(130 days)
The intended use of the Sysmex® CA-500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The instrument uses citrated human plasma to perform coagulation tests.
The Sysmex® CA-500 series is a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The manufacturer has modified the series to include two new models with immunological testing capability. The proposed Sysmex CA-500 series can now provide accurate and precise test results for up to five parameters simultaneously and in random access. The CA-500 uses clot, chromogenic and immunological detection technologies for determination of the various parameters.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. A table of acceptance criteria and the reported device performance:
The document presents two types of performance data: method comparison studies (comparing the CA-500 to predicate devices) and precision studies (evaluating the CA-500's internal consistency). The "acceptance criteria" are implied by the results needing to demonstrate substantial equivalence and acceptable precision for in vitro diagnostic use. Specific quantitative criteria are provided for the precision study.
| Test / Metric | Acceptance Criteria (Implied for Method Comparison, Explicit for Precision) | Reported Device Performance (CA-500) |
|---|---|---|
| Method Comparison Studies (vs. CA-7000 or CA-6000 Predicate Devices) | High Coefficient of Correlation (r) and linear regression close to Y=X (slope ~1, intercept ~0) for substantial equivalence. | D-Dimer Assay (Advanced D-Dimer): r=0.992, Y = 1.01X + 0.14 |
| PT, seconds (Thromborel® S): r=0.999, Y = 1.00X - 0.50 | ||
| PT, INR (Thromborel® S): r=0.999, Y = 0.89X + 0.11 | ||
| Derived Fibrinogen (Thromborel® S): r=0.998, Y = 1.08X + 0.04 | ||
| PT, seconds (Innovin®): r=0.999, Y = 1.03X - 0.26 | ||
| PT, INR (Innovin®): r=0.999, Y = 1.08X - 0.09 | ||
| Derived Fibrinogen (Innovin®): r=0.995, Y = 1.09X - 0.17 | ||
| PT, seconds (Thromboplastin C Plus): r=0.997, Y = 1.00X - 0.20 | ||
| PT, INR (Thromboplastin C Plus): r=0.998, Y = 1.00X - 0.00 | ||
| Derived Fibrinogen (Thromboplastin C Plus): r=0.998, Y = 1.12X + 0.03 | ||
| APTT (Actin®): r=0.982, Y = 1.00X - 0.20 | ||
| APTT (Actin® FS): r=0.983, Y = 1.00X + 0.10 | ||
| APTT (Actin® FSL): r=0.990, Y = 1.00X + 0.10 |
All R-values are very close to 1, and regression equations show slopes generally close to 1 and intercepts close to 0, indicating strong correlation and agreement with the predicate devices. |
| Precision Studies (Total %CV) | Max. Error Criteria (%CV) specified for each assay/control level. | PT, Seconds (Thromborel® S): 0.9% and 1.5% (Max. 5% CV)
PT, INR (Thromborel® S): 0.8% and 1.3% (Max. 5% CV)
Derived Fibrinogen (Thromborel® S): 1.6% and 2.5% (Max. 10% CV)
PT, Seconds (Innovin®): 0.4% and 1.8% (Max. 5% CV)
PT, INR (Innovin®): 0.4% and 1.8% (Max. 5% CV)
Derived Fibrinogen (Innovin®): 2.8% and 3.4% (Max. 10% CV)
PT, Seconds (Thromboplastin C Plus): 0.4% and 1.8% (Max. 5% CV)
PT, INR (Thromboplastin C Plus): 0.7% and 3.5% (Max. 5% CV)
Derived Fibrinogen (Thromboplastin C Plus): 1.9% and 1.6% (Max. 10% CV)
APTT (Dade® Actin): 3.5% and 1.4% (Max. 5% CV)
APTT (Dade® Actin FS): 0.5% and 1.5% (Max. 5% CV)
APTT (Dade® Actin® FSL): 0.4% and 1.5% (Max. 5% CV)
D-Dimer (Advanced D-Dimer): 2.9% and 2.0% (Max. 15% CV)
All reported Total %CV values are well within the specified maximum error criteria, indicating excellent precision. |
2. Sample size used for the test set and the data provenance:
- Test Set Sample Sizes:
- Method Comparison Studies:
- D-Dimer Assay: 390 samples
- PT (Thromborel® S): 248 samples
- Derived Fibrinogen (Thromborel® S): 248 samples
- PT (Innovin®): 243 samples
- Derived Fibrinogen (Innovin®): 247 samples
- PT (Thromboplastin C Plus): 245 samples
- Derived Fibrinogen (Thromboplastin C Plus): 245 samples
- APTT (Actin®): 864 samples
- APTT (Actin® FS): 857 samples
- APTT (Actin® FSL): 864 samples
- Precision Studies:
- For each assay and control level, 40 measurements (e.g., PT (Thromborel® S) at Control Plasma N: 40 measurements; PT (Thromborel® S) at Ci-Trol® Level 3: 40 measurements, etc.).
