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The Access TPO Antibody assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroperoxidase antibody (TPOAb) levels in human serum and plasma using the Access Immunoassay Systems.

The detection of TPOAb is an aid in the diagnosis of thyroid autoimmune disorders.

The Access TPO Antibody assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroperoxidase antibody (TPO Ab) levels in human serum and plasma using the Access Immunoassay Systems.

The Access TPO Antibody Calibrators are intended to calibrate the Access TPO Antibody assay for the quantitative determination of TPO Antibody levels in human serum and plasma using the Access Immunoassay Systems.

The Access TPO Antibody assay is a sequential two-step immunoenzymatic ("sandwich") assay. A sample is added to a reaction vessel with paramagnetic particles coated with thyroperoxidase protein. The serum or plasma TPO Ab binds to the thyroperoxidase. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of analyte in the sample. Analyte concentration is automatically determined from a stored calibration.

The provided document, a 510(k) summary for the Beckman Coulter Access TPO Antibody assay, describes the analytical performance studies conducted to demonstrate substantial equivalence to a predicate device. This is a common regulatory pathway for in vitro diagnostic devices, focusing on demonstrating that the new device is as safe and effective as a legally marketed predicate device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

The document presents acceptance criteria implicitly through the study designs and results, as it's a submission for an IVD kit rather than an AI/ML algorithm. The performance is assessed by comparing the new device (Access TPO Antibody Assay on Dxl 9000 Access Immunoassay System) to its predicate device (Access TPO Antibody Assay on Access 2 Immunoassay System).

Table of Acceptance Criteria and Reported Device Performance:

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The Access Thyroglobulin Antibody II assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin antibody levels in human serum and plasma using the Access Immunoassay Systems. The measurement of thyroid autoantibodies may aid in the diagnosis of Hashimoto's disease, nontoxic goter, and Graves' disease.

The Access Thyroqlobulin Antibody II assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin antibody levels in human serum and plasma using the Access Immunoassay Systems. The measurement of thyroid autoantibodies may aid in the diagnosis of Hashimoto's disease, nontoxic goiter, and Graves' disease.

The Access Thyroglobulin Antibody II assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffers. The assay is run on Access 2 Immunoassay Analyzers.

The device modifications described in this submission impact the Access Thyroqlobulin Antibody II reagent pack only; they do not impact or change the other components that are used with this reagent pack. The modification does not affect the intended use or indications of the device or alter the fundamental scientific technology of the device.

A description of the reagent pack is provided below.

Here's an analysis of the provided text, outlining the acceptance criteria and study details for the "Access Thyroglobulin Antibody II" device:

Device: Access Thyroglobulin Antibody II

The study in the document focuses on the modified Access Thyroglobulin Antibody II assay and compares it to the previously cleared predicate device (Access Thyroglobulin Antibody II Assay, FDA 510(k) Number K112933). The goal is to demonstrate substantial equivalence of the modified device.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present acceptance criteria in a dedicated table format. Instead, it describes performance characteristics and the results obtained. I've reconstructed a table based on the implicit criteria derived from the reported performance, especially where a target value or range is given (e.g., for imprecision, biases, or correlation).

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Immunoassay for the in vitro quantitative determination of antibodies to thyroglobulin in human serum and plasma. The anti-Tg autoantibodies determination is used as an aid in the detection of autoimmune thyroid diseases in conjunction with other laboratory and clinical findings.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 411 immunoassay analyzer.

The Elecsys Anti-Tg immunoassay makes use of a competitive test principle using biotinylated human antigen and monoclonal human anti-Tg antibodies labeled with a ruthenium complex. The Elecsys Anti-Tg immunoassay is intended for the quantitative determination of antibodies to thyroglobulin in human serum and plasma. It is intended for use on the cobas e immunoassay analyzers.

Results are determined via a calibration curve which is instrument-specifically generated by 2 point calibration and a master curve provided via the reagent barcode or e barcode.

The provided text describes the performance evaluation of the Elecsys Anti-Tg immunoassay, a diagnostic device, and its acceptance criteria. Here's a breakdown of the requested information based on the text:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly present a single table labeled "Acceptance Criteria" with corresponding "Reported Device Performance" in a direct side-by-side format. Instead, it describes various performance evaluations and states whether "All predefined acceptance criteria was met" for each. However, we can reconstruct a table based on the provided details for the non-clinical performance evaluation.

2. Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Test Set Sample Sizes:
  • Precision: Not explicitly stated, but includes "Human serum 1-5" and "PC THYRO1-2" (presumably replicates for each, as per CLSI EP05-A3 which requires sufficient replicates).
  • Lot-to-lot Reproducibility: "three reagent lots" (number of samples per lot not specified).
  • Analytical Sensitivity (LoB, LoD, LoQ): Not explicitly stated, determined according to CLSI EP17-A2 which has sample size recommendations.
  • Linearity: "Six dilution series" using "native human serum samples and sample pools" (number of samples/pools not specified).
  • Endogenous Interferences: Not explicitly stated per substance, but mentions "Six endogenous substances."
  • Analytical Specificity/Cross-Reactivity: Not explicitly stated (for anti-TPO).
  • Exogenous Interferences: "17 commonly and 14 specially used pharmaceutical compounds" (number of samples not stated).
  • Sample Matrix Comparison: "blood from 13 donors" (tested across serum, K2-EDTA, K3-EDTA plasma, and serum separation tubes from 3 manufacturers).
  • Method Comparison to Predicate: "total of 129 human serum samples."
• Data Provenance: The document does not specify the country of origin for the data or whether the studies were retrospective or prospective. It is a "510(k) Summary" for an FDA submission, reporting on laboratory performance studies. Given they are "non-clinical performance evaluation," these are typically controlled laboratory studies.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This device is an in-vitro diagnostic (IVD) immunoassay. The ground truth for such devices is established through analytical testing against reference materials, established methods, and clinical samples with known characteristics, not typically by expert consensus in the same way as an imaging AI. The "ground truth" here is the precise concentration or presence/absence of the analyte (thyroglobulin antibodies) as determined by the study's reference method or expected values for standards/controls.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable for this type of IVD analytical performance study. Adjudication methods like 2+1 or 3+1 are common in clinical trials or imaging studies where expert readers interpret results, but not for direct quantitative measurements from an immunoassay. The acceptance criteria are based on statistical analysis of quantitative results (e.g., precision, linearity, recovery, regression).

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

Not applicable. This is an immunoassay for determining antibody levels, not an imaging device or an AI intended to assist human readers. Hence, no MRMC study was performed, and human reader improvement with AI assistance is not relevant to this device's evaluation.

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

This entire non-clinical performance evaluation section (4. NON-CLINICAL PERFORMANCE EVALUATION) describes the standalone performance of the Elecsys Anti-Tg immunoassay (a device, not an AI algorithm). The measurements are performed by the "cobas e 411 immunoassay analyzer," which acts as the "algorithm" or automated system. There's no human "in the loop" for the direct measurement results themselves, though human operators are involved in running the tests and interpreting the results in a clinical setting.

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

The ground truth for the analytical performance studies (precision, linearity, sensitivity, interferences, stability) is based on:

• CLSI guidelines: The studies adhere to specific Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., EP05-A3, EP17-A2, EP06-Ed2), which define how such analytical characteristics are determined using reference materials, spiked samples, and statistical methods.
• Reference Standards/Materials: Implied in sections like "Traceability/Standardization" against the NIBSC 65/93 Standard, and the use of calibrators (Anti-Tg CalSet) and controls (PreciControl ThyroAB).
• Known Sample Characteristics: For linearity, samples with varying known concentrations are typically used. For interference studies, samples spiked with known interferents are used.
• Predicate Device Comparison: For method comparison, the predicate device's results serve as a comparative reference.

8. The sample size for the training set

Not applicable in the context of an immunoassay. This device is an in-vitro diagnostic test kit (reagents) used on an existing analyzer. It does not involve a "training set" in the machine learning sense. The "development" or "training" of such a diagnostic involves optimizing the chemical and biological components of the assay (reagents, antibodies, detection method) and calibrating the system across a range of known concentrations.

