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EliA anti-TG Immunoassay is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroglobulin (TG) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TG uses the EliA IgG method on the instrument Phadia 250.

EliA anti-TG Immunoassay is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroglobulin (TG) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TG uses the EliA IgG method on the instrument Phadia 2500/5000.

EliA anti-TPO Immunoassay is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroid peroxidase (TPO) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TPO uses the EliA IgG method on the instrument Phadia 250.

EliA anti-TPO Immunoassay is intended for the in vitro quantitative measurement of IgG antibodies directed to thyroid peroxidase (TPO) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of autoimmune thyroiditis and Graves' disease in conjunction with other laboratory and clinical findings. EliA anti-TPO uses the EliA IgG method on the instrument Phadia 2500/5000.

EliA Thyroid Positive Control 250 is intended for laboratory use in monitoring the performance of in vitro measurement of antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG) with Phadia 250 using the EliA IgG method.

EliA Thyroid Positive Control 2500/5000 is intended for laboratory use in monitoring the performance of in vitro measurement of antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG) with Phadia 2500/5000 using the EliA IgG method.

The method specific reagents on Phadia® 250 and Phadia® 2500/5000 are identical: they are only filled in different containers. Each device consists of:

• EliA anti-TG wells are coated with a human thyroglobulin antigen 4 carriers (16 wells each), ready to use; or EliA anti-TPO wells are coated with a human recombinant thyroid peroxidase
• antigen 4 carriers (16 wells each), ready to use; EliA Sample Diluent: PBS containing BSA, detergent and 0.095% sodium azide - 6 bottles, 48 mL each, ready to use; or 6 bottles, 400 mL each, ready to use;
• -EliA IgG Conjugate 50 or 200: ß-Galactosidase labeled anti-IgG (mouse monoclonal antibodies) in PBS containing BSA and 0.06% sodium azide - 6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use
• -EliA Thyroid Positive Control 250 or 2500/5000: Human serum containing IqG antibodies to TG and TPO in PBS containing BSA, detergent and 0.095% sodium azide - 6 single use vials, 0.3 mL each, ready to use;
• EliA Negative Control 250 or 2500/5000: Human sera from healthy donors in -PBS containing BSA, detergent and 0.095% sodium azide - 6 single-use vials, 0.3 mL each, ready to use;
• -EliA IgG Calibrator Strips: Human IqG (0, 4, 10, 20, 100, 600 µq/L) in PBS containing BSA, detergent and 0.095% sodium azide - 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
• -EliA IgG Curve Control Strips: Human IgG (20 µg/L) in PBS containing BSA, detergent and 0.095% sodium azide - 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
• -EliA IqG Calibrator Well: Coated with mouse monoclonal antibodies - 4 carriers (12 wells each), ready to use.

The Phadia EliA Immunodiagnostic System is an automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages except the positive and negative controls are required to carry out an EliA anti-TG or anti-TPO test.

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as a formal table with pass/fail values. Instead, the document presents performance characteristics and demonstrates that the device meets these characteristics, implying they are the de facto acceptance criteria. I will infer these criteria from the studies conducted.