- Method Comparison Studies:
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It describes the samples as "citrated human plasma" and refers to "Control Plasma N" and "Path. Plasmapool" for validation, suggesting laboratory-obtained samples rather than patient-specific demographic data from a specific geographical location.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided in the document. For in vitro diagnostic devices like this coagulation analyzer, the "ground truth" is typically established by the reference methods performed on the predicate device or by established control materials with known values, not by independent expert interpretation in the same way it would be for imaging diagnostics. The study compares the new device's results to those of the predicate devices.
4. Adjudication method for the test set:
This information is not applicable for this type of device study. Adjudication methods (like 2+1, 3+1) are typically used in studies where human interpretation of data (e.g., medical images) is involved and discrepancies need to be resolved to establish ground truth. For an automated coagulation analyzer, the "ground truth" for method comparison is the measurement obtained from the predicate device, and for precision, it's the instrument's own internal consistency against known controls.
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:
This is not applicable to this device. The Sysmex® Automated Coagulation Analyzer CA-500 is an automated instrument, not an AI-assisted diagnostic tool that human readers use. Therefore, no MRMC study or assessment of human reader improvement with AI assistance was performed.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The performance presented for the Sysmex® Automated Coagulation Analyzer CA-500 is inherently standalone (algorithm/instrument only performance). As an automated analyzer, its primary function is to process samples and provide results without direct human interpretive intervention at the point of measurement. The studies quantify the agreement of its measurements with predicate devices and its internal precision.
7. The type of ground truth used:
The ground truth used for these studies is based on:
- Reference measurements from legally marketed predicate devices: For the method comparison studies, the results obtained from the Sysmex® Automated Coagulation Analyzer CA-7000 and CA-6000 (which are themselves established and cleared devices) served as the reference standard against which the CA-500's measurements were compared.
- Known values of control materials: For the precision studies, "Control Plasma N," "Ci-Trol® Level 3," "Path. Plasmapool," "Adv. D-D Control 1," and "Adv. D-D Control 2" were used. These are standard laboratory control materials with established reference ranges or target values that enable the assessment of an instrument's accuracy and precision.
8. The sample size for the training set:
This information is not provided and is generally not applicable in the context of traditional automated laboratory instruments. These instruments are typically developed and validated using engineering principles, analytical chemistry, and statistical methods rather than machine learning models that require distinct "training sets." The studies described are validation and performance testing, not model training.
9. How the ground truth for the training set was established:
As noted in point 8, the concept of a "training set" and "ground truth for the training set" as used in machine learning is not applicable to this device and its validation. The device's operational parameters and algorithms are designed and verified against established principles of coagulation testing and validated using control materials and comparison with predicate devices.
§ 864.5400 Coagulation instrument.
(a)
Identification. A coagulation instrument is an automated or semiautomated device used to determine the onset of clot formation for in vitro coagulation studies.(b)
Classification. Class II (special controls). A fibrometer or coagulation timer intended for use with a coagulation instrument is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.