(115 days)
MDA® D-Dimer is a homogeneous latex particle based immunoassay (LIA) for the quantitative determination of cross-linked fibrin degradation products containing the D-dimer domain in citrated human plasma. The assay is designed for use on the MDA® 180 automated coagulation analyzer.
D-dimer is elevated in disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT), and pulmonary omboliom and pulmonary embolism.
Organon Teknika's MDA®D-Dimer is a homogeneous latex particle based immunoassay (LIA) for the quantitative determination in human plasma of cross-linked fibrin degradation products containing the D-Dimer domain in human plasma.
D-Dimer containing fibrin degradation products (FbDP) fragments are released when cross-linked fibrin is degraded by plasmin. Cross-linked fibrin is formed when fibrinogen is cleaved by thrombin to form fibrin monomers, which then spontaneously polymerize and are cross-linked by Factor XIIIa. Thrombin is required to cleave fibrinogen as well as to activate Factor XIII. Plasmin-formation is triggered when a fibrin clot is formed. Plasmin degrades some of the cross-linked fibrin and the resulting level of D-Dimer is, therefore, an indirect measure of thrombin generation and subsequent clot formation.
D-Dimer is elevated in disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT), pulmonary embolism. Also, D-Dimer has been reported in the literature to be elevated in other thrombotic conditions.
MDA®D-Dimer is a quantitative homogeneous-phase immunoassay using latex microparticles to photooptically detect binding of specific monoclonal antibody to D-Dimer. These latex particles aggregate only in the presence of fibrin derivatives containing the D-Dimer domain. The rate of latex microparticle aggregation is proportional to the concentration of D-Dimer in the sample. D-Dimer concentration may be interpolated from a reference curve.
Here's a summary of the acceptance criteria and study details for the MDA® D-Dimer device, based on the provided 510(k) submission:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct numerical targets in this document. Instead, the study aims to demonstrate "substantial equivalence" to predicate devices, focusing on accuracy (correlation) and precision.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (MDA® D-Dimer) |
|---|---|---|
| Accuracy | Demonstrates strong correlation with predicate device (Fibrinostika® FbDP EIA) | Slope: 1.005, Intercept: 0.293, Correlation: 0.91 (compared to Fibrinostika® FbDP EIA) |
| Precision | Low within-run and total variability for positive and normal controls | |
| Positive Control (1.51 µg FEU/ml) | SD (within-run): 0.06 µg FEU/ml, CV (within-run): 3.83%, SD (total): 0.10 µg FEU/ml, CV (total): 6.67% | |
| Normal Control (0.28 µg FEU/ml) | SD (within-run): 0.02 µg FEU/ml, CV (within-run): 6.97%, SD (total): 0.04 µg FEU/ml, CV (total): 12.65% | |
| Specificity | Aggregates in the presence of cross-linked fibrin degradation products D-dimer and D-dimer E | Achieved (stated that "MDA D-Dimer Latex Reagent aggregates in the presence of cross-linked fibrin degradation products D-dimer and D-dimer E.") |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: For accuracy testing, 175 samples were used ("Reference Method Fibrinostika® FbDP EIA, n=175").
- Data Provenance: Not explicitly stated. The document does not specify the country of origin of the data or whether it was retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- This device is an in-vitro diagnostic (IVD) assay. The "ground truth" for the test set is established by comparison to a legally marketed predicate device (Fibrinostika® FbDP EIA). Therefore, no human experts were used to establish ground truth in the way one would for image-based diagnostic AI. The predicate device's results served as the reference.
4. Adjudication Method for the Test Set
- Not applicable as the ground truth was established by another device (predicate device), not through human expert consensus requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size
- No, an MRMC comparative effectiveness study was not done. This is an IVD device, not a diagnostic imaging AI requiring human reader performance evaluation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, a standalone performance evaluation was done. The MDA® D-Dimer device's performance (accuracy, precision, specificity) was evaluated directly against a predicate device and its own internal controls. The results presented are for the device operating independently.
7. The Type of Ground Truth Used
- The ground truth for the accuracy study was established by comparison to a legally marketed predicate device, specifically the Fibrinostika® FbDP EIA. For precision, internal controls with established values were used.
8. The Sample Size for the Training Set
- This document describes the validation of a laboratory assay, not a machine learning algorithm that typically has a distinct training set. Therefore, the concept of a "training set" in the context of AI is not applicable here. The device is an immunoassay, the "training" would be the initial assay development and calibration performed by the manufacturer. No specific "training set" size for an algorithm is provided or relevant.
9. How the Ground Truth for the Training Set Was Established
- Again, since this is a laboratory immunoassay validation and not an AI algorithm, the concept of establishing ground truth for a "training set" is not applicable in the same way. The assay is developed and manufactured to detect specific analytes (D-dimer) with established chemical and biological principles. The "ground truth" during development would rely on known D-dimer concentrations and biological samples to ensure the assay performs as expected.
§ 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).