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The Atellica IM Thyroglobulin (Tg) assay is for in vitro diagnostic use in the quantitative measurement of thyroglobulin in human serum and plasma (EDTA and lithium heparin) using the Atellica IM Analyzer.

Thyroglobulin measurements are used as an aid in monitoring differentiated thyroid cancer patients who have undergone thyroidectomy with or without radioiodine ablation.

The Atellica IM Thyroglobulin (Tg) assay includes:

• Tg ReadyPack primary reagent pack:
  • Lite Reagent: mouse monoclonal anti-human Tg antibody labeled with acridinium ester (~1.13 μg/mL); bovine serum albumin (BSA); mouse IgG; buffer; stabilizers; preservatives (7.5 mL/reagent pack).
  • Solid Phase: streptavidin-coated paramagnetic microparticles preformed with biotinylated mouse monoclonal antihuman Tg antibody (~267 μg/mL); BSA; mouse IgG; buffer; stabilizers; preservatives (15.0 mL/reagent pack).
• Ancillary Well Reagent: BSA; bovine gamma globulin; buffer; preservatives (6.0 mL/reagent pack).
• Tg CAL: After reconstitution, human thyroglobulin; BSA; buffer; stabilizers; preservatives (2.0 mL/vial).

The following devices are sold separately:

• Atellica IM Tg MCM:
  • MCM 1: After reconstitution, bovine serum albumin (BSA); buffer; stabilizers; preservatives (1.0 mL/vial).
  • MCM 2–5: After reconstitution, various levels of human thyroglobulin; BSA; buffer; stabilizers; preservatives (1.0 mL/vial).

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for the Atellica IM Thyroglobulin (Tg) assay:

Device: Atellica IM Thyroglobulin (Tg) Assay
Purpose: Quantitative measurement of thyroglobulin in human serum and plasma as an aid in monitoring differentiated thyroid cancer patients who have undergone thyroidectomy with or without radioiodine ablation.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document describes various performance characteristics, which serve as acceptance criteria for the device. The reported performance is directly from the summary.

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

• Clinical Performance Test Set Sample Size: 291 serum samples collected from 189 subjects.
• Data Provenance:
  • The document states "A prospective, multi-center study was conducted." This indicates prospective data collection across multiple sites.
  • The country of origin is not explicitly stated in the provided text.
  • All samples were from subjects diagnosed with differentiated thyroid cancer, 6 or more weeks following thyroidectomy or radioiodine ablation.

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

• The document does not specify the number of experts or their qualifications for establishing the ground truth (structural disease). It simply states: "SD [Structural Disease] was established and classified as either positive or negative by cross-sectional or functional imaging results."
• This suggests that the ground truth was derived from standard clinical imaging reports rather than a consensus of independent expert readers specifically for this study.

4. Adjudication Method for the Test Set

• The document does not describe an adjudication method for the test set's ground truth (structural disease). It implies that the imaging results themselves provided the classification. This means there was no adjudication process as typically seen with multiple human readers reviewing images.

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

• No, an MRMC comparative effectiveness study was not done.
• This study is for an in vitro diagnostic (IVD) assay (a lab test), not an AI-assisted imaging or diagnostic tool where human readers work with or without AI. The performance metrics presented are for the analytical and clinical performance of the assay itself, comparing its results to a ground truth (structural disease status), not to human reader performance or improvement with AI.

6. If a Standalone Performance Study Was Done

• Yes, this is effectively a standalone (algorithm only) performance study.
• The Atellica IM Tg assay is an automated in vitro diagnostic device. Its performance characteristics (sensitivity, specificity, precision, linearity, etc.) are evaluated intrinsically, independent of human interpretation of the assay result values. The output is a quantitative measurement of thyroglobulin.

7. The Type of Ground Truth Used

• Ground truth for clinical performance: Structural disease (SD) status obtained from "cross-sectional or functional imaging results."
• Ground truth for analytical performance (LoB, LoD, LoQ, Precision, etc.): Established through laboratory protocols and reference materials (e.g., CLSI guidelines, certified reference materials like BCR CRM 457, spiked samples, control materials).

8. The Sample Size for the Training Set

• The document does not specify a separate training set or its sample size for the Atellica IM Tg assay.
• For IVD assays like this, the "training" is typically inherent in the assay's development and optimization process (e.g., reagent formulation, calibration curve development), which uses various known samples and standards, rather than a distinct, labeled "training dataset" as would be seen for a machine learning algorithm. The performance characteristics studies presented are akin to a "verification/validation set."

