(15 days)
For the quantitative determination of alpha-fetoprotein (AFP) in the following: human serum, as an aid in managing non-seminomatous testicular cancer when used in conjunction with physical examination, histology/pathology, and other clinical evaluation procedures, using the Bayer Diagnostics ACS:180 Automated Chemiluminescence System or the ADVIA Centaur System.
The Bayer Diagnostics ACS:180 & ADVIA Centaur AFP immunoassay is a two-site immunoassay using direct chemiluminometric technology, which uses constant amounts of two antibodies. The first antibody, in the Lite Reagent, is a purified polyclonal rabbit anti-AFP antibody labeled with acridinium ester. The second antibody, in the Solid Phase, is a monoclonal mouse anti-AFP antibody covalently coupled to paramagnetic particles. A direct relationship exists between the amount of AFP present in the patient sample and the amount of relative light units (RLU's) detected by the system.
The provided text describes the performance data for the ACS:180 & ADVIA Centaur AFP Immunoassay. Here's an analysis based on your request:
1. Table of Acceptance Criteria and Reported Device Performance
| Feature | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Sensitivity | Detect AFP concentration within a specified range/minimum. | ADVIA Centaur: |
- Measures AFP up to 1000 ng/mL.
- Minimum detectable concentration: 1.3 ng/mL.
ACS:180: - Measures AFP up to 1000 ng/mL.
- Minimum detectable concentration: 0.19 ng/mL. |
| Accuracy | High correlation with predicate/alternate methods (e.g., r > 0.95). | ADVIA Centaur vs. ACS:180 (N=498): - Equation: ADVIA Centaur AFP = 1.05 (ACS:180 AFP) - 0.3 ng/mL
- Correlation coefficient (r) = 0.99
ACS:180 vs. Alternate Methods: - Abbott IMX (N=504): ACS:180 = 0.94(Abbott IMX) + 4.6
- Kallestd AFP/Ob (N=1575): ACS:180 = 0.92(Kallestd AFP/Ob) + 6.2
- Abbott mEIA (N=183): ACS:180 = 0.97(Abbott mEIA) - 1.0
- Kallestd AFP/Ob (N=477): ACS:180 = 1.10(Kallestd AFP/Ob) + 1.0 |
Note on Acceptance Criteria: The document does not explicitly state specific numerical acceptance criteria for correlation coefficients or minimum detectable limits. Instead, it presents the performance data in comparison to a predicate device (ACS:180 for ADVIA Centaur) and other established methods. The "acceptance criteria" are implied by the excellent correlation values (r=0.99 for ADVIA Centaur vs. ACS:180) which are typically considered a strong indicator of agreement in such assays.
2. Sample Sizes Used for the Test Set and Data Provenance
- ADVIA Centaur Accuracy Test Set: 498 serum samples.
- ACS:180 Accuracy Test Set (vs. alternate methods):
- vs. Abbott IMX: 504 samples
- vs. Kallestd AFP/Ob (first test): 1575 samples
- vs. Abbott mEIA: 183 samples
- vs. Kallestd AFP/Ob (second test): 477 samples
- Data Provenance: Not explicitly stated. The document describes clinical performance data but does not specify the country of origin of the data or whether it was retrospective or prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- This information is not provided in the document. The study compares the device's measurements to existing established methods (predicate device and alternate AFP methods), not to a ground truth established by human experts in the traditional sense of image or pathology review.
4. Adjudication Method for the Test Set
- Not applicable. The "ground truth" for these tests are the results from the established existing immunoassay methods. There is no mention of human adjudication as would be relevant for subjective assessments.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No. This type of study is typically done for diagnostic imaging devices where human interpretation is a key component. The ACS:180 & ADVIA Centaur AFP Immunoassay is an in vitro diagnostic (IVD) immunoassay that provides quantitative results. Therefore, an MRMC study is not relevant for this device.
6. Standalone Performance Study
- Yes, standalone performance was assessed. The "Performance Data" section details the sensitivity (minimum detectable concentration) and accuracy (correlation with predicate and other immunoassay methods) of the devices themselves, without direct human intervention in the result generation. The device outputs a quantitative value for AFP concentration based on its internal processes.
7. Type of Ground Truth Used
- The "ground truth" in this context is the results obtained from legally marketed and established predicate/alternate AFP immunoassay methods. The study aims to demonstrate that the new devices produce results that are highly correlated and comparable to these existing, accepted methods.
8. Sample Size for the Training Set
- This information is not provided in the document. Immunoassays typically involve calibration and validation rather than a "training set" in the machine learning sense. The document describes performance data, likely from validation studies, rather than development or training phases.
9. How the Ground Truth for the Training Set Was Established
- Not applicable / Information not provided. As mentioned above, the concept of a "training set" and "ground truth" for it, as typically used in machine learning, does not align with the description of this immunoassay. The document focuses on demonstrating performance against established methods.
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.