(50 days)
For in vitro quantitative measurement of cortisol in human serum, plasma (EDTA or heparin) or urine.
For in vitro use in monitoring the performance of the VITROS Immunodiagnostic System when used for the measurement of cortisol in human serum, plasma (EDTA or heparin) or urine.
The VITROS Immunodiagnostic Products Cortisol assay is an in vitro quantitative measurement of cortisol in human serum or plasma (EDTA or heparin) or urine. The system is comprised of three main elements: The VITROS Immunodiagnostic Products (Reagent Pass, Calibrators, and Controls), the VITROS Immunodiagnostic System instrumentation, and common reagents used by the VITROS System in each assay.
Acceptance Criteria and Study for VITROS CORTISOL assay (K983990)
This submission describes the VITROS CORTISOL assay which is intended for the in vitro quantitative measurement of cortisol in human serum or plasma (EDTA or heparin) or urine. The study presented aims to demonstrate substantial equivalence to the predicate device, the ABBOTT TDx Cortisol assay.
1. Acceptance Criteria and Reported Device Performance
The provided document details a comparison between the VITROS CORTISOL assay and the predicate device, ABBOTT TDx Cortisol assay, rather than explicit acceptance criteria with pre-defined thresholds. The primary method for demonstrating substantial equivalence was a Deming's Regression analysis and a comparison of analytical characteristics.
| Device Characteristic | Acceptance Criteria (Implied by Predicate) | Reported Device Performance (VITROS CORTISOL assay) |
|---|---|---|
| Calibration Range | Comparable to predicate (3 - 1655 nmol/L) | 3 - 1700 nmol/L (Comparable to predicate) |
| Basic Principle | Solid phase immunoassay (Same as predicate) | Solid phase immunoassay (Same as predicate) |
| Tracer | No specific numerical criterion, but expected to be effective. | Enzyme labeled (Predicate is Fluorescein labeled - a difference but deemed acceptable) |
| Instrumentation | Immunodiagnostic System (Named Abbott TDx for predicate) | VITROS Immunodiagnostic System (Specific to device) |
| Sample Type | Serum, plasma or urine (Same as predicate) | Serum, plasma (EDTA or heparin) or urine (Same as predicate, with specific anticoagulants mentioned) |
| Antibody | No specific numerical criterion, but expected to be effective. | Sheep polyclonal anti-cortisol antibody biotinylated antibody reagent (Predicate uses Mouse monoclonal and Goat polyclonal anti-cortisol antibody reagent) |
| Regression Analysis | Correlation and close agreement with predicate. | VITROS Cortisol assay = 0.83 x Abbott TDx Cortisol assay = 16.1 nmol/L |
| Analytical Performance | Demonstrated analytical sensitivity, specificity, precision, dilution, and expected values comparable to predicate. | Tests were performed to obtain analytical sensitivity, specificity, precision, dilution, and expected values. (Specific results not provided in this summary, but referenced in the package insert). |
Note on Acceptance Criteria: The document primarily focuses on demonstrating "substantial equivalence" rather than pre-defined quantitative acceptance criteria. The performance of the VITROS Cortisol assay, as described by the Deming's Regression and the qualitative comparisons, was deemed sufficiently similar to the predicate to establish equivalence.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The document states that "samples from a variety of clinical categories" were used for the regression analysis and other performance tests. However, the exact numerical sample size for the test set is not explicitly provided in the summary.
- Data Provenance: The document does not specify the country of origin for the data. The data is stated to be from "patient specimens covering a variety of clinical categories," implying retrospective clinical samples were likely used for method comparison and validation.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This specific study is an in vitro diagnostic device (IVDD) assay for measuring a biochemical analyte (cortisol). The "ground truth" for such assays is typically established by reference methods or comparison to a cleared predicate device, rather than expert human interpretation of images or clinical assessments.
Therefore, the concept of "number of experts used to establish the ground truth" and their "qualifications" as it applies to image-based diagnostics does not apply in the same way to this type of IVDD study. The accuracy of the measured cortisol level itself is the ground truth, assessed through its correlation with the predicate device and other analytical validations.
4. Adjudication Method for the Test Set
Given that this is an IVDD assay for quantitative measurement of cortisol, and the "ground truth" is established by comparison to a predicate device and analytical validation, an "adjudication method" in the context of expert review (e.g., 2+1, 3+1 for imaging studies) is not applicable. The comparison is based on quantitative analytical results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted for this device. This type of study is relevant for diagnostic devices where human readers interpret results, such as imaging or pathology, and the AI's role is to assist or replace human interpretation. The VITROS CORTISOL assay is an automated in vitro quantitative measurement system, not a device requiring human interpretation in the same manner. Therefore, the effect size of human readers improving with AI assistance is not relevant or measurable in this context.
6. Standalone Performance Study (Algorithm Only Without Human-in-the-Loop Performance)
Yes, in essence. The entire evaluation of the VITROS CORTISOL assay, as described, is a standalone performance assessment of the an algorithm/system only (the immunoassay process and instrumentation). There is no "human-in-the-loop" once the sample is loaded and the assay begins. The performance characteristics (regression, analytical sensitivity, specificity, etc.) are inherent to the device and its reagents operating independently.
7. Type of Ground Truth Used
The "ground truth" for the test set was implicitly established by:
- Comparison to a legally marketed predicate device: The ABBOTT TDx Cortisol assay's measurements served as the primary reference for demonstrating agreement (via Deming's regression).
- Analytical validation: The study also conducted tests to obtain "analytical sensitivity, specificity, precision, dilution and expected values." These analytical performance characteristics, based on established reference materials and methods, contribute to the determination of the assay's accuracy and reliability, forming a scientific basis for its performance.
8. Sample Size for the Training Set
The document does not explicitly mention a training set or its sample size. This is common for predicate-based IVDD submissions that rely on established biochemical principles and comparisons rather than machine learning algorithms requiring explicit training data. The development of such an assay involves extensive formulation, reagent optimization, and internal validation, but this is not typically referred to as a "training set" in the same way as for AI/ML algorithms.
9. How the Ground Truth for the Training Set Was Established
As no explicit "training set" is mentioned in the context of an AI/ML algorithm, the question of how its ground truth was established is not applicable. The "ground truth" for establishing the assay's performance was, as described above, based on comparison with a predicate device and rigorous analytical validation.
§ 862.1205 Cortisol (hydrocortisone and hydroxycorticosterone) test system.
(a)
Identification. A cortisol (hydrocortisone and hydroxycorticosterone) test system is a device intended to measure the cortisol hormones secreted by the adrenal gland in plasma and urine. Measurements of cortisol are used in the diagnosis and treatment of disorders of the adrenal gland.(b)
Classification. Class II.