EliA anti-TG Immunoassay

EliA anti-TPO Immunoassay

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

• Precision/Reproducibility:
  • EliA anti-TG/TPO on Phadia 250/2500/5000: 8 samples, each with 252 replicate determinations (21 runs x 3 instruments x 7 runs each over 7 days).
  • Data Provenance: Not explicitly stated, implied to be internal lab studies.
• Linearity/Assay Reportable Range:
  • EliA anti-TG/TPO on Phadia 250/2500/5000: 6-7 patient serum samples.
  • Data Provenance: Not explicitly stated, implied to be internal lab studies.
• Detection Limit (LoB/LoD):
  • EliA anti-TG/TPO on Phadia 250/2500/5000: Four analyte-free samples and four low antibody concentration blood donor samples. Each measured in 36 replicates (6 replicates x 6 runs). Total of 8 samples x 36 replicates = 288 measurements.
  • Data Provenance: Not explicitly stated, implied to be internal lab studies using blood donors.
• Endogenous Interference:
  • EliA anti-TG/TPO: Three serum samples (one negative, one near cut-off, one high positive). Each spiked with different interfering substances or blanks and analyzed in triplicates. Runs repeated twice.
  • Data Provenance: Not explicitly stated, implied to be internal lab studies.
• Reference Sera:
  • EliA anti-TG: 8 samples from CAP.
  • EliA anti-TPO: 8 samples from CAP and 12 samples from UK-NEQAS.
  • Data Provenance: External proficiency testing programs (CAP, UK-NEQAS).
• Carry-over:
  • Phadia 250: A serum sample (diluted 1:2 and 1:20). Tested with EliA Ro (another assay) to demonstrate instrument's general carry-over performance.
  • Data Provenance: Not explicitly stated, implied to be internal lab studies.
• Assay Cut-off / Expected Values:
  • EliA anti-TG/TPO: 604 apparently healthy blood donor samples.
  • Data Provenance: Caucasian, African American, Hispanic, and Asian individuals, almost equally distributed by sex and age. (Source country not specified but "blood donor samples" are typically collected prospectively for such studies).
• Method Comparison and Clinical Sensitivity/Specificity:
  • EliA anti-TG/TPO: 718 serum samples from patients with various thyroid and autoimmune conditions (Graves' disease, autoimmune thyroiditis, non-AI thyroid disease, connective tissue disease, Crohn's disease, ulcerative colitis, primary biliary cirrhosis, HIV, HCV, HBV, other infection, cancer, rheumatoid arthritis, hypergamma-globulinemia, systemic lupus erythematosus, Sjögren's syndrome, celiac disease, type 1 diabetes mellitus, type II diabetes mellitus, pregnant women of all trimesters, pre-eclampsia, miscarriage, thyroid cancer, myasthenia gravis, pernicious anemia, chronic lymphocytic thyroiditis, sub-acute thyroiditis, multi-nodular goiter).
  • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective).
• Matrix Comparison:
  • EliA anti-TG/TPO: 57 patients from whom serum, lithium heparin plasma, and EDTA plasma were collected.
  • Data Provenance: Not explicitly stated, implied to be patient samples.

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 use of "experts" in the context of diagnostic performance studies. For immunoassay devices like these, ground truth is typically established by:

• Reference Methods: Comparison to a legally marketed predicate device (VarelisA TG Antibodies, VarelisA TPO Antibodies) as seen in the method comparison study.
• Clinical Diagnosis: For sensitivity and specificity, samples are categorized based on "diagnosis" (e.g., Graves' disease, autoimmune thyroiditis). This implies a clinical ground truth, but the details of how these diagnoses were established (e.g., by how many clinicians, their specialties, or experience levels) are not provided.
• External Reference Sera: For reference sera evaluation, targets are established by external institutions like CAP and UK-NEQAS, which rely on peer groups or provider definitions.

Therefore, there's no mention of a specific number of experts or their qualifications establishing ground truth in the way one might see for image-based diagnostics.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method for establishing ground truth, such as 2+1 or 3+1 expert consensus. Instead, it relies on established clinical diagnoses for sensitivity/specificity studies and predicate device results for method comparison.

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 MRMC comparative effectiveness study was done. This device is an in vitro diagnostic (IVD) immunoassay, not an AI-assisted diagnostic tool for human readers. Its performance is evaluated intrinsically and in comparison to a predicate device, not in terms of human reader improvement.

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

The device is a standalone immunoassay system (EliA anti-TG Immunoassay and EliA anti-TPO Immunoassay run on Phadia 250/2500/5000 instruments). Its performance is inherently "standalone" in the sense of being an automated laboratory test without direct human interpretive input at the point of result generation. Results are quantitative values that clinicians interpret. Therefore, the entire analytical and clinical performance section describes the device's standalone performance.

