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The EUROIMMUN IFA 40: HEp-20-10 is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of antibodies against cell nuclei (ANA) in human serum. This test system is used as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other laboratory and clinical findings.

The test system consists of BIOCHIPs coated with HEp-20-10 cells. It includes a fluorescein-labeled goat anti-human IgG, a positive and negative control, salt for PBS, Tween 20, embedding medium, cover glasses and instruction booklet. Reagent trays for the TITERPLANE technique are required but ordered separately.

Here's a breakdown of the acceptance criteria and study information for the EUROIMMUN IFA 40: HEp-20-10 device, based on the provided text:

Acceptance Criteria and Device Performance

Study Details

2. Sample Size and Data Provenance

• Qualitative Comparison Study (Method comparison with predicate device):
  • Test Set Sample Size: 200 blinded prospective samples.
  • Data Provenance: Department of Clinical Pathology & Laboratory Medicine at the University of Pennsylvania (USA). Samples obtained from patients sent for routine ANA screening.
• Semi-Quantitative/Quantitative Comparison Study (Method comparison with predicate device):
  • Test Set Sample Size: 156 blinded prospective samples.
  • Data Provenance: Samples obtained from patients sent for routine ANA screening (location not explicitly stated but implied to be the same clinical setting as the qualitative study given the continuous description and similar sample acquisition method).
• Assay Cut-off Verification:
  • Test Set Sample Size: 138 samples.
  • Data Provenance: EUROIMMUN US Inc. laboratory (USA). Serum samples sent in for antibody testing, collected in sequential order for two days.
• Expected Values/Reference Range Study:
  • Test Set Sample Size: 200 sera from normal healthy adult blood donors.
  • Data Provenance: University hospital Lübeck, Germany.
• Analytical Performance Studies (Precision/Reproducibility, Linearity, Analytical Specificity, Interfering Substances):
  • Data Provenance: All performed at EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany, unless stated otherwise. The Inter-Observer Reproducibility Study was performed in a US Laboratory setting.
  • Sample Sizes: Vary per study (e.g., 10-fold repeated measurements for Intra-Assay, 20 repeated for Inter-Assay, 6 for Inter-Lot, 14 positive and 1 negative for Semi-quantitative Reproducibility, 6 for Linearity, 20 for Interfering substances). Specific numbers for each analytical study are provided in the "Performance Characteristics" section.

3. Number of Experts used to establish the ground truth for the test set and the qualifications of those experts

• Qualitative and Semi-Quantitative/Quantitative Comparison Studies:
  • Number of Experts: Two primary technicians, with a third decisive technician in case of discrepancies.
  • Qualifications: "Technicians" are mentioned. No specific background (e.g., years of experience, specific certifications) is provided.
• Analytical Performance Studies (e.g., Reproducibility, Linearity, Analytical Specificity, Interfering Substances):
  • Generally, the evaluation was performed by "the same technician" or "two different technicians," with a third technician for resolution in Inter-Observer Reproducibility. No specific qualifications are detailed.
• Assay Cut-off Verification & Expected Values/Reference Range Studies:
  • "As per the American College of Rheumatology" is cited for an expected prevalence range, indicating reliance on established medical guidelines/expert consensus for context, but not for direct ground truth labeling of individual samples in these specific studies. Samples were tested as per instructions for use by technicians.

4. Adjudication method for the test set

• Qualitative and Semi-Quantitative/Quantitative Comparison Studies:
  • Adjudication Method: "Visual fluorescence microscopy evaluation was performed by two different technicians independently. In case of a discrepant result a 3rd technician was decisive." This is a 2+1 adjudication method.
• Inter-Observer Reproducibility:
  • Adjudication Method: "separate independent reading of the Inter-Assay slides by a 2nd technician. In case of discrepancies a 3th technician would have been decisive." This is also a 2+1 adjudication method.

5. 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.

• No, a multi-reader multi-case (MRMC) comparative effectiveness study focusing on human readers improving with AI vs. without AI assistance was not performed. This device is an in-vitro diagnostic test kit that relies on human microscopy reading, not an AI-assisted diagnostic tool for image interpretation. The comparison studies were between the new device and a predicate device, both relying on human visual interpretation.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

• No, a standalone algorithm-only performance study was not done. The device is an IFA test system that requires human visual interpretation via a fluorescent microscope.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

• Qualitative and Semi-Quantitative/Quantitative Comparison Studies: The ground truth was established by the predicate device (ImmunoConcepts® HEp-2000 ANA-Ro IFA), interpreted by technicians with a 2+1 adjudication. Discrepancies were sometimes confirmed using "FDA cleared assays" (e.g., blot tests), which serve as a higher-level reference standard.
• Analytical Specificity (Cross-reactivity): The CDC Centers for Disease Control and Prevention reference panel (characterized by the CDC) was used as ground truth.
• Assay Cut-off Verification & Expected Values/Reference Range Studies: The ground truth for individual samples was their status as positive or negative based on the device's interpretation at a specific dilution. The reference range and prevalence context were established by comparing against published ranges from the American College of Rheumatology.
• Precision/Reproducibility, Linearity, Interfering Substances: Ground truth implicitly involved the expected behavior of the samples (e.g., 0-4+ intensity, specific patterns, decreasing intensity with dilution) as evaluated by trained technicians.

