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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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For use in the verification of the calibration established by the Elecsys Anti-TSHR reagent on the indicated Elecsys and cobas e immunoassay analyzers.

The Elecsys Anti-TSHR CalCheck is a lyophilized product consisting of human anti-TSHR antibodies in human serum matrix. During manufacture, the analytes are spiked into the matrix at the desired concentration levels.

The provided text describes the 510(k) premarket notification for the Elecsys Anti-TSHR CalCheck, a quality control material. However, it does not contain detailed information regarding acceptance criteria, specific study results, sample sizes for test or training sets, ground truth establishment methods, expert qualifications, or details about comparative effectiveness studies (MRMC) or standalone algorithm performance.

The document primarily focuses on establishing substantial equivalence to a predicate device (Elecsys C-Peptide CalCheck K040157) based on intended use, levels, format, handling, and stability. While it mentions that "The Elecsys Anti-TSHR CalCheck was evaluated for value assignment and Performance Characteristics stability," it does not provide the results of these evaluations or specific acceptance criteria.

Therefore, many of the requested details cannot be extracted from the provided text.

Here's what can be inferred or stated based on the available information:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Sample size for test set: Not specified.
• Data provenance: Not specified. The study was conducted by Roche Diagnostics, but the origin of the samples (e.g., country of origin, retrospective/prospective) is not mentioned.

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

• This device is a quality control material for an immunoassay analyzer. The "ground truth" for a quality control material typically refers to its assigned value and stability characteristics, which are determined through laboratory testing and characterization. It does not typically involve human expert interpretation in the same way an imaging diagnostic device might. Therefore, the concept of "experts establishing ground truth" in this context is not directly applicable, and no information on such experts is provided.

4. Adjudication method for the test set

• Not applicable as this is a quality control material and not a diagnostic algorithm requiring human adjudication of 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, an MRMC study was not done. This is a quality control material, not an AI-powered diagnostic device, so MRMC studies are not relevant.

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

• Not applicable. This is a quality control material, not an algorithm.

7. The type of ground truth used

• The "ground truth" for a quality control material (like Elecsys Anti-TSHR CalCheck) would be its assigned values for the analyte, determined through rigorous laboratory characterization and potentially traceability to reference materials. The document states it was "evaluated for value assignment," implying this type of ground truth was established by the manufacturer.

8. The sample size for the training set

• Not applicable. This is a quality control material, not an AI or machine learning algorithm that requires a training set. The "samples" described would be batches of the CalCheck material itself, which are characterized for their properties.

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

• Not applicable, as no training set for an algorithm is involved.

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

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

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

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

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

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

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

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

• Test Set Sample Size:
  • Method Comparison: 212 clinical samples.
  • Precision (Internal Studies): The number of samples for precision evaluation is not explicitly stated but implied to be sufficient for calculating CVs at various concentrations.
• Data Provenance: Not explicitly stated (e.g., country of origin). The document mentions "clinical samples" but doesn't specify if they are retrospective or prospective, or their geographical source.

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

• Experts: Not applicable in the traditional sense for this type of IVD (In Vitro Diagnostic) device. The "ground truth" or reference for the method comparison study is obtained by comparing the Elecsys Anti-TSHR Immunoassay results against the predicate device (BRAHMS LUMItest TRAK human Assay). The predicate device itself acts as the "reference method" in this context.
• Qualifications: Not applicable, as expert review of samples to establish ground truth is not described.

4. Adjudication Method for the Test Set

• Adjudication Method: Not applicable. The method comparison directly compares the quantitative output of the investigational device to the predicate device. There is no mention of human expert adjudication to resolve discrepancies between the devices.

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

• MRMC Study: No, an MRMC comparative effectiveness study was not done. This device is an immunoassay for quantitative determination of TSH receptor autoantibodies, not an AI-assisted diagnostic imaging or interpretation device that would involve human readers.

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

• Standalone Performance: Yes, the performance metrics (precision, measuring range, LoQ, LoB, LoD, analytical specificity, and method comparison) presented are for the Elecsys Anti-TSHR Immunoassay operating as an automated, standalone diagnostic system. There is no human interpretation component integrated into the assay's performance claims. The "human-in-the-loop" equivalent for such an assay would be the medical professional interpreting the quantitative results in the context of a patient's clinical picture, which is outside the scope of the device's standalone analytical performance.

7. The Type of Ground Truth Used

• Type of Ground Truth: For the method comparison, the "ground truth" is established by the predicate device's measurements (BRAHMS LUMItest TRAK human Assay). The document explicitly states "A comparison of the Elecsys Anti-TSHR assay (y) with BRAHMS LUMItest TRAK human (x) using clinical samples gave the following correlations." This indicates a direct comparison to an already cleared and accepted method, rather than a separate gold standard like pathology or long-term outcomes data for determining TSHR autoantibody levels.

8. The Sample Size for the Training Set

• Training Set Sample Size: Not provided or applicable in the context of this document. This submission describes an immunoassay based on a competition principle with streptavidin-coated microparticles and electrochemiluminescence detection. It's a biochemical assay, not a machine learning or AI algorithm that typically requires a distinct training set. The reported data pertains to the validation of the finalized assay.

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

• Ground Truth for Training Set: Not applicable. As it's an immunoassay technology, there isn't a "training set" in the machine learning sense. The assay development would involve optimizing reagents, protocols, and calibration, which are internal to the assay's design and not typically referred to as "training" with a distinct "ground truth" dataset in this context.

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