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The ADVIA® Centaur Intact Parathyroid (iPTH) assay is for in vitro diagnostic use in the quantitative determination of intact parathyroid hormone (iPTH) in EDTA plasma or serum using the ADVIA Centaur and ADVIA Centaur XP systems. This assay is intended to be used to aid in the differential diagnosis of hyperparathyroidism and hypoparathyroidism.

Device Description

The ADVIA Centaur iPTH assay is a two-site sandwich immunoassay using direct chemiluminometric technology, which uses constant amounts of an antihuman PTH antibody in the Lite Reagent and an antihuman PTH antibody in the Solid Phase Reagent. The first antibody is a polyclonal goat antihuman PTH (N-terminal 1-34) antibody labeled with acridinium ester. The second antibody is a biotinylated polyclonal goat antihuman PTH (39-84 region) antibody that is preformed to streptavidin coated paramagnetic latex particles in the Solid Phase reagent.

AI/ML Overview

The provided text describes the ADVIA® Centaur Intact Parathyroid Hormone (iPTH) Assay, a device intended for the quantitative determination of iPTH in EDTA plasma or serum to aid in the differential diagnosis of hyperparathyroidism and hypoparathyroidism. The document focuses on demonstrating the substantial equivalence of a modified version of this assay to its predicate device.

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

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly list "acceptance criteria" in a separate table for each performance characteristic with pass/fail outcomes. Instead, it describes various performance studies and presents their results, implying that these results met internal criteria for demonstrating substantial equivalence. Based on the described tests, here's a reconstructed table of implicit acceptance criteria and the reported performance:

Performance Characteristic	Implicit Acceptance Criteria (based on study design and intent)	Reported Device Performance
Precision	CVs within acceptable clinical limits; comparable to predicate.	Pool 1: 16.1 pg/mL, 7.7% Total CV
Control 1: 38.7 pg/mL, 4.7% Total CV
Pool 2: 62.8 pg/mL, 3.7% Total CV
Control 2: 185 pg/mL, 3.2% Total CV
Control 3: 663 pg/mL, 2.8% Total CV
Pool 3: 839 pg/mL, 3.9% Total CV
Pool 4: 1698 pg/mL, 3.2% Total CV
Detection Limits (LoB, LoD, LoQ)	LoB, LoD, LoQ established and clinically acceptable. Compare favorably to predicate (implied, though not directly shown).	LoB: 0.1 pg/mL
LoD: 2.7 pg/mL
LoQ: 6.3 pg/mL
Linearity / Assay Range	Linear response across the claimed assay range.	Regression: y = 0.98x - 4.98, R = 1.00
Assayed range: 4.4 to 2021 pg/mL (claimed range 6.3 - 1900 pg/mL)
High Dose Hook Effect	No high dose hook effect observed.	No high dose hook was observed for either reagent lot (tested up to 144,000 pg/mL).
Interfering Substances	Bias ≤ 10% effect at specified interferent levels.	Hemoglobin (500mg/dL): 4% and -1% bias
Triglycerides (3000mg/dL): 7% and -4% bias
Conjugated Bilirubin (40mg/dL): 7% and 0% bias
Unconjugated Bilirubin (40mg/dL): 7% and 8% bias
Biotin (1000ng/mL): 8% and 6% bias
Cross-reacting Substances	Low to no cross-reactivity with related substances, except for clinically expected interactions.	PTH 7-84: ~51% cross-reactivity (noted as an exception, implying this level is understood or acceptable)
All other listed cross-reactants (PTH 1-34, 39-68, 39-84, 44-68, 53-84, Calcitonin, Beta-Cross Laps, Osteocalcin): showed 0.0% to 0.2% cross-reactivity (very low).
Method Comparison	Good correlation with the predicate device (R-value close to 1, slope near 1, intercept near 0).	EDTA Plasma: y = 0.98x + 10.6, R = 1.00 (N=106, range 11.8 - 1862 pg/mL)
Serum: y = 1.00x + 5.0, R = 1.00 (N=105, range 9.8 - 1868 pg/mL)
Expected Values (Reference Range Verification)	Percentage of samples falling within the predicate's reference range (12-85 pg/mL) should be high (e.g., ≥95%).	Plasma (Lot 1 & 2): 100.0% within range
Serum (Lot 1): 97.5% within range
Serum (Lot 2): 95.0% within range
Stability	Reagent stability confirmed for claimed periods.	On-board stability: 28 days (with 14-day calibration interval). Reagent stable until printed date at 2-8°C.