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

• As a traditional IVD assay, there isn't a "training set" in the sense of a machine learning model.
• Ground truth for assay development and calibration: This would have been established using reference materials (like BCR CRM 457), characterized control samples, and potentially a large panel of clinically characterized patient samples used during the assay's development and optimization phases. These activities are part of the broader product development lifecycle rather than a distinct "training set" with ground truth generated by experts in the context of a clinical study for submission. Standardization is explicitly noted as traceable to BCR CRM 457, which serves as a primary standard for establishing the quantitative accuracy of the assay.

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Access Thyroglobulin assay is a paramagetic particle, chemiluminescent immunossay for the quantitative determination of thyroglobulin levels in human serum and plasma using the Access Immunoassay Systems. This device is intended to aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy), and who lack serum thyroglobulin antibodies.

The Access Thyroglobulin assay consists of the reagent pack and calibrators. Other items needed to run the assay include the Access Thyroglobulin Sample Diluent, substrate and wash buffer. The Access Tg assay along with the Access wash buffer and substrate are designed for use with the Access Immunoassay Systems in a clinical laboratory setting.

Lumi-Phos PRO substrate was used with this pack. The modification does not affect the indications of the device or alter the fundamental scientific technology of the device.

The provided text is a 510(k) summary for the Access Thyroglobulin assay, which is a diagnostic device and not an AI/ML device. Therefore, many of the requested categories related to AI/ML device studies, such as "Number of experts used to establish the ground truth," "Adjudication method," "MRMC comparative effectiveness study," and "sample size for the training set," are not applicable.

However, I can extract the relevant information regarding acceptance criteria and study results for this diagnostic device.

Acceptance Criteria and Reported Device Performance for Access Thyroglobulin Assay (K240927)

1. Table of Acceptance Criteria and the Reported Device Performance

2. Sample sizes used for the test set and the data provenance

• Method Comparison: N = 187 samples. Data provenance is not specified (e.g., country of origin, retrospective/prospective).
• Imprecision: For each sample, N = 88 or 80. Data provenance is not specified.
• Reproducibility: For each sample, N = 75. Data provenance is not specified.
• Linearity, LoB, LoD, LoQ: Sample sizes for specific points within the linearity study or number of samples for LoB/LoD/LoQ determinations are not explicitly given, but the studies were conducted using "multiple samples," "multiple reagent lots," and "multiple days." Data provenance is not specified.

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

This is a quantitative immunoassay for measuring thyroglobulin levels. The 'ground truth' for such a device is established by the analytical reference measurement procedures using a reference method or known concentrations, rather than expert consensus on diagnostic images or clinical assessments. Therefore, this question is not applicable in the context of this device.

4. Adjudication method for the test set

Not applicable for a quantitative immunoassay. The comparison is statistical analysis of measured values against a predicate device or expected values from reference materials.

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 not an AI/ML device involving human readers or interpretation.

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

The device is an automated immunoassay system. The performance studies ("Method Comparison," "Imprecision," "Reproducibility," "Linearity," "Detection Capability") represent the standalone performance of the assay and instrument without human interpretation of raw signals influencing the final quantitative result.

7. The type of ground truth used

For this immunoassay device, the "ground truth" implicitly refers to:

• Reference measurements from the predicate device (Access 2 Immunoassay System): Used for the method comparison study.
• Known concentrations/reference materials: Used to assess imprecision, linearity, and detection capabilities (LoB, LoD, LoQ) against expected values.

8. The sample size for the training set

Not applicable. This is a traditional diagnostic device, not an AI/ML device that requires a training set.

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

Not applicable, as there is no training set for this type of device.

Ask a specific question about this device

Access Thyroglobulin assay is a paramagetic particle, chemiluminescent immunossay for the quantitative determination of thyroglobulin levels in human serum and plasma using the Access Immunoassay Systems. This device is intended to aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy), and who lack serum thyroglobulin antibodies.

The Access Thyroqlobulin assay consists of the reagent pack and calibrators. Other items needed to run the assay include the Access Thyroglobulin Sample Diluent, substrate and wash buffer. The Access Tq assay along with the Access wash buffer and substrate are designed for use with the Access Immunoassay Systems in a clinical laboratory setting.

The change does not impact or change the other components that are used with this reagent pack. The modification does not affect the indications of the device or alter the fundamental scientific technology of the device.

A description of the reagent pack is provided below.

The provided document is a 510(k) Premarket Notification from the FDA for the Access Thyroglobulin assay. It does not describe an AI/ML-based medical device. Therefore, many of the requested criteria about AI/ML studies (such as MRMC studies, ground truth establishment for training sets, number of experts for test set ground truth, etc.) are not applicable to this submission.

The acceptance criteria and study proving the device meets them are related to the analytical performance of an immunoassay, not a software algorithm.

Here's a breakdown based on the provided text, addressing the applicable points and noting where information is not present or not relevant to AI/ML:

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

The document focuses on demonstrating substantial equivalence to a predicate device, primarily through a matrix comparison study for a new sample type (plasma in addition to serum). The "acceptance criteria" are implied by the statistical analyses and acceptable ranges for slope, intercept, and correlation coefficient in the matrix comparison, aiming for agreement between the new sample type and the established serum sample type.