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

As there is no "training set" in the AI/machine learning sense, this question is not applicable. The development process for an immunoassay involves extensive research and development to create reagents that accurately quantify the target analyte. Calibration is done using reference materials with assigned values, and the assay's performance characteristics (as detailed in section 4) are then rigorously validated.

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Immunoassay for the in vitro quantitation of autoantibodies to thyroid stimulating hormone (TSH) receptor in human serum using a human thyroid stimulating monoclonal antibody. The anti-TSH receptor determination is used in the assessment of patients suspected of Graves' disease (autoimmune hyperthyroidism).

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e 601 immunoassay analyzers.

The Elecsys Anti-TSHR is used for the in vitro quantitative determination of autoantibodies to TSHR receptor in human serum using a human thyroid stimulating monoclonal antibody. It is intended for use on the cobas e 601 immunoassay analyzer. The cobas e family of analyzers uses electrochemiluminescence immunoassay "ECLIA" technology.

Here's an analysis of the provided text to extract the acceptance criteria and study information for the Elecsys Anti-TSHR device:

Acceptance Criteria and Device Performance for Elecsys Anti-TSHR

The Elecsys Anti-TSHR is an immunoassay for the in vitro quantitative determination of autoantibodies to the TSH receptor in human serum, used in the assessment of patients suspected of Graves' disease.

1. Table of Acceptance Criteria and Reported Device Performance:

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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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The IMMULITE® 2000 TSI (thyroid-stimulating immunoglobulins) Assay is an in vitro diagnostic immunoassay for the semi-quantitative determination of thyroid stimulating autoantibodies specific to thyroid stimulating hormone receptors (TSHR) in human serum (including Serum Separator tubes) or plasma (K2-EDTA or lithium heparin). The IMMULITE® 2000 TSI Assay is for use on the IMMULITE® 2000 system. The measurement of thyroid stimulating autoantibodies, in conjunction with other clinical and laboratory findings, is used as an aid in the diagnosis of patients suspected of having Graves' disease.

The IMMULITE® TSI Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE® TSI Assay on the IMMULITE® 2000 Systems.

The IMMULITE 2000 TSI assay kit consists of the following components:

• TSI bead pack coated with MAb (3D7) anti-TSHR anchor antibody and hTSHR Capture Chimera
• TSI reagent wedge containing hTSHR-Chimera alkaline phosphatase conjugate
• TSI adjustors: low and high, containing TSI negative heat-inactivated bovine serum and thyroid stimulating human MAb (M22)
• TSI controls: negative, low, and high, containing TSI negative human serum and thyroid stimulating MAb (M22)
• Multi-Diluent 2

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied from the "Drift Specifications" for stability and the statistical measures for precision and method comparison. The device performance is the "reported performance".

