(83 days)
The ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein (CRP) in human serum and plasma (lithium heparin or potassium EDTA) on the ADVIA Chemistry systems. In acute phase response, increased levels of a number of plasma proteins, including CRP, are observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders, and associated diseases. High sensitivity CRP (hsCRP) measurements may be used as an independent risk marker for the identification of individuals at risk for future cardiovascular disease. Measurement of hsCRP, when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for recurrent events in patients with stable coronary disease or acute coronary syndromes.
The ADVIA Chemistry CardioPhase High Sensitivity C-Reactive Protein Calibrators are for in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the CardioPhase High Sensitivity C-Reactive Protein method.
The ADVIA Chemistry CardioPhase™ High Sensitivity C-Reactive Protein assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein (CRP) in human serum and plasma on the ADVIA Chemistry systems. The CardioPhaseTM hsCRP latex reagent is a suspension of uniform polystyrene latex particles coated with anti-CRP antibody. When serum or plasma containing CRP is mixed with the latex reagent, agglutination takes place resulting in an increase in turbidity. This turbidity is measured at 571 nm. The CRP concentration in serum or plasma is determined from a calibration curve that is generated with the calibrators.
The ADVIA® Chemistry CardioPhase™ High Sensitivity C-Reactive Protein Calibrators consist of six (6) levels of protein stabilized matrices containing varying concentrations of recombinant human CRP. The Calibrators have targeted values (lot specific) of 0, 0.53, 1.05, 1.58, 5.25, and 10.50 mg/L.
The calibrators (1 mL/vial) are liquid and ready to use. Storage is at 2 - 8℃.
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:
Important Note: The provided document is a 510(k) summary for an in vitro diagnostic (IVD) device, specifically a C-Reactive Protein (CRP) assay. For IVDs, the "device performance" and "acceptance criteria" are typically related to analytical performance (e.g., precision, accuracy, linearity, interference) rather than diagnostic accuracy (e.g., sensitivity, specificity, AUC) in the way a medical imaging AI would be evaluated. The "ground truth" and "experts" mentioned in your request are more relevant to AI/imaging diagnostics. Therefore, I will adapt the answers to fit the context of this IVD device.
Acceptance Criteria and Device Performance for ADVIA® Chemistry CardioPhase High Sensitivity C-Reactive Protein (hsCRP) Assay (K081294)
1. Table of Acceptance Criteria and Reported Device Performance
Since this is an IVD device, acceptance criteria are generally established against pre-defined analytical performance targets or by demonstrating substantial equivalence to a predicate device. The document explicitly states that "All of the evaluation studies gave acceptable results compared to the predicate device." While specific numerical acceptance limits aren't always explicitly listed in the summary, the reported performance metrics are presented in comparison to the predicate or against generally accepted analytical standards for such assays.
| Performance Characteristic | Acceptance Criteria (Implied/Compared to Predicate) | Reported Device Performance (ADVIA Chemistry CardioPhase hsCRP) |
|---|---|---|
| Imprecision (Within Run CV%) | Comparable to predicate device; generally low CV% for IVD assays. | Levels (mg/L): |
- 0.21: 3.2%
- 1.04: 1.1%
- 3.12: 0.8%
- 10.27: 1.4% |
| Imprecision (Total CV%) | Comparable to predicate device; generally low CV% for IVD assays. | Levels (mg/L): - 0.21: 4.2%
- 1.04: 1.2%
- 3.12: 1.3%
- 10.27: 1.6% |
| Method Comparison (Correlation with Predicate) | Strong linear correlation (e.g., slope near 1, intercept near 0, highrvalue) with predicate. | Regression Equation (Passing Bablok): Y = 1.00x + 0.01
Regression Equation (Least Squares): Y = 1.01x - 0.01
Correlation Coefficient (r): 0.998 |
| Interfering Substances (Effect % Change) | Minimal interference (e.g., within +/- 10% or pre-defined clinical significance). | Effect (Max % Change from listed substances): - Hemoglobin: -9%
- Lipids: -7%
- Bilirubin, free: 4%
- Bilirubin, conjugated: 0%
- Rheumatoid Factor: 8% |
| Analytical Range | Appropriately wide and clinically relevant range. | 0.16 to 10 mg/L |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Method Comparison (Test Set): 167 (for serum samples comparing the new device to the predicate).
- Data Provenance: The document does not specify the country of origin or whether the data was retrospective or prospective. Given the nature of laboratory method comparison studies, these are typically prospective evaluations using clinical samples collected for testing.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This is not applicable in the typical sense for this IVD assay. For an IVD, the "ground truth" for method comparison is essentially the result obtained from the established, legally marketed predicate device. The analytical validity is determined by how closely the new device's results correlate with the predicate, rather than by expert interpretation of individual cases.
4. Adjudication Method for the Test Set
Not applicable. There is no adjudication process involving human experts interpreting results to establish a ground truth for a quantitative immunoassay like this. The comparison is purely numerical between two analytical instruments/methods.
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. MRMC studies are relevant for medical imaging diagnostics where human readers (e.g., radiologists) interpret images, and AI might assist in that interpretation. This document describes an automated laboratory assay for measuring a biomarker (CRP), not an imaging AI.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, in the context of an IVD, the performance outlined is the "standalone" performance of the assay system itself. The reported imprecision, method correlation, and interference studies describe how the ADVIA Chemistry CardioPhase hsCRP assay performs autonomously on the ADVIA 1650 system. The human involvement is in operating the instrument and interpreting the quantitative results, not in a diagnostic interpretation loop that the device enhances or replaces.
7. The Type of Ground Truth Used
For the analytical performance studies:
- Method Comparison: The "ground truth" was established by the results from the predicate device (Siemens Healthcare CardioPhase™ High Sensitivity CRP on the BNII Systems). The objective was to show that the new device's measurements align with those of an already accepted method.
- Imprecision, Interfering Substances, Analytical Range: These studies used known concentrations of analytes (e.g., controls, spiked samples) as their internal reference ("ground truth") to measure the device's consistency, susceptibility to interference, and operational range.
8. The Sample Size for the Training Set
Not applicable in the context of this traditional IVD assay. "Training set" refers to data used to train machine learning algorithms. This device is a biochemical assay, not an AI/ML product, and therefore does not have a "training set" in that sense. Its development involved chemical and engineering optimization, and its performance is demonstrated through analytical studies.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for this type of device.
§ 866.5270 C-reactive protein immunological test system.
(a)
Identification. A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.(b)
Classification. Class II (performance standards).