(104 days)
The Stratus® CS Acute Care™ D-dimer assay (DDMR) is an in vitro diagnostic test for the quantitative measurement of cross-linked fibrin degradation products (D-dimer) in human citrated or heparinized plasma on the Stratus® CS analyzer. The Stratus® CS Acute Care™ DDMR assay is intended for use in conjunction with a non-high clinical pretest probability (PTP) assessment model to exclude pulmonary embolism (PE) disease and as an aid in the diagnosis of venous thromboembolism (VTE) [deep vein thrombosis (DVT) or pulmonary embolism (PE)]. This assay is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings.
The Stratus® CS Acute Care™ D-Dimer method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology. In this procedure, dendrimer linked monoclonal antibody is added to the center portion of a square piece of glass fiber paper in the DDMR TestPak. This antibody recognizes a distinct antigenic site on the D-dimer molecule. Sample is then added onto the paper where it reacts with the immobilized antibody. After a short incubation, a conjugate consisting of enzyme-labeled monoclonal antibody directed against a second distinct antigenic site on the D-dimer molecule is pipetted onto the reaction zone of the paper. During this second incubation period, enzyme-labeled antibody reacts with the bound D-dimer, forming an antibodyantigen-labeled antibody sandwich. The unbound labeled antibody is later eluted from the field of view of the Stratus® CS STAT Fluorometric Analyzer (Stratus® CS analyzer) by applying a substrate wash solution to the center of the reaction zone. By including substrate for the enzyme within the wash solution, initiation of enzyme activity occurs simultaneously with the wash. The enzymatic rate of the bound fraction increases directly with the concentration of D-dimer in the sample. The reaction rate can then be measured by an optical system that monitors the reaction rate via front surface fluorescence. All data analysis functions are performed by the microprocessor within the analyzer.
Acceptance Criteria and Device Performance for Stratus® CS Acute Care™ D-Dimer Assay
This document summarizes the acceptance criteria and performance of the Stratus® CS Acute Care™ D-Dimer assay as described in the provided 510(k) summary (K110303).
1. Table of Acceptance Criteria and Reported Device Performance
The study evaluated the performance of the Stratus® CS Acute Care™ D-Dimer assay against a clinical cutoff of 450 ng/mL [µg/L] (FEU) for the exclusion of Pulmonary Embolism (PE).
Acceptance Criteria (Implied by Predicate Device Equivalence and Clinical Relevance for PE Exclusion):
While explicit numerical acceptance criteria for sensitivity, specificity, and NPV are not directly stated as pass/fail thresholds, the study aims to demonstrate substantial equivalence to the Innovance D-Dimer assay and clinical utility for PE exclusion, implying that the performance metrics should be comparable to or ideally exceed those required for safe and effective PE exclusion. For D-dimer assays used to exclude PE, high sensitivity and negative predictive value (NPV) are critical. The reported values are generally considered acceptable for this application.
Reported Device Performance:
Citrated Plasma: In all patients
| Instrument | PE Patients (n) | Cutoff ng/mL [µg/L] FEU | Sensitivity (CL) % | Specificity (CL) % | NPV (CL) % |
|---|---|---|---|---|---|
| Stratus® CS analyzer | 655 | 450 | 98.9 (94.1 – 100.0) | 42.5 (38.3 – 46.7) | 99.6 (97.7 – 100.0) |
Citrated Plasma: In Patients with low and moderate pre-test probability
| Instrument | PE Patients (n) | Cutoff ng/mL [µg/L] FEU | Sensitivity (CL) % | Specificity (CL) % | NPV (CL) % |
|---|---|---|---|---|---|
| Stratus® CS analyzer | 625 | 450 | 98.7 (92.9 – 100.0) | 43.0 (38.8 – 47.3) | 99.6 (97.7 – 100.0) |
Heparinized Plasma: In all patients
| Instrument | PE Patients (n) | Cutoff ng/mL [µg/L] FEU | Sensitivity (CL) % | Specificity (CL) % | NPV (CL) % |
|---|---|---|---|---|---|
| Stratus® CS analyzer | 427 | 450 | 98.3 (91.1 – 100.0) | 29.7 (25.1 – 34.7) | 99.1 (95.0* – 100.0) |
| *95.04 |
Heparinized Plasma: In Patients with low and moderate pre-test probability
| Instrument | PE Patients (n) | Cutoff ng/mL [µg/L] FEU | Sensitivity (CL) % | Specificity (CL) % | NPV (CL) % |
|---|---|---|---|---|---|
| Stratus® CS analyzer | 401 | 450 | 97.9 (88.7 – 100.0) | 29.9 (25.2 – 35.0) | 99.1 (94.9 – 100.0) |
2. Sample Size Used for the Test Set and Data Provenance
- Citrated Plasma: 730 consecutive patients initially, 655 patients remaining after exclusions for final analysis.