Acceptance Criteria (Implied by Study Design for Matrix Comparison):
For the Matrix Comparison study, the implicit acceptance criteria are that the Passing-Bablok linear regression results (slope, intercept, and correlation coefficient) demonstrate substantial equivalence between the new sample types (Li-heparin plasma, Na-heparin plasma) and serum. While explicit numeric acceptance criteria are not stated, typically for such comparisons, a slope close to 1, an intercept close to 0, and a high correlation coefficient (e.g., >0.97) are expected within their confidence intervals.

Reported Device Performance (Matrix Comparison):

Other Performance Claims Transferred from Predicate:
The document states that claims for "method comparison, imprecision, reproducibility, high-dose hook effect, linearity, dilution recovery, detection capability and analytical specificity are being transferred from file K220972." This implies these studies were performed and met acceptance criteria for the predicate device, and the current modification (addition of plasma sample type) does not invalidate them. Explicit tables for these are not in the provided text.

2. Sample sizes used for the test set and the data provenance

• Test Set Sample Size: For the Matrix Comparison study, 45 matched sets of serum and plasma samples were used for each comparison (Li-heparin plasma vs Serum, and Na-heparin plasma vs Serum). The minimum specified was 40 matched sets.
• Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. Given it's a clinical lab device, the samples would typically be from clinical settings.

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

This is not applicable as the device is an immunoassay, not an AI/ML device relying on human interpretation of images or other complex data for ground truth. The "ground truth" here is the quantitative measurement of thyroglobulin by the predicate method (serum measurement) against which the new sample type (plasma measurement) is compared. The reference values are analytical measurements, not expert consensus.

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

Not applicable for an immunoassay analytical validation. The ground truth (serum concentration) is established by the assay itself, not by human adjudication.

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 not an AI/ML device, and there are no "human readers" interpreting images assisted by AI.

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

Yes, in a sense. The "standalone" performance for this device refers to its analytical performance as a laboratory test. The Matrix Comparison study assesses the device's capability to accurately measure thyroglobulin in plasma samples compared to serum samples, without human interpretive input affecting the measurement itself. The results shown in point 1 demonstrate this "standalone" analytical performance.

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

The ground truth for the matrix comparison study was the quantitative thyroglobulin concentration measured in human serum using the previously cleared Access Thyroglobulin assay. The new sample types (plasma) were compared to these established serum values.

8. The sample size for the training set

Not applicable. This is not an AI/ML device that requires a training set. The assay's parameters are determined through reagent development and analytical validation, not machine learning training.

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

Not applicable, as there is no training set for this type of device.

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Immunoassay for the in vitro quantitative determination of thyroglobulin in human serum and plasma. Determination of Tg is used as an aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy). The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

The Tg II immunoassay makes use of a two-step, double antigen sandwich principle using a biotinylated monoclonal Tg-specific antibody and monoclonal Tg-specific antibodies labeled with a ruthenium complex. The Tg II immunoassay is intended for the in vitro quantitative determination of thyroglobulin in human serum and plasma. Determination of Tg is used to aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy). 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 Elecsys Tg II device is an immunoassay intended for the in vitro quantitative determination of thyroglobulin in human serum and plasma, used as an aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery.

Here's an analysis of its acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly list "acceptance criteria" for all performance measures in a comparative table against the reported performance. However, based on the studies conducted and their results, one can infer the implicit acceptance criteria by observing the measured performance and statements like "All deviations from linearity met the specification" or "Non-significant interferences were defined as %interferences within ± 10 %".

Below is a table summarizing the reported device performance, with inferred acceptance criteria where direct ones are not explicitly stated, but are implied by the reported "met specifications" or similar statements.

Study Information:

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

• Clinical Performance Study (Combined Cohorts):

  • Sample Size: 530 samples available for analysis.
  • Data Provenance:
    • Origin: Collected from 9 sites across the U.S.
    • Nature:
      • Longitudinal Cohort: Serum samples collected from subjects 4-12 weeks post-thyroidectomy (with/without radioiodine ablation) and at 4 additional time points (6, 12, 18, 24 months post-surgery/ablation).
      • Cross-sectional Cohort: Samples collected from subjects with structural disease at a single visit. This cohort was used to increase the number of observations from patients with structural disease.

• Reference Range Study:

  • Sample Size: 244 healthy males and 219 healthy females (total 463).
  • Data Provenance: Not explicitly stated (e.g., age range is given, but not country of origin, retrospective/prospective).