• Repeatability %CV: Ranged from 3.5% to 7.0%.
• Within Lab %CV: Ranged from 5.0% to 8.3%. |
  | Linearity/Reportable Range | Linearity data for % Difference to be ± 15% or 0.50 IU/L (whichever is greater). | Linearity data for % Difference was shown to be ± 15% or 0.50 IU/L (whichever is greater) for most samples; tested within range 0.50 - 40.0 IU/L. |
  | Assay/Component Stability Drift | Reagents and Beads:
• Control 1 at ≤ -60°C: ≤ 15% from Day 0 mean
• Control 2 at ≤ -60°C: ≤ 10% from Day 0 mean
• CVM 1 at ≤ -60°C: ≤ 0.15 IU/L from Day 0 mean
• MDP 1: ≤ 20% from Day 0 mean
• MDP 4: ≤ 10% from Day 0 mean
• Cal J: ≤ 10% from Day 0 mean
  (Also, all Control results must be within QC established range to validate the run). | Stability Claims Achieved:
• Kit, unopened: 12 Months (2-8 °C)
• Bead Pack, open: 90 Days (2-8 °C)
• Reagent wedge, open and on-board: 90 Days (2-8 °C)
• Sample diluent, open: 30 Days (2-8 °C)
• Sample diluent, open frozen aliquotted: 6 Months (-20 °C)
• Adjustors open: 90 Days (2-8 °C)
• Adjustors frozen aliquotted: 4 Months (-20 °C)
• Controls open: 90 Days (2-8 °C)
• Controls frozen aliquotted: 6 Months (-20 °C)
• CVM, unopened: 12 Months (2-8 °C)
• CVM, opened and reconstituted: 30 Days (2-8 °C)
  Sample Stability: 24 hours at 20-25°C, 7 days at 2-8°C, and 12 months at -20°C for serum and plasma. |
  | Limit of Blank (LoB) | LoB should be low enough for clinical utility. | Highest LoB by lot was determined to be 0.03 IU/L. |
  | Limit of Detection (LoD) | LoD should be low enough for clinical utility. | Highest LoD by lot was determined to be 0.06 IU/L. |
  | Analytical Specificity (Interference) | No interference (≤ 10% different than control sample). | Interferents (Intralipid, Hemoglobin, Bilirubin, K2-EDTA): No interference (≤ 10% difference) except for hemoglobin (≥ 200mg/dL potentially affects recovery) and short draw K2-EDTA (may result in under-recovery).
  HAMA: Individual sample bias of 90% for positive, negative, and overall). | Positive Agreement: 95.8% (95% CI: 93.0 – 97.7)
  Negative Agreement: 87.7% (95% CI: 84.5 - 90.5)
  Overall Agreement: 91.0% (95% CI: 88.8 - 92.9) |
  | Matrix Comparison (Regression Coefficient) | Strong correlation (e.g., R-value > 0.95 or 0.98). | SST Serum: Slope 1.01, Intercept 0.00, Correlation Coefficient 0.99
  K2-EDTA Plasma: Slope 1.03, Intercept -0.01, Correlation Coefficient 0.99
  Lithium Heparin Plasma: Slope 0.99, Intercept -0.01, Correlation Coefficient 0.99 |
  | Clinical Sensitivity and Specificity (at 0.55 IU/L cut-off) | High clinical sensitivity and specificity (generally >95%). | Clinical Sensitivity: 98.6% (95% CI: 96.8 – 99.5)
  Clinical Specificity: 98.5% (95% CI: 96.8 – 99.5) |
  | Reference Range (97.5th percentile) | Clinically appropriate range. | 180 measurements). Data provenance not specified.

• LoD: 5 TSI serum samples, tested in 4 replicates using 3 reagent kit lots for 3 days on 3 systems (total 36 observations per sample). Data provenance not specified.
• Analytical Specificity (Interference): Three serum pools (for endogenous interferents), HAMA positive serum, RF positive serum, and six potential biological interferent samples. Data provenance not specified.
• Method Comparison: 811 serum samples from patients with Graves' disease, other thyroid or autoantibody diseases. Specimens tested at two external sites and one internal site for the IMMULITE 2000 TSI assay, and at one external site for the Thyretain device. Data provenance not explicitly stated, but implies mixed sources (internal/external, likely retrospective patient samples).
• Matrix Comparison: Graves' Disease sets of matched serum and plasma samples (clot tube, lithium heparin, SST, K2-EDTA). Sample size not specified. Data provenance not specified.
• Clinical Sensitivity and Specificity: 361 treated and untreated hyperthyroid Graves' disease patients and 404 individuals with other thyroid or autoimmune diseases. Data provenance not specified (likely retrospective clinical samples).
• Reference Range: 842 serum samples from apparently healthy males (n=151), non-pregnant females (n=155), first trimester (n=169), second trimester (n=191), and third trimester (n=176) pregnant donors. Data provenance not specified.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

The document does not specify the number or qualifications of experts used to establish the ground truth for any of the test sets. For example, for clinical sensitivity and specificity, it refers to "Graves' Disease Diagnosis" and "other thyroid or autoimmune diseases" but does not detail how these diagnoses were definitively established or by whom. Similarly, for the method comparison, it refers to patient samples for Graves' disease or other thyroid/autoantibody diseases without detailing expert adjudication of these conditions.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The document does not describe any specific adjudication method for establishing ground truth diagnoses for the patient samples used in the studies. The diagnoses are simply stated as existing, implying they were pre-determined or established through typical clinical practice, rather than through a separate expert adjudication process for the study.

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 was not done. This is an immunoassay device, not an imaging AI device that involves human readers interpreting cases. The comparison study was a "Method Comparison" between the new Immulite 2000 TSI assay and a predicate immunoassay device (Thyretain TSI Reporter BioAssay), analyzing patient samples.

