(132 days)
For in vitro diagnostic use in the quantitative, serial determination of CA 125 in human serum and to aid in the management of patients with ovarian carcinoma using the ADVIA Centaur® System. The test is intended for use as an aid in monitoring patients previously treated for ovarian cancer. Serial testing for CA 125 in the serum of patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence. The test is also intended for use as an aid in the management of ovarian cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment. It is recommended that the Bayer ADVIA Centaur CA 125 II assay be used under the order of a physician trained and experienced in the management of gynecological cancers. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.
The ADVIA Centaur CA 125 II assay is a fully automated, single step sandwich immunoassay using direct, chemiluminescent technology. The Lite Reagent is composed of the monoclonal mouse antibody, OC125, specific for CA 125, labeled with acridinium ester and the monoclonal mouse antibody M11, specific for CA 125, labeled with fluorescein. The Solid Phase is composed of purified monoclonal mouse capture antibody, which is covalently coupled to paramagnetic particles. The sample is incubated with both Lite Reagent and Solid Phase simultaneously for 40 minutes. After incubation, the immuno-complex is washed. The measured chemiluminescence is directly proportional to the quantity of CA 15-3 antigen in the sample.
This document describes the premarket notification (510(k)) for the ADVIA Centaur CA 125 II assay, an in vitro diagnostic device used to quantitatively determine CA 125 levels in human serum to aid in the management and monitoring of ovarian carcinoma patients.
Here's the breakdown of the acceptance criteria and the study results from the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state formal acceptance criteria in a table format with specific thresholds before presenting results. However, it implicitly uses substantial equivalence to a predicate device as the primary acceptance criterion. The key performance metric used to demonstrate this equivalence is correlation and regression analysis between the new device and the predicate device.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (ADVIA Centaur CA 125 II vs. Immuno 1 CA 125 II) |
|---|---|---|
| Correlation Coefficient (r) | High correlation (e.g., close to 1) between new device and predicate | 0.992 |
| Regression Equation (Deming Regression) | Close agreement (slope near 1, intercept near 0) | ADVIA Centaur CA 125 II = 1.025 (Immuno 1) + 1.14 U/mL |
| Clinical Sensitivity (Longitudinal Monitoring) | Not explicitly defined as a threshold, but demonstrated | 93.5% |
| Clinical Specificity (Longitudinal Monitoring) | Not explicitly defined as a threshold, but demonstrated | 38.5% |
2. Sample Size and Data Provenance for the Test Set
The primary study for substantial equivalence to the predicate device involved:
- Sample Size: 227 samples
- Data Provenance: Not explicitly stated (e.g., country of origin). The study was likely conducted by the manufacturer, Bayer Corporation. It is a retrospective comparison based on existing samples.
- Another study for monitoring: 44 ovarian cancer patients (retrospective clinical study).
3. Number of Experts and their Qualifications for Ground Truth
The document does not mention the use of experts to establish a "ground truth" for the test set in the traditional sense of image analysis or diagnostic decision-making.
For the comparison study, the "ground truth" was essentially the results obtained from the predicate device (Bayer Immuno-1 CA 125 II assay). Therefore, no external experts were used to establish this specific ground truth.
For the retrospective clinical study on monitoring, the changes in clinical status were compared to the Centaur CA 125 II results. The clinical status would have been determined by physicians trained and experienced in the management of gynecological cancers, as indicated in the intended use statement. The exact number of these physicians or their specific qualifications for assessing clinical status in this study are not provided.
4. Adjudication Method for the Test Set
No adjudication method (e.g., 2+1, 3+1) is mentioned or implied for either the primary equivalence study or the clinical monitoring study. The comparison was directly between the new device and the predicate device's measurements, and between the new device's measurements and observed clinical status.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was mentioned. This type of study is more common for diagnostic imaging devices where human readers interpret results. The ADVIA Centaur CA 125 II assay is an automated immunoassay, and its performance is evaluated against chemical and clinical measures, not human reader interpretation.
6. Standalone (Algorithm Only) Performance Study
Yes, a standalone performance study was done. The entire submission focuses on the performance of the ADVIA Centaur CA 125 II assay itself (the "algorithm only," in this context, refers to the automated immunoassay system) without human interpretation as part of its core function, other than a physician's decision-making based on the quantitative result.
The reported performance metrics (correlation coefficient, regression equation, sensitivity, and specificity) are all based on the device's direct output.
7. Type of Ground Truth Used
- For the substantial equivalence study: The predicate device's results (Bayer Immuno-1 CA 125 II assay) served as the proxy "ground truth" for comparison. This is a common approach for in vitro diagnostics where a new test is compared to a previously cleared, established method.
- For the clinical monitoring study: The "ground truth" for evaluating sensitivity and specificity was changes in the clinical status of patients, which would be determined by physicians based on various clinical parameters and outcomes (e.g., disease progression, regression, recurrence). This can be classified as outcomes data or clinical assessment.
8. Sample Size for the Training Set
The document does not explicitly state a separate "training set" size. Given the nature of a 510(k) submission for an immunoassay, the device itself (the assay and analyzer) would have been developed and optimized prior to these validation studies. Therefore, the concept of a "training set" as it applies to machine learning algorithms might not be directly transferrable or explicitly detailed in such a submission. The studies described are more akin to validation or test sets for the finished device.
9. How Ground Truth for the Training Set Was Established
As no explicit "training set" is mentioned in the context of ground truth establishment, this information is not provided. The development and optimization of the assay would involve standard clinical chemistry and immunoassay development practices, where reference materials and known concentrations are used to calibrate and fine-tune the assay's performance characteristics.
§ 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.