(132 days)
The Dade Behring Stratus® CS D-dimer method is an in vitro diagnostic test intended for use with the Stratus® CS fluorometric analyzer for the determination of cross-linked fibrin degradation products (D-dimer) in plasma.
The Dade Behring Stratus® CS D-dimer TestPak method is an enzyme-linked fluorescent immunoassay that consists of a five(5)- well, plastic cartridge (TestPak) designed for use only on the Dade Behring Stratus® CS fluorometric analyzer. Within the TestPak cartridge is a small square of embedded glass fiber paper. Reagents and sample are added through an opening onto the glass fiber paper. Following incubation, the enzyme-labeled antibody and the bound D-dimer fraction react. The enzymatic rate of the bound fraction increases with the concentration of the D-dimer in the sample and is measured via fluorescence. Dilutions, if needed, may be accomplished via utilization of the Stratus®CS DilPak (diluent) cartridges. All data analysis functions are performed automatically by the analyzer.
Here's an analysis of the provided text, focusing on the acceptance criteria and the study that proves the device meets those criteria:
Device: Dade Behring Stratus® CS D-dimer method
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state "acceptance criteria" in a formal, enumerated list. Instead, the demonstration of equivalence relies on comparing performance characteristics with a predicate device. The primary performance metric presented is the correlation between the new device and the predicate.
| Acceptance Criteria (Inferred from Predicate Comparison) | Reported Device Performance (Dade Behring Stratus® CS D-dimer Method) |
|---|---|
| Strong correlation with predicate device | Correlation Coefficient: 0.923 (compared to bioMerieux Vitek VIDAS® D-dimer Assay) |
| Slope close to 1.0 when compared to predicate device | Slope: 0.995 (compared to bioMerieux Vitek VIDAS® D-dimer Assay) |
| Minimal intercept when compared to predicate device | Intercept: 159 ng/mL (compared to bioMerieux Vitek VIDAS® D-dimer Assay) |
| Comparable intended use | In vitro diagnostic test for the quantitative measurement of cross-linked fibrin degradation products (D-dimer) in human citrated or heparinized plasma. |
| Comparable technological design | Automated Fluorescent immunoassay; 450nm; Alkaline phosphatase = conjugate; 4-methylumbelliferyl phosphate = substrate. |
| Comparable assay range | 6 - 5000 ng/mL (Predicate: 45 - 1000 ng/mL, the Stratus CS has a wider reported range, which is generally considered an improvement or acceptable difference if analytical performance holds.) |
| Comparable sample type | Whole blood/plasma (Predicate: plasma. The Stratus CS accepts whole blood/plasma, implying an acceptable difference or broader utility.) |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size: n = 123 clinical patient samples.
- Data Provenance: The samples were "clinical patient samples" and were tested at Dade Behring (Glasgow, Delaware), USA. The text does not explicitly state if the study was retrospective or prospective, but the phrasing "clinical patient samples were tested" typically implies these were existing samples, making it likely a retrospective analysis of previously collected samples.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This is an in vitro diagnostic device for measuring a biomarker in blood. The ground truth for such devices is typically established by:
- The results from a well-established, legally marketed predicate device (as is the case here).
- Reference methods or highly accurate laboratory techniques.
The concept of "experts" in the sense of clinicians or radiologists interpreting images is not applicable here. The "ground truth" for the performance comparison is the result obtained from the bioMerieux Vitek VIDAS® D-dimer Assay.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable. This is a comparison of two quantitative laboratory assays. Adjudication methods involving multiple human readers are used for diagnostic imaging or subjective assessments, not for objective biomarker measurements. The "adjudication" in this context is the direct comparison of the numerical results from the two devices.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This is not an AI-assisted diagnostic imaging device or one that involves human interpretation of results in the way an MRMC study would apply. It's a laboratory assay.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, in a way. The "Dade Behring Stratus® CS D-dimer method" and the "bioMerieux Vitek VIDAS® D-dimer Assay" are both automated systems that perform the measurement and data analysis without human intervention in the result generation. The comparison performed ("split sample comparison") assesses the standalone performance of the new device against the predicate device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for comparison was the results obtained from a legally marketed predicate device, specifically the bioMerieux Vitek VIDAS® D-dimer Assay (K973819). The new device's performance was evaluated based on how closely its measurements correlated with those of the predicate device.
8. The sample size for the training set
The document does not explicitly mention a separate "training set" or its size for the development of the Dade Behring Stratus® CS D-dimer method. For in vitro diagnostic assays, the development often involves iterative optimization and calibration using various reagent lots and known concentration samples, rather than a distinct "training set" in the machine learning sense. The validation of the device's performance is demonstrated through the comparative study described.
9. How the ground truth for the training set was established
As no specific "training set" is described, this question is not fully applicable. However, the foundational "ground truth" for developing such an assay would typically be established using:
- Reference materials/calibrators: Samples with precisely known D-dimer concentrations.
- Established analytical methods: High-precision laboratory techniques to determine true concentrations during development.
The continuous calibration process mentioned ("Calibration curve updated for each lot, using one level (triplicate) and every 60 days, thereafter") indicates an ongoing internal "ground truthing" process for each manufactured lot.
§ 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).