7. The Type of Ground Truth Used

• Clinical Diagnosis: For clinical sensitivity and specificity studies, samples were linked to known diagnoses such as "Graves' Disease" and "Autoimmune Thyroiditis." The basis for these diagnoses (e.g., pathology, clinical outcomes, or expert opinion) is not detailed beyond being "clinically defined."
• Predicate Device: For method comparison, the reference standard was the legally marketed predicate device (VarelisA TG Antibodies and VarelisA TPO Antibodies).
• External Program Targets: For reference sera, the ground truth was the targets set by CAP (College of American Pathologists) and UK-NEQAS (United Kingdom National External Quality Assessment Service). These targets are often established by peer consensus or by the program providers.

8. The Sample Size for the Training Set

The document describes studies for validation of performance characteristics but does not explicitly mention a "training set" in the context of machine learning or AI development. Since these are immunoassays, they are based on biochemical reactions and calibration rather than a machine learning model that requires training data. The calibration process uses specific calibrator materials.

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

As this is an immunoassay and not an AI/ML device, the concept of a "training set" with established ground truth doesn't apply in the same way. The device is calibrated using:

• EliA IgG Calibrator Strips: Human IgG at defined concentrations (0, 4, 10, 20, 100, 600 µq/L). These calibrators are traceable to the International Reference Preparation (IRP) 67/86 of Human Serum Immunoglobulins A, G and M from WHO. New batches are compared to a secondary standard or the IRP directly to ensure correct concentration. This traceability constitutes the "ground truth" for calibration.
• EliA IgG Curve Control Strips: Human IgG (20 µg/L) for monitoring calibration curve performance.

The "ground truth" for the calibrators is therefore established through established international reference standards and their traceability.

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EliA Scl-70s is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Scl-70 in human serum and plasma (heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (diffuse form) in conjunction with other laboratory and clinical findings. EliA Scl-70s uses the EliA IgG method on the instrument Phadia 100.

EliA Scl-70s is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to Scl-70 in human serum and plasma (heparin, EDTA) as an aid in the clinical diagnosis of scleroderma (diffuse form) in conjunction with other laboratory and clinical findings. EliA Scl-70s uses the EliA IgG method on the instrument Phadia 250.

The Phadia EliA immunodiagnostic system is automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages except the positive and negative controls are required to carry out an EliA Scl-70° test.

The acceptance criteria and study detailed in the provided document pertain to the EliA™ Scl-70S Immunoassay, an in vitro semi-quantitative test for IgG antibodies directed to Scl-70.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria for the clinical performance (sensitivity and specificity). However, it reports the performance of the EliA Scl-70S based on its clinical study. For analytical performance, the acceptance criteria are implied by the reported results meeting generally accepted ranges for such assays.