- Heparinized Plasma: 468 consecutive patients initially, 427 patients remaining after exclusions for final analysis.
- Data Provenance: The study was a multi-center study. The document does not specify the countries of origin but states it's a "multi-center study." The data is prospective, collected from consecutive patients presenting to the emergency department with suspected PE.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The document does not explicitly state the number of experts used to establish the ground truth or their qualifications in detail. However, the ground truth for PE diagnosis appears to be established through a combination of imaging methods (e.g., spiral CT and/or VQ scan) for patients with positive D-dimer and/or high PTP, and a three-month follow-up for patients with negative D-dimer/low/moderate PTP or negative imaging results. This implies that the diagnosis of PE was made by medical professionals (e.g., radiologists, clinicians) utilizing established diagnostic protocols but does not specify individual expert roles for establishing a "ground truth" for the test set.
4. Adjudication Method for the Test Set
The document does not describe an explicit adjudication method (e.g., 2+1, 3+1) for establishing the ground truth diagnoses. The diagnostic process involved imaging (spiral CT, VQ scan) and clinical follow-up for three months. It is implied that standard clinical practices and interpretations were followed for these diagnostic procedures, rather than a specific consensus or adjudication process among multiple independent experts to establish the ground truth for each case.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not performed. This study focuses on the performance of the device (assay) itself in a standalone manner, rather than as an aid to human interpretation.
6. If a Standalone Study Was Done
Yes, a standalone study of the algorithm's performance (the D-dimer assay) was done. The reported sensitivity, specificity, and negative predictive value are directly from the assay's performance against the established clinical ground truth for PE. There is no human-in-the-loop component for these reported performance metrics.
7. The Type of Ground Truth Used
The ground truth used was a combination of:
- Imaging Data: Spiral CT and/or VQ scans were used for patients with positive D-dimer results and/or high pre-test probability (PTP).
- Outcomes Data (Clinical Follow-up): Patients with negative D-dimer results and low or moderate PTP (or negative imaging results) were followed for three months to evaluate potential development of PE. This follow-up serves as an outcome-based ground truth to confirm the absence of PE.
8. The Sample Size for the Training Set
The document does not specify a separate training set. This 510(k) submission describes a clinical validation study, implying that the D-dimer assay and its cutoff of 450 ng/mL [µg/L] (FEU) were already established, likely based on previous research or predicate device characteristics. The study described here acts as a test set for validating the performance of the assay rather than for training a new algorithm.
9. How the Ground Truth for the Training Set Was Established
As no explicit training set is described, the method for establishing ground truth for a training set is not applicable to the information provided. The study focuses on evaluating the assay's performance on a validation dataset.
§ 864.7320 Fibrinogen/fibrin degradation products assay.
(a)
Identification. A fibrinogen/fibrin degradation products assay is a device used to detect and measure fibrinogen degradation products and fibrin degradation products (protein fragments produced by the enzymatic action of plasmin on fibrinogen and fibrin) as an aid in detecting the presence and degree of intravascular coagulation and fibrinolysis (the dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels).(b)
Classification. Class II (performance standards).