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

Precision: 7 samples (4 EDTA plasma pools, 3 commercial control materials). No specific provenance (country of origin) mentioned, but likely clinical samples and commercial controls from within Siemens' testing facilities or sourced according to industry standards.
Detection Limits (LoB, LoD, LoQ): A single blank (Multi-Diluent 11) and 5 test samples (spiked/diluted plasma samples). Each sample tested n=6 x 2 instruments x 5 days (total n=60 per reagent lot for 2 reagent lots). Provenance not specified.
Linearity / Assay Range: 12 test concentrations (pools). Provenance not specified.
High Dose Hook Effect: One hook sample. Provenance not specified.
Interfering Substances: Two patient plasma pools. Provenance not specified.
Cross-reacting Substances: A plasma sample with endogenous iPTH and an assay-specific diluent. Provenance not specified.
Method Comparison: 106 unaltered native matched serum and plasma samples. No specific provenance (country of origin) or retrospective/prospective status explicitly stated. Clinical samples are typically retrospective or prospectively collected for validation studies.
Expected Values (Reference Range Verification): 40 plasma and 40 serum samples. Obtained from "apparently healthy individuals" (implying human clinical samples). Provenance not specified.

All studies appear to be retrospective in nature, as they involve testing existing samples or prepared samples under controlled conditions to evaluate device performance characteristics.

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

For this type of in vitro diagnostic device (immunoassay), ground truth is not typically established by human expert review in the same way it would be for imaging diagnostics.

Ground truth for quantitative assays like this one is generally established through:
- Reference Methods: Highly accurate and precise laboratory methods (e.g., mass spectrometry). While not explicitly stated for all measurements, this is the gold standard for establishing true analyte concentrations.
- Predicate Device: For method comparison, the predicate device's results serve as the comparison "truth" against which the modified device is evaluated.
- Defined Concentrations: For studies like linearity, precision, and detection limits, samples are often prepared with known, spiked, or characterized concentrations.

There is no mention of human "experts" establishing ground truth for individual test samples. The "experts" involved are implied to be the laboratory personnel, scientists, and statisticians who designed and conducted the studies, and who interpret the results against established statistical and clinical criteria (e.g., CLSI guidelines).

4. Adjudication Method for the Test Set

Not applicable for this type of quantitative diagnostic assay. Adjudication methods like 2+1 or 3+1 are typically used in imaging studies where multiple human readers assess findings and resolve discrepancies. Here, the "truth" for evaluation is based on quantitative measurements.

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 a laboratory immunoassay, not an AI-assisted diagnostic imaging device that involves human readers.

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

Yes, this is a standalone device. The performance characteristics (precision, linearity, detection limits, interference, cross-reactivity, method comparison) are all evaluations of the assay itself, demonstrating its analytical performance without any human intervention beyond standard laboratory procedures for running the test. It's a fully automated system for quantitative determination.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

The ground truth used in these studies is primarily based on:

Reference standards/known concentrations: For linearity, precision, and detection limit studies, samples are often prepared with known concentrations or characterized against highly accurate reference methods.
Values from the predicate device: For method comparison, the results obtained from the predicate device serve as the comparative "ground truth."
Clinical status for reference ranges: Normal healthy individuals are used to verify the expected reference range.

8. The Sample Size for the Training Set

Not applicable in the traditional sense of machine learning. This device is an immunoassay, not a machine learning algorithm that requires a "training set" to learn a model. Its performance is based on the chemical and immunological reactions of the assay components.

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

Not applicable for the reasons stated above (not an ML-based device requiring a training set). The assay's performance is driven by its reagent formulation and instrument design, which are developed and validated through iterative testing and process control during manufacturing.

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