(90 days)
The Sysmex® Automated Blood Coagulation Analyzer 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
- . Coagulation Factor V with Dade® Innovin®
- . Coagulation Factor VII with Dade® Innovin®
- . Coagulation Factor VIII with Dade® Actin® FSL
- . Coagulation Factor IX with Dade® Actin® FSL
- . Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent
- . Factor V Leiden with Factor V Leiden Assay
- . Protein C with Protein C Reagent
- . Antithrombin (AT) with INNOVANCE® Antithrombin
- Protein C with Berichrom® Protein C
- D-dimer with INNOVANCE® D-Dimer
The performance of this device has not been established in neonate and pediatric patient populations.
Intended Use for Factor V Leiden Assay:
The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use.
Intended Use for Coagulation Factor VIII Deficient Plasma:
In vitro diagnostic reagents for the determination of the activity of coagulation factors VIII, IX, XI and XII in human plasma by coagulation methods.
Intended Use for Coagulation Factor IX Deficient Plasma:
In vitro diagnostic reagents for the determination of the activity of coagulation factor VIII, IX, XI and XII in human plasma by coagulation methods.
Intended Use for LA1 Screening and LA2 Confirmation Reagents:
LA1 Screening Reagent and LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants.
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, Calibrators, and Consumable materials. The subject of this 510(k) notification are reagent applications which perform the coagulation tests Factor V Leiden with Factor V Leiden Assay, Coagulation Factor VIII with Dade® Actin FSL®, Coagulation Factor IX with Dade® Actin FSL®, Lupus Anticoagulant with LA 1 Screening Reagent and LA 2 Confirmation Reagent. The analysis principles used on the instrument are reflected by the reagent application testing provided in this 510(k) notification and is described in the below table.
Here's a breakdown of the acceptance criteria and study information for the Sysmex® Automated Blood Coagulation Analyzer CS-5100, based on the provided text:
Important Note: The provided document is a 510(k) summary for a medical device. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, rather than proving absolute safety and effectiveness from scratch. Therefore, the "acceptance criteria" discussed are primarily related to showing that the new device performs comparably to the predicate for specific applications, and "ground truth" is often established by comparing to the predicate device's results.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria values in the format of a table as it pertains to specific numerical thresholds for accuracy, sensitivity, or specificity. Instead, the acceptance criteria for most studies (Method Comparison, Reproducibility, Detection Capability, Linearity) are generally described as "met the predetermined acceptance criteria." However, for the Factor V Leiden Cut-off Study, specific performance metrics (Sensitivity and Specificity) are provided and imply acceptance criteria. For the Method Comparison, the implicit acceptance criterion is that the results demonstrate equivalence to the predicate device, as confirmed by Passing-Bablok regression and Bland-Altman plots.
Here's an attempt to extract and summarize:
| Study/Application | Acceptance Criteria (Implicit/Explicit) | Reported Device Performance |
|---|---|---|
| Method Comparison (all applications listed) | Results between proposed and predicate devices demonstrate equivalence through Passing-Bablok regression and Bland-Altman plots. | Passing-Bablok: Slope near 1, Intercept near 0 (e.g., Factor V Leiden: y = 0.976x + 0.058, r=0.983) |
| Reproducibility (all applications listed) | Met predetermined acceptance criteria for Within Run and Total %CV. | Example: Factor V Leiden Within Run %CV: 0.70 - 4.82 (Site-specific ranges); Total %CV: 0.90 - 5.25 (Site-specific ranges) |
| Detection Capability | Data met predetermined acceptance criteria supporting lower limit of clinically reportable range. | For Coagulation Factor VIII: Measured Limit of Quantitation 2.52% of norm (Clinical Reportable Range 3.0% of norm) |
| Linearity & Measuring Range | All reagents met predetermined acceptance criteria supporting clinically reportable range. | For Coagulation Factor VIII: Measured Linear Range 2.12 – 246.41% (Clinical Reportable Range 3.0 – 182.0%) |
| Factor V Leiden Cut-off Study | High sensitivity and specificity (implied 95% CI covering satisfactory performance). | Sensitivity = 100.0% (95.0% CI = 98.3 – 100.0%); Specificity = 100.0% (95.0% CI = 97.7 – 100.0%) |
2. Sample Size and Data Provenance for Test Set
- Method Comparison:
- Sample Sizes:
- Factor V Leiden: N = 495 (combined from 4 sites)
- Coagulation Factor VIII: N = 432 (combined from 4 sites)
- Coagulation Factor IX: N = 475 (combined from 4 sites)
- LA 1 Screening Reagent: N = 369 (combined from 3 sites, 1 site had N=4)
- LA 2 Confirmation Reagent: N = 353 (combined from 3 sites, 1 site had N=17)
- LA Ratio: N = 306 (combined from 3 sites, 1 site had N=4)
- Data Provenance: 4 external sites, 3 in the United States and 1 in Germany. Retrospective or prospective is not explicitly stated for individual samples, but the comparison uses "patient samples" and "were measured on both the predicate device... as well as the new device."