• Expected Values in DTC post-thyroidectomy:

  • Sample Size: 127 subjects with differentiated thyroid cancer (100 female; 27 male) with no evidence of disease for 4 or more years post-total/near total thyroidectomy.
  • Data Provenance: Not explicitly stated.

• Precision (Within-laboratory): 84 runs for each sample.

• Reproducibility (Site-to-site): 146-149 runs for each sample.

• LoB, LoD, LoQ, Linearity, Hook Effect, Interference, Cross-reactivity, Stability Studies: Varying number of samples/replicates as described in the respective sections (e.g., LoB/LoD: 5 native samples, 2 replicates/run, 6 runs over 4 days; LoQ: 7 low-level human serum samples, 5 replicates/run, 1 run/day over 5 days).

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

The document does not explicitly state the number of experts or their specific qualifications for establishing the ground truth of "structural disease" in the clinical study. However, the definition of structural disease is provided:

• Ground Truth Definition: "Structural disease was defined as evidence of disease on ultrasound, cross sectional or functional imaging, or biopsy proven disease as determined by the investigator."
• Implied Experts: This definition suggests that the "investigator" (likely a medical professional such as an endocrinologist, radiologist, or pathologist, depending on the type of evidence) determined the presence of structural disease. The number of such investigators involved in determining ground truth per patient or across the study is not specified.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method (e.g., 2+1, 3+1) for establishing the ground truth of structural disease. It states that structural disease was "determined by the investigator." This implies a single determination rather than a consensus or adjudicated process among multiple experts for each case.

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

No, an MRMC comparative effectiveness study was not explicitly done. The study focuses on the standalone performance of the Elecsys Tg II assay rather than comparing human reader performance with and without AI assistance. The device itself is an immunoassay, not an AI imaging interpretation tool that would typically involve human readers.

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

Yes, the studies presented are primarily standalone (algorithm only) performance evaluations. The Elecsys Tg II is an automated immunoassay system, and its performance (sensitivity, specificity, precision, accuracy, linearity, stability, etc.) is measured directly on biological samples without active human interpretation assistance in the analytical or clinical performance reported here. The "results are determined via a calibration curve which is instrument-specifically generated."

7. The Type of Ground Truth Used

• Clinical Performance Study: The ground truth for the clinical performance study (sensitivity, specificity, NPV, PPV) was based on structural disease (SD+ or SD-). This was determined by:
  • Evidence of disease on ultrasound.
  • Cross-sectional or functional imaging.
  • Biopsy-proven disease.
  • These were "determined by the investigator."
• Analytical Studies: For analytical performance (LoB, LoD, LoQ, linearity, interference, stability), the ground truth generally involved:
  • Reference standards/materials: e.g., CRM 457.
  • Known analyte concentrations: Obtained by spiking or using characterized serum pools.
  • Clinical laboratory standards: (e.g., CLSI guidelines).

8. The Sample Size for the Training Set

The document does not mention a separate "training set" for the Elecsys Tg II device in the context of machine learning or AI algorithms. As an immunoassay, the "training" analogous to an AI system would be the development and optimization of the assay reagents, protocols, and calibration curves. The provided information relates to the validation of the final product. The "calibration curve" is established for the assay, which is a form of internal "training" for the instrument's interpretation of signal to concentration.

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

As noted above, for an immunoassay, there isn't a "training set" in the typical AI sense. The development of the assay relies on establishing accurate measurements against recognized reference standards and materials (e.g., CRM 457, characterized serum pools with known thyroglobulin concentrations). These standards serve as the "ground truth" to ensure the assay accurately quantifies thyroglobulin. The assay is then calibrated using these standards to accurately relate the measured signal (chemiluminescent emission) to the thyroglobulin concentration in patient samples.

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Access Thyroglobulin assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin levels in human serum using the Access Immunoassay Systems. This device is aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy), and who lack serum thyroglobulin antibodies.

Access Thyroqlobulin assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin levels in human serum using the Access Immunoassay Systems. This device is intended to aid in monitoring for the presence of persistent or recurrent /metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy), and who lack serum thvroglobulin antibodies.

The Access Tg assay consists of the reagent pack and calibrators. Other items needed to run the assay include the Access Tg sample diluent substrate and wash buffer. The Access Tg assay along with the Access wash buffer and substrate are designed for use with the Access Immunoassay Systems in a clinical laboratory setting.

The device modification described in this submission impacts the Access Thyroqlobulin reagent pack only; the change does 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.

The provided text describes the Beckman Coulter Access Thyroglobulin assay, a chemiluminescent immunoassay for the quantitative determination of thyroglobulin levels in human serum. This device is intended to aid in monitoring for persistent or recurrent/metastatic differentiated thyroid cancer (DTC) in patients who have undergone thyroid surgery and lack serum thyroglobulin antibodies.

