clinical Sensitivity and Specificity), the "clinical characterization" of the sera implies that a clinical diagnosis was used as ground truth. This would typically involve review by clinicians, potentially specialists in nephrology or rheumatology, based on a combination of clinical symptoms, other laboratory tests, and potentially biopsy results. However, the exact number and qualifications are not provided.
- For Table 2 (Relative Sensitivity and Specificity vs. GBM IFA), the Immunofluorescence Assay (IFA) results are used as the comparator, which serves as a form of ground truth or an established benchmark. The interpretation of IFA typically requires experienced laboratory personnel or pathologists.
- For Table 3 (Relative Sensitivity and Specificity vs. Alternate ELISA), another commercial ELISA is used as the comparator, also serving as an established benchmark.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method (like 2+1 or 3+1) for resolving discrepancies in diagnostic classifications for the ground truth. It relies on "clinical characterization" or comparison with established methods (IFA, alternate ELISA).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The study focuses on the performance of the in-vitro diagnostic device itself, not on the improvement of human readers with or without AI assistance. The device is a laboratory assay, not a tool for interpretation by human readers in the same way an imaging AI might be.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented are essentially standalone performance evaluations of the Wielisa anti-GBM Test Kit. This is an immunoassay that produces quantitative results (optical density, then arbitrary units) and then applies defined cut-offs (e.g., 20 units positive) to classify samples. There is no "human-in-the-loop" interaction in the interpretation of the assay's output as part of the primary device function itself, beyond a clinician interpreting the final numerical result provided by the kit in the context of a patient's overall clinical picture.
7. The Type of Ground Truth Used
- Clinical Sensitivity and Specificity (Table 1): Clinical diagnosis based on "clinical characterization" of the sera. This would likely stem from a combination of patient symptoms, medical history, other diagnostic tests, and potentially pathology (e.g., kidney biopsy for anti-GBM nephritis).
- Relative Sensitivity and Specificity vs. GBM IFA (Table 2): Results from Immunofluorescence Assay (IFA) for GBM antibodies. IFA is considered a standard method for detecting these antibodies.
- Relative Sensitivity and Specificity vs. Alternate ELISA (Table 3): Results from an alternate commercial ELISA for anti-GBM antibodies. This serves as a comparison against another established in-vitro diagnostic approach.
8. The Sample Size for the Training Set
The document does not explicitly mention a separate "training set" or "validation set" in the context of machine learning. For an ELISA kit, development typically involves optimizing reagents and conditions using various samples, but this is not typically referred to as a "training set" in the same way as in AI/ML. The provided sample sizes (272, 68, 122) appear to be for the performance evaluation/testing of the device with established parameters.
9. How the Ground Truth for the Training Set Was Established
Since a "training set" in the AI/ML sense is not explicitly described, neither is the method for establishing its ground truth. However, for the development of such an assay, the "ground truth" used during optimization would typically involve well-characterized patient samples with confirmed diagnoses (e.g., biopsy-proven Goodpasture syndrome, healthy controls, or patients with other well-defined autoimmune diseases).
§ 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).