(370 days)
For the quantitative determination of cross-linked fibrin degradation products (D-dimers) in human plasma on Siemens Healthcare Diagnostics and Sysmex® Coagulation Systems. The INNOVANCE® D-Dimer assay is intended for use in conjunction with a non-high clinical pretest probability (PTP) assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE).
Polystyrene particles covalently coated with a monoclonal antibody (8D3) are aggregated when mixed with samples containing D-dimer. The D-dimer crosslinkage region has a stereosymmetrical structure, i.e. the epitope for the monoclonal antibody occurs twice. Consequently, one antibody suffices in order to trigger an aggregation reaction, which is then detected turbidimetrically via the increase in turbidity.
Here's a breakdown of the acceptance criteria and study information for the INNOVANCE® D-Dimer assay:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct numerical targets in the provided text. However, the study aims to demonstrate that the device performs with sufficient sensitivity and Negative Predictive Value (NPV) to reliably exclude DVT, especially in patients with an unlikely pre-test probability. Based on the presented data, the implied acceptance criteria would be a sensitivity and NPV close to or at 100% for the intended use.
| Metric | Acceptance Criteria (Implied) | Reported Device Performance (All Patients) | Reported Device Performance (Unlikely PTP Patients) |
|---|---|---|---|
| Sensitivity | ≥ 96% (based on lower CL) | 100.0% (96.1 – 100.0% CL) | 100.0% (83.9 – 100.0% CL) |
| Specificity | Not directly, but >30% (for practical use) | 34.5% (29.4 – 39.9% CL) | 37.0% (31.0 – 43.4% CL) |
| NPV | ≥ 96% (based on lower CL) | 100.0% (96.8 – 100.0% CL) | 100.0% (96.0 – 100.0% CL) |
Study Proving Device Meets Acceptance Criteria:
The study referenced is a multi-center clinical evaluation evaluating the INNOVANCE® D-Dimer assay on the BCS® / BCS® XP System to exclude DVT.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Total Patients: 455 consecutive patients initially enrolled.
- Patients for Final Analysis: 426 patients (29 were excluded)
- Patients with unlikely pre-test probability: 267 patients.
- Data Provenance: The study was a "multi-center study," suggesting data was collected from multiple clinical sites. The text doesn't explicitly state the country of origin, but the manufacturer is German, and the contact information is for the US. It is a prospective study as it involved "consecutive patients presenting to the emergency department" and follow-up for three months.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The text does not specify the number of experts used or their qualifications to establish the ground truth for the test set.
4. Adjudication Method for the Test Set
The text does not explicitly state an adjudication method for the test set. The diagnostic certainty (ground truth) appears to have been established through a combination of imaging methods (compression ultrasound and/or venography) for positive D-dimer results, and a three-month follow-up for negative D-dimer and negative imaging results. This implicitly suggests that the attending clinicians/radiologists' assessments, informed by these methods, served as the ground truth.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not done. This study focuses on the standalone performance of the D-dimer assay.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, a standalone performance study was done. The results presented (Sensitivity, Specificity, NPV) are for the INNOVANCE® D-Dimer assay performed at a specific cutoff, independent of human interpretation of the D-dimer value itself, other than applying the PTP model. The assay's performance is then compared to the established ground truth of DVT.
7. The Type of Ground Truth Used
The ground truth used was a combination of:
- Imaging methods: Compression ultrasound and/or venography for patients with positive D-dimer results.
- Outcomes data: Three-month follow-up for patients with negative D-dimer results and those with negative imaging results, to evaluate for the potential development of DVT.
8. The Sample Size for the Training Set
The document does not specify a separate training set or its sample size. The study described appears to be a validation study of the device against clinical outcomes, rather than a development and training study for an algorithm. D-dimer assays traditionally involve established biochemical principles and cutoffs, rather than machine learning algorithms that require explicit training sets.
9. How the Ground Truth for the Training Set Was Established
Since no explicit training set or machine learning algorithm development is described, the method for establishing ground truth for a training set is not applicable in this context. The 0.50 mg/L (FEU) cutoff is a pre-established clinical cutoff for D-dimer assays.
§ 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).