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510(k) Data Aggregation
(532 days)
For in vitro diagnostic use in the quantitative determination of human chorionic gonadotropin (hCG) in serum or plasma (EDTA or lithium heparin) using the ADVIA Centaur® XP system.
Human chorionic gonadotropin measurements are intended for use as an aid in the early detection of pregnancy.
The ADVIA Centaur® Total hCG assay reagents come in the following configurations:
5 ReadyPack primary reagent packs containing ADVIA Centaur Total hCG Lite Reagent and Solid Phase ADVIA Centaur and ADVIA Centaur CP Total hCG Master Curve card (250 Tests)
1 ReadyPack primary reagent pack containing ADVIA Centaur Total hCG Lite Reagent and Solid Phase ADVIA Centaur and ADVIA Centaur CP Total hCG Master Curve card (50 Tests)
The ReadyPack consists of the following:
ADVIA Centaur ThCG ReadyPack® primary reagent pack; Lite Reagent: 5.0 mL/reagent pack polyclonal goat anti-hCG antibody (~0.1 µg/mL) labeled with acridinium ester in buffered saline with sodium azide (0.1%) and preservatives
ADVIA Centaur ThCG ReadyPack primary reagent pack; Solid Phase Reagent: 22.5 mL/reagent pack monoclonal mouse anti-hCG antibody (~0.02 mg/mL) covalently coupled to paramagnetic particles in buffered saline with sodium azide (0.1%) and preservatives
ADVIA Centaur ThCG ReadyPack ancillary reagent pack; ThCG Diluent: 25.0 mL/reagent pack buffered heat-treated equine serum with EDTA, sodium azide (
This document describes the validation of the ADVIA Centaur® Total hCG assay, primarily focusing on the addition of plasma (EDTA and lithium heparin) sample claims.
Here's an analysis of the acceptance criteria and the studies that demonstrate the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Detection Capability | LOQ (Limit of Quantification), LOD (Limit of Detection), LOB (Limit of Blank) within specified ranges. | LOQ: 4.0 mIU/mL (IU/L) |
| LOD: 3.0 mIU/mL (IU/L) | ||
| LOB: 2.0 mIU/mL (IU/L) | ||
| Precision | CV% within acceptable limits for various hCG concentrations (specified in CLSI EP05-A3). | Serum A (Mean 6.63 mIU/mL): Repeatability CV 4.4%, Between-Run CV 1.3%, Between-Day CV 3.6%, Within-Lab CV 5.8% |
| Serum B (Mean 15.85 mIU/mL): Repeatability CV 3.3%, Between-Run CV 2.8%, Between-Day CV 2.0%, Within-Lab CV 4.8% | ||
| Serum C (Mean 819.28 mIU/mL): Repeatability CV 2.5%, Between-Run CV 2.7%, Between-Day CV 1.5%, Within-Lab CV 4.0% | ||
| Control 1 (Mean 7.43 mIU/mL): Repeatability CV 4.1%, Between-Run CV 2.0%, Between-Day CV 4.3%, Within-Lab CV 6.2% | ||
| Control 2 (Mean 24.64 mIU/mL): Repeatability CV 2.5%, Between-Run CV 0.6%, Between-Day CV 2.3%, Within-Lab CV 3.5% | ||
| Control 3 (Mean 164.66 mIU/mL): Repeatability CV 1.8%, Between-Run CV 0.5%, Between-Day CV 1.6%, Within-Lab CV 2.5% | ||
| Method Comparison (vs. Predicate) | High correlation (r value close to 1) and a slope and intercept indicating agreement (slope near 1, intercept near 0). | Equation: ADVIA Centaur Total hCG = 0.96 (Atellica IM ThCG assay) - 3.0 mIU/mL |
| Correlation coefficient (r): 0.997 | ||
| Specimen Equivalence | Slope of 0.90–1.10 for alternate tube types versus serum, and high correlation coefficients. | Dipotassium EDTA plasma vs. Serum (N=53): Slope 0.99, Intercept 0.3, r 1.00 |
| Lithium heparin plasma vs. Serum (N=51): Slope 1.01, Intercept -0.3, r 1.00 | ||
| Linearity | Results spanning the entire assay range meet acceptance criteria. | Results met acceptance criteria, supporting an analytical measuring range from 4.0 mIU/mL to 1000 mIU/mL. |
| Dilution Recovery | % Recovery within an acceptable range (typically 90-110% or similar). | Mean % Recovery: 1:2 dilution (91%), 1:4 dilution (98%), 1:8 dilution (95%), 1:16 dilution (101%). Individual recovery values varied, but overall means were within typical acceptable ranges. |
| Interferences | % Bias from interfering substances within acceptable limits (typically ±10% or similar). | Human Serum Albumin: -0.3% to -0.2% bias |
| Acetaminophen: -0.5% to 2.7% bias | ||
| Acetylsalicylic acid: 0.4% to 2.7% bias | ||
| Heparin: -8.2% to 1.6% bias | ||
| Ibuprofen: -1.4% to 0.3% bias | ||
| EDTA: 1.8% to 4.1% bias | ||
| Ethanol: -1.1% to 2.7% bias | ||
| Atropine: -1.5% to 0.0% bias | ||
| Caffeine: 1.1% to 6.1% bias | ||
| Gentisic acid: -1.1% to 4.3% bias (All seem to meet typical ±10% bias acceptance criterion). | ||
| HIL Interference | % Bias from Hemolysis, Icterus, and Lipemia within acceptable limits. | Bilirubin (Conjugated): -1.0% to 3.3% bias |
| Bilirubin (Unconjugated): -0.8% to 1.7% bias | ||
| Hemoglobin: -0.5% to 1.3% bias | ||
| Intralipid: -3.3% to -3.7% bias (All seem to meet typical ±10% bias acceptance criterion). | ||
| Expected Values (Reference Range) | Established reference intervals for non-pregnant and postmenopausal females. | Non-Pregnant Females (Age: ≤40, N=130): 0.03 – 0.6 mIU/mL |
| Postmenopausal Females (Age: ≥41, N=150): 0.02 – 2.9 mIU/mL | ||
| Cross-Reactivity | Minimal interference from related hormones (FSH, TSH, LH, hGH, PRL). | Data provided for various hCG concentrations with and without cross-reactants. For example, for FSH at 500mIU/mL, hCG values without cross-reactant ranged from 0.5-493.1 mIU/mL, and with cross-reactant ranged from 1.6-475.4 mIU/mL. Similar data for TSH, LH, hGH, and PRL. (Implied acceptance is that the cross-reactants do not significantly alter the hCG measurement, which the provided data appears to support given the relative magnitudes). |
| Sample Handling/Stability | Stability for specified conditions (refrigeration, room temp, on-board, freeze/thaw cycles). | Storage refrigerated (2-8°C) for up to 48 hours. |
| Storage at room temperature (25°C) for up to 8 hours. | ||
| Kept on-board (30°C) for up to 8 hours. | ||
| Frozen and thawed up to 1 time. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Detection Capability: No specific sample size disclosed for LOB/LOD/LOQ determination in this summary.
