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The ADVIA Centaur Anti-Thyroid Peroxidase II (aTPOII) assay is for in vitro diagnostic use in the quantitative measurement of autoantibodies against thyroid peroxidase in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur XP system.

Anti-thyroid peroxidase (aTPO) measurements are used, in conjunction with a clinical assessment, as an aid in the diagnosis of autoimmune thyroiditis and/or Graves' disease.

The ADVIA Centaur Anti-Thyroid Peroxidase II (aTPOII) consists of:

• aTPOII ReadyPack® primary reagent pack (Lite Reagent, Solid Phase)
• aTPOII CAL
  Devices sold separately and included in the ADVIA Centaur® Anti-Thyroid Peroxidase II (aTPOII) are:
• ADVIA Centaur aTPOII MCM (MCM 1, MCM 2–4)
• ADVIA Centaur aTPOII QC
• ADVIA Centaur aTPOII DIL ReadyPack ancillary reagent pack

N/A

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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:

Study Details:

This submission focuses on an In Vitro Diagnostic (IVD) assay (Access TPO Antibody), not an AI/ML algorithm. Therefore, many of the questions related to AI/ML development (training set, experts for ground truth, MRMC studies) are not directly applicable in the way they would be for an AI-based medical device. However, I will interpret them in the context of an IVD assay where possible, based on standard IVD validation practices.

1. Sample Size Used for the Test Set and Data Provenance:

   • Method Comparison: N = 219 patient samples.
   • Imprecision: N = 80 replicates (for each of 5 samples).
   • Linearity & Detection Capability: Sample sizes for these studies are not explicitly stated, but are governed by CLSI guidelines (EP06-Ed2 and EP17-A2 respectively), which typically involve analyzing serially diluted samples.
   • Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be analytical performance studies conducted on patient samples, but whether they were retrospective or prospective is not specified. Given the nature of an IVD, these are typically conducted prospectively in a lab setting using banked or newly collected samples.

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

   • Not Applicable in the traditional AI/ML sense. For an IVD assay, the "ground truth" for the test set is either:
     • Clinical Diagnosis: For the diagnostic claim ("aid in the diagnosis of thyroid autoimmune disorders"), the ground truth would be established by independent clinical diagnosis (e.g., by endocrinologists) typically using a variety of clinical data and other diagnostic tests. This information is usually part of clinical utility studies, which are not detailed in this analytical performance summary.
     • Reference Method/Predicate Product: For the analytical performance studies like Method Comparison, the "ground truth" or reference is the result obtained from the predicate device (Access TPO Antibody Assay on Access 2 Immunoassay System). The predicate device itself is validated against established (often clinical) criteria.
     • Known Concentrations/Materials: For linearity, imprecision, and detection capability studies, the "ground truth" is established by using characterized materials with known concentrations, or by measuring the variability around the mean of repeated measurements. This doesn't involve medical experts in the adjudication sense.

3. Adjudication Method for the Test Set:

   • Not Applicable. Adjudication is typically for subjective interpretations (like image reading). For an IVD, the results are quantitative measurements from an instrument. The "adjudication" is essentially the statistical analysis (e.g., Passing-Bablok regression, CV calculations) of these quantitative results against predefined criteria or a reference method.

4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

   • No. An MRMC study is relevant for interpreting subjective data (like medical images) where human readers are involved. This document describes the analytical performance of an in vitro diagnostic assay that produces quantitative results, not an image interpretation or decision support AI.

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

   • Yes, in the context of an IVD. The entire analytical performance evaluation (Method Comparison, Imprecision, Linearity, Detection Capability) describes the standalone performance of the Access TPO Antibody assay on the Dxl 9000 system. It functions automatically based on its chemiluminescent immunoassay technology to produce a quantitative result. There is no "human-in-the-loop" aspect to the measurement itself, though human lab personnel operate the instrument and interpret the results.

