(114 days)
The Sysmex CS-2100i 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 pediatric patient populations.
The Sysmex CS-2100i 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
- 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-2100i. All other established indications, performance and technology characteristics as cleared under K151259 remain unchanged.
Here's an analysis of the acceptance criteria and study detailed in the provided document:
The document describes the Sysmex CS-2100i, a fully automated blood coagulation analyzer, and focuses on the expansion of its use for the INNOVANCE® D-Dimer assay for the exclusion of Deep Vein Thrombosis (DVT).
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for the DVT exclusion performance. Instead, it reports the diagnostic performance metrics obtained from the study. The implication is that these reported metrics were deemed acceptable for market clearance.
| Performance Metric | Acceptance Criteria (Implicit from context or general clinical requirements) | Reported Device Performance (US and OUS sites combined) |
|---|---|---|
| Sensitivity | High (crucial for DVT exclusion – to minimize false negatives) | 97.5% (95% LCL = 91.3%) |
| Specificity | 46.1% (95% LCL = 43.3%) | |
| Negative Predictive Value (NPV) | Very High (crucial for DVT exclusion – to minimize false negatives and rule out DVT) | 99.7% (95% LCL = 98.7%) |
| NPV (standardized to 15% prevalence) | 99.1% (95% LCL = 96.6%) | |
| Positive Predictive Value (PPV) | 10.5% (95% LCL = 8.5%) | |
| PPV (standardized to 15% prevalence) | 24.2% (95% LCL = 20.2%) |
Note: The FDA's clearance implies that the reported NPV of 99.7% (and 99.1% standardized) met the necessary threshold for indicating substantial equivalence for DVT exclusion, as a high NPV is critical for "ruling out" the disease.
2. Sample Size Used for the Test Set and Data Provenance
- Total Initial Patient Sample Size: 1907 consecutive outpatients.
- Excluded from Analysis: 368 patients (including 213 with previously documented or chronic DVT).
- Patients for Final Analysis: 1317 patients.
- US Sites: 803 patients
- OUS (Outside US) Sites: 514 patients
- Data Provenance: Multicenter study. Data was collected prospectively from patients in the US and Europe (OUS sites are likely European, given the company's origin in Germany). The study included consecutive outpatients presenting to emergency or ambulatory departments.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The document specifies that the reference standard for DVT diagnosis involved imaging methods, e.g., ultrasound, and a 3-month follow-up to evaluate potential DVT development. It does not explicitly state the number or specific qualifications of experts (e.g., radiologists, vascular specialists) involved in interpreting these imaging studies or clinical follow-ups. However, "Reference (Imaging and 3-month follow-up)" implies that the ground truth was established by standard clinical diagnostic procedures, which inherently involve qualified medical professionals.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method for conflicting interpretations of imaging results or clinical diagnoses. It states that 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," and "Patients with a negative D-dimer result with the D-dimer assay used at the respective study center underwent imaging at the physician's discretion." All patients with a negative clinical diagnosis were followed up. This suggests that the final clinical diagnosis, incorporating imaging and follow-up, served as the ground truth. There is no mention of multiple expert readers or a consensus process for the ground truth determination itself, beyond the standard practices for diagnostic imaging interpretation and clinical follow-up.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. The study described is a diagnostic accuracy study for the device (Sysmex CS-2100i with INNOVANCE® D-Dimer) in a standalone manner compared to clinical ground truth. It is not an MRMC comparative effectiveness study involving human readers with and without AI assistance. Therefore, there is no effect size reported for human readers improving with AI.
6. Standalone Performance Study
Yes. The study evaluates the standalone performance of the INNOVANCE® D-Dimer assay on the Sysmex CS-2100i system. The performance metrics (Sensitivity, Specificity, NPV, PPV) are calculated for the device's output (D-dimer result
§ 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.