(508 days)
The EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) kit is an immune line-blot strip test intended for the qualitative detection of IgG class antibodies against 8 different antigens: AMA-M2, M2-3E (BPO), Sp100, PML, gp210, LKM-1, LC-1 and SLA/LP in human serum and plasma (EDTA, Li-heparin, Citrate). Detection of these antibodies is used as an aid in the diagnosis of autoimmune liver diseases in conjunction with other laboratory and clinical findings.
The EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) consists of antigen coated test strips, a positive control, alkaline phosphatase-labelled anti-human 1gG conjugate, sample buffer, wash buffer concentrate, NBT/BCIP substrate solution tray, test instruction, evaluation protocol and reaction control card.
The EUROIMMUN EUROLINE Profile Autoimmune Liver Disease 8 Ag (IgG) Kit is an immune line-blot strip test intended for the qualitative detection of IgG class antibodies against 8 different antigens: AMA-M2, M2-3E (BPO), Sp100, PML, gp210, LKM-1, LC-1 and SLA/LP as an aid in the diagnosis of autoimmune liver diseases.
Here's an analysis of the provided information regarding the acceptance criteria and study proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state quantitative acceptance criteria (e.g., "sensitivity must be >X%"). Instead, substantial equivalence is claimed based on agreement with predicate devices and clinical sensitivity/specificity in diseased and control populations. The "acceptance criteria" are implied to be satisfactory agreement with predicates and clinically relevant sensitivity and specificity values.
| Antigen | Performance Metric | Reported Device Performance (%) (95% C.I.) |
|---|---|---|
| AMA-M2 and/or M2-3E | Positive agreement with predicate (n=281) | 95.1% (88.9 – 98.4%) |
| Negative agreement with predicate (n=293) | 98.9% (95.9 – 99.9%) | |
| Sensitivity for PBC (n=205) | AMA-M2: 85.4% (79.8 - 89.9%) | |
| M2-3E: 78.0% (71.8 - 83.5%) | ||
| Specificity for PBC (n=529) | AMA-M2: 99.1% (97.8 - 99.7%) | |
| M2-3E: 99.6% (98.6 - 100.0%) | ||
| Sp100 | Positive agreement with predicate (n=34) | 94.4% (81.3 – 99.3%) |
| Negative agreement with predicate (n=252) | 99.2% (97.2 – 99.9%) | |
| Sensitivity for PBC (n=205) | 26.3% (20.5 - 32.9%) | |
| Specificity for PBC (n=529) | 99.8% (99.0 - 100.0%) | |
| PML | Sensitivity for PBC (n=205) | 28.3% (22.2 - 35.0%) |
| Specificity for PBC (n=529) | 99.2% (98.1 - 99.8%) | |
| gp210 | Positive agreement with predicate (n=33, but 30 discrepant) | 100.0% (89.4 – 100.0%) (Note: Significant discrepancies with predicate noted, but agreement calculated as 100% due to all predicate positives being positive in device. Device showed higher sensitivity.) |
| Negative agreement with predicate (n=231) | 88.5% (84.0 – 92.1%) | |
| Sensitivity for PBC (n=205) | 33.2% (26.8 - 40.1%) | |
| Specificity for PBC (n=529) | 97.2% (95.4 - 98.4%) | |
| LKM-1 | Positive agreement with predicate (n=50) | 92.6% (82.1 – 97.9%) |
| Negative agreement with predicate (n=267) | 98.9% (96.8 – 99.8%) | |
| Sensitivity for AIH (n=163) | 12.3% (7.7 - 18.3%) | |
| Sensitivity for AIH Type 2 (n=21) | 85.7% (63.7 - 97.0%) | |
| Specificity for AIH (n=571) | 99.8% (99.0 - 100.0%) | |
| LC-1 | Sensitivity for AIH (n=163) | 9.2% (5.2 - 14.7%) |
| Sensitivity for AIH Type 2 (n=21) | 66.7% (43.0 - 85.4%) | |
| Specificity for AIH (n=571) | 99.6% (98.7 - 100.0%) | |
| SLA/LP | Positive agreement with predicate (n=30) | 100.0% (88.4 – 100.0%) |
| Negative agreement with predicate (n=266) | 99.6% (97.9 – 100.0%) | |
| Sensitivity for AIH (n=163) | 9.2% (5.2 - 14.7%) | |
| Sensitivity for AIH Type 1 (n=142) | 10.6% (6.0 - 16.8%) | |
| Specificity for AIH (n=571) | 98.8% (97.5 - 99.5%) |
2. Sample Sizes Used for the Test Set and Data Provenance:
- Method Comparison (with predicate devices): 295 clinically characterized samples for most antigens.