6. The Type of Ground Truth Used:

   • Known concentrations, reference method results (predicate device), and statistical averages.
     • For Method Comparison, the "ground truth" for comparison is the result obtained from the predicate Access 2 Immunoassay System.
     • For Imprecision, the "ground truth" is the mean concentration of the samples derived from repeated measurements, and the variability around that mean.
     • For Linearity, the ground truth is derived from known dilutions of a high-concentration material.
     • For Detection Capability (LoB, LoD, LoQ), the ground truth involves the statistical analysis of measurements of blank samples and low-concentration samples.

7. The Sample Size for the Training Set:

   • Not Applicable. This is an IVD assay relying on chemical and immunological reactions, not a machine learning algorithm that requires a "training set" in the AI/ML sense. The device's parameters are determined during its design and optimization phases by Beckman Coulter, based on established immunoassay principles.

8. How the Ground Truth for the Training Set was Established:

   • Not Applicable. As above, there is no "training set" for this type of device in the AI/ML context. The assay's performance characteristics (e.g., reactivity, linearity, precision) are inherent to its reagent formulation and instrument design, which are optimized by the manufacturer using internal R&D processes guided by scientific principles and regulatory standards.

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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 goiter, 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 is a sequential two-step immunoenzymatic ("sandwich") assay. A sample is added to a reaction vessel with paramagnetic particles coated with the thyroglobulin protein. The TgAb in the sample binds to the thyroglobulin coated on the particles. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. The thyroglobulin-alkaline phosphatase conjugate is added and binds to the TgAb.

After second 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.

Here's a detailed breakdown of the acceptance criteria and study information for the Beckman Coulter Access Thyroglobulin Antibody II device, extracted from the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The primary goal of this submission (K240996) is to demonstrate substantial equivalence of the same device on a new instrument platform (Dxl 9000 Access Immunoassay Analyzer) compared to its predicate on the Access 2 Immunoassay System. Therefore, the "acceptance criteria" are largely derived from the established performance of the predicate device.

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

• Method Comparison Study (CLSI EP09c):
  • Sample Size: N = 114
  • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, such studies typically use clinical samples that may be either retrospectively collected or prospectively collected for validation purposes.
• Imprecision Study (CLSI EP05-A3):
  • Sample Size: 3 distinct "Samples" (concentrations) were tested. Each sample was tested 80 times (duplicate R.L per day for a minimum of 20 days).
  • Data Provenance: Not explicitly stated. Assumed to be laboratory samples or controls prepared for method validation.
• Reproducibility Study (CLSI EP05-A3):
  • Sample Size: 5 distinct "Samples" (concentrations) were tested. Each sample was tested 75 times (replicates of 5 per day for a minimum of 5 days on 3 instruments).
  • Data Provenance: Not explicitly stated. Assumed to be laboratory samples or controls prepared for method validation.
• Detection Capability (LoB, LoD, LoQ) Study (CLSI EP17-A2):
  • Sample Size: Not explicitly stated for each determination, but these studies typically involve multiple replicates of blank, low-level, and higher-level samples.
  • Data Provenance: Not explicitly stated. Assumed to be laboratory samples or controls.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This document describes a clinical laboratory device (an immunoassay), not an AI/imaging device requiring expert interpretation of results for ground truth. Therefore, the concepts of "experts to establish ground truth" (in the context of clinical interpretation or diagnosis from an image) and their "qualifications" are not applicable here.

For this type of device, ground truth is established through:

• Reference Methods / Predicate Devices: The Access 2 Immunoassay System (predicate) served as the comparator for the method comparison study to assess the "truth" of the Dxl 9000 system's measurements.
• Certified Reference Materials/Standards: Calibrators and controls with known analyte concentrations, often traceable to international standards, are used to establish accuracy and calibration.
• Clinical Diagnosis: For the "Indications for Use," the device aids in diagnosis, meaning its results are interpreted by clinicians in conjunction with other clinical information. The diagnostic accuracy studies (sensitivity, specificity) in relation to a "gold standard" clinical diagnosis are typically part of a larger clinical trial not detailed in this specific 510(k) summary for a platform change.