- Precision: 320 total replicates for each of the 6 samples (3 serum, 3 control) over 20 days (e.g., 2 runs/day x 20 days x 2 replicates/run).
- Method Comparison: 117 samples (range 7.6 to 977.6 mIU/mL).
- Specimen Equivalence: 53 pairs for Dipotassium EDTA plasma vs. Serum; 51 pairs for Lithium heparin plasma vs. Serum.
- Linearity: Samples spanning the entire assay range. Specific number not provided.
- Dilution Recovery: Multiple samples tested across 4 dilution ratios (1:2, 1:4, 1:8, 1:16). Number of individual samples varies per dilution.
- Interferences (General, HIL): Not explicitly stated, but performed "used the paired-difference approach" at two analyte concentrations for each interferent.
- Expected Values (Reference Range): 130 non-pregnant females (≤40) and 150 postmenopausal females (≥41).
- Cross-Reactivity: Not explicitly stated, but multiple hCG values (low to high) tested against each cross-reactant.
Data Provenance: The document does not explicitly state the country of origin for the clinical samples. It is a submission by Siemens Healthcare Diagnostics, Inc. based in Tarrytown, New York, USA, suggesting the work was likely conducted or overseen in the USA, but the origin of patient samples is not specified. The studies are retrospective, as they involve characterizing the performance of the assay with collected samples, rather than following patients prospectively as part of the study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
For in vitro diagnostic assays like this, which measure an analyte (hCG), the "ground truth" is typically the concentration of the analyte itself, often established by a reference method or highly characterized reference materials for standardization, or by the clinical diagnosis. This is not a device where human experts (e.g., radiologists) interpret images or clinical data to establish a ground truth.
- Standardization: The ADVIA Centaur Total hCG assay is traceable to the World Health Organization (WHO) 5th IS 7/364 reference material. This material itself serves as the 'ground truth' for defining hCG concentration.
- Expected Values: The reference range study for Non-Pregnant and Postmenopausal Females established through a CLSI guideline, where the "ground truth" for non-pregnant status would be clinical assessment, and the hCG measurement would be the result to define the range.
Therefore, the concept of "number of experts used to establish ground truth" as it applies to image interpretation or clinical diagnosis is not directly applicable here. The ground truth is fundamentally analytical (traceability to reference standards) and clinical classification (e.g., non-pregnant status).
4. Adjudication Method for the Test Set
Not applicable for this type of in vitro diagnostic device study. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies where individual expert opinions need to be reconciled for clinical endpoints or image interpretations. Here, the studies are analytical performance evaluations.
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 device is an in vitro diagnostic assay, not an AI-assisted diagnostic imaging device or a system involving human readers interpreting outputs.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described are for the standalone analytical performance of the ADVIA Centaur® Total hCG assay. The device measures hCG quantitatively; its performance characteristics (precision, linearity, interference, etc.) are inherent to the assay and instrument system, independent of human interpretation of the measurement itself. The "without human-in-the-loop" concept applies.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The ground truth depends on the specific performance characteristic:
- Analytical Ground Truth: For characteristics like method comparison, linearity, dilution recovery, interferences, and cross-reactivity, the ground truth is often defined by:
- Reference Methods: The predicate device (Atellica IM ThCG assay)
- Spiked Samples: Known concentrations of analyte or interfering substances added to samples.
- Traceability to International Standards: WHO 5th IS 7/364 reference material.
- Clinical Ground Truth: For the "Expected Values" study, the ground truth of "non-pregnant" or "postmenopausal" status would be established through clinical assessment of the individuals providing the samples.
8. The Sample Size for the Training Set
This document describes a 510(k) submission for an in vitro diagnostic (IVD) assay, not a machine learning or AI algorithm development. Therefore, the concept of a "training set" in the context of AI is not applicable. The assay's methods are based on established immunoassay principles, and the performance characteristics are determined through analytical validation studies.
9. How the Ground Truth for the Training Set Was Established
As explained in point 8, the concept of a training set for an AI/ML algorithm is not relevant for this traditional IVD assay validation. The assay is developed based on scientific and chemical principles, and its performance is validated against specific criteria using various types of samples.
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