(91 days)
The Access GI Monitor assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 19-9 antigen levels in human serum and plasma using the Access Immunoassay Systems. This device is indicated for use in the measurement of CA 19-9 antigen to aid in the management of pancreatic cancer patients. The test is useful as an aid in monitoring of disease status in those patients having confirmed pancreatic cancer whose serum CA 19-9 antigen levels exceed 10 U/mL, the cut-off value for individuals who are Lewis blood group antigen negative. Serial testing for patient CA 19-9 antigen concentrations should be used in conjunction with other clinical methods used for monitoring pancreatic cancer.
The Access GI Monitor reagents, calibrators, and the Access Immunoassay Analyzers (Access, Access 2, Synchron LXi 725, and UniCel Dxl 800) comprise the Access Immunoassay Systems for the quantitative determination of CA 19-9 antigen in human serum and plasma.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria / Performance Metric | Reported Device Performance |
|---|---|
| Imprecision: | |
| - Within-run CV | 1.7% CV to 6.4% CV |
| - Within-laboratory CV | 2.4% CV to 5.7% CV |
| - Total Imprecision CV | 3.0% CV to 8.9% CV |
| Analytical Sensitivity: | 0.8 U/mL |
| Dilution Recovery (Linearity): | Average recovery of 96% (ranging from 93% to 100%) |
| Methods Comparison (with predicate): | y = 0.9569x + 2.5726, r = 0.9007 |
| Sample Type Comparison (Serum vs. Plasma): | y = 0.9842x - 0.5002, r = 0.9995 |
| Analytical Specificity: | No significant interference from therapeutic drugs, similar compounds, or common sample contaminants (bilirubin, hemoglobin, triglycerides, human serum albumin, rheumatoid factor). |
| Reagent Stability (opened): | 56 days |
| Calibrator Stability (opened): | 90 days |
| Calibration Curve Stability: | 56 days |
| Clinical Sensitivity (relative to predicate): | 96.6% |
| Clinical Specificity (relative to predicate): | 94.6% |
| Agreement (with predicate): | 95.1% |
2. Sample Size Used for the Test Set and Data Provenance
- Imprecision: Not explicitly stated, but concentrations ranged from approximately 17 to 1665 U/mL. The study involved running samples to establish within-run, within-laboratory, and total imprecision.
- Dilution Recovery (Linearity): 6 human samples were diluted.
- Methods Comparison: 405 samples were used, ranging from 0.0 to 236.0 U/mL.
- Sample Type Comparison: 80 matched serum and lithium heparin plasma samples, ranging from 0.0 to 1650.9 U/mL.
- Clinical Studies (Reference Limit): The "apparently healthy subject population" was used to establish the 95th percentile (35 U/mL CA 19-9) as the upper reference limit. The size of this population is not specified.
- Clinical Studies (Pancreatic Cancer Monitoring): Patients diagnosed with pancreatic cancer were monitored. The number of patients is not specified.
- Clinical Studies (Sensitivity/Specificity): "Pancreatic cancer monitoring subjects" were used. The number of subjects is not specified.
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective for any of the studies. However, the mention of "human Dildion Nooorory (evels" (likely meant to be "human dilution recovery levels") and "human serum and plasma" samples suggests human biological samples were used.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document does not mention the use of experts to establish ground truth for the test set. Instead, the performance evaluations (imprecision, linearity, specificity, methods comparison, sample type comparison, stability) rely on laboratory measurements and comparisons to a predicate device. The clinical studies compare the device's performance to the predicate device's performance in terms of monitoring patient status and determining relative sensitivity and specificity.
4. Adjudication Method for the Test Set
No adjudication method is mentioned as the studies are primarily analytical performance assessments and comparisons to a predicate device, rather than studies requiring expert consensus on outputs.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) immunoassay, not an imaging or diagnostic device that involves human readers interpreting results.
6. If a Standalone Performance (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies described are all "standalone" in the sense that they evaluate the performance of the immunoassay system (reagents, calibrators, and analyzer) itself, without direct human interpretation of the assay results as part of the performance metrics. The results (CA 19-9 levels) are quantitative measurements produced by the automated system.
7. The Type of Ground Truth Used
- Analytical Studies:
- Imprecision, Analytical Sensitivity, Dilution Recovery, Stability, Analytical Specificity: The "ground truth" for these studies is inherent in the design of the experiments, where known concentrations of analytes, controlled dilutions, or specific interfering substances are used to assess the device's ability to accurately and reproducibly measure CA 19-9.
- Methods Comparison: The "ground truth" is the established predicate device (Fujirebio Diagnostics CA 19-9 RIA assay). The new device's measurements are compared to those of the predicate.
- Sample Type Comparison: The "ground truth" is the agreement between a person's serum and plasma samples when measured by the same device.
- Clinical Studies:
- Reference Limit: The "ground truth" is derived from the distribution of CA 19-9 levels in purportedly "healthy" individuals which establishes a statistical reference.
- Pancreatic Cancer Monitoring: The "ground truth" for assessing monitoring effectiveness appears to be the observed clinical course of pancreatic cancer patients and how the device's CA 19-9 measurements "paralleled results obtained with the predicate device."
- Sensitivity/Specificity: The "ground truth" is derived from diagnosed pancreatic cancer patients and the reference ranges (URL) for both the new device and the predicate device, implying comparison to a clinical diagnosis (presumed true positive/negative status) as well as the predicate device's established performance.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning. This device is an immunoassay, the development of which typically involves extensive R&D and optimization (which could be considered analogous to training) but is not usually described with a distinct "training set" in the same way as AI/ML algorithms. The analytical and clinical studies described are for the performance evaluation of the finalized device.
9. How the Ground Truth for the Training Set Was Established
As explained above, there isn't a "training set" in the common AI/ML sense presented in this document. The development and optimization of the immunoassay would have involved chemical and biological principles to ensure accurate binding, detection, and quantification of the CA 19-9 antigen. The ground truth for such development would involve precise measurements of known antigen concentrations, characterized antibodies, and optimized reaction conditions.
§ 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.