(368 days)
The Elecsys HE4 assay is an immunoassay for the quantitative determination of HE4 in human serum and plasma. The assay is used as an aid in monitoring the recurrence or progressive disease in patients with epithelial ovarian cancer. Serial testing for patient HE4 assay values should be used in conjunction with other clinical findings used for monitoring ovarian cancer.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.
The Elecsys HE4 assay is a sandwich immunoassay which includes a biotinylated monoclonal, murine HE4-specific IgG antibody as capture and a ruthenium labeled monoclonal, murine HE4-specific IgG antibody as signal.
Here's a breakdown of the acceptance criteria and study information for the Elecsys HE4 Assay, based on the provided text.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Elecsys HE4 Assay are primarily demonstrated through comparison with a predicate device (Abbott Architect HE4) and through its own labeled performance characteristics. The key performance metrics are listed below:
| Feature | Acceptance Criteria (Implied / Predicate Device Performance) | Reported Elecsys HE4 Assay Performance |
|---|---|---|
| Measuring Range | 20-1,500 pmol/L (Predicate) | 15-1,5000 pmol/L |
| Precision (Within-run) | 3.0% CV @ 49.0 pmol/L (Predicate) | 1.8% CV @ 25.3 pmol/L |
| 2.2% CV @ 174.4 pmol/L (Predicate) | 1.4% CV @ 45.7 pmol/L | |
| 2.4% CV @ 687.3 pmol/L (Predicate) | 1.8% CV @ 53.7 pmol/L | |
| 3.1% CV @ 38.4 pmol/L (Predicate) | 1.6% CV @ 142.0 pmol/L | |
| 2.9% CV @ 189.7 pmol/L (Predicate) | 1.6% CV @ 345.0 pmol/L | |
| 2.9% CV @ 1114.7 pmol/L (Predicate) | 1.5% CV @ 779.0 pmol/L | |
| (Not reported for predicate for 1437.0 pmol/L) | 1.3% CV @ 1437.0 pmol/L | |
| Precision (Total) | 3.3% CV @ 49.0 pmol/L (Predicate) | 3.7% CV @ 25.3 pmol/L |
| 3.1% CV @ 174.4 pmol/L (Predicate) | 4.2% CV @ 45.7 pmol/L | |
| 3.3% CV @ 687.3 pmol/L (Predicate) | 4.2% CV @ 53.7 pmol/L | |
| 3.8% CV @ 38.4 pmol/L (Predicate) | 4.3% CV @ 142.0 pmol/L | |
| 3.1% CV @ 189.7 pmol/L (Predicate) | 3.4% CV @ 345.0 pmol/L | |
| 3.3% CV @ 1114.7 pmol/L (Predicate) | 2.7% CV @ 779.0 pmol/L | |
| (Not reported for predicate for 1437.0 pmol/L) | 4.2% CV @ 1437.0 pmol/L | |
| Analytical Sensitivity | Limit of Detection: ≤ 15 pmol/L (Predicate) | Limit of Blank (LoB) 5.0 pmol/L; Limit of Detection (LoD) 15.0 pmol/L; Limit of Quantitation (LoQ) 20.0 pmol/L with a total allowable error of 30% |
| Analytical Specificity | No cross reactivity with CA 125, CA 15-3, CA 19-9, CEA, AFP (Predicate) | Proteins (WFDC family) Reactivity: Elafin/SKALP at 54,500 pmol/L 0.025%; SLPI at 20,833 pmol/L 0.088 |
| Hook Effect | No high-dose hook effect up to 83,000 pmol/L (Predicate) | No high-dose hook effect at HE4 concentrations up to 40,000 pmol/L |
| Interfering Substances | Unaffected by various levels of Hemoglobin, Bilirubin, Triglycerides, HAMA, RF, etc. (Predicate) | Unaffected by various levels of Hemoglobin, Bilirubin, Triglycerides, Biotin, Rheumatoid Factor, HAMA, IgG. (Specific concentrations listed) |
| Clinical Performance (Sensitivity at 14% change) | 54% (Predicate) | 50.62% (41/81) |
| Clinical Performance (Specificity at 14% change) | 79% (Predicate) | 77.41% (257/332) |
2. Sample Size Used for the Test Set and Data Provenance
- Clinical Study for Sensitivity and Specificity:
- Test Set Size: 81 sequential pairs from patients with disease progression (for sensitivity) and 332 sequential pairs from patients without disease progression (for specificity).
- Data Provenance: The document does not explicitly state the country of origin. It notes "clinically characterized samples" and "subjects with ovarian cancer" but does not specify if the data is retrospective or prospective. Given the nature of monitoring recurrence, it is highly likely to be prospective data collected over time.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not provide information on the number or qualifications of experts used to establish the ground truth for the clinical test set (i.e., whether patients had disease progression or not). The ground truth appears to be based on "clinically characterized samples" which would likely involve standard clinical assessments, possibly including imaging, biopsy results, and physician evaluations, but details are not given.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for establishing the ground truth of disease progression or non-progression for the clinical test set. The term "clinically characterized samples" suggests that the disease status was determined through routine clinical diagnosis and monitoring processes.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not conducted. This device is an in-vitro diagnostic (IVD) assay that directly measures a biomarker, not an imaging or interpretive AI device where human reader improvement would be relevant.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented represent standalone performance of the Elecsys HE4 Assay (an algorithm/assay only) without human-in-the-loop performance. The device provides a quantitative measurement of HE4.
7. The Type of Ground Truth Used
The ground truth used for the clinical sensitivity and specificity evaluation appears to be clinical outcome data (disease progression vs. no disease progression) derived from "clinically characterized samples."
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning, as this is an immunoassay and not an AI/ML-based device that would typically have a separate training phase with a distinct training set. The data presented for performance characteristics (precision, linearity, sensitivity, specificity) are related to the assay's analytical and clinical validation.
9. How the Ground Truth for the Training Set was Established
As this is an immunoassay, the concept of a "training set" as understood in AI/ML is not directly applicable. The assay's development and optimization would rely on established biochemical and analytical methods, with calibration against known standards. The "standardization" of the Elecsys HE4 Assay against the HE4 EIA method from Fujirebio Diagnostics, Inc., serves a similar purpose to establishing a foundational "ground truth" for the assay's measurements.
§ 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.