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

Yes, the studies presented are all standalone validations of the Immulite 2000 TSI assay system. It is an automated immunoassay for in vitro diagnostic use, meaning it provides results directly from patient samples without human interpretation of images or other complex data requiring "human-in-the-loop" decision-making. The performance characteristics (precision, linearity, detection limits, clinical sensitivity/specificity, etc.) reflect the algorithm/device's performance alone.

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

The ground truth for the clinical studies (clinical sensitivity/specificity, method comparison) appears to be clinical diagnosis of Graves' disease or other thyroid/autoimmune diseases. For analytical performance studies (precision, linearity, LoB, LoD, interference), the ground truth is based on spiking known concentrations, using negative samples, or established reference standards like the NIBSC standard.

8. The sample size for the training set

The document does not explicitly mention a "training set" in the context of machine learning. This is a traditional immunoassay, not an AI device that typically involves distinct training and test sets in the same manner. The studies describe validation sets, not training sets for model development.

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

As there is no distinct "training set" in the context of an AI/machine learning model as understood in typical AI/ML submissions, this question is not directly applicable. For traditional assays, calibrators are used to establish the measurement and are themselves calibrated against reference materials (e.g., NIBSC standard 08/204 for the Immulite 2000 TSI assay).

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The Thyretain ™ TSI Reporter BioAssay is intended for the qualitative detection in serum of thyroid stimulating autoantibodies to the thyroid stimulating hormone (TSH) receptors (TSHRs) on the thyroid. The detection of these stimulating autoantibodies, in conjunction with other clinical and laboratory findings, may be useful as an aid in the differential diagnosis of patients with Graves' disease (GD).

The number of wells tested per Positive, Reference and Negative control has been reduced from three to two for each. The number of wells tested per patient specimen has been reduced from three to two.

The provided submission (K092229) is a special 510(k) for a device modification; therefore, it primarily focuses on demonstrating that the device, post-modification, remains substantially equivalent to its predicate device. This type of submission usually doesn't include new, large-scale clinical studies with specific acceptance criteria as would be found in a De Novo or PMAs. Instead, it relies on bridging data to show the modification doesn't negatively impact performance.

Here's an analysis based on the provided text:

Device: Thyretain™ TSI Reporter BioAssay (Modified)

Predicate Device: Thyretain™ TSI Reporter BioAssay (K083391)

Modification: Reduction of the number of wells tested per Positive, Reference, and Negative control from three to two. Reduction of wells tested per patient specimen from three to two.

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state formal acceptance criteria in a quantitative manner (e.g., "sensitivity must be >90%"). Instead, the performance assessment aims to demonstrate that the modified device remains equivalent to the predicate, particularly in its non-clinical performance.

Note: "Attachment 2" which would contain the detailed study site data is not provided in the input, so specific quantitative performance metrics like sensitivity, specificity, or agreement with the predicate are not available in this summary. The assessment focuses on risk analysis.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document refers to "study site data" in "Attachment 2". However, the details of this data, including sample size, provenance (country of origin), and whether it was retrospective or prospective, are not provided in the given text extract.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not provided in the given text extract. Given this is a modification to an in vitro diagnostic (IVD) device, the ground truth would likely refer to established diagnostic methods or clinical outcomes, rather than expert interpretation of images.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This information is not provided in the given text extract. It is unlikely to be relevant for this type of IVD modification, which assesses analytical performance rather than interpretation by human readers.

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 MRMC comparative effectiveness study was not done. This is an in vitro diagnostic device (a bioassay) for detecting autoantibodies, not an imaging device that requires human interpretation or AI assistance.

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

This question is not applicable in the context of this device. The Thyretain™ TSI Reporter BioAssay is a laboratory assay for detecting antibodies, not an algorithm. The "performance" refers to the analytical performance of the assay itself. The submission is not about an algorithm, but a modification to the assay's procedure (number of wells).

