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The D-dimer (DDMR) method on the Stratus® CS STAT fluorometric analyzer is an in vitro diagnostic test for the quantitative measurement of cross-linked fibrin degradation products (D-dimer) in human citrated or heparinized plasma. The Stratus® CS DDMR method is intended for use as an aid in the diagnosis of venous thromboembolism (VTE) [deep vein thrombosis (DVT) or pulmonary embolism (PE)].

The Stratus® CS DDMR procedure 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 antibody-antigenlabeled antibody sandwich. The unbound labeled antibody is later eluted from the field of view of the 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.

Here's an analysis of the provided text regarding the Stratus® CS D-Dimer Assay:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a numerical target for sensitivity, specificity, or NPV. Instead, it presents the device's performance characteristics in a clinical study. We can infer that these reported values were deemed acceptable for market clearance.

The cutoff used for these performance metrics was 450 ng/mL.

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size: 832 VTE patients were included in the clinical study.
• Data Provenance: Not explicitly stated. The document doesn't specify the country of origin or whether the data was retrospective or prospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

This information is not provided in the given document. The document only mentions a "Clinical Study Summary" without detailing the methodology of ground truth establishment, including the number or qualifications of experts.

4. Adjudication Method for the Test Set

This information is not provided in the given document.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

This information is not provided in the given document. The study described focuses on the standalone performance of the device rather than a comparative effectiveness study with human readers, with or without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes. The reported performance characteristics (sensitivity, specificity, NPV) are for the Stratus® CS D-Dimer Assay as a standalone diagnostic test. The description of the device's operation (solid phase Radial Partition Immunoassay (RPIA) technology, optical system, microprocessor for data analysis) indicates it's an automated process without direct human intervention in the result generation.

7. The Type of Ground Truth Used

The ground truth used was the diagnosis of Venous Thromboembolism (VTE) for patients (DVT or PE). The document implies a clinical reference standard, where patients were definitively diagnosed as having VTE or not, against which the D-dimer assay results were compared. However, the specific method for establishing this clinical diagnosis (e.g., imaging, clinical probability scores) is not detailed.

8. The Sample Size for the Training Set

The document does not provide information on a separate training set. The reported clinical study appears to be the primary study for performance evaluation, and it mentions a single "VTE Patients" sample size of 832. For diagnostic devices like this, calibration and internal validation often happen during development, but a distinct "training set" in the machine learning sense is not explicitly described.

9. How the Ground Truth for the Training Set Was Established

Since no separate training set is explicitly mentioned or detailed, this information is not provided.

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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.

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.

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The Stratus® CS D-dimer CalPak is an in vitro diagnostic product used to calibrate the Stratus® D-dimer method on the Stratus® CS STAT fluorometric analyzer. This calibrator is intended for medical purposes to establish points of reference that are used in the determination of D-dimer concentration in human specimens.

The Stratus® CS D-dimer CalPak consists of a plastic cartridge (CalPak) containing human D-dimer in a liquid, buffered bovine protein matrix in each of three wells. The CalPak is designed for use only on the Stratus® CS analyzer.

This document is a 510(k) premarket notification for a calibrator device, not an AI/ML diagnostic or prognostic device that would typically have performance metrics like sensitivity, specificity, or AUC against a ground truth. Therefore, many of the requested categories (e.g., sample size for test set, number of experts, adjudication method, MRMC study, standalone performance, training set size) are not applicable to this type of submission.

The document focuses on demonstrating substantial equivalence to a predicate device, which is the primary regulatory pathway for calibrators. The key aspects are the comparison of intended use, design, and performance characteristics (though specific performance data like accuracy or precision of the calibration itself are not detailed in this summary).

Here's an attempt to address the applicable parts of your request based on the provided text:

Acceptance Criteria and Device Performance for Stratus® CS D-dimer CalPak

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample size used for the test set and the data provenance

• Not Applicable. This submission is for a calibrator, which primarily demonstrates substantial equivalence to a predicate device. It does not involve a "test set" in the context of evaluating a diagnostic algorithm's performance against patient data. The "test" mentioned relates to the calibration procedure itself (e.g., "After completion of each test, the recovered values are automatically calculated...").

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

• Not Applicable. See point 2.

4. Adjudication method for the test set

• Not Applicable. See point 2.

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/ML device.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

• Not Applicable. This is not an AI/ML device.

7. The type of ground truth used

• Not Applicable directly in a diagnostic performance sense. For a calibrator, the "truth" is established by the known concentration of the D-dimer within the calibrator material itself, which is then used to set the instrument's reference points for measuring unknown samples. The document doesn't detail the method of how the D-dimer concentration in the calibrator was precisely determined, but it would involve analytical chemistry and highly controlled reference materials.

8. The sample size for the training set

• Not Applicable. This is not an AI/ML device.

9. How the ground truth for the training set was established

• Not Applicable. This is not an AI/ML device.

Study Proving Acceptance Criteria:

The "study" that proves the device meets its "acceptance criteria" is the 510(k) premarket notification process itself, specifically the comparison to the predicate device.

The document explicitly states:

"Both the Dade Behring Stratus® CS D-dimer CalPak and the VIDAS® D-dimer calibrator products are intended to calibrate their respective closed system methods utilizing similar designs consisting of human blood products in a buffered, bovine protein-based matrix."

"The Stratus® CS D-dimer CalPak is substantially equivalent in intended use and design to the VIDAS® D-dimer calibrator as noted above."

This statement, reviewed and accepted by the FDA (as indicated by the clearance letter), serves as the evidence that the device meets the regulatory acceptance criteria for market entry as a substantially equivalent device. The underlying details of the analytical performance of the calibrator (e.g., its accuracy, stability, commutability) would have been part of the full 510(k) submission, even if not fully detailed in this summary. However, the core "proof" presented here for regulatory acceptance relies on this substantial equivalence argument.

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