(25 days)
The TROP method is used on the Dimension® RxL clinical chemistry system with the heterogeneous immunoassay module to quantitatively measure cardiac troponin-1 in human serum and plasma. Measurements of TROP aid in the diagnosis of myocardial infarction and in the risk stratification of patients with acute coronary syndromes with respect to their relative risk of mortality.
The TROP method is a one-step enzyme immunoassay. Sample is incubated with chromium dioxide particles (CrOz) coated with a monoclonal antibody specific for cardiac troponin-1 and conjugate reagent [alkaline phosphatase (ALP) labeled monoclonal antibody specific for cardiac troponin-I] to form a particle/cardiac troponin-I/conjugate sandwich. Unbound conjugate and analyte are removed by magnetic separation and washing. The sandwich bound ALP initiates an amplification cascade. ALP dephosphorylates synthetic flavin adenine dinucleotide phosphate (FADP) to give FAD. FAD binds to APO D-amino acid oxidase and converts it to active holo D-amino acid oxidase. Each molecule of holo D-amino acid oxidase then produces multiple molecules of hydrogen peroxide (H2O2), which in the presence of horseradish peroxidase (HRP), converts 3,5-dichloro-2-hydroxybenzenesulfonic acid (DCHBS) and 4-aminoantipvrine (4-AAP) to a colored product that absorbs at 510nm. The color measured is directly proportional to the concentration of cardiac troponin-I present in the patient sample.
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Substantial Equivalence to Predicate Device: The primary acceptance criterion for this 510(k) submission is to demonstrate substantial equivalence to the legally marketed predicate device, the Stratus® Cardiac Troponin-I Fluorometric Enzyme Immunoassay. This is based on comparable technology, monoclonal antibodies, detection method, solid support, specimen type, sample size, intended use, and indications for use. | Achieved: The TROP method for the Dimension® RxL system is deemed "substantially equivalent in principle and performance" to the Stratus® Cardiac Troponin-I assay. |
| Correlation Coefficient: A strong positive correlation between results from the new device and the predicate device, indicating consistent measurement across a range of troponin-I concentrations. | Achieved: A correlation coefficient of 0.9918 was reported. This indicates a very strong positive linear relationship between the two assays. |
| Slope (Regression Analysis): A slope close to 1, demonstrating that the measurements from both devices change at a similar rate. | Achieved: A slope of 1.10 was reported. While not exactly 1, it is close, suggesting a generally comparable rate of change, perhaps with a slight proportional difference. |
| Intercept (Regression Analysis): An intercept close to 0, indicating minimal constant bias between the two devices. | Achieved: An intercept of -0.075 ng/mL was reported. This value is close to zero, suggesting a very small negative bias, which is acceptable for demonstrating substantial equivalence. |
| Measurement Range: The device should be able to measure cardiac troponin-I within a clinically relevant range. | Achieved: The study included samples ranging from 0.00 to 47.87 ng/mL, which covers a significant portion of the clinically relevant range for cardiac troponin-I in diagnosing myocardial infarction. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 111 clinical patient samples.
- Data Provenance: The document does not explicitly state the country of origin. It refers to "clinical patient samples," implying they were obtained from a clinical setting, likely in the US given the FDA submission. The study is retrospective in the sense that these were pre-existing patient samples used for comparison.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not describe the use of experts to establish a "ground truth" for the test set in the traditional sense of diagnostic imaging or clinical interpretation.
For this type of in vitro diagnostic (IVD) device, the "ground truth" for the comparison study is the measurement result from the predicate device (Stratus® Cardiac Troponin-I assay). The performance of the new device is being compared against the established performance of the predicate. Therefore, the "experts" in this context would be the developers and regulatory approvers of the predicate device, although their specific qualifications are not detailed in this document.
4. Adjudication Method for the Test Set
No adjudication method is described. As mentioned above, the comparison is against the predicate device's results, not an independent assessment by experts requiring adjudication.
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 in vitro diagnostic (IVD) device designed for quantitative measurement of a biomarker in serum/plasma. It is not an imaging or AI-assisted diagnostic device that involves human readers or interpretation of complex medical cases. Therefore, an MRMC study is not applicable and was not performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
This refers to the performance of the device itself (the TROP method on the Dimension® RxL system) without human interpretation affecting the measurement of troponin-I. The comparison study is a standalone performance assessment of the new IVD device against an existing one. The results of the new device are directly compared to the results of the predicate device.
7. The Type of Ground Truth Used
For this comparison study, the ground truth is the quantitative measurement of cardiac troponin-I provided by the predicate device (Stratus® Cardiac Troponin-I Fluorometric Enzyme Immunoassay). The objective was to show that the new device produces results that are highly correlated and comparable to the predicate.
8. The Sample Size for the Training Set
The provided summary does not detail a "training set" in the context of machine learning or AI models. This is a traditional IVD device comparison. The method itself was likely developed and calibrated using internal data, but that is not referred to as a "training set" in this document.
9. How the Ground Truth for the Training Set Was Established
Since there is no "training set" described in the context of the 510(k) submission for an AI/ML device, this question is not directly applicable. For the development of an IVD, the initial calibration and development of the assay would typically rely on:
- Reference standards: Materials with known concentrations of cardiac troponin-I.
- Spiked samples: Healthy samples to which known amounts of troponin-I are added.
- Clinical samples: Samples from patients with known clinical diagnoses (e.g., confirmed MI) to evaluate clinical performance and establish reference ranges.
However, the specific details of this initial development and calibration are not part of the 510(k) substantial equivalence comparison provided.
§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.
(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.