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

The submission is for an immunoassay. The ground truth for such an assay would typically be established by:

• Reference methods: Comparison to established, clinically validated assays for the same analyte.
• Clinical diagnosis: Correlation with the clinical diagnosis of Graves' disease (GD), which would involve a combination of clinical symptoms, other laboratory findings, and potentially outcomes data over time.
• Pathology: Less likely to be the primary ground truth for an antibody assay, but could be part of the broader clinical picture for Graves' disease.

The provided text does not explicitly state the type of ground truth used for the "study site data" referenced.

8. The sample size for the training set

This information is not provided in the given text extract. For an IVD assay modification, there isn't typically a "training set" in the machine learning sense. Any data used to validate the modified procedure would be considered a "test set" or verification/validation data.

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

As there is no "training set" in the context of this IVD device, this question is not applicable. Any ground truth for validation samples would be established by methods similar to those described in point 7.

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The TheraTest EL-Anti-TPO™ is an enzyme immunoassay for the qualitative detection or quantitative determination of IgG class antibodies against thyroid peroxidase (TPO) in human serum. The TheraTest EL-Anti-TPO™ assay is intended for use as an aid in the diagnosis of autoimmune thyroid disorders in conjunction with other clinical and laboratory findings.

The TheraTest EL-Anti-Thyroglobulin™ is an enzyme immunoassay for the qualitative detection or quantitative determination of IgG class antibodies against thyroglobulin in human serum. The TheraTest EL-Anti-ThyroglobulinTM assay is intended for use as an aid in the diagnosis of autoimmune thyroid disorders in conjunction with other clinical and laboratory findings.

Not Found

This looks like a 510k clearance letter for a medical device. There is no information in the document to extract an answer for the user's request. There is no mention of acceptance criteria or study details within the given text.

Therefore, I cannot answer the question.

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The Thyretain ™ TSI Reporter BioAssay is intended for the qualitative detection in serum of thyroid stimulating autoantibodies to the thyroid stimulating hormone (TSH) receptors (TSHRs) on the thyroid. The detection of these stimulating autoantibodies, in conjunction with other clinical and laboratory findings, may be useful as an aid in the differential diagnosis of patients with Graves' disease (GD).

The Thyretain ™ TSI Reporter BioAssay (TSI Reporter) utilizes a patented bioassay technology to detect thyroid stimulating immunoglobulin (TSI) in human serum. Genetically engineered Chinese hamster ovary (CHO) cells, expressing a chimeric form' of the human thyroid stimulating hormone receptor (TSHR) and a cyclic adenosine monophosphate (cAMP) induced luciferase reporter gene, are cryogenically preserved and provided in measured aliquots. The CHO Mc4 cell line has a nucleic acid sequence encoding a chimeric human TSH receptor, designed for reduced response to thyroid blocking immunoglobulin (TBI) activity. Thus, the hTSH receptor, comprised of 730 amino acids, has amino acid residues 262 to 335 replaced by the equivalently located 73 amino acid residues of the rat Luteinizing Hormone receptor to form the chimeric TSHR. This chimeric receptor is linked to a firefly luciferase reporter gene in operable combination with a glycoprotein hormone a-subunit promoter. The cells are seeded and grown for 15 to 18 hours to confluent monolayers in a 96-well plate. Patient sera, reference control, positive and normal controls and are diluted with a proprietary reaction buffer (RB), added to the cell monolayers and allowed to react with the cells for 3 hours. During this induction period TSI, if present in the patient serum, bind to the chimeric human TSHR on the cell surface. This binding event induces a signaling cascade resulting in increased production of intra-cellular cAMP. This increased production of cAMP is evidenced by increased production of luciferase. At the conclusion of the 3 hour induction period the cells are lysed. Luciferase levels are then measured using a luminometer. A significant increase in luminescence over the Reference Control indicates the presence of TSI antibodies in the sample.

Here's a summary of the acceptance criteria and the studies that prove the device meets them, based on the provided text:

Thyretain™ TSI Reporter BioAssay: Acceptance Criteria and Study Summary

The provided document describes the Thyretain™ TSI Reporter BioAssay as an in-vitro diagnostic device intended for the qualitative detection of thyroid stimulating autoantibodies (TSI) in human serum, to aid in the differential diagnosis of Graves' disease (GD). The performance was assessed through non-clinical and clinical studies, primarily comparing it to a legally marketed predicate device, the KRONUS TSH Receptor Antibody (TRAb) Coated Tube (CT) Assay Kit.