Here's a breakdown of the acceptance criteria and the studies that prove the device meets these criteria:

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

The document does not explicitly present a table of acceptance criteria alongside reported performance for all aspects. Instead, acceptance criteria are generally mentioned within the description of each study. Below is a compilation of the criteria and reported performance for key studies.

Note: For Imprecision and Reproducibility, specific acceptance criteria (e.g., maximum allowable %CV) are not explicitly stated. The tables provide the observed performance metrics (SD, %CV) and imply that these are acceptable.

2. Sample size used for the test set and the data provenance

• Method Comparison: 102 serum samples.
• Imprecision: Not explicitly stated as a general sample count; involved multiple samples (6 different samples with varying concentrations) run in duplicate over 20 days.
• Reproducibility:
  • Study 1: 2 samples run in 3 replicates.
  • Study 2: 3 samples run in 5 replicates.
• High-dose Hook Effect: Not specified how many samples or what types were used, but concentrations up to 40,000 ng/mL were tested.
• Linearity: Serum samples were used across the assay range.
• Dilution Recovery: Serum samples were used across and above the assay range.
• Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ): Not explicitly stated how many individual samples were used for these studies, but they were determined based on specific testing procedures.
• Analytical Specificity (Cross-reactivity): Serum patient samples at two thyroglobulin concentrations (approx. 20 ng/mL and 100 ng/mL) were used. The number of unique patient samples is not specified.
• Analytical Specificity (Interference): Patient serum samples containing two levels of Thyroglobulin (approx. 25.0 ng/mL and 100.0 ng/mL) were used. The number of unique patient samples is not specified.

Data Provenance: The document does not specify the country of origin for the data or whether the samples were collected retrospectively or prospectively. It consistently refers to the use of "human serum" or "patient serum samples."

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

This information is not applicable to this type of device (an in-vitro diagnostic immunoassay). The ground truth for such assays is established by the intrinsic biochemical properties and analytical performance of the assay itself (e.g., accuracy against reference methods, precision, detection limits using reference standards or well-characterized samples), rather than expert interpretation of images or clinical cases.

4. Adjudication method for the test set

This information is not applicable to this type of device. Adjudication methods like 2+1 or 3+1 are typically used in studies involving expert interpretation (e.g., radiology for AI-assisted diagnosis), where there might be disagreement among experts. For an immunoassay, the results are quantifiable and objective measurements, not subject to subjective adjudication.

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

This information is not applicable to this device. An MRMC study is relevant for imaging devices or AI-assisted diagnostic tools where human readers are interpreting cases. The Access Thyroglobulin assay is an automated laboratory test that directly measures a biomarker, without a "human reader" component in the interpretation of the primary data within the context of an MRMC study.

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

The Access Thyroglobulin assay is a standalone device in the sense that it performs the measurement algorithmically via its chemiluminescent immunoassay system without direct human interpretation of the raw signal output. The "algorithm only" performance is what these analytical studies (imprecision, linearity, LoD, etc.) demonstrate. Human involvement is in sample preparation, loading, and interpretation of the final quantitative result.

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

The ground truth for this device is based on analytical performance characteristics established through:

• Reference methods or predicate device comparison (for method comparison study).
• Use of well-characterized samples or reference materials (e.g., for LoB, LoD, LoQ, linearity).
• Known concentrations of potential cross-reactants and interferents (for analytical specificity studies).
• Statistical analysis of repeated measurements (for imprecision and reproducibility).

8. The sample size for the training set

This document describes the performance studies for a modificated device that is compared to a previously cleared predicate and is not a new AI/machine learning device that typically involves a distinct "training set." The studies mentioned are validation studies, not training. Therefore, a specific "training set sample size" is not applicable in the context of this submission. The development and optimization of the immunoassay reagents and protocols would have occurred during the assay's development, but this document focuses on its validation.

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

As there is no "training set" in the context of an AI/machine learning model for this immunoassay submission, the question of how its ground truth was established is not applicable. The "ground truth" for the performance studies described in this document is derived from established analytical methods, reference materials, and the comparative performance against the predicate device.

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The Access Thyroglobulin assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin levels in human serum and plasma, using the Access Immunoassay Systems. This device is intended to aid in the monitoring for the presence of local and metastatic thyroid tissue in patients who have had thyroid gland ablation (using thyroid surgery with or without radioactivity) and who lack serum thyroglobulin antibodies.

The Access® Thyroglobulin reagents consist of reagent packs, calibrators, substrate and wash buffer.

The provided text describes a 510(k) summary for the Access® Thyroglobulin Reagents on the Access® Immunoassay Systems. The submission is for a modification to add a new instrument platform (Beckman Coulter UniCel™ DxI 800 Access® Immunoassay System) to the existing system. The core of the study is to demonstrate substantial equivalence between the new instrument platform and the previously cleared Access 2 system.

