(350 days)
The AxSYM® CA 15-3" assay is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative measurement of CA 15-3 assay values in human serum and plasma (EDTA) to aid in the management of breast cancer patients. Serial testing for patient CA 15-3 assay values should be used in conjunction with other clinical methods for monitoring breast cancer.
AxSYM CA 15-3 is a microparticle enzyme immunoassay for the quantitative measurement of CA 15-3 assay values in human serum and EDTA plasma on the AxSYM System. AxSYM CA 15-3 employs Abbott Calibrators and Controls.
Here's an analysis of the provided text regarding the Abbott AxSYM CA 15-3 assay, focusing on acceptance criteria and study details.
The document describes a 510(k) submission for the Abbott AxSYM CA 15-3 assay, demonstrating its substantial equivalence to a predicate device, the BIOMIRA Diagnostics Inc. TRUQUANT BR RIA assay. The focus is on comparing the performance of the new device against the predicate.
Acceptance Criteria and Reported Device Performance
The core of the acceptance criteria is based on demonstrating substantial equivalence to the predicate device (BIOMIRA Diagnostics Inc. TRUQUANT BR RIA). This is assessed through various performance metrics.
| Acceptance Criteria Item (Implicit based on comparison) | Reported Device Performance (AxSYM CA 15-3) | Reported Predicate Performance (TRUQUANT BR RIA) | Outcome / Comment |
|---|---|---|---|
| Correlation Coefficient (Linear Regression) | 0.888 | N/A (compared against) | Achieved |
| Slope (Linear Regression) | 0.67 | N/A (compared against) | Achieved |
| Y-intercept (Linear Regression) | 4.2 U/mL | N/A (compared against) | Achieved |
| Dynamic Range | 0 - 250 U/mL | 0 - 200 U/mL | Similar |
| Analytical Sensitivity | 0.3 U/mL | 7.0 U/mL | Superior |
| Area Under the Curve (ROC Analysis) | 0.69 | 0.70 | Essentially Equivalent |
| Concordance at Reference Values | 91% | N/A (measured between assays) | Achieved |
| Sensitivity (at Claimed Reference Value) | 54% (95% CI=25-81) | 62% (95% CI=32-86) | Similar |
| Specificity (at Claimed Reference Value) | 94% (95% CI=85-99) | 91% (95% CI=80-97) | Similar |
| Serial Tracking Trends | Comparable trending results | Comparable trending results | Achieved |
Note: The acceptance criteria are implicitly defined by the need to show "substantially equivalent" performance to the predicate device across these metrics. No specific numerical thresholds for equivalence are explicitly stated beyond the reported results themselves.
Study Details
2. Sample Size and Data Provenance
- Test Set (Linear Regression): 560 specimens
- Data Provenance: Not explicitly stated, but clinical specimens for a medical device submitted for FDA approval typically involve multi-center studies. The origin is not specified as retrospective or prospective; however, the context of establishing substantial equivalence suggests these were likely existing or newly collected samples used for method comparison.
- Test Set (ROC Analysis):
- Apparently healthy females: 160
- Benign breast patients: 30
- Malignant breast patients: 228
- Total: 418 specimens
- Data Provenance: Not explicitly stated as retrospective or prospective.
- Test Set (Serial Tracking): 24 malignant breast patients
- Data Provenance: Not explicitly stated.
- Test Set (Blinded Study - Sensitivity/Specificity):
- Patients: 79 stage II and stage III breast cancer patients (77 evaluable)
- Total specimens: 359 specimens from 77 patients. These specimens were likely collected over time per patient for serial monitoring.
- Data Provenance: The study was a "blinded study," indicating a prospective or at least carefully controlled collection and evaluation process. Country of origin is not specified.
3. Number of Experts and Qualifications (Ground Truth)
The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the test sets. For a device measuring CA 15-3 levels as an aid in breast cancer management, the ground truth would likely be established through:
- Patient Diagnosis: Clinical diagnosis of breast cancer (stage II/III, malignant vs. benign based on biopsy/pathology).
- Patient Status: Disease progression, relapse, or remission, determined by clinical follow-up and conventional diagnostic methods.
4. Adjudication Method
The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for establishing the ground truth of the test sets. The determination of "malignant breast patients," "benign breast patients," and "apparently healthy females" would be based on established clinical diagnostic procedures, likely involving multiple specialists (oncologists, pathologists) in standard medical practice, rather than a specific adjudication protocol for a reader study.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted or described. This submission is for an immunoassay device, not an AI-powered diagnostic imaging tool that requires human interpretation. Therefore, the concept of human readers improving with or without AI assistance is not applicable here.
6. Standalone Performance Study
Yes, a standalone performance study was done. The entire submission focuses on validating the performance of the algorithm only (the AxSYM CA 15-3 assay) by comparing its quantitative measurements, dynamic range, sensitivity, specificity, and trending capabilities to a predicate device. The results reported (correlation coefficient, slope, ROC AUC, sensitivity, specificity) all represent the intrinsic performance of the assay itself, without human-in-the-loop interpretation being part of the device under review.
7. Type of Ground Truth Used
The ground truth used in these studies appears to be based on:
- Clinical Diagnosis/Pathology: For categorizing patients as "apparently healthy," "benign breast patients," or "malignant breast patients." This would typically rely on biopsy results, imaging, and clinical assessment by healthcare professionals.
- Clinical Outcomes/Monitoring: For serial tracking data and assessing sensitivity/specificity related to relapse. This implies follow-up data on patient health status.
8. Sample Size for the Training Set
The document does not provide any information regarding a training set or its sample size. This is consistent with a traditional immunoassay device submission where the method itself is being validated against a predicate, rather than an AI model that requires a distinct training phase.
9. How Ground Truth for Training Set Was Established
Since no training set is mentioned, this information is not applicable or provided in the document.
§ 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.