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" for clinical performance in a numerical format that would typically precede a study. Instead, it presents the results of comparative studies against a predicate device and clinical sensitivity/specificity. The implied acceptance is that the device demonstrates comparable performance to the predicate and acceptable clinical utility (sensitivity and specificity).

• Positive Percent Agreement (PPA): 93.8% (95% CI: 88.2% to 96.8%)
• Negative Percent Agreement (NPA): 89.5% (95% CI: 84.0% to 93.2%)

Site 3-NC (n=231 valid specimens):

• Positive Percent Agreement: 74.6% (95% CI: 63.5% to 83.3%)
• Negative Percent Agreement: 97.5% (95% CI: 93.8% to 99.0%)
  Post-hoc analysis removing hypothyroid patients at Site 3-NC increased PPA to 81.5% (95% CI: 70.4% to 89.1%). |
  | Clinical Sensitivity/Specificity | Not explicitly stated as a numerical criterion for acceptance, but demonstrated to provide useful diagnostic information. | Study with 249 characterized specimens:
• Clinical Sensitivity: 92.0% (46/50 Graves Disease positive)
• Clinical Specificity: 99.5% (198/199 Other autoimmune diseases and healthy controls negative) |

2. Sample Sizes and Data Provenance

• Non-Clinical Studies:
  • Assay Cutoff:
    • "Training set": 30 subjects with diagnosed Graves' disease and 44 normal subjects.
    • "Testing-set" (pre-clinical verification): 50 GD positive sera, 140 normal sera.
  • Precision (Intra-assay, Inter-assay, Inter-Day): Varies per test; for Inter-Day, n=120 for high, medium, low TSI serum, n=40 for normal serum, n=80 for controls.
  • Reproducibility:
    • Panel 1: 4 specimens tested at multiple sites (3 sites, with one having 2 technicians). Each site/technician performed testing twice a day over 8 days, leading to 180 total tests for each sample (3 sites x 2 tests/day x 8 days x 4 samples = 192, or 3 sites x 2 techs x 2 tests/day x 8 days = 96 for specific site/tech data, actual calculation seems to be 180 total for "positive ratio").
    • Panel 2: 3 samples tested at 2 sites twice a day for 5 days, totaling 60 tests for each sample (2 sites x 2 tests/day x 5 days x 3 samples = 60).
• Clinical Performance Studies:
  • Comparative Study:
    • Combined Sites 1-COH and 2-MN: 312 specimens initially, 299 analyzed (1 excluded for insufficient quantity, 12 excluded due to indeterminate results on comparator).
    • Site 3-NC: 247 specimens initially, 231 analyzed (16 excluded due to indeterminate results on comparator).
  • Clinical Sensitivity and Specificity: 249 characterized specimens.
• Data Provenance: The document implies the data is retrospective/archived samples, as it refers to "patients with diagnosed Graves' disease," "normal subjects with no known or clinically diagnosed thyroid disease," and "sera obtained from physicians with diagnostic information." The multi-site nature (COH, MN, NC) suggests geographical diversity within the US. There is no explicit mention of the country of origin for all samples.

3. Number of Experts and Qualifications for Ground Truth

• Non-Clinical Studies (Assay Cutoff): Ground truth was established based on "diagnosed Graves' disease" and "normal subjects with no known or clinically diagnosed thyroid disease," implied to be clinical diagnosis by physicians. No specific number or qualifications of experts are provided.
• Clinical Performance Studies (Comparative Study, Clinical Sensitivity/Specificity):
  • The "ground truth" for the comparative study was the results from the KRONUS TSH Receptor Antibody (TRAb) Coated Tube (CT) Assay Kit (the predicate device). This implies that the predicate device's results were accepted as the reference for comparison against the subject device.
  • For the Clinical Sensitivity and Specificity study, specimens were "249 characterized specimens" categorized as "Graves Disease" and "Other autoimmune diseases and healthy controls." This categorization itself acts as the ground truth. The method of characterization (e.g., expert clinical diagnosis, pathology) is not explicitly detailed, but it is implied to be based on clinical diagnosis ("Diagnosis"). No specific number of experts or their qualifications are provided for establishing these fundamental diagnoses.