Here's an analysis of the acceptance criteria and study as requested:

1. Table of acceptance criteria and the reported device performance

Note: The specific numerical values or ranges for "established acceptance criteria" are not provided in the summary. The document only states that the criteria were met.

2. Sample size used for the test set and the data provenance

The document states that "method comparison, precision and analytical sensitivity studies were conducted." However, it does not provide any details on the sample sizes used for these studies or the data provenance (e.g., country of origin, retrospective/prospective).

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

This information is not applicable to this type of device and study. The device is an immunoassay for quantitative determination of a biomarker, not an imaging or diagnostic device requiring expert interpretation for ground truth. The ground truth for such assays would typically be defined by reference methods or established laboratory standards.

4. Adjudication method for the test set

This information is not applicable as the study design does not involve human readers or interpretations that would require adjudication.

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

This information is not applicable. This is a laboratory immunoassay device, not an AI-assisted diagnostic tool that involves human readers.

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

Yes, a standalone performance study was done. The "Supporting Data" section indicates that "method comparison, precision and analytical sensitivity studies were conducted" for the Access Thyroglobulin assay on the DxI system to demonstrate substantial equivalence to the Access 2 system. This refers to the analytical performance of the instrument and reagents as a standalone system.

7. The type of ground truth used

The document does not explicitly state the "type of ground truth" in terms of clinical outcomes or pathology. For an immunoassay seeking substantial equivalence for a new instrument platform, the "ground truth" or reference for comparison would typically be the performance of the legally marketed predicate device (Access® Thyroglobulin Reagents on the Access® Immunoassay Systems on the Access 2 system). The studies would aim to show that the new platform produces equivalent analytical results (method comparison, precision, analytical sensitivity) to the predicate.

8. The sample size for the training set

This information is not applicable. The device is an immunoassay system, not an AI/machine learning algorithm that requires a "training set" in the conventional sense. The "training" for such a system involves calibration using specific calibrator materials mentioned in the device description.

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

This information is not applicable for the reasons stated in point 8. The "ground truth" for calibration would be established by the manufacturer based on certified reference materials or established laboratory standards for the calibrators.

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DYNOtest Tg-pluS is a immunoradiometric assay (IRMA) for the quantitative determination of thyroglobulin in human serum. It is intended to aid in the monitoring for the presence of local or metastatic thyroid tissue in patients who have had thyroid gland ablation (by surgery with or without radioiodine therapy). DYNOtest Tg-pluS is also indicated for detecting the presence of thyroid tissue in patients with differentiated thyroid cancer when used with radioiodine whole body scans after recombinant thyrotropin (TSH) stimulation or thyroid hormone withdrawal. DYNOtest Tg-pluS includes a recovery test to aid in the detection of interfering anti-thyroglobulin antibodies or other substances.

DYNOtest Tg-pluS is a two-step immunoradiometric assay for the quantitative determination of thyroglobulin in human serum using a coated tube technique. Two antigen specific antibodies that recognize different binding sites on the antigen (thyroglobulin) are used in excess. In the first step, thyroglobulin in the sample, standard or control binds to rabbit anti-human Tg polyclonal antibodies attached to the solid phase. Following incubation, unbound thyroglobulin and serum components are washed from the tube. In the second step, the radioactive tracer (mouse antihuman thyroglobulin monoclonal antibody) reacts with the bound antigen forming a sandwich complex fixed to the side of the tube. Following a second incubation, unreacted tracer is washed from the tube and remaining radioactivity in the tubes is measured. The measured radioactivity is directly proportional to the quantity of thyroglobulin in the sample, standard or control. The standard curve is used to derive the thyroglobulin concentration in the patients samples.

Recovery Test: Because non-specific interferents and anti-thyroglobulin antibodies can result in falsely low thyroglobulin values, DYNOtest Tg-pluS includes a recovery test, the purpose of which is to aid in the detection of such interferences. In the recovery test, recovery buffer containing a known quantity of thyroglobulin, is added to the patient sample. In parallel, the recovery buffer is added to a recovery reference sample (thyroglobulin free serum). The patient sample, recovery sample and recovery reference sample are all run using DYNOtest Tg-pluS. The percentage recovery is determined by subtracting the patient Tg value from the patient recovery sample and dividing this result by the recovery reference Tg value:

Recovery Tg - Patient Tg x 100 = % Recovery Recovery reference Tg

Recovery values between 70% and 130% are considered valid. Values <70% and >130% are due to interferences; these patient results should be considered invalid.

Here's an analysis of the provided text, focusing on the acceptance criteria and the study used to evaluate the DYNOtest Tg-pluS device:

Acceptance Criteria and Device Performance for DYNOtest Tg-pluS

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria with specific threshold values for the clinical study. Instead, it presents the results of a clinical performance study and a comparison to a predicate device. The effective acceptance criteria can be inferred from the reported performance characteristics.

2. Sample Size and Data Provenance for the Test Set

• Sample Size for Test Set:
  • Clinical Performance Study: 133 patients diagnosed with thyroid cancer.
  • Predicate Device Comparison: 133 samples from patients diagnosed with thyroid cancer (likely the same cohort as the clinical performance study).
  • Interference from Tg auto-antibodies: 77 sera.
• Data Provenance: The clinical performance study was prospective in the sense that the device was evaluated on a specific set of categorized patients. The location of the test set is specified as occurring "at a single site," but the country of origin is not explicitly stated. Given the manufacturer is German (BRAHMS AG) and the distributor is US-based (BRAHMS Diagnostica LLC), it's possible the clinical site was in the US or Germany.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the number or qualifications of experts used to establish the ground truth for the test set.

4. Adjudication Method for the Test Set

The document does not describe a specific adjudication method (like 2+1 or 3+1). The "ground truth" (reference methodology) was established based on a combination of existing diagnostic results.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study focuses on the performance of the in-vitro diagnostic (IVD) device itself, not on how human readers' performance might change with or without AI assistance. The device is an assay, not an AI imaging interpretation tool.

6. Standalone Performance Study

Yes, the studies reported are for the standalone performance of the DYNOtest Tg-pluS device. The clinical performance section, including sensitivity, specificity, PPV, and NPV, directly evaluates the algorithm/assay without human-in-the-loop performance modifications.

7. Type of Ground Truth Used

The ground truth for the clinical performance study was established using a combination of existing clinical diagnostic results and reference methods:

• "Tg results from a reference method (immunochemiluminescent method)"
• "results from radioiodine whole body scans following TSH stimulation by administration of recombinant TSH or withdrawal of thyroid hormone therapy."
• Patients were categorized into three groups: (1) free of thyroid tissue, (2) active metastatic disease, and (3) residual thyroid/thyroglossal duct remnants.

For the auto-antibody interference study, the ground truth was based on samples that "tested positive for Tg auto antibodies using a radioimmunometric assay (DYNOtest anti-TGn)."

8. Sample Size for the Training Set

The document does not specify a separate training set or its sample size. This type of in-vitro diagnostic assay (IRMA) typically relies on extensive analytical validation and calibration to established standards (like CRM 457, in this case) rather than a "training set" in the machine learning sense. The "standards" and "controls" mentioned in the device description are used for calibration and quality control, not for training a predictive algorithm in the same way an AI model would be trained.

9. How Ground Truth for the Training Set Was Established

Since a distinct "training set" in the context of machine learning is not mentioned or applicable to this type of assay, the concept of establishing ground truth for it is also not applicable here. The assay is calibrated against a standard (CRM 457), which serves as a known reference for target values.

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The Nichols Institute Diagnostics Chemiluminescence Thyroglobulin is a two-site immunometric assay for the quantitative measurement of thyroglobulin in human serum. The assay is intended to aid in monitoring for the presence of local and metastatic thyroid tissue in patients who have had prior thyroidectorny (using surgery with or without radioiodine). This assay is also indicated for monitoring thyroglobulin levels in combination with radioiodine whole body scans after either rhTSH administration or thyroid hormone withdrawal for detecting presence of thyroid tissue in patients with well-differentiated thyroid cancer. The assay should only be used on patients who lack thyroglobulin autoantibodies.

The Chemiluminescence Thyroglobulin kit has sufficient reagents for 100 tests. The throglobulin assay is a chemiluminescence sandwich immunoassay assay utilizing a biotinylated goat antiassay 1s a cheinnummicscented sunding monoclonal antibody labeled with acriding for detection. thyrogloutin for captare and a modio monomal and seprosilicate glass tube followed by the A U.200-IIL Serum Sample 1s added to a 12×10 uline and 0.050 mL of acridinium labeled antithyroglobulin reagents. Samples are also run at a 1/10 dilution (hook detection tube) to check for t thyroglountif teagents. Butiples are also in the assay. An avidin-coated bead is then added to the polentially mixture. The assay incubates at room temperature for 16-24 hours on top of a horizontal rotator set & 180 ± 10 rpm. Thyroglobulin in the serum sample binds to the biotinylated antibody and acridinium labeled antibody to form a sandwich-complex. Because of the high affinity between biotin and avidin, the captured sandwich complex binds to the avidin-coated bead. Free oetween brom and avidin, the capitaled antibody are separated from the complex bound to the bead by aspiration of the reaction mixture and subsequent washing. The tubes containing the washed beads are placed into a luminometer, which automatically injects Trigger 1 and 2, initiating the chemiluminescence reaction. The light is quantified by the luminometer and minating the onomianinessonts (RLU). The amount of acridinium labeled antibody bound is directly proportional to the concention of thyroglobulin in the sample. A log-log standard curve uncectly proportional to the concentration of the ordinate versus the respective concentration of each IS gelleration of proting the mount NFO shecissa. The concentration of thyroglobulin is determined directly from the standard curve.

