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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.

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.

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The EUROIMMUN Anti-SLA/LP ELISA (IgG) test kit is intended for the qualitative detection of IgG class autoantibodies against SLA/LP in human serum and plasma. It is used as an aid in the diagnosis of autoimmune hepatitis, type 1, in coniunction with other laboratory and clinical findings.

The EUROIMMUN Anti-SLA/LP ELISA (IgG) consists of a microwell ELISA plate coated with SLA/LP antigen, calibrator, positive and negative control, peroxidase-labelled anti-human IgG conjugate, sample buffer, wash buffer concentrate, TMB chromogen/substrate solution and stop solution.

Here's a detailed breakdown of the acceptance criteria and the study proving the device meets them, based on the provided document:

Acceptance Criteria and Device Performance Study for EUROIMMUN Anti-SLA/LP ELISA (IgG)

The EUROIMMUN Anti-SLA/LP ELISA (IgG) test kit is intended for the qualitative detection of IgG class autoantibodies against SLA/LP in human serum and plasma, used as an aid in the diagnosis of autoimmune hepatitis, type 1, in conjunction with other laboratory and clinical findings.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria with specific numerical thresholds for each performance characteristic (e.g., "Sensitivity must be >X%"). Instead, it presents the results of various studies as proof of the device's performance, implying that these results are considered acceptable for market clearance. The comparison to a predicate device and the clinical study results form the basis of showing substantial equivalence.

Based on the provided information, the following table summarizes the key performance metrics and the reported results:

• Samples with Mean Ratios 0.2 to 0.9 (Negative Expected): 0% positive, 100% negative.
• Samples with Mean Ratios 1.1 to 4.9 (Positive Expected): 100% positive, 0% negative.
  Result: Sufficient, as no positive sample was found negative and vice versa. |
  | Inter-assay reproducibility (no positive sample found negative and vice versa). | Based on 24 determinations over 6 different runs for 8 samples across different ratio ranges:
• Samples with Mean Ratios 0.2 to 0.8 (Negative Expected): 0% positive, 100% negative.
• Samples with Mean Ratios 1.2 to 5.4 (Positive Expected): 100% positive, 0% negative.
  Result: Sufficient, as no positive sample was found negative and vice versa. |
  | Lot-to-Lot reproducibility (no positive sample found negative and vice versa). | Based on QC samples using different lots over the measurement range:
• Positive Samples (Mean Ratios 5.6, 7.6, 9.7, 0.9, 3.1, 3.9): 100% positive, 0% negative.
• Negative Samples (Mean Ratios 0.1): 0% positive, 100% negative.
  Result: Sufficient, as no positive sample was found negative and vice versa. |
  | Analytical Specificity / Cross-reactivity |
• Panel of 18 sera serologically positive for antibodies against LKM were tested.
  Result: All 18 sera were negative in the Anti-SLA/LP ELISA (IgG), indicating no cross-reactivity. |
  | Interference |
• Concentrations of up to 1000 mg/dL for hemoglobin, 2000 mg/dL for triglyceride, and 40 mg/dL for bilirubin were tested.
  Result: Individual recovery was within 90 - 119%. No significant interference observed. |
  | Method Comparison with Predicate Device | |
  | Negative Agreement with predicate device | Result: 96.9% (154/159), 95% C.I.: 92.8% - 99.0% |
  | Positive Agreement with predicate device | Result: 100.0% (31/31), 95% C.I.: 88.8% - 100.0% |
  | Overall Agreement with predicate device | Result: 97.4% (185/190), 95% C.I.: 94.0% - 99.1% |
  | Matrix Comparison (Serum vs. Plasma) | The 95% C.I. of the slope contains 1.0 and the 95% C.I. of the intercept contains 0 for EDTA plasma, Heparin plasma, and Citrate plasma when compared to serum.
• EDTA plasma: y = -0.02 + 1.00x (95% C.I. intercept: -0.14 to 0.18, 95% C.I. slope: 0.94 to 1.06)
• Heparin plasma: y = 0.02 + 1.00x (95% C.I. intercept: -0.06 to 0.21, 95% C.I. slope: 0.94 to 1.03)
• Citrate plasma: y = 0.04 + 0.99x (95% C.I. intercept: -0.18 to 0.16, 95% C.I. slope: 0.94 to 1.05)
  Result: This condition indicates equivalence of concentration between serum and corresponding plasma matrices. Coefficients of determination were >0.99 and %BIAS from serum was 88-120%. |
  | Clinical Sensitivity for AIH Type 1 | Result: 27.7% (95% C.I.: 17.3 - 40.2%) |
  | Clinical Specificity |
• Excluding AIH/PBC overlap samples: Result: 100.0% (95% C.I.: 99.2 - 100.0%) (435/435 negative out of 435 control samples).
• Including AIH/PBC overlap samples: Result: 99.3% (95% C.I.: 98.1 - 99.9%) (447/450 negative out of 450 control samples). |
  | Expected values/Reference range for healthy blood donors | - 150 apparently healthy blood donors tested.
• Cut-off ratio 1.0.
  Result: All 150 blood donors found negative (0 positives, 150 negatives). Highest value was Ratio 0.8, Mean value 0.1. |

