(145 days)
The Ultegra Rapid Platelet Function Assay (RPFA) is a semi-quantitative, whole blood platelet function assay used to measure glycoprotein (GP) IIb/IIIa receptor blockade in patients treated with abciximab. Ultegra RPFA results should be interpreted in conjunction with other clinical and laboratory data available to the clinician.
The Ultegra System is a turbidimetric based optical detection system which measures platelet induced aggregation as an increase in light transmittance. The system consists of a stand-alone analyzer and disposable test cartridge with reagents based on microbead agglutination technology. The quality control system includes an electronic control and two levels of liquid control. The analyzer controls assay sequencing, establishes the assay temperature, controls the reagent-sample mixing for the required duration, determines the degree of platelet function, displays the results and status information to the user, and performs self-diagnostics. The test cartridge contains a lyophilized preparation of human fibrinogen coated beads, thrombin receptor activating peptide (iso-TRAP), buffer, and preservative. The patient sample is citrated whole blood, which is automatically dispensed from the blood collection tube into the test cartridge by the analyzer, with no blood handling required by the user.
The Ultegra RPFA is based upon the ability of activated platelets to bind fibrinogen. Fibrinogen coated microparticles agglutinate in whole blood in proportion to the number of unblocked platelet GP Ilb/IIIa receptors. The rate of microbead agglutination is more rapid and reproducible if platelets are activated. Therefore the reagent iso-TRAP is incorporated into the assay to induce platelet activation without fibrin formation. As activated platelets bind and agglutinate fibrinogen coated beads, there is an increase in light transmittance. The analyzer is designed to measure this change in optical signal due to agglutination.
Here's an analysis of the provided text, focusing on the acceptance criteria and the study used to demonstrate the device meets those criteria:
1. Table of Acceptance Criteria and Reported Device Performance
The text does not explicitly state pre-defined acceptance criteria in terms of specific thresholds for slope, intercept, or correlation. Instead, it presents a comparative study against a predicate device and relies on the statistical measures derived from that comparison to demonstrate substantial equivalence. Therefore, the "acceptance criteria" are implied by the results of the comparison to the predicate.
| Performance Metric | Implied Acceptance Criteria (via Predicate Comparison) | Reported Device Performance (Ultegra RPFA vs. CHRONO-LOG) |
|---|---|---|
| Correlation (r) | High correlation with predicate (CHRONO-LOG) | 0.89 |
| Slope (Regression) | Slope demonstrating a relationship to predicate | 2.91 |
| Intercept (Regression) | Intercept demonstrating a relationship to predicate | -48.58 |
| Qualitative Overlap | Visual overlap in time course of platelet inhibition with predicate and RBA (Reference Method) | Figure 1 (Visually demonstrates overlap of RPFA, AGG, and RBA over time) |
2. Sample Sizes and Data Provenance
- Test Set Sample Size:
- Patients: 120 patients
- Samples: Patients had samples taken at three time points (Baseline, During infusion, Post infusion), implying 360 total samples (120 patients * 3 time points), though this is not explicitly stated as 360 unique measurements for correlation.
- Data Provenance:
- Country of Origin: Not explicitly stated, but the submission is to the US FDA, and the company is based in San Diego, California, suggesting a US-centric study.
- Retrospective or Prospective: Prospective. The study was "designed to study GP IIb/IIIa receptor blockade in patients undergoing percutaneous coronary intervention and receiving abciximab." Samples were "obtained at four clinical sites" at specific, defined time points.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The concept of "experts establishing ground truth" as typically seen in image or data interpretation studies is not directly applicable here. The ground truth for the device's performance is established by comparison to:
- Predicate Device: CHRONO-LOG Platelet Aggregometry. This is considered the established method.
- Reference Method: Receptor Binding Assay (RBA). This is presented as another objective measure of GP IIb/IIIa receptor blockade.
Therefore, no human experts were involved in subjectively interpreting images or data to create a "ground truth" for the test set. The ground truth is derived from established laboratory methods.
4. Adjudication Method
Not applicable. As described above, the ground truth is established by objective laboratory measurements from a predicate device and a reference method, not through expert review that would require adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not performed. This type of study primarily applies to scenarios where human readers interpret data (e.g., medical images) and AI provides assistance. The Ultegra RPFA is an automated analytical device, not a human-in-the-loop diagnostic aid.
6. Standalone Performance Study
Yes, a standalone performance study was done for the Ultegra RPFA in comparison to a predicate device and a reference method. The "Performance Characteristics" section details this study, comparing the Ultegra RPFA's results directly against:
- CHRONO-LOG Platelet Aggregometry (predicate)
- Receptor Binding Assay (RBA) (a different, objective measure of the same physiological effect)
The reported correlation (r=0.89) and the visual overlap in Figure 1 demonstrate the Ultegra RPFA's standalone performance in relation to these established methods.
7. Type of Ground Truth Used
The ground truth used was based on results from a predicate device (CHRONO-LOG Platelet Aggregometry) and an objective reference method (Receptor Binding Assay - RBA). These are considered direct laboratory measurements of platelet function and receptor blockade.
8. Sample Size for the Training Set
The document does not explicitly mention a separate "training set" or its size. This likely indicates that the device's algorithms were developed and optimized internally by Accumetrics, and the described clinical study served as a validation/test set to demonstrate performance rather than a training set for machine learning models. Clinical trials of this nature in medical device submissions often focus on validation against established methods.
9. How the Ground Truth for the Training Set Was Established
Since no separate "training set" with ground truth establishment is described, this question is not applicable based on the provided text. The development of the device likely involved internal verification and validation against known standards and laboratory results, but these details are not part of this 510(k) summary.
§ 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).