- Sample Sizes:
- Reproducibility Studies:
- Sample Sizes: Not explicitly stated as number of patient samples, but testing used 2 runs per day, 2 replicates per run, over 20 days. These studies typically use control materials at various levels rather than a large set of unique patient samples for performance assessment.
- Data Provenance: 1 external site in Germany, 2 external sites in the United States.
- Detection Capability Studies:
- Sample Sizes: Not specified beyond stating "calibrated assays."
- Data Provenance: Not specified beyond referring to the method.
- Linearity & Measuring Range:
- Sample Sizes: Not specified beyond stating "calibrated assays."
- Data Provenance: Not specified beyond referring to the method.
- Reference Interval Studies:
- Sample Sizes:
- Factor V Leiden: N = 193
- Coagulation Factor VIII: N = 190
- Coagulation Factor IX: N = 188
- LA 1 Screening Reagent (fresh): N = 185
- LA 1 Screening Reagent (frozen): N = 191
- LA 2 Confirmation Reagent (fresh): N = 185
- LA 2 Confirmation Reagent (frozen): N = 191
- LA1/LA2 Ratio (fresh): N = 184
- LA1/LA2 Ratio (frozen): N = 191
- Data Provenance: 3 clinical study sites in the United States.
- Sample Sizes:
- Factor V Leiden Cut-off Study:
- Sample Size: N = 381 (of which N = 127 from the US)
- Data Provenance: Citrated plasma samples from patients submitted for thrombophilia screening were collected by three different clinical sites (one site in the US and two sites in Germany). The samples were frozen.
3. Number of Experts and Qualifications for Ground Truth
The document does not mention the use of "experts" in the traditional sense of clinicians or radiologists establishing ground truth. For coagulation analyzers, the "ground truth" is typically established by comparing the new device's measurements to a reference method or a predicate device's measurements that are already accepted as accurate and reliable.
- In the Method Comparison study, the predicate device (Sysmex® CA-1500) serves as the reference for comparison, meaning its results are the "ground truth" against which the new device's results are measured for equivalence.
- In the Factor V Leiden Cut-off Study, the "ground truth" for confirming the presence of the Factor V Leiden variant was established by the Factor V Leiden genotype (PCR method). The number of experts involved in performing or interpreting these PCR tests is not specified, but they would typically be laboratory professionals trained in molecular diagnostics.
4. Adjudication Method for the Test Set
No explicit adjudication method (like "2+1" or "3+1") is described, as the studies are primarily quantitative comparisons against established methods or predicate device results, rather than subjective interpretations requiring adjudication by multiple readers.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC study was done. This type of study (comparing human reader performance with and without AI assistance) is typically relevant for interpretative diagnostic devices, such as imaging systems, where human experts make diagnoses. The Sysmex® CS-5100 is an automated blood coagulation analyzer that provides quantitative measurements, not interpretations, so an MRMC study is not applicable here.
6. Standalone Performance Study (Algorithm Only)
Yes, standalone performance studies were done. All the studies described (Method Comparison, Reproducibility, Detection Capability, Linearity, Reference Interval, Factor V Leiden Cut-off Study) assess the performance of the Sysmex® CS-5100 device itself, functioning independently, without human-in-the-loop interpretation or intervention in the measurement process. The device outputs quantitative results, and these studies evaluate the accuracy, precision, and clinical relevance of those outputs.
7. Type of Ground Truth Used
- Method Comparison: Comparison against the results obtained from the predicate device (Sysmex® CA-1500), which is itself a legally marketed device with established performance.
- Factor V Leiden Cut-off Study: Factor V Leiden genotype (PCR method). This is a definitive molecular pathology test.
- Detection Capability, Linearity, Reference Interval studies: These generally establish the device's inherent analytical characteristics against internal standards or established statistical methodologies (CLSI guidelines), rather than using an external "ground truth" from experts or a pathology panel in the same way an interpretative diagnostic device might.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning. The Sysmex® CS-5100 is a an automated laboratory instrument for performing coagulation tests, not a software algorithm that undergoes a training phase with a distinct dataset. The performance data presented are for validation/testing of the device's operational capabilities across predefined assays using various samples.
9. How Ground Truth for the Training Set Was Established
Since a "training set" in the machine learning sense is not applicable or explicitly mentioned for this device, a method for establishing its ground truth is also not provided. The development and calibration of such instruments typically involve rigorous analytical methods and the use of certified reference materials and control samples, rather than a "ground truth" established from a large dataset for algorithm training.
§ 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.