4. Adjudication Method for the Test Set

Not applicable. As this is an immunoassay device assessing quantitative levels of an antibody, there is no "adjudication method" in the sense of reconciling divergent expert interpretations of qualitative or semi-quantitative data. The "test set" results—the quantitative values—are compared statistically to the reference method (predicate device) and assessed against performance specifications (imprecision, linearity, detection limits).

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for AI/imaging devices where multiple human readers interpret complex cases (e.g., medical images) and AI assistance might improve their performance. This document is for a medical laboratory immunoassay for quantitative measurement of thyroglobulin antibody, not an AI-assisted diagnostic tool for human interpretation.

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

While the device operates "standalone" in the sense that the instrument performs the assay and generates a quantitative result without human intervention during the analytical process, this is not an "algorithm-only" study in the context of AI. The performance studies (imprecision, linearity, method comparison, detection capability) represent the standalone analytical performance of the instrument/reagent system. The "human-in-the-loop" would be the clinician interpreting the numerical result in the context of a patient's overall clinical picture, but the device itself functions automatically.

7. The Type of Ground Truth Used

• Quantitative Reference Values: For the performance studies, the ground truth is established through various means:
  • Method Comparison: The results obtained from the predicate device (Access Thyroglobulin Antibody II on the Access 2 Immunoassay System) serve as the reference standard.
  • Imprecision & Reproducibility: Derived from repeated measurements of samples (often control materials or pooled patient samples) to assess variability. The "true" value for these samples is either assigned by the manufacturer or determined through extensive testing.
  • Linearity: Determined by creating serially diluted samples from a high-concentration sample, where the expected concentration of each dilution is the "ground truth."
  • Detection Capability (LoB, LoD, LoQ): Established using blank samples and low-concentration spiked samples, with statistical methods determining the lowest detectable/quantifiable levels.

8. The Sample Size for the Training Set

This document does not describe a machine learning or AI algorithm development that would typically involve a "training set." The studies described are for analytical validation of an immunoassay on a new instrument platform, focusing on demonstrating equivalent performance to a predicate device. Therefore, a "training set" in the AI sense is not applicable.

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

Not applicable, as there is no "training set" in the context of AI or machine learning for this immunoassay device.

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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).

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

• Method Comparison: n = 123 samples. Data provenance not specified (country of origin, retrospective/prospective).
• Imprecision: Not specified, but involved reagent lots and instrument details suggest laboratory testing.
• Reproducibility: Not specified, but involved reagent lots and instrument details suggest laboratory testing.
• High-dose Hook Effect: Not specified how many samples were tested, but concentrations up to 50,000 IU/mL were used.
• Linearity: Not specified how many samples were tested, but both serum and plasma samples were used.
• Sensitivity (LoB, LoD, LoQ): Not specified how many samples were used, but involved 2 reagent lots and 2 instruments over a minimum of 3 days (LoB) or 5 days (LoD, LoQ).
• Analytical Specificity:
  • Cross-reactive disease states: "Samples with potential cross-reactive disease states were tested." Number of samples not specified.
  • Potential interferents: "Patient serum samples containing two levels of thyroglobulin antibody at clinically relevant concentrations of approximately 4 IU/mL and 100 IU/mL." Number of samples not specified, but specific interferents (like biotin at 3510 ng/mL) were tested.
• Matrix Comparison: Fifty (50) matched sets of serum, lithium heparin plasma, and EDTA plasma samples.

Data Provenance: The document does not specify the country of origin for any of the samples used in these studies, nor does it explicitly state if the studies were retrospective or prospective, though "patient samples" implies retrospective collection or prospective enrollment for the study.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This device is an in vitro diagnostic (IVD) immunoassay, not an imaging device typically requiring expert interpretation for ground truth. Therefore, the concept of "experts" establishing ground truth in the traditional sense of clinical diagnosis (e.g., radiologists, pathologists) does not directly apply here.

For IVDs, "ground truth" is typically established by:

• Reference methods/devices.
• Certified reference materials.
• Pathology or histopathology (for certain tests).
• Clinical outcomes/diagnosis (for certain tests).
• Known concentrations in spiked samples or characterized panels.

