(236 days)
The HE4 EIA is an enzyme immunometric assay for the quantitative determination of HE4 in human serum. The assay is to be used as an aid in monitoring 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 methods used for monitoring ovarian cancer.
The HE4 EIA is a solid-phase, non-competitive immunoassay based upon the direct sandwich technique based on two mouse monoclonal antibodies, 2H5 and 3D8, directed against two epitopes in the C-WFDC domain of HE4. Calibrators, controls and patient samples are incubated together with biotinylated Anti-HE4 monoclonal antibody (MAb) 2H5 in streptavidin coated microstrips. HE4 present in calibrators or samples is adsorbed to the streptavidin coated microstrips by the biotinylated Anti-HE4 MAb during the incubation. The strips are then washed and incubated with HRP labeled Anti-HE4 MAb 3D8. After washing, buffered Substrate/Chromogen reagent (hydrogen peroxide and 3, 3', 5' tetra-methyl-benzidine) is added to each well and the enzyme reaction is allowed to proceed. During the enzyme reaction a blue color will develop if antigen is present. The intensity of the color is proportionate to the amount of HE4 present in the samples. The color intensity is determined in a microplate spectrophotometer at 620 nm (or optionally at 405 nm after addition of Stop Solution). Calibration curves are constructed for each assay by plotting absorbance value versus the concentration for each calibrator. The HE4 concentrations of patient samples are then read from the calibration curve.
The provided text describes the HE4 EIA Kit, its intended use, and performance characteristics for monitoring epithelial ovarian cancer. Here's a breakdown of the information requested:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" for clinical performance. Instead, it presents the results of a study and lists sensitivity and specificity at various percent changes in HE4 concentration. The study aimed to demonstrate the device's effectiveness as an aid in monitoring recurrence or progressive disease. For the purpose of this table, I will present the reported performance at a 25% change in HE4 concentration, as this was the change used in the main 2x2 table and discussed in the text. Other performance characteristics are listed as "The HE4 EIA Kit precision is ≤ 15% total CV," etc. which can be considered performance goals or criteria.
| Performance Characteristic/Acceptance Criteria | Reported Device Performance |
|---|---|
| Precision (Total CV) | ≤ 15% |
| Linearity (Mean Recovery) | Within 15% of expected |
| Functional Sensitivity (CV 20%) | 25% change)** |
| Sensitivity (Concordance to Progression) | 60% (76/126) |
| Specificity (Concordance to No Progression) | 75% (171/228) |
| Total Concordance | 70% (247/354) |
2. Sample Size Used for the Test Set and the Data Provenance
- Sample Size for Test Set: 80 patients, contributing to a total of 354 pairs of observations (mean of 4.4 observations per patient).
- Data Provenance: Not explicitly stated (e.g., country of origin). The study appears to be retrospective based on "serial serum samples" from patients, but this is not explicitly confirmed as prospective or retrospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
The document does not specify the number of experts used or their qualifications for establishing the ground truth ("change in disease status"). It simply refers to "disease status."
4. Adjudication Method for the Test Set
The document does not specify an adjudication method (e.g. 2+1, 3+1, none) for determining the ground truth for the test set.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
This is an immunoassay device, not an imaging or diagnostic device involving human "readers" or AI assistance in the way an MRMC study would typically evaluate. Therefore, no MRMC comparative effectiveness study involving human readers with or without AI assistance was performed or is applicable here. The study compares the device's output to "disease status."
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance characteristics and monitoring study described are for the device (HE4 EIA Kit) in a standalone capacity, i.e., without a human-in-the-loop performance evaluation in the context of its primary monitoring function. The "Intended Use" states it should be used "in conjunction with other clinical methods," implying it is an aid to a physician's overall assessment, but the performance data presented is for the assay itself.
7. The Type of Ground Truth Used
The ground truth used was "changes in disease status" for ovarian cancer patients. The method for determining "disease status" is not explicitly defined (e.g., pathology, clinical follow-up, imaging results, outcomes data), but it is implied to be a clinical assessment.
8. The Sample Size for the Training Set
The document does not specify a separate "training set" or sample size for training. This is an immunoassay kit, where "training" typically refers to the development and optimization of the assay itself (e.g., antibody selection, reagent concentrations), which is not detailed in terms of patient sample sizes. The performance studies described appear to be validation or verification studies.
9. How the Ground Truth for the Training Set Was Established
As no explicit "training set" with associated ground truth is mentioned in the context of machine learning or algorithm development, this information is not applicable or provided. The ground truth for the performance studies (test set) was based on "changes in disease status," as described in point 7.
§ 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.