2. Sample Sizes Used for the Test Set and Data Provenance

• Precision/Reproducibility:
  • Intra-assay: 20 determinations for each of 8 samples.
  • Inter-assay: 24 determinations for each of 8 samples over 6 different runs.
  • Lot-to-Lot: 6 determinations (3 lots x 2 runs) for 4 samples and 16 to 38 determinations (n lots x 1 run) for 5 samples.
  • Provenance: Not specified, but likely internal lab samples/controls as part of device development and validation.
• Analytical Specificity (Cross-reactivity):
  • 18 sera positive for antibodies against LKM.
  • Provenance: Not specified.
• Interference:
  • 5 different specimens at different anti-SLA/LP concentrations (ratio 0.4 - 10.0), spiked with interfering substances.
  • Provenance: Not specified.
• Method Comparison with Predicate Device:
  • Total samples: 190 samples (167 initial, plus 23 additional samples created by mixing positive samples to cover the lower range).
    • 58 from AIH patients
    • 66 from PBC patients
    • 15 from patients with AIH/PBC overlap syndrome
    • 28 from patients with viral hepatitis
  • Demographics: 30 men and 137 women, age 1 to 87 years (average 50 years).
  • Provenance: "A study was performed in cooperation with a university clinical hospital," indicating a retrospective cohort from a clinical setting. Country of origin not specified, but likely within the geographic region of the university clinical hospital.
• Matrix Comparison:
  • 16 sample pairs (serum and corresponding plasma).
  • Provenance: Not specified.
• Clinical Study:
  • Total samples: 515 clinically characterized samples.
    • 65 from AIH-1 patients
    • 68 from AIH-2 patients
    • 15 from patients with AIH/PBC overlap syndrome
    • 367 from other control groups (including viral hepatitis, toxic liver damages, steatohepatitis, PBC, PSC, and other autoimmune diseases like MCTD, celiac disease, Diabetes Type I, Hashimoto, Grave's disease, ulcerative colitis).
  • Provenance: "Performed in cooperation with several university, hospital and private laboratories," indicating a retrospective cohort drawn from multiple clinical sites. Country of origin not specified.
• Expected Values/Reference Range (Healthy Donors):
  • 150 apparently healthy blood donors (mixed age and sex).
  • Provenance: Not specified, but likely a healthy donor pool (e.g., blood bank).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

• The document does not explicitly state the number of experts or their specific qualifications for establishing the ground truth for any of the test sets (e.g., for the clinical study patients).
• For the "Method Comparison with Predicate Device" and "Clinical Study," samples were "clinically characterized" or from specific patient groups (e.g., "AlH patients," "AlH-1 patients"). This implies that the diagnosis (ground truth) was established through standard clinical practice by treating physicians and potentially confirmed by specialists, but the specific number and qualifications of these "experts" in the context of the study are not provided.

4. Adjudication Method for the Test Set

The document does not specify an adjudication method (e.g., 2+1, 3+1) for establishing the ground truth diagnoses or for interpreting the results during the studies. The clinical characterization of samples likely represents the consensus diagnosis from the participating clinical sites.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance was not done. This device is an in vitro diagnostic (IVD) ELISA kit for qualitative detection of autoantibodies, not an imaging or decision support AI device that would typically involve human-in-the-loop performance studies or require effect size reporting for human reader improvement.