In this document:

• The "Method Comparison" used a "commercially available immunoassay" as a comparator, which serves as a de facto reference for comparison.
• Analytical specificity testing used "potential cross-reactive disease states" and "potential interferents" for which the expected results (presence/absence of Thyroglobulin Antibody, or known interference levels) would be pre-established or determined by a reference method.
• Sensitivity studies (LoB, LoD, LoQ) involve statistical calculations based on repeated measurements of samples with very low or zero analyte concentrations, not expert consensus.
• Concentration ranges for linearity were established using characterized samples.

Therefore, no information on human experts establishing ground truth is provided, as it's not relevant for this type of device validation.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are typically used for studies where multiple human readers interpret medical images or complex data, and their interpretations need to be reconciled to establish a ground truth.

Since this is an in vitro diagnostic device measuring an analyte concentration, and the gold standard for comparison typically involves laboratory methods or reference materials, an adjudication method for a test set is not applicable or described in this document. The "ground truth" for the various performance characteristics is established by analytical methods and comparisons to reference standards or predicate devices.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This type of study is relevant for medical imaging devices where the performance of human readers, with and without AI assistance, is evaluated using a set of cases. This document describes an in vitro diagnostic device, an immunoassay, which does not involve human interpretation of images or complex data in a way that MRMC studies would be applicable.

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

Yes, the studies described are all standalone performance evaluations of the Access Thyroglobulin Antibody II assay. This means the studies assess the device's ability to measure thyroglobulin antibody levels independent of human intervention in the interpretation of the result in the context of the device's analytical performance. The Access Immunoassay Systems are automated, and the assay's performance metrics (imprecision, linearity, sensitivity, specificity, etc.) are solely based on the analytical capabilities of the device itself.

7. The Type of Ground Truth Used

The type of "ground truth" used varies depending on the specific study:

• Method Comparison: A "commercially available immunoassay" served as the comparative standard. The results from this predicate/reference immunoassay formed the basis for comparing the new device's measurements.
• Imprecision & Reproducibility: Ground truth is implicit in the known characteristics of the control materials or spiked samples used, and the statistical variability observed from repeated measurements defines the performance.
• High-dose Hook Effect & Linearity: Ground truth is established by using samples with known or precisely characterized concentrations, often prepared by dilution or spiking.
• Sensitivity (LoB, LoD, LoQ): Statistical models are used based on repeated measurements of blank samples and samples with very low (but known) analyte concentrations.
• Analytical Specificity:
  • Cross-reactive disease states: Likely involved samples from patients with these conditions, where the presence/absence of TgAb would have been characterized by a reference method or clinical diagnosis. The "ground truth" then is the expected TgAb status based on the sample's origin.
  • Potential interferents: Involved adding known concentrations of interfering substances to samples with known TgAb concentrations. The "ground truth" is the expected TgAb concentration without interference.
• Matrix Comparison: Used matched samples from different matrices (serum, plasma), where the inherent TgAb concentration within a given patient sample is the ground truth against which each matrix measurement is compared.

In summary, the ground truth for this IVD device is primarily established through comparisons to established reference methods/predicate devices, known concentrations in characterized samples (spiked or diluted), and statistical analysis of performance with control materials.

8. The Sample Size for the Training Set

The document describes studies for validation of a modified device, demonstrating substantial equivalence to a predicate. It does not mention a "training set" in the context of developing an algorithm or AI model. This is an immunoassay, not a machine learning model that typically requires a large training dataset. The studies focus on analytical performance rather than diagnostic accuracy determined by a machine learning pipeline.

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

As noted above, there is no mention of a "training set" or "ground truth" established for training in this document, as the device is an immunoassay not based on a trainable algorithm.

