(204 days)
The Chrono-log Model 490 4+4 Aggregometer is intended for use for in-vitro diagnostic use for measuring Platelet Aggregation in Platelet Rich Plasma.
This device is intended to be used in a clinical laboratory environment by laboratory technicians.
For use only with light transmission aggregometry assays cleared for use with the Chrono-log Platelet Aggregometry systems.
The Chrono-log™ Model 490 4+4 Aggregometer measures platelet function on patient samples using LTA which measures a change in optical density of platelet rich plasma. The Model 490 4+4 is also used to run the Ristocetin Cofactor Assay to aid in diagnosis of patients with von Willebrand disease. The instrument comes with a starter kit of reagents and supplies. The output of the Model 490 4+4 can be connected to either a strip chart recorder or to a Computer. Software is provided with the computer interface option. The computer interface option is used to collect data only. The computer is not used for diagnosis or treatment and does not have any control over or input into the Model 490 4+4 Aggregometer.
LTA or Born method of platelet aggregation measures the change in optical density of a Platelet Rich Plasma (PRP) sample in comparison to optical density of a Platelet Poor Plasma (PPP) sample. The PRP sample, platelets in a suspension of plasma, is isolated from an anticoagulated blood sample by a relatively low centrifugation. The PPP sample is prepared by centrifuging the blood sample at a relatively high force. The Chrono-log sample chambers are designed so that a beam of infra red light shines through two cuvettes. one containing PRP (the sample) and one containing PPP (the reference). Silicon photodiodes detect the light able to pass through the samples: PRP is arbitrarily considered to be 0% light transmission or 0% aggregation: PPP is considered to be 100% light transmission or 100% aggregation. When a stimulus is added to the cuvette containing PRP and the platelets respond forming aggregates, more light is allowed to pass through the PRP sample. The change in light transmission, recorded over time, shows a trend towards the platelet poor plasma, or 100% light transmission. A graphical tracing of the change in optical density during the course of platelet aggregation is produced either on a strip chart recorder or on a computer using Chrono-log provided software. This device is designed to be used in the clinical laboratory as an in vitro diagnostic tool. The 490 4+4 varies from the predicate devices only in the number of channels.
The document describes the acceptance criteria and the study proving the device, Chrono-log™ Platelet Aggregometer, Model 490 4+4, meets these criteria, primarily through demonstrating substantial equivalence to a predicate device (Chrono-log™ Whole Blood Lumi-Aggregometer Model 700).
Here's the breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by demonstrating "strong correlation" and "good agreement" with the predicate device, as well as maintaining performance specifications (though specific numerical targets for metrics like R-squared or bias are not explicitly stated as pre-defined acceptance criteria, they function as such in the reported performance metrics). The device's performance is gauged by the Coefficient of Variation (which seems to be used interchangeably with R-squared in this context, given the R2 mentions in the conclusion) between the new device and the predicate.
| Acceptance Criteria (Implied) | Reported Device Performance (Coefficient of Variation / R$^2$) |
|---|---|
| Strong correlation/equivalence to predicate for all samples | 0.9771 (for all 114 comparison tests) |
| Strong correlation for normal samples (500 µL) | 0.9648 |
| Strong correlation for aspirin samples (500 µL) | 0.9943 |
| Strong correlation for normal samples (250 µL) | 0.9758 |
| Strong correlation for aspirin samples (250 µL) | 0.9871 |
| Strong correlation for Arachidonic Acid reagent | 0.9945 |
| Strong correlation for Epinephrine reagent | 0.9509 |
| Strong correlation for Collagen reagent | 0.9786 |
| Strong correlation for ADP reagent | 0.9421 |
| Strong correlation for Ristocetin reagent | 0.9863 |
| Clinically insignificant bias (Bland Altman Plot) | Bias of -4.56, 2SD cut-off not beyond historical levels |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Optical Aggregation: 114 comparison tests in total.
- Volume Comparison: A "small subset" of tests was used to compare 500uL and 250uL samples (8 normal samples in 500 µL, 8 aspirin samples in 500 µL, 8 normal samples in 250 µL, 8 aspirin samples in 250 µL).
- Data Provenance:
- The study involved "patient samples" from "four normal, healthy, drug-free subjects" and "a subject taking aspirin." Additionally, samples treated with ticagrelor and GPIIb/IIIa antagonist, and deficient vW plasma with lyophilized platelets were used to demonstrate abnormal results.
- The document does not explicitly state the country of origin for the data/samples but implies it was conducted by the manufacturer, Chrono-log Corp., based in Havertown, PA, USA.
- Retrospective or Prospective: The testing appears to be prospective or specially collected for this comparison study, as it describes the collection and testing of specific subject samples (normal, aspirin, treated with inhibitors) on both the new and predicate devices.
3. Number of Experts Used to Establish Ground Truth and Qualifications
The document does not describe the use of experts to establish a "ground truth" for the performance study. The study focuses on demonstrating equivalence to a predicate device using measured values of platelet aggregation, not on expert interpretation of results. The "ground truth" for the device's function is the direct measurement of optical density changes in plasma samples, interpreted as percentage aggregation.
4. Adjudication Method for the Test Set
Not applicable. The study compares objective quantitative measurements from two devices, not subjective interpretations requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This device is a measurement instrument (platelet aggregometer) and its performance is evaluated based on quantitative agreement with a predicate device, not on human reader performance or improvement with AI assistance.
6. Standalone (Algorithm Only) Performance
Yes, the study primarily demonstrates standalone performance of the device (Chrono-log Model 490 4+4) by comparing its measurements directly to those of the predicate device (Chrono-log Model 700). There is no AI algorithm involved; it's a direct hardware and measurement comparison. The software provided with the computer interface option is explicitly stated to "collect data only" and "is not used for diagnosis or treatment and does not have any control over or input into the Model 490 4+4 Aggregometer."
7. Type of Ground Truth Used
The "ground truth" is established by the measurements from the predicate device (Chrono-log Model 700). The study aims to show that the new device's measurements are substantially equivalent to those of the already legally marketed and established predicate device. It relies on the predicate device's accepted performance as the de facto standard for comparison.
8. Sample Size for the Training Set
Not applicable. This device is a medical measurement instrument, not an AI/ML model that requires a "training set" in the conventional sense. The "training" for the device would be its engineering design, calibration, and manufacturing processes.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for an AI/ML model. The predicate device's established performance serves as the reference point for the new device's engineering design and verification.
§ 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).