(227 days)
The ADVIA Centaur Vitamin D Total (VitD) assay is for the in vitro diagnostic use in the quantitative determination of total 25 (OH) vitamin D in human serum and plasma (EDTA, lithium heparin, sodium heparin) using the ADVIA Centaur XP system. The ADVIA Centaur VitD assay is intended as an aid in the determination of vitamin D sufficiency.
The ADVIA Centaur Vitamin D Total (VitD) Calibrators is for in vitro diagnostic use in calibrating ADVIA Centaur® systems Vitamin D Total (VitD) assay.
The ADVIA Centaur Vitamin D Total (VitD) QC is for in vitro diagnostic use to monitor the precision and accuracy of the ADVIA Centaur® VitD assay on the ADVIA Centaur systems.
The ADVIA Centaur® Vitamin D Total (VitD) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur VitD assay.
The ADVIA Centaur Vitamin D Total assay is a one-pass 18 minute competitive immunoassay that uses an anti-fluorescein labeled (FITC) monoclonal antibody covalently bound to paramagnetic particles (PMP), one monoclonal antibody labeled with acridium ester (AE), and a Vitamin D analog labeled with fluorescein. An inverse relationship exists between the amount of Vitamin D present in the patient sample and the amount of relative light units (RLUs) detected by the system.
Here's a summary of the acceptance criteria and study information for the ADVIA Centaur Vitamin D Total Assay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to the predicate device and the successful results for various performance characteristics. The document states that "All of the evaluation studies gave acceptable results compared to the predicate device." Therefore, the reported performance is within the acceptable range as defined by the predicate device and established analytical standards.
| Performance Characteristic | Acceptance Criteria (Implied by Predicate/Standards) | Reported Device Performance (ADVIA Centaur Vitamin D Total Assay) |
|---|---|---|
| Analytical Sensitivity | Acceptable for Vitamin D test systems (vs. K021163) | LoB = 1.60 ng/mL, LoD = 3.2 ng/mL, LoQ = 4.2 ng/mL |
| Imprecision (Total CV) | Comparable to predicate for similar levels | Level 11.7 ng/mL: 11.1% |
| Level 18.0 ng/mL: 9.6% | ||
| Level 32.4 ng/mL: 9.8% | ||
| Level 49.9 ng/mL: 8.2% | ||
| Level 55.8 ng/mL: 7.8% | ||
| Level 132.1 ng/mL: 4.8% | ||
| Specificity (Cross-Reactivity) | Low cross-reactivity for related compounds | 1,25 (OH)2 Vitamin D2: 4.0% |
| 1,25 (OH)2 Vitamin D3: 1.0% | ||
| 25 OH Vitamin D2: 104.5% | ||
| 25 OH Vitamin D3: 100.7% | ||
| Paricalcitol: 0.1% | ||
| 3-epi-25-OH Vitamin D3: 1.1% | ||
| Vitamin D2: 0.5% | ||
| Vitamin D3: 0.3% | ||
| Interfering Substances | ≤ 10% change in results for specified concentrations | Hemoglobin: 155 mg/dL |
| Triglycerides: 540 mg/dL | ||
| Conjugated Bilirubin: 40 mg/dL | ||
| Unconjugated Bilirubin: 40 mg/dL | ||
| Cholesterol: 350 mg/dL | ||
| Uric Acid: 20 mg/dL | ||
| Human Immunoglobulin: 12 g/dL | ||
| Method Comparison (Correlation with Predicate) | Strong correlation (vs. K021163) | n = 195, r = 0.960, Slope = 1.0, Y-intercept = +2.22 |
| Serum/Plasma Equivalency | No significant differences between tube types | R values: Serum vs. SST: 0.994, Serum vs. EDTA: 0.993, Serum vs. Lithium Heparin: 0.992, Serum vs. Sodium Heparin: 0.992 |
2. Sample Sizes Used for the Test Set and Data Provenance
- Method Comparison: n = 195 samples. The provenance of this data (country of origin, retrospective/prospective) is not explicitly stated.
