(307 days)
VIDAS® D-Dimer Exclusion II™ is an automated quantitative test for use on the instruments of the VIDAS family for the immunoenzymatic determination of fibrin degradation products (FbDP) in human plasma (sodium citrate, CTAD) using the ELFA technique (Enzyme Linked Fluorescent Assay). VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical pretest probability assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE.
The VIDAS® D-Dimer Exclusion II assay is an automated quantitative test for use on the instruments of the VIDAS family for the determination of fibrin degradation products (FbDP) in human plasma (sodium citrate) using the ELFA (Enzyme-Linked Fluorescent Assay) technique. VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical pretest probability assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE.
The assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR), a pipette tip-like device, serves as the solid phase as well as the pipetting device for the assay. The assay reagents are ready-to-use and pre-dispensed in the sealed reagent strips (STRs). The individual kit components are described in detail on the following pages.
All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times.
First, the sample is taken by the SPR, diluted and then cycled in and out of the SPR several times. The antigen binds to the anti-FbDP immunodobulins coated on the SPR. Unbound components are eliminated during a washing step. In the second step, the conjugate that contains an alkaline phosphatase labeled anti-FbDP monoclonal antibody is cvcled in and out of the SPR to form a sandwich. Unbound components are eliminated during the washing steps.
A detection step is then performed. The substrate (4-Methyl-umbellifery) phosphate) is cycled in and out of the SPR. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone), the fluorescence of which is measured at 450 nm. The intensity of fluorescence is proportional to the concentration of antigen present in the sample. At the end of the assay, results are automatically calculated by the instrument in relation to the calibration curve stored in memory. The results are then printed.
Acceptance Criteria and Study for VIDAS® D-Dimer Exclusion II Assay
This analysis focuses on the information provided in the 510(k) Summary for the VIDAS® D-Dimer Exclusion II Assay (K112818).
1. Table of Acceptance Criteria and Reported Device Performance
The provided document primarily focuses on demonstrating substantial equivalence to a predicate device rather than explicitly stating acceptance criteria for new device performance. However, by comparing the VIDAS® D-Dimer Exclusion II (DEX2) with its predicate (VIDAS® D-Dimer Exclusion), we can infer the performance metrics that were deemed acceptable for the new device. The "reported device performance" are the values presented for the VIDAS® D-Dimer Exclusion II Assay.
| Metric | Acceptance Criteria (Inferred from Predicate) | Reported Device Performance (VIDAS® D-Dimer Exclusion II) |
|---|---|---|
| Intended Use | Exclusion of DVT & PE in outpatients with pretest probability model | Exclusion of DVT & PE in outpatients with pretest probability model |
| Assay Technique | ELFA | ELFA |
| Automated | Yes | Yes |
| Assay Duration | Similar to or improved from 35 min, 35 sec | 19 minutes, 57 seconds (Improved) |
| SPR Coating | Anti-FbDP monoclonal mouse antibodies | Anti-FbDP monoclonal mouse antibodies (No preservative) |
| Calibration Frequency | Improved from 14 days | 28 days (Improved) |
| Sample Type | Citrated plasma | Citrated or CTAD plasma (Expanded) |
| Assay Range | 45-10,000 ng/mL | 45-10,000 ng/mL |
| Clinical Cut-Off | 500 ng/mL | 500 ng/mL |
| Linearity | 45-5,000 ng/mL | 45-10,000 ng/mL (Improved) |
| Detection Limit | ≤ 45 ng/mL | ≤ 45 ng/mL |
| Hook Effect | 400,000 ng/mL | 400,000 ng/mL |
| Specificity (Fibrinogen) | No cross-reactivity | = X), then Y would be considered acceptable. The "Normal Values" for DEX2 (90% less than 500 ng/mL) is slightly lower than the predicate (96%), but in the context of a qualitative D-Dimer Exclusion assay where values below the cut-off are considered negative, this might still be deemed acceptable if the overall clinical sensitivity and specificity for DVT/PE exclusion remain robust. |
2. Sample Size Used for the Test Set and Data Provenance
The document states "A summary of the non-clinical results is presented in the table below," referring to the detailed comparison table. This table includes analytical performance data.
- Sample Size for Test Set: The specific sample sizes for each analytical performance test (e.g., linearity, precision, interference, specificity) are not provided in this summary. The table indicates values for these tests (e.g., CV at specific ng/mL levels), implying that tests were conducted, but the number of samples or replicates used for each test is not detailed.
