(67 days)
The intended use of the Sysmex® CA-1500 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 the following parameters and calculated parameters:
Clotting Analysis Parameters
- Prothrombin Time (PT) .
- Activated Partial Thromboplastin Time (APTT) .
- Fibrinogen (Clauss) .
Chromogenic Analysis Parameters
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Antithrombin III .
Calculated Parameters -
. PT Ratio
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PT INR
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PT % ●
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Extrinsic Factors (II, V, VII, X) ● Intrinsic Factors (VIII, IX, XI, XII) .
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Derived Fibrinogen ●
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Factor Assays % Activity .
The CA-1500 is substantially equivalent in intended use and technological characteristics to the Sysmex® Automated Coagulation Analyzer CA-6000, Sysmex Corporation, Kobe, Japan, which was cleared by FDA under Document Control Nos. K964139 and K992321; or the Behring Coagulation Timer (BCT), Dade Behring, Marburg, Germany which was cleared by FDA under Document Control No. K955278.
Here's an analysis of the provided text regarding the Sysmex® Automated Coagulation Analyzer CA-1500, focusing on acceptance criteria and the supporting study:
The provided document is a 510(k) Summary of Safety and Effectiveness Information for the Sysmex® Automated Coagulation Analyzer CA-1500, submitted to the FDA in 1999. It focuses on demonstrating substantial equivalence to predicate devices, primarily through method comparison and precision studies.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific thresholds (e.g., "r > 0.95"). Instead, it reports the performance metrics achieved in comparison and precision studies, implying these demonstrate "similarity" or acceptable performance when compared to predicate devices. The key performance indicators used are the Coefficient of Correlation (r) for method comparison and various Coefficient of Variation (%CV) for precision.
Below is a table summarizing the reported device performance from the provided study, which serves as the de-facto demonstration of meeting acceptance for substantial equivalence:
| Test | Performance Metric (Method Comparison) | Reported Value (Method Comparison) | Predicate Device | Performance Metric (Precision - Total %CV) | Reported Range (Precision - Total %CV) |
|---|---|---|---|---|---|
| Prothrombin Time (Innovin®, Seconds) | Coefficient of Correlation (r) | 0.999 | CA-6000 | Total %CV | 0.6 - 1.4 |
| Prothrombin Time (Innovin®, INR) | Coefficient of Correlation (r) | 0.999 | CA-6000 | Total %CV | 0.6 - 1.4 |
| Prothrombin Time (Thromborel® S, Seconds) | Coefficient of Correlation (r) | 0.998 | BCT | Total %CV | 2.1 - 3.0 |
| Prothrombin Time (Thromborel® S, %) | Coefficient of Correlation (r) | 0.996 | BCT | Total %CV | 3.6 - 4.2 |
| Derived Fibrinogen | Coefficient of Correlation (r) | 0.945 | BCT | Total %CV | 4.7 - 2.6 |
| Activated Partial Thromboplastin Time | Coefficient of Correlation (r) | 0.995 | CA-6000 | Total %CV | 2.4 - 2.0 |
| Fibrinogen (Clauss) | Coefficient of Correlation (r) | 0.985 | CA-6000 | Total %CV | 3.2 - 9.2 |
| Factor VII | Coefficient of Correlation (r) | 0.997 | CA-6000 | Total %CV | 2.7 - 3.0 |
| Factor VