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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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