(71 days)
The Vitros® CEA is an in vitro assay intended for the quantitative measurement of carcinoembyronic antigen (CEA) in human serum and plasma (EDTA or heparin) to aid in the prognosis and management of cancer patients in whom changing concentrations of CEA are observed.
The VITROS ECi Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum, plasma or urine. Coated microwells are used as the solid phase separation system. The system is comprised of three main elements: 1. The VITROS Immunodiagnostic Products (in this case VITROS Immunodiagnostic Products CEA Reagent Pack, VITROS Immunodiagnostic Products CEA Calibrators, which are combined by the VITROS ECi System to perform the VITROS CEA assay). 2. The VITROS ECi Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits. 3. Common reagents used by the VITROS System in each assay.
Acceptance Criteria and Device Performance for VITROS® Immunodiagnostic Products CEA Assay
This report describes the acceptance criteria and the study that demonstrates the VITROS® Immunodiagnostic Products CEA assay meets those criteria.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the VITROS® Immunodiagnostic Products CEA assay are primarily based on demonstrating substantial equivalence to a legally marketed predicate device, the Abbott AxSYM CEA Assay. This equivalence is established through various analytical characteristic comparisons and clinical performance evaluations.
| Acceptance Criterion | Reported Device Performance |
|---|---|
| Substantial Equivalence (Overall) | The VITROS CEA assay performs substantially equivalent to the approved predicate device (Abbott AxSYM CEA Assay). Equivalence was demonstrated using commercially available reagents and patient specimens. |
| Correlation with Predicate Device | VITROS CEA assay = 1.06 x [Abbott AxSYM CEA assay] + 0.124 (ng/mL) with a correlation coefficient of 0.977. |
| Analytical Sensitivity | 0.3 ng/mL (Predicate device: 0.5 ng/mL). The VITROS CEA assay demonstrates slightly better analytical sensitivity. |
| Calibration Range (Reportable Range) | 0 - 400 ng/mL (Predicate device: 0.5 - 500 ng/mL). This range is comparable. |
| Clinical Performance (Patient Distributions) | In clinical studies of apparently healthy individuals, patients with malignant disease, and patients with a variety of non-malignant diseases, the VITROS CEA assay exhibited distribution results that parallel expected distributions for these patient types. This indicates appropriate clinical utility across different patient populations. |
| Serial Monitoring Study | The serial monitoring study demonstrated that the VITROS CEA assay is substantially equivalent to the predicate device in patients previously treated for colorectal cancer. This confirms its utility for monitoring disease progression/recurrence. |
| Other Analytical Characteristics | Tests were performed to obtain specificity, precision, and dilution validation results. (Specific numerical details for these are not provided in the summary but are referenced to the package insert). These characteristics are implicitly accepted as meeting a standard comparable to or better than the predicate device for substantial equivalence. |
| Intended Use | The device demonstrated performance suitable for its intended use: quantitative measurement of CEA in human serum and plasma (EDTA or heparin) to aid in the prognosis and management of cancer patients in whom changing concentrations of CEA are observed. The performed studies align with this intended use (e.g., studies in cancer patients, serial monitoring). |
2. Sample Size and Data Provenance
- Test Set Sample Size: The document does not explicitly state the exact sample size for the test set used in the correlation and clinical performance studies. It mentions "samples from a variety of clinical categories" and "patient specimens from patients who are normal, undergoing therapeutic and/or undergoing diagnostic evaluation."
- Data Provenance: The document does not specify the country of origin of the data. It indicates that the studies involved "patient specimens from patients who are normal, undergoing therapeutic and/or undergoing diagnostic evaluation" and "patients previously treated for colorectal cancer," suggesting retrospective or prospective clinical samples were used, likely drawn from a clinical laboratory or hospital setting.
3. Number of Experts and Qualifications for Ground Truth
- This device is an in vitro diagnostic assay that provides quantitative numerical results (CEA concentration). The "ground truth" for such devices is typically established by comparing the device's output to a reference method or a legally marketed predicate device's output.
- Therefore, the concept of "experts" establishing ground truth in the traditional sense (e.g., radiologists interpreting images) is not directly applicable here. The "experts" would be the clinical laboratory professionals who performed the reference measurements and interpreted the data for analysis. Their qualifications would involve expertise in in vitro diagnostic testing and laboratory medicine. The document does not specify the number of such professionals.
4. Adjudication Method
- Adjudication methods like 2+1 or 3+1 are typically used in studies involving subjective interpretations (e.g., image reading).
- For an in vitro diagnostic quantitative assay, adjudication is not usually performed in this manner. The comparison is between the numerical output of the new device and the numerical output of the predicate device/reference method. Any discrepancies would be analyzed statistically, not through panel review.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not performed. This type of study is relevant for diagnostic devices where human readers interpret outputs (e.g., medical images) and the AI aims to improve their performance.
- This device is an automated in vitro diagnostic test that provides a direct numerical result, not an interpretation for human readers to act upon or be "assisted" by.
6. Standalone Performance Study
- Yes, a standalone performance study was done. The entire submission details the performance of the VITROS CEA assay as a standalone algorithm/device in generating quantitative CEA measurements.
- The comparison studies directly pitted the VITROS CEA assay against the predicate device to establish its direct performance, not its performance in assisting a human. The correlation coefficient, analytical sensitivity, and clinical distribution data all represent the standalone performance of the VITROS CEA assay.
7. Type of Ground Truth Used
The primary ground truth used for performance evaluation was:
- Predicate Device Measurements: The results obtained from the Abbott AxSYM CEA Assay (P830066) served as the direct comparator and primary "ground truth" for demonstrating substantial equivalence.
- Expected Clinical Distributions: For the clinical performance, the "expected distributions" for CEA levels in apparently healthy individuals, patients with malignant disease, and patients with non-malignant diseases served as the ground truth. This is based on established medical knowledge and clinical guidelines for CEA interpretation.
8. Sample Size for the Training Set
- This document describes a 510(k) premarket notification for a traditional in vitro diagnostic assay, not a machine learning or AI-based device that typically requires a large "training set" for model development.
- Therefore, the concept of a separate "training set" with a distinct sample size for algorithm development is not applicable in the context of this device. The development and validation of such assays involve rigorous analytical studies (precision, linearity, interference, etc.) using various characterized samples and clinical studies for performance comparison against established methods.
9. How the Ground Truth for the Training Set Was Established
- As concluded in point 8, the concept of a "training set" for an AI algorithm is not applicable here.
- The "ground truth" or reference values for the development and testing of this type of in vitro diagnostic assay are established through reference methods, certified reference materials, and established clinical measurements from predicate devices or other validated assays. These are subject to strict quality control and laboratory standards.
§ 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.