- Composition: 99 from patients with autoimmune hepatitis (AIH), 104 from patients with primary biliary cirrhosis (PBC), 42 from patients with viral hepatitis, and 50 from patients with rheumatoid arthritis (RA).
- Additional: 6 to 29 artificial samples for each antigen (created by mixing positive and negative samples) were used for samples close to the cut-off for predicate ELISA testing only.
- Provenance: "obtained from different sources". The specific country of origin is not mentioned. The study appears to be retrospective based on the description of using "clinically characterized samples."
- Clinical Studies (Sensitivity and Specificity): Panels with a total of 734 samples.
- PBC Sensitivity Panel: 205 patients with primary biliary liver cirrhosis.
- PBC Specificity Panels: 163 Autoimmune hepatitis, 39 Viral hepatitis, 19 Primary sclerosing cholangitis, 308 Further controls (various autoimmune diseases and healthy donors). Total = 529.
- AIH Sensitivity Panel: 163 Autoimmune hepatitis (Type 1 and Type 2 breakdowns provided).
- AIH Specificity Panels: 205 Primary biliary liver cirrhosis, 39 Viral hepatitis, 19 Primary sclerosing cholangitis, 308 Further controls. Total = 571.
- Provenance: "obtained from different sites". Specific country of origin is not mentioned. Appears retrospective.
- Expected Values/Reference Range: 150 healthy blood donors.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- The ground truth for the clinical characterization of samples (AIH, PBC, etc.) was established based on criteria from established medical organizations:
- AIH cases: Criteria of the International Autoimmune Hepatitis Group (IAIHG) and recommendations from the American Association for the Study of the Liver Diseases (AASLD).
- PBC cases: Consensus statements of the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL), including the presence of disease-related autoantibodies (specifically AMA).
- The document does not specify the number or qualifications of individual experts who applied these criteria to the specific patient samples. It relies on the robust nature of the established diagnostic criteria themselves.
4. Adjudication Method for the Test Set:
- For the EUROIMMUN EUROLINE device, the visual interpretation of band intensity was done by comparison with a reaction control card. The impact of different readers was assessed: "different samples covering the whole range of antigens were evaluated by three different technicians and under 3 different light conditions... No deviation was observed between the individual readings and from the light conditions." This indicates no formal adjudication process between different readers as performance was consistent.
- For the method comparison, borderline predicate results were excluded from agreement calculations, but no explicit adjudication method for reconciling discrepant results between the device and predicate is described beyond noting the discrepancies and potential reasons for them (e.g., gp210 antigen differences).
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done:
- No, a formal MRMC comparative effectiveness study was not performed in the sense of comparing human readers' performance with and without AI assistance to quantify an effect size of AI improvement.
- The study includes an assessment of reader variability for the device itself ("different samples... evaluated by three different technicians"), which is a form of multiple-reader assessment, but not a comparative effectiveness study involving AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- The device is an immune lineblot strip test that requires visual interpretation of band intensity by a human technician. Therefore, a standalone algorithm-only performance was not performed because human interpretation is an integral part of the assay procedure. "The test strips can be evaluated visually by comparison of the band intensity with the reaction control card."
7. The Type of Ground Truth Used:
- Expert Consensus / Clinical Criteria: The primary ground truth for patient classification (AIH, PBC, etc.) was based on established clinical diagnostic criteria from international and national medical organizations (IAIHG, AASLD, EASL).
- Predicate Device Results: For the method comparison study, the results from the Inova Quanta Lite ELISAs (recognized predicate devices) served as a comparative "ground truth" to assess the agreement of the new device. Both positive and negative agreement were calculated relative to these predicate results.
- Serologically Characterized Panels: For cross-reactivity studies, "serologically characterized panels" were used.
8. The Sample Size for the Training Set:
- The document does not explicitly mention a "training set" as this is a traditional in-vitro diagnostic (IVD) assay, not an AI/machine learning device that typically undergoes a distinct training phase.
- The device development would likely involve internal optimization and validation using various samples, but these are not formally disclosed as a "training set" with specific sizes in this 510(k) summary.
9. How the Ground Truth for the Training Set Was Established:
- As a formal "training set" is not described for this IVD product, the establishment of ground truth for such a set is not applicable in the context of this document. The assay's performance is validated against clinical classifications and predicate device results in the test and clinical study sets.
§ 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).