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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:

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

• Precision (Repeatability & Intermediate Precision): 5 human serum samples (4 native, 1 spiked) and 2 controls (PC ThyroAB) were tested over 21 days with 2 replicates per run, 2 runs per day. (Total of 84 replicates per sample/control for repeatability and intermediate precision calculations).
• Lot-to-Lot Reproducibility: 5 human serum samples (4 native, 1 spiked) were tested with 2 replicates per run, 2 runs per day, for 3 reagent lots (n = 28 determinations per lot per sample, totaling 3x7x2x2 measurements over 3 lots for each sample).
• Analytical Sensitivity (LoB, LoD, LoQ):
  • LoB: Five blank samples with two replicates each per run, for 6 runs on ≥ three days, across three reagent lots. (Total 60 determinations for analyte-free samples).
  • LoD: Five low analyte samples with two replicates each per run, for 6 runs on ≥ three days, across three reagent lots. (60 replicates per sample per reagent lot).
  • LoQ: Samples tested across three reagent lots for 5 days, one run per day (25 replicates per sample per reagent lot).
• Linearity/Assay Reportable Range: Three high analyte human serum samples (serum pools) were diluted to create 14 concentrations (13 dilutions). Samples were measured in triplicate within a single run.
• Endogenous Interference (Biotin, Hemolysis, Bilirubin, Lipemia, Rheumatoid Factors): Not explicitly stated, but typically involves a few serum samples spiked with interferents and compared to unspiked controls. Each sample was spiked with the interfering substance, another aliquot was spiked with isotonic NaCl solution (dilution pool), and the interfering pool was diluted into the dilution pool (in 10% increments for some).
• Analytical Specificity/Cross-Reactivity: One native human serum sample pool with a low concentration of anti-TSHR was used.
• Exogenous Interferences (Drugs): Two human serum samples (native serum pools) were used.
• Method Comparison to Predicate:
  • Agreement: 260 clinical samples from the "intended use population".
  • Regression Analysis: A subset of 120 samples, evenly distributed across the measuring range, from the 260 collected samples.

Data Provenance:

• For the "Expected values" (Table 2), an external study used samples from 436 apparently healthy individuals, 210 patients with thyroid diseases without Graves' disease, and 102 patients with untreated Graves' disease.
• For the non-clinical performance evaluation, samples used were primarily "human serum pools" (native and spiked) and controls.
• For the Method Comparison, "clinical samples from the intended use population" were used.

The document does not explicitly state the country of origin or whether the data was retrospective or prospective beyond referring to "clinical samples" and an "external study."

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

This document describes an in vitro diagnostic immunoassay. The concept of "experts establishing ground truth for a test set" as typically understood in AI/imaging studies (e.g., radiologists reviewing images) is not directly applicable here. The "ground truth" for an immunoassay is typically established by reference methods, clinical diagnosis, or by defining specific concentrations for spiked samples or control materials.

For the "Expected Values" in Table 2, an external study was used where an "optimal cutoff of 1.75 IU/L was determined" based on diagnoses of apparently healthy individuals, those with thyroid diseases without Graves', and those with untreated Graves' disease. This implies a clinical diagnostic ground truth, but not direct "expert adjudication" in the sense of multiple experts assigning labels to individual cases for comparison.

4. Adjudication Method for the Test Set:

Not applicable in the context of an immunoassay performance study as described. Clinical diagnoses or reference assays serve as the "ground truth" rather than expert adjudication of individual test cases.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done:

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging interpretation devices involving human readers, not for an automated immunoassay such as the Elecsys Anti-TSHR.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done:

Yes, the studies described are all standalone performance evaluations of the Elecsys Anti-TSHR device itself. This device is an automated immunoassay system that provides quantitative results without human interpretation in the loop as part of its primary function. Its performance characteristics (precision, sensitivity, linearity, interference, method comparison) are evaluated directly.

7. The Type of Ground Truth Used:

• Clinical Diagnosis/Disease State: For "Expected Values" (Sensitivity and Specificity), the ground truth was based on patient cohorts: apparently healthy individuals, patients with thyroid diseases (without Graves'), and patients with untreated Graves' disease.
• Reference Methods/Known Concentrations: For analytical performance studies (Precision, Analytical Sensitivity, Linearity, Interference, Cross-Reactivity), the ground truth was established by:
  • Using predefined control materials with known values.
  • Using native human serum pools.
  • Spiking samples with known concentrations of analyte or interfering substances.
  • Comparison against a predicate device (Elecsys Anti-TSHR Immunoassay K080092) for method comparison.