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

Acceptance Criteria and Device Performance

The core of the acceptance criteria seems to be framed around demonstrating substantial equivalence to a predicate device and showing clinical utility for its intended use. While explicit numerical acceptance criteria for sensitivity, specificity, etc., weren't
fully specified as pre-defined targets in the document, the clinical study's results (especially in Table 3) serve as the evidence for meeting acceptable performance for market clearance.

Table of Acceptance Criteria and Reported Device Performance

Study Details

2. Sample size used for the test set and the data provenance

• Method Comparison Study (N=121):
  • Sample Size: 121
  • Data Provenance: Not explicitly stated, but likely from a clinical laboratory or reference lab given the NCCLS guidelines. It is
    retrospective, as samples were "assayed in parallel."
• Clinical Performance Study (Haugen BR et al, 1999 JCEM):
  • Sample Size: Up to 162 patients with eligible whole body scan results. Specific sub-cohorts are mentioned for various analyses (e.g., N=44 for THT baseline negative, N=117 for combined withdrawal Tg + WBS positive, etc.). All patients had negative thyroglobulin autoantibody results.
  • Data Provenance: Retrospective – The samples were sourced from a published clinical study (Haugen BR et al, 1999 JCEM 84: 3877-3885), where permission was obtained to use the samples. The study involved patients with well-differentiated thyroid cancer. The country of origin is not explicitly stated, but Haugen's affiliations often suggest US-based research.

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

• Method Comparison Study: Ground truth was established by the predicate device (Kronus OptiQuant™ Thyroglobulin kit) results. No human experts are described for establishing ground truth for this phase.
• Clinical Performance Study: The ground truth was based on a "diagnostic standard" which combined clinical parameters including radioiodine whole body scans (WBS) and serum Tg measurements (from the initial study, which used a sensitive Tg radioimmunoassay (Tg RIA) and later the Nichols Tg ICMA). The interpretation of these diagnostic standards implies expert judgment (e.g., "positive withdrawal scan," "positive post-therapeutic scan," "radioiodine uptake was found outside the thyroid bed considered positive for metastatic disease"). However, the document does not specify the number or qualifications of experts who established these diagnostic standards for the original Haugen study.

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

The document does not describe an adjudication method like 2+1 or 3+1 by multiple readers/experts. The ground truth for the clinical performance study was derived from a diagnostic standard that combined WBS and Tg results, implying a clinical consensus or established diagnostic protocol, rather than an adjudication process between independent expert interpretations of the test results.

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 conducted. This device is an in vitro diagnostic (IVD) assay (a blood test), not an AI-assisted diagnostic imaging or interpretation tool that typically involves human readers. The clinical study compares the performance of the assay (Nichols Chemiluminescence Thyroglobulin assay) under different clinical scenarios (e.g., rhTSH stimulation vs. thyroid hormone withdrawal), and in combination with WBS, against a defined diagnostic standard.

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

The Nichols Institute Diagnostics Chemiluminescence Thyroglobulin assay inherently operates as a "standalone" device in the sense that it provides a quantitative measurement of thyroglobulin. The results are then interpreted by clinicians. The clinical study did evaluate the performance of the "withdrawal serum Tg ICMA results alone" against the diagnostic standard, reporting a sensitivity of 88% and specificity of 100%. This represents its standalone diagnostic performance when not combined with WBS.

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

The ground truth for the clinical performance study was a "diagnostic standard" combining a positive withdrawal whole body scan (WBS) and/or a positive post-therapeutic scan or a serum Tg ICMA of 10 ng/mL or more (for THT baseline Tg results), or a positive withdrawal WBS result or a positive post-therapeutic WBS and/or a serum Tg ICMA of 2.0 ng/mL or more (for other situations). This is a composite ground truth based on clinical imaging (WBS) and laboratory results (Tg levels), interpreted within established clinical guidelines for identifying residual or recurrent thyroid tissue. It implicitly relies on expert interpretation of WBS and the clinical significance of Tg levels.

8. The sample size for the training set

The document does not provide information on a training set sample size. The study described is a performance evaluation of the already developed assay. For IVDs, "training set" typically refers to samples used during the assay's development and optimization, rather than a separate formal clinical training dataset as seen with machine learning algorithms.

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

As no training set is explicitly described in the context of this 510(k) summary, there is no information on how its ground truth was established. For IVD assays, ground truth for development samples would typically involve well-characterized patient samples with known clinical diagnoses or confirmed pathology, often collected in house or through commercial biobanks.

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