- Data Provenance: Not explicitly stated. Given that bioMérieux, Inc. is the submitter (located in Hazelwood, MO, USA), the studies were likely conducted in the USA or through their global facilities. The summary does not specify whether the data is retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This is a an in vitro diagnostic device measuring D-Dimer levels. For such devices, "ground truth" for analytical performance studies is typically established by:
- Reference Methods: Comparing the new assay's results against established reference methods or highly accurate laboratory techniques.
- Reference Materials: Using certified reference materials or plasma samples with known D-Dimer concentrations.
- Clinical Diagnosis: For clinical performance, the ground truth for DVT/PE would be established by definitive diagnostic imaging (e.g., ultrasonography, CTPA) and/or medical record review, not by "experts" in the sense of adjudicating images.
The summary does not mention any "experts" being used to establish ground truth for the analytical test set in the way one would for diagnostic imaging. Instead, the performance is compared to the predicate device and established analytical methodologies.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are primarily used in studies involving subjective interpretation, often in imaging or clinical assessments where multiple readers provide opinions, and inconsistencies need resolution.
Since the VIDAS® D-Dimer Exclusion II Assay is an automated quantitative immunoassay, the results are numerical and objective. Therefore, an adjudication method in the sense of resolving conflicting interpretations is not applicable to the analytical performance tests described in this summary. The "results are automatically calculated by the instrument," which minimizes the need for human adjudication of raw data.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. An MRMC comparative effectiveness study is not mentioned. Such studies are typically conducted for diagnostic imaging devices where human readers interpret medical images, and the AI's impact on their performance is assessed. The VIDAS® D-Dimer Exclusion II Assay is an in vitro diagnostic device, and its performance is assessed analytically and clinically, not through human-in-the-loop image interpretation.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, in essence. The VIDAS® D-Dimer Exclusion II is an automated assay. Its "performance" as described (assay range, linearity, precision, specificity, etc.) is the standalone performance of the instrument and reagents. The results are automatically calculated by the instrument.
However, it's crucial to note that the device's intended use is "in conjunction with a clinical pretest probability assessment model." This means that while the assay itself is standalone, its clinical utility for DVT/PE exclusion requires human interpretation of the assay result combined with a clinical pretest probability assessment. The output of the device (D-Dimer concentration) is an algorithmic result, but its application in patient management involves a human clinician.
7. The Type of Ground Truth Used
For the analytical performance characteristics summarized, the ground truth would be established by:
- Reference Standards/Materials: For linearity, detection limit, hook effect, and precision, samples with known, precisely measured concentrations of D-Dimer or related substances are used.
- Interference Substances: Known concentrations of interfering substances (e.g., hemoglobin, bilirubin, rheumatoid factor, drugs) are added to samples to determine their impact.
- Reference Assays: For method comparison (implicitly to the predicate, and typically to other established D-Dimer assays), results are compared against those from a recognized reference method.
For the stated Intended Use (exclusion of DVT/PE in outpatients), the ultimate ground truth in clinical studies (which are not detailed in this analytical performance summary but are foundational for such devices) would be definitive clinical diagnosis of DVT or PE, typically established by objective imaging studies (e.g., compression ultrasonography for DVT, CT Pulmonary Angiography for PE) and clinical follow-up. This summary focuses on the analytical performance, not the full clinical validation study details.
8. The Sample Size for the Training Set
This document is a 510(k) summary for an immunoassay, not a machine learning or AI-based device that would typically have a separate "training set" for an algorithm. The "training set" concept is not applicable here in the conventional AI/ML sense.
For an immunoassay, the "training" equivalent would be the extensive R&D and validation work done to optimize reagent concentrations, incubation times, antibody selection, and assay parameters. This process would involve many experiments with various sample types and concentrations, but it's not described as a discrete "training set" like in AI.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" in the AI/ML context with an established ground truth is not applicable to this immunoassay. The development and optimization of the assay would rely on:
- Biochemical Principles: Understanding antigen-antibody reactions, enzyme kinetics, and fluorescent detection.
- Calibrators and Controls: Precisely manufactured substances with known concentrations, used to establish the calibration curve and monitor assay performance.
- Validation Studies: Iterative experiments using a wide range of patient samples (with D-dimer levels determined by reference methods or clinical diagnosis) to optimize and verify performance characteristics like sensitivity, specificity, and linearity.
These activities during the assay development process serve a similar function to a training set in that they guide the refinement of the assay, but the specifics are not detailed in this regulatory summary.
§ 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).