8. The Sample Size for the Training Set:

The document describes performance evaluation studies, not the development or training of an AI algorithm. Therefore, there is no "training set" in the context of artificial intelligence or machine learning. The studies described are for validation and verification of the device's performance characteristics.

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

As there is no "training set" for an AI model mentioned in the context of this immunoassay, this question is not applicable. The device's underlying principles are based on electrochemiluminescence immunoassay (ECLIA) technology, not machine learning that requires a training set.

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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".

*Specific Answers to Questions:

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

• Precision/Reproducibility: 6 serum samples and low/high kit controls, tested in duplicate in two runs per day over 20 days (total 80 replicates per sample). Data provenance not specified (likely internal laboratory data, prospective for the study).
• Linearity: TSI positive and TSI negative samples from "several commercial vendors." Data provenance not specified.
• LoB: 5 TSI negative samples, tested with 3 reagent lots, 2 runs, 2 replicates per run for 3 days (total >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 Access Thyroglobulin Antibody II assay is a paramagnetic 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 reagents, Thyroglobulin Antibody II calibrators, and the Access Immunoassay analyzers comprise the Access lmmunoassay System for the quantitative determination of thyroglobulin antibody in human serum and plasma.

Here's a breakdown of the acceptance criteria and study information for the Access Thyroglobulin Antibody II for use on the Access Immunoassay Systems, as extracted from the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the "Summary of Studies" section, which describes the performance characteristics that were measured and deemed acceptable for demonstrating substantial equivalence. Exact numerical acceptance thresholds for each test (e.g., "imprecision must be less than X%") are not explicitly stated as distinct criteria, but the reported performance values are presented as evidence of meeting acceptable levels.

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

• Sample Size: 397 samples were used for the method comparison study. The LoB study used 221 samples. The number of samples for other studies (imprecision, linearity, analytical specificity) is not explicitly stated, although "samples with autoimmune disease state" were "tested" for analytical specificity.
• Data Provenance: Not explicitly stated (e.g., country of origin). The data is from a prospective study, as it involves running samples on both the new device and the predicate device for comparison and performance characterization.

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

This device is an in vitro diagnostic (IVD) immunoassay that measures an analyte (thyroglobulin antibody) directly. Therefore, there is no "ground truth" established by human experts in the way that would apply to image-based diagnostic AI. The "ground truth" for method comparison and performance comes inherently from the measurements of the predicate device and established analytical methods.

4. Adjudication Method for the Test Set

Not applicable, as the device is an immunoassay and does not involve human interpretation or adjudication for its raw output. The "comparison" is between the new device's quantitative output and the predicate device's quantitative output.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement with AI vs. Without AI Assistance

Not applicable. This device is an automated immunoassay system, not an AI-assisted diagnostic tool that aids human readers in interpretation.

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

Yes, the studies described are standalone performance evaluations of the device (immunoassay system), as it functions as an automated system producing quantitative results. There is no "human-in-the-loop" component for the actual measurement process.

7. The Type of Ground Truth Used

The "ground truth" used for comparison, particularly in the method comparison study, is the quantitative measurement provided by the predicate device (Access Thyroglobulin Antibody II, K062516). For other performance metrics (imprecision, linearity, LoB, LoD), the "ground truth" is derived from established analytical methods and reference materials (e.g., NIBSC Anti-Thyroglobulin Serum, Human First International Reference Preparation, WHO Coded 65/93 for standardization).

8. The Sample Size for the Training Set

Not applicable. This device is an immunoassay, not a machine learning or AI algorithm that requires a "training set" in the conventional sense. The "training" for such devices typically involves calibration using specific calibrators as described ("Utilizes a stored calibration curve").

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

Not applicable. As described above, there isn't a "training set" in the AI/ML context. The calibration of the immunoassay system uses specific calibrators, and its standardization is based on NIBSC Anti-Thyroglobulin Serum, Human First International Reference Preparation, WHO Coded 65/93.

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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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