(270 days)
The CORA PlateletMapping System is intended for in vitro diagnostic use to provide qualitative assessment of platelet function. The CORA System records the kinetic changes in a sample of heparinized whole blood as the sample clots.
The CORA System PlateletMapping Assay Cartridge provides four channels of dried-in-place reagents, HKH (Kaolin with Heparinase), Activator F, AA and ADP (one reagent in each channel). In combination, MA parameter results from these four reagents are used to calculate the parameters platelet % Inhibition and % Aggregation for AA and ADP.
Results from the CORA analysis should not be the sole basis for a patient diagnosis, but should be evaluated together with the patient's medical history, the clinical picture and, if necessary, further hemostasis tests.
The CORA System with CORA PlateletMapping Assay Cartridge is indicated for use with adult patients where an evaluation of their blood hemostasis properties is desired. Hemostasis evaluation with the CORA PlateletMapping System is used to assess clinical conditions in cardiovascular surgery and cardiology procedures to assess hemorrhage or thrombosis conditions.
The CORA PlateletMappingSystem consists of a four-channel diagnostic analyzer with integrated computer module, system reagents (ActF, AA, ADP and HKH) and microfluidic test cartridge. Reagents are dried-in-place within the cartridges during manufacturing.
To perform a test, a disposable CORA PlateletMapping Assay Cartridge is inserted into the analyzer. Blood is added to an entry port on the cartridge and drawn into the cartridge under analyzer control. The amount of the sample drawn into the cartridge is automatically determined by the volume of the blood chambers in the cartridge. Once in the disposable, the sample is metered into as many as four separate analysis channels, depending upon the assay being performed. Reconstitution of reagents dried within the cartridge is accomplished by moving the sample back and forth through reagent chambers, under the control of microfluidic valves and bellows within the cartridge. After each sample has been mixed with reagent, it is delivered to a test cell where it is monitored for changes due to coagulation. Excess sample material is moved under microfluidic control into an enclosed waste chamber within the cartridge.
The CORA technology is based on a disposable containing up to four independent measurement cells. Each cell consists of a short vertically-oriented injection molded tube (ring) with a diameter of 2.5mm and a length of 4.5mm. Detection of clotting in the CORA System is performed optically. Under control of the analyzer, approximately 20uL of prepared sample is delivered to the tube, where a meniscus naturally forms at each end of the tube. The tube is positioned so that the lower meniscus partially blocks light traveling from a collimated source toward a photodiode.
During testing, a piezoelectric actuator drives the measurement cell(s) through a motion profile composed of summed sinusoids at different frequencies. The profile has a maximum amplitude of under 10um and contains frequencies from 10-500Hz. Some, but not all, of the measurement cell motion will induce motion in the sample meniscus, which will be detected by the photodiode. The resulting motion of the meniscus is monitored optically and analyzed by the analyzer to calculate the resonant frequency and modulus of elasticity (stiffness) of the sample. By performing a Fast Fourier Transform (FFT) on meniscus motion data, it is possible to determine the frequencies of input motion that caused the greatest deflection of the sample (these are called the resonant frequencies).
Resonance is the tendency of a material or structure to oscillate with greater amplitude at some frequencies than others. The exact frequencies at which resonance occurs will depend on the stiffness and mass of the sample. Stiffness, in turn, is a function of a material's modulus of elasticity and the boundary conditions to which the material is exposed, such as the geometry and materials of a test cell. By holding these boundary conditions and sample mass constant from run to run, the CORA System allows direct comparison of elasticity between samples.
In a typical test, blood that has been delivered to the measurement cell will not clot for several minutes. During this time the sample has no inherent stiffness except that provided by surface tension, and since this remains constant the measured resonant frequencies will not change. Once clotting begins, however, the elastic modulus and thus the resonant frequencies increase rapidly. In tests where clotting does not occur, the resonant frequency of the sample will not change. During coagulation, however, a clot will bind to the test tube (ring) and the resonant frequency will rise with increasing firmness of the clot. The CORA Analyzer collects meniscus motion data, tracks changing resonant frequencies and analyzes the frequency data to provide parameters describing the clot. Results are presented in a format identical to the TEG 5000.
The CORA System with PlateletMapping Assay is intended for in vitro diagnostic use to provide a qualitative assessment of platelet function. The system records kinetic changes in heparinized whole blood samples as they clot, calculating % Inhibition and % Aggregation for AA and ADP parameters.
Here's an analysis of the acceptance criteria and the study performance for the CORA System with PlateletMapping Assay:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for the clinical performance. Instead, it presents the device's sensitivity and specificity and compares them to the predicate device, the TEG 5000 Platelet Mapping Assay.
| Metric | CORA System Performance | Predicate Device (TEG 5000) Performance |
|---|---|---|
| ADP | ||
| Sensitivity | 74.5% (95% CI: 64.7-82.8%) | 94.9% (95% CI: 88.5-98.3%) |
| Specificity | 82.9% (95% CI: 77.7-87.4%) | 39.0% (95% CI: 29.7-49.1%) |
| AA | ||
| Sensitivity | 84.0% (95% CI: 77.8-89.0%) | 88.4% (95% CI: 82.8-92.7%) |
| Specificity | 86.5% (95% CI: 80.4-91.2%) | 50.0% (95% CI: 29.1-70.9%) |
For analytical precision, the reported data indicates the variability (SD and %CV) across various factors (reagent lot, operator, analyzer, day, and repeatability) for MA parameters in HKH, and indicates that the percent positive and negative agreement for AA and ADP % aggregation inhibition at low and high level is 100%. However, no specific acceptance criteria for precision are provided.