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

• Sample Size for Analytical Performance Tests:
  • Precision/Reproducibility: 3 samples for Phadia 250, 1 batch for Phadia 100.
    • Phadia 100: 84 replicate determinations per sample (21 runs: 3 instruments x 7 runs each, over 7 days).
    • Phadia 250: 252 replicate determinations per sample (21 runs: 3 instruments x 7 runs each, over 7 days).
  • Linearity: 4 patient serum samples.
  • Hook Effect: One high positive serum sample.
  • Detection Limit (LoB/LoD): 6 blood donors. Each measured in 12 replicates in each of 6 runs on 6 different days (432 replicates per sample).
  • Endogenous Interference: 5 serum samples (2 negative, 2 around cut-off, 1 positive).
• Sample Size for Comparison Studies:
  • Method Comparison with Predicate Device: 390 serum samples.
    • Collected from patients with Scleroderma (SSc, n = 101), CREST (n = 33), MCTD (n = 37), SLE (n = 34), Sjögren's syndrome (SS, n = 26), Poly/Dermatomyositis (PM/DM, n = 5), Rheumatoid arthritis (RA, n = 30), various cancers (n = 20), various bacterial infections (n = 24), various viral infections (n = 26), and technical samples positive or equivocal for EliA Scl-70° (n = 54).
  • Matrix Comparison: 50 patients (serum, lithium heparin plasma, EDTA plasma collected from each).
  • Instrument Comparison: 24 positive, 8 equivocal, and 4 negative samples (total 36).
• Sample Size for Clinical Studies:
  • Clinical Sensitivity and Specificity: 336 clinically defined sera.
    • Diagnostic groups: Scleroderma (SSc, n=101) and Controls (n=235) which include other connective tissue diseases, bacterial/viral infections, cancer, and rheumatoid arthritis.
  • Assay Cut-off / Expected values: 400 apparently healthy blood donor samples from Caucasian individuals (equally distributed by sex and age).
• Data Provenance: The document does not explicitly state the country of origin for the patient or blood donor samples. It is implied to be retrospective as samples were "collected from patients with diagnosis of..." for the comparison and clinical studies. For the assay cut-off, "400 apparently healthy blood donor samples from Caucasian individuals" were used.

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

The document does not specify the number of experts used or their qualifications to establish the ground truth for the clinical diagnosis of scleroderma (SSc) or other conditions in the test set. It states "clinically defined sera from patients with scleroderma or other connective tissue diseases, bacterial or viral infections, cancer or rheumatoid arthritis," implying that the diagnosis was based on standard clinical practice rather than a dedicated expert panel for this study.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for establishing ground truth diagnoses for the clinical test set. Clinical findings are referenced as the basis for diagnosis ("clinically defined sera"), but no specific multi-reader adjudication process is mentioned for the study itself.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed or reported in this document. The device is a laboratory immunoassay, and its performance is evaluated against a predicate device and clinical diagnoses, not as an aid to human readers in interpreting images or other data.

6. Standalone (i.e., algorithm only without human-in-the-loop performance) Study

Yes, the study is inherently a standalone performance evaluation of the immunoassay itself. The reported performance characteristics (precision, linearity, detection limits, clinical sensitivity, specificity) reflect the algorithm's (immunoassay's) ability to detect the target antibodies in patient samples without direct human-in-the-loop interpretation once the sample is loaded into the automated Phadia instruments. The results are quantitative (EliA U/mL) leading to a categorical output (negative, equivocal, positive) based on predefined cut-offs.

7. The Type of Ground Truth Used

The ground truth used for the clinical study was clinical diagnosis. The document states "336 clinically defined sera from patients with scleroderma or other connective tissue diseases, bacterial or viral infections, cancer or rheumatoid arthritis." This implies that the ground truth was established by medical professionals through standard diagnostic procedures (e.g., patient history, physical examination, other laboratory tests, imaging, etc.) to arrive at a clinical diagnosis.

For the method comparison, the ground truth was essentially the results from the predicate device (INOVA QuantaLite™ Scl-70 ELISA), against which the new device's technical agreement was measured.

8. The Sample Size for the Training Set

The document does not explicitly describe a separate training set for the device's development or a study related to training a machine learning model. This immunoassay device is a chemical/biological test system with predefined reagents and a specific detection methodology, not a machine learning algorithm that typically requires a distinct training phase with a labelled dataset. Its calibration employs calibrators and controls.

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

As there is no explicit training set discussed in the context of machine learning or algorithm training, this question is not directly applicable. For the immunoassay, the "ground truth" for calibration and controls would be established by the manufacturer through rigorous characterization and standardization of the calibrator and control materials, often traceable to international reference preparations (e.g., WHO standards for IgG). The document mentions that "New batches of IgG calibrators are compared to a secondary standard (standardized with the IRP) or the IRP directly and adjusted accordingly to meet the correct concentration."

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