- Imprecision: n = 160 (Total CV). It's typically from replicate measurements on control samples over multiple runs.
- Specificity: Not a sample size in the traditional sense, but tested with specific concentrations of various compounds.
- Interfering Substances: Tested as described in CLSI Document EP7-A2. Specific sample sizes for each interfering substance are not provided, but it would involve spiking known concentrations into samples.
- Serum/Plasma Equivalency: n = 231 matched specimens drawn in different tube types. The provenance of this data (country of origin, retrospective/prospective) is not explicitly stated.
The document does not specify the country of origin of the data or whether the studies were retrospective or prospective for the various performance characteristics.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information is generally not applicable to an in vitro diagnostic (IVD) assay like the ADVIA Centaur Vitamin D Total Assay. The "ground truth" for these assays is usually established through:
- Reference Methods: For method comparison, the predicate device (IDS 25-OH Vitamin D EIA assay, K021163) or a recognized reference method like LC-MS/MS (mentioned for traceability of the ADVIA Centaur assay) serves as the comparator.
- Known Concentrations: For analytical sensitivity, imprecision, specificity, and interfering substances, the "ground truth" is based on precisely prepared samples with known concentrations of the analyte or interfering substances.
Therefore, no panel of human experts was used to establish ground truth for this device.
4. Adjudication Method for the Test Set
Not applicable. As this is an IVD assay measuring biochemical analytes, there is no adjudication process involving human review for the "test set" in the way one might see in imaging studies. The results are quantitative and compared against established analytical methods or known values.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
No. An MRMC study is not relevant for this type of IVD device, which is an automated assay for blood analysis. MRMC studies are typically performed for diagnostic imaging devices where human interpretation is a critical component.
6. Standalone Performance Study
Yes, the studies described (Analytical Sensitivity, Imprecision, Specificity, Interfering Substances, Serum/Plasma Equivalency) represent the standalone performance of the ADVIA Centaur Vitamin D Total Assay. The "Method Comparison" against the predicate device also serves to demonstrate that the algorithm (assay) performs comparably to an already established method without human interpretation required for its output.
7. Type of Ground Truth Used
The ground truth used for this device includes:
- Reference Assay/Predicate Device: For method comparison, the results generated by the IDS 25-OH Vitamin D EIA assay (K021163) served as the comparator.
- Traceability to LC-MS/MS: The ADVIA Centaur assay's traceability to LC-MS/MS (Liquid Chromatography-Mass Spectrometry) indicates that for its fundamental accuracy and standardization, it references a highly precise and accurate analytical method often considered a gold standard for vitamin D measurement.
- Known/Spiked Concentrations: For studies like analytical sensitivity, imprecision, specificity, and interfering substances, the ground truth is based on samples with precisely known concentrations of the analyte or potential interfering substances.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI, as this is a traditional immunoassay. For such assays, method development and optimization phases involve extensive testing to establish reagent formulations, reaction conditions, and calibration algorithms. The data used for this developmental work is not typically reported as a "training set" in the same way it would be for an AI-based device.
9. How the Ground Truth for the Training Set Was Established
As this is a traditional immunoassay and not an AI/ML device, the concept of a "training set" with established ground truth as understood in AI development is not directly applicable. Instead, the assay's performance characteristics (calibration, linearity, imprecision, accuracy) would have been optimized and validated using a combination of:
- Reference standards: Materials with assigned values, often traceable to higher-order reference methods like LC-MS/MS.
- Clinical samples: Patient samples covering a range of analyte concentrations.
- Spiked samples: Samples with known quantities of analyte added.
- Internal quality control materials: Samples with established target values.
The "ground truth" during development would be established through careful analytical measurements using these standards and methods to ensure the assay accurately quantifies vitamin D.
§ 862.1825 Vitamin D test system.
(a)
Identification. A vitamin D test system is a device intended for use in clinical laboratories for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). Vitamin D test systems must comply with the following special controls:(1) Labeling in conformance with 21 CFR 809.10 and
(2) Compliance with existing standards of the National Committee on Clinical Laboratory Standards.