8. The sample size for the training set

• The document does not mention a training set, as this is an in-vitro diagnostic test kit that is read visually by technicians, not a machine learning or AI-based diagnostic tool that would typically require a training set.

9. How the ground truth for the training set was established

• Not applicable, as no training set for an algorithm was mentioned or used.

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The EUROIMMUN Anti-Glutamate receptor (type NMDA) IFA is intended for the qualitative determination of autoantibodies against glutamate receptor (type NMDA) in human serum. It is used as an aid in the diagnosis of anti-glutamate receptor (type NMDA) autoimmune encephalitis in conjunction with other laboratory and clinical findings.

The EUROIMMUN IFA is an assay for standardized detection of anti-glutamate receptor (type NMDA) antibodies utilized in each laboratories familiar with indirect immunofluorescence. The non-transfected cells are used as a control to simplify differentiation of potential co-existing and non-specific reactivity such as ANA. The test kit consists of slides, which contain BIOCHIPs coated with glutamate receptor (type NMDA) transfected cells and non-transfected cells, fluorescein-labelled anti-human IgG (goat), a positive control for transforced volle and non new and of a negative control, a salt for preparation of PBS, Tween 20, embedding medium, cover glasses and an instruction booklet.

The acceptance criteria and study proving the device meets them are detailed below based on the provided text.

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state quantitative acceptance criteria for sensitivity and specificity. However, based on the studies presented, we can infer the desired clinical performance. The reported device performance is directly from the clinical studies.

Note: The "acceptance criteria (inferred)" are based on typical expectations for diagnostic assays intended to aid in diagnosis. The document does not provide specific numerical targets prior to presenting the results.

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

The 'test set' for clinical performance was composed of samples across four clinical studies. The data provenance includes both retrospective and prospective elements.

• Study 1: 47 serum samples (29 anti-glutamate receptor (type NMDA) encephalitis, 18 other encephalopathies) from the US (Prospective, though the specific collection method isn't detailed, it implies collection for diagnostic purposes). Additionally, 100 adult healthy blood donors from Germany (Prospective/Retrospective, general population screening).
• Study 2: 2990 patients screened for encephalitis of unknown origin; 6 samples ultimately tested (6 women) from Germany (Retrospective).
• Study 3: 8 samples from patients with anti-glutamate receptor (type NMDA) encephalitis from Germany (Prospective/Retrospective, not explicitly stated).
• Study 4: 9 samples from patients with anti-glutamate receptor (type NMDA) encephalitis and 13 from patients with other encephalopathies from Italy (Prospective/Retrospective, not explicitly stated).

Combined Test Set Sample Sizes:

• Positive cases (anti-NMDA encephalitis): 29 + 5 (from 6) + 8 + 9 = 51 (overall 52 based on table summary, possibly one case from study 2 was reclassified as positive, or a rounding difference)
• Negative cases (other encephalopathies/healthy donors): 18 + 100 + 13 = 131

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

The document does not specify the number of experts or their qualifications who established the ground truth for the test set. It mentions "patients diagnosed with anti-gluatamate receptor (type NMDA) encephalitis" and "controls with other encephalopathies," implying established clinical diagnoses. It also states the device is used "in conjunction with other laboratory and clinical findings," suggesting that the ground truth patients were diagnosed by a combination of clinical specialists (e.g., neurologists) and potentially other laboratory tests, but the specific expert review process for the test set is not detailed.

4. Adjudication Method for the Test Set:

The document does not describe a formal adjudication method (e.g., 2+1, 3+1) for establishing the ground truth of the test set cases. The cases are described as "patients diagnosed with," implying that their diagnosis served as the ground truth.

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:

The document describes an indirect immunofluorescent antibody assay (IFA) which is a laboratory test requiring visual interpretation by a human. However, it does not involve AI or a multi-reader, multi-case (MRMC) comparative effectiveness study of human readers with or without AI assistance. The device is not an AI-based diagnostic tool for image analysis as described in the context of improving human reader performance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

Not applicable. The device is an IFA kit, which inherently requires human interpretation of fluorescence under a microscope. It is not an algorithm that performs standalone analysis.

7. The Type of Ground Truth Used:

The ground truth used for the clinical studies appears to be based on clinical diagnosis of anti-glutamate receptor (type NMDA) encephalitis or other encephalopathies. For healthy controls, the implied ground truth is the absence of the disease. The phrase "patients diagnosed with" suggests a consensus among clinicians and potentially other diagnostic tests, but not explicitly pathology or a specific "outcomes data" in the sense of long-term follow-up beyond diagnosis.

8. The Sample Size for the Training Set:

The document does not describe a specific "training set" for the device, as it is a laboratory assay (IFA kit) rather than a machine learning or AI algorithm that requires a separate training phase with labeled data. The development of the assay likely involved internal optimization and validation, but this is not referred to as a "training set" in the context of device performance testing.

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

Not applicable, as a distinct training set (in the context of machine learning) is not described for this IFA kit.

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