6. Standalone (Algorithm Only Without Human-in-the-loop Performance)

Yes, the performance data presented (precision, analytical specificity, clinical sensitivity, specificity, method comparison) reflects the standalone (algorithm-only) performance of the ELISA kit. As an IVD kit, its output is a quantitative ratio which is then interpreted qualitatively (positive/negative) based on a predefined cut-off. There is no human-in-the-loop directly affecting the assay's output. Clinicians would then interpret these results in conjunction with other clinical findings.

7. The Type of Ground Truth Used

• For Analytical Studies (Precision, Specificity, Interference): The "ground truth" was based on predefined characteristics of the samples (e.g., known positive/negative samples, samples spiked with interferents, samples with known LKM antibodies).
• For Method Comparison with Predicate Device: The ground truth was the result obtained from the FDA-cleared Inova Quanta Lite SLA ELISA (the predicate device), alongside the clinical diagnoses of the patients from whom the samples were drawn.
• For Clinical Studies: The ground truth was based on clinical characterization and diagnosis of the patients (e.g., "Autoimmune hepatitis type 1 (AIH-1) patients", "AIH/PBC overlap syndrome", "Viral hepatitis"). This type of ground truth represents outcomes data and expert clinical judgment based on recognized diagnostic criteria for these conditions, rather than a single gold-standard pathological finding for every case.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI development. This device is an ELISA kit, which is a biochemical assay, not an AI/ML algorithm that undergoes a distinct training phase in the same manner. The development and optimization of the assay (e.g., antigen selection, reagent concentrations, incubation times) would be analogous to a "training" process, but this is done through biochemical and analytical validation, not with a distinct data-driven training set in the AI sense.

9. How the Ground Truth for the Training Set Was Established

As noted above, a "training set" in the AI/ML sense is not applicable here. The "ground truth" for the development of the assay would come from internal studies using known positive and negative samples, characterized by established clinical diagnoses or reference methods, to optimize the assay's performance characteristics (e.g., cut-off determination, reagent concentrations). The clinical study and predicate device comparison data then serve as the independent validation of the optimized assay.

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The QUANTA Lite™ SLA (soluble liver antigen) kit is an enzyme-linked immunosorbent assay (ELISA) for the semi-quantitative detection of anti-SLA (soluble liver antigen) antibody of the IgG class in human serum. This test is intended to aid in the diagnosis of conditions with elevated levels of anti-SLA antibody including autoimmune hepatitis (AIH).

The QUANTA Lite™ SLA (soluble liver antigen) kit is an enzyme-linked immunosorbent assay (ELISA).

This document is a 510(k) clearance letter from the FDA for the QUANTA Lite™ SLA ELISA device, not a study report. Therefore, it does not contain the detailed information necessary to fully answer the request regarding acceptance criteria and a study proving device performance as it would typically be found in a clinical study report or a 510(k) summary.

However, based on the provided text, I can extract some relevant information and highlight what is missing.

Information Extracted from the Document:

• Device Name: QUANTA Lite™ SLA (Soluble Liver Antigen) ELISA
• Intended Use: Semi-quantitative detection of anti-SLA (soluble liver antigen) antibody of the IgG class in human serum, intended to aid in the diagnosis of conditions with elevated levels of anti-SLA antibody including autoimmune hepatitis (AIH).

Missing Information (and why it's missing from this type of document):

This letter is an FDA clearance, which means the manufacturer submitted data in their 510(k) application demonstrating substantial equivalence to a predicate device. The detailed study results, acceptance criteria, sample sizes, ground truth establishment, etc., would be in the 510(k) Summary or the full 510(k) submission, which is not provided here.

Therefore, I cannot populate the table or answer most of the specific questions.

Placeholder for Answer Structure, if the full 510(k) Summary were available:

Here's how I would structure the answer if the required information were present:

1. Table of Acceptance Criteria and Reported Device Performance

(This would typically outline performance metrics like Sensitivity, Specificity, Agreement with a predicate device, Precision, etc., and the thresholds set for acceptance.)

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