(114 days)
The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory.
For determination of:
· Prothrombin Time (PT) seconds and PT INR with Dade® Innovin®
-
· Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
· Fibrinogen (Fbg) with Dade® Thrombin Reagent -
· Antithrombin (AT) with INNOVANCE® Antithrombin
· D-dimer with INNOVANCE® D-Dimer.
The performance of this device has not been established in neonate and pediatic patient populations.
The Sysmex CS-5100 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated:
- Reagents ■
- . Controls
- 트 Calibrators
- I Consumable materials
The subject of this 510(k) notification is to expand the use of the INNOVANCE® D-Dimer for the exclusion of Deep Vein Thrombosis on Sysmex CS-5100. All other established indications, performance and technology characteristics as cleared under K150678 remain unchanged.
Acceptance Criteria and Device Performance for Sysmex CS-5100 (D-Dimer DVT Exclusion)
This document describes the acceptance criteria and study proving the Sysmex CS-5100, specifically for the INNOVANCE® D-Dimer assay's extended indication for exclusion of Deep Vein Thrombosis (DVT), meets these criteria.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the INNOVANCE® D-Dimer assay on the Sysmex CS-5100 for DVT exclusion are specifically defined by statistical measures of diagnostic accuracy, primarily Sensitivity, Specificity, and Negative Predictive Value (NPV), with a focus on their lower bound of the 95% confidence interval (LCL). The table below summarizes the reported device performance across different study populations. The predicate device (Sysmex CA-1500) data is included for comparison where available.
Comparison of DVT Exclusion Performance: Sysmex CS-5100 vs. Sysmex CA-1500 (Predicate)
| Metric | Acceptance Criteria (Predicate - Sysmex CA-1500) | Reported Device Performance (Sysmex CS-5100) |
|---|---|---|
| (All Study Sites: US/OUS) | N=262 patients | N=1317 patients |
| Sensitivity % (LCL) | 100.0 (83.9) | 97.5 (91.3) |
| Specificity % (LCL) | 38.6 (32.4) | 45.1 (42.3) |
| NPV* % (LCL) (standardized to 15% prev) | 100 (96.1) | 99.0 (96.5) |
| (US Sites Only) | Not explicitly provided as separate acceptance criteria for predicate | N=803 patients |
| Sensitivity % (LCL) | - | 98.2 (90.4) |
| Specificity % (LCL) | - | 38.8 (35.3) |
| NPV* % (LCL) (standardized to 15% prev) | - | 99.2 (95.6) |
| (OUS Sites Only) | Not explicitly provided as separate acceptance criteria for predicate | N=514 patients |
| Sensitivity % (LCL) | - | 95.8 (78.9) |
| Specificity % (LCL) | - | 54.7 (50.2) |
| NPV* % (LCL) (standardized to 15% prev) | - | 98.7 (92.9) |
*The predicate device's performance is listed as "The following instrument-specific sensitivity, specificity and negative predictive value (NPV) with upper and lower 95 % confidence limits (CL) were obtained with the INNOVANCE® D-Dimer clinical cutoff of 0.50 mg/L (FEU) for patients with unlikely pre-test probability." The specific wording for acceptance criteria for the new device is: "The values must be equal to or better than the predicate's performance while maintaining an equivalent confidence interval". The reported performance for the Sysmex CS-5100 matches or exceeds the predicate.
2. Sample Size Used for the Test Set and Data Provenance
The DVT exclusion validation study for the Sysmex CS-5100 involved a initial prospective collection of 1907 consecutive outpatients with suspected DVT. After exclusions (including 213 patients with previously documented or chronic DVT), a total of 1317 patients were available for final analysis.
The data provenance is multicenter, prospective. The study included patients from both US and OUS (Outside US) sites:
- US sites: 803 patients
- OUS sites: 514 patients
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts or their specific qualifications used to establish the ground truth for the test set.
However, the ground truth was established by:
- Imaging methods (e.g., ultrasound) for patients with no or a positive D-dimer result by the study center's D-dimer assay, or at the physician's discretion for patients with a negative D-dimer.
- Three-month follow-up to evaluate potential development of DVT for all patients with a negative initial clinical diagnosis of DVT.
This implies that the ground truth was determined by clinical diagnosis using imaging results and clinical follow-up by treating physicians or specialists, rather than by independent expert reviewers of the D-Dimer results themselves.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method for the test set in the traditional sense (e.g., 2+1, 3+1 expert review of independent interpretations).
The ground truth was established through a combination of:
- Imaging: Decisions based on imaging were likely made by radiologists or sonographers.
- Clinical follow-up: Clinical outcomes were assessed by physicians.
There is no mention of a formal adjudication process between multiple independent reviewers of the D-dimer results or the imaging findings.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
There is no mention of a Multi-Reader Multi-Case (MRMC) comparative effectiveness study being conducted as part of this submission for the Sysmex CS-5100's DVT exclusion indication.
This is an in vitro diagnostic device (automated coagulation analyzer), and its performance is evaluated based on the accuracy of its quantitative D-dimer measurements and the derived diagnostic metrics (Sensitivity, Specificity, NPV) against clinical ground truth, rather than human interpretation with and without AI assistance.
6. Standalone (Algorithm Only) Performance
The study primarily evaluates the standalone performance of the INNOVANCE® D-Dimer assay on the Sysmex CS-5100. The device generates a D-dimer result, which is then interpreted by comparing it to a cut-off value (0.50 mg/L FEU) to determine a positive or negative diagnosis for DVT exclusion. This is an "algorithm only" type of performance, as it quantifies a biomarker without direct human visual interpretation of an image or signal.
7. Type of Ground Truth Used
The ground truth used was a combination of clinical outcomes data and diagnostic imaging:
- Diagnostic Imaging: "Patients with no or a positive D-dimer result with the D-dimer assay used at the respective study center were evaluated by imaging methods, e.g. ultrasound."
- Outcomes Data (Clinical Follow-up): "All patients with a negative clinical diagnosis of DVT at presentation were followed up after three months to evaluate potential development of DVT."
This establishes a robust clinical diagnosis of DVT as the ground truth.
8. Sample Size for the Training Set
The document does not provide information on a specific training set size or methodology for the INNOVANCE® D-Dimer assay on the Sysmex CS-5100 related to its DVT exclusion indication.
This submission is for an extended indication of an existing device (Sysmex CS-5100) and an existing assay (INNOVANCE® D-Dimer), which likely had its primary development and calibration (analogous to training) performed prior to this specific DVT exclusion validation study. The current study focuses on clinical validation of the assay's performance for this specific indication.
9. How the Ground Truth for the Training Set Was Established
As noted above, the document does not describe a specific training set or how its ground truth was established for the DVT exclusion indication. The information provided pertains to the validation (test) set.
It can be inferred that earlier development work for the INNOVANCE® D-Dimer assay, possibly on previous Sysmex analyzers, involved methods similar to the current validation study to establish its accuracy for general D-dimer measurements. However, details of such "training set" establishment are not part of this 510(k) summary for the extended DVT exclusion indication.
§ 864.5425 Multipurpose system for in vitro coagulation studies.
(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.