4. Adjudication Method

• The document does not describe an adjudication method for establishing ground truth using multiple experts.
• For the comparative study, discordant results between the subject device and the predicate device were analyzed, especially at Site 3-NC. The analysis focused on patient TSH results and ATA guidelines for hypothyroidism to explain the discrepancies, rather than an expert adjudication of the initial diagnosis. No multi-reader, observer, or expert consensus adjudication is described for the ground truth of the patient samples.

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

• No MRMC comparative effectiveness study is described where human readers' performance with and without AI assistance is evaluated. The device is an in-vitro diagnostic assay read by a luminometer, not an AI interpreting images for human readers.

6. Standalone Performance

• Yes, the clinical performance studies (both the comparative study and the clinical sensitivity/specificity study) describe the standalone performance of the Thyretain™ TSI Reporter BioAssay. The device produced its own results (positive/negative) which were then compared to either the predicate device's results or defined clinical diagnoses.

7. Type of Ground Truth Used

• Non-Clinical (Assay Cutoff): Clinical diagnosis of Graves' disease or no known thyroid disease.
• Clinical Performance (Comparative Study): The results of the predicate device (KRONUS TSH Receptor Antibody (TRAb) Coated Tube (CT) Assay Kit) were used as the reference for comparison.
• Clinical Performance (Clinical Sensitivity and Specificity): Clinical diagnosis ("Graves Disease", "Other autoimmune diseases and healthy controls"). This would typically be established based on a combination of clinical signs/symptoms, other laboratory tests, and possibly imaging, by a physician.

8. Sample Size for the Training Set

• For establishing the preliminary assay cutoff:
  • 30 subjects with diagnosed Graves' disease.
  • 44 normal subjects with no known or clinically diagnosed thyroid disease.
  • (An additional "testing-set" of 50 GD positive sera and 140 normal sera was used for verification).

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

• The ground truth for the training set (for assay cutoff determination) was established through clinical diagnosis: "subjects with diagnosed Graves' disease" and "normal subjects with no known or clinically diagnosed thyroid disease." This implies traditional clinical assessment by physicians.

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(1) Elecsys Anti-TSHR immunoassay: Immunoassay for the in vitro quantitative determination of autoantibodies to TSH receptor in human serum using a human thyroid stimulating monoclonal antibody. The anti-TSH receptor determination is used in the assessment of patients with suspect Graves' disease (autoimmune hyperthyroidism).
The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.
(2) Elecsys PreciControl ThyroAB is used for quality control of the Elecsys Anti-TSHR immunoassay on the Elecsys and cobas e immunoassay analyzers.

(1) The Elecsys Anti-TSHR immunoassay is a three step competition principle immunoassay with streptavidin-coated microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2 point calibration and a master curve provided with the reagent bar code.
(2) The Elecsys PreciControl ThyroAB is a lyophilized product consisting of human serum with added Anti-TSHR antibody (human) in two concentration ranges. During manufacture, the antibody is spiked into the matrix at the desired concentration levels.
Note: The reagent and quality control material are packaged separately.

The provided document describes the Elecsys Anti-TSHR Immunoassay and its substantial equivalence to a predicate device, the BRAHMS LUMItest TRAK human Assay (K033454). The document does not clearly define explicit "acceptance criteria" in a typical clinical study sense with predetermined thresholds for sensitivity, specificity, accuracy, or other performance metrics the device must meet. Instead, it focuses on demonstrating comparable performance to a legally marketed predicate device.

The study presented is primarily a method comparison study and a precision study.

Here's an analysis of the requested information based on the provided text:

1. Table of "Acceptance Criteria" and Reported Device Performance

As mentioned, there are no explicitly stated "acceptance criteria" with numerical thresholds that the device must meet in this document. Instead, the focus is on demonstrating "substantial equivalence" through comparable performance to the predicate device. Therefore, the table below will present the performance of the Elecsys Anti-TSHR Immunoassay alongside the claimed comparable performance of the predicate device. The implied "acceptance criteria" are that the new device's performance should be similar to or better than the predicate.

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