2. Sample Size Used for the Test Set and Data Provenance
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Reference Range Determination (Clinical Performance):
- Sample Size: Up to 55 normal volunteer subjects were taken at each of the three clinical sites, totaling approximately 150 samples.
- Data Provenance: Prospective, collected from normal volunteer subjects by three clinical sites representing demographic populations of the three areas regarding age, race, and gender.
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Method Comparison (Clinical Performance):
- Sample Size: Not explicitly stated, but the study was conducted on "patient samples" from "surgical patients and normal donors (for CORA)." The sensitivity and specificity percentages are derived from these samples.
- Data Provenance: The patients were undergoing heart surgery or PCI procedures, with blood samples drawn pre- and post-surgery and in the ICU. This indicates a prospective collection within a clinical setting. The study was conducted at three clinical sites.
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Analytical Precision (Non-Clinical Performance):
- Sample Size: For HKH, blood draws from 3 donors (Hypo, Normal, Hyper). For AA and ADP Percent Aggregation and Inhibition, blood draws from 2 donors (Normal, Abnormal). Each testing scenario involved 5 non-consecutive days, 2 operators, 3 reagent lots, 12 analyzers, and 2 replicates. This results in n=120 for each MA parameter level (Hypo, Hyper, Normal) for HKH.
- Data Provenance: The testing was performed in Coramed's laboratory, suggesting internally generated data.
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Interference (Non-Clinical Performance):
- Sample Size: Not explicitly stated.
- Data Provenance: Performed in Coramed's laboratory.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the use of experts to establish a "ground truth" in the traditional sense (e.g., radiologists interpreting images).
- For the Reference Ranges, the ground truth is established by selecting "normal volunteer subjects" and then deriving the range from their results. This is based on a statistical approach to define normalcy within the tested population.
- For the Method Comparison, the ground truth for determining disease status (e.g., platelet dysfunction) is implicitly established through clinical diagnosis of "surgical patients or PCI procedures" who are known to have conditions where blood hemostasis properties evaluation is desired. However, the exact method of confirming ground truth for individual results to calculate sensitivity and specificity (e.g., by another gold standard method, pathology, or expert clinical diagnosis) is not detailed. The comparison is made against the TEG 5000 as a predicate, which usually implies that the predicate serves as a reference, but a true independent ground truth for classification is not explicitly defined in the provided text.
4. Adjudication Method (for the test set)
No adjudication method involving experts is mentioned for clinical performance results. The sensitivity and specificity would be derived by comparing the CORA device's output against the "true" clinical status of the patients, or the predicate device's output, but the process of determining that "true" status is not elaborated in terms of an adjudication panel.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
This is an in vitro diagnostic device for assessing platelet function, not an imaging device typically involving human readers interpreting results. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed or described in this document.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies presented appear to be standalone performance assessments of the CORA System. The "system" is an automated analyzer that generates quantitative results (MA, % Aggregation, % Inhibition). Its performance (precision, reference ranges, sensitivity, specificity) is evaluated directly, without explicitly describing a human-in-the-loop interaction in the context of the performance data. While the "results from the CORA analysis should not be the sole basis for a patient diagnosis, but should be evaluated together with the patient's medical history, the clinical picture and, if necessary, further hemostasis tests," this statement refers to the clinical application rather than the performance study design.
7. The Type of Ground Truth Used
- Reference Ranges: The ground truth is effectively derived from the measurements of a healthy reference population (normal volunteer subjects) to establish what is considered "normal."
- Method Comparison: The ground truth for calculating sensitivity and specificity is implicitly clinical diagnosis of patients undergoing cardiovascular procedures, where blood hemostasis evaluation is desired. However, the specific gold standard or method used to classify each patient's 'true' platelet function status (e.g., by another established assay, pathology, or expert clinical assessment) against which the CORA results are benchmarked is not explicitly defined. The comparison also heavily relies on the predicate device (TEG 5000), suggesting that the predicate might serve as a de facto reference for classification if an independent gold standard was not available or used. It states "studies were conducted... on patient samples following CLSI EP09-A3 Guideline," which typically involves comparison to a reference method.
8. The Sample Size for the Training Set
The document does not explicitly describe a "training set" in the context of an AI/machine learning model. The CORA System is an automated diagnostic device based on physical measurement techniques (e.g., resonance, optical detection), not typically an AI system that requires a training set. The descriptions of "precision testing" and "reference ranges" are for analytical and clinical validation, not algorithm training.
9. How the Ground Truth for the Training Set Was Established
Since no "training set" for an AI/machine learning model is described, the question of how its ground truth was established is not applicable.
§ 864.5700 Automated platelet aggregation system.
(a)
Identification. An automated platelet aggregation system is a device used to determine changes in platelet shape and platelet aggregation following the addition of an aggregating reagent to a platelet-rich plasma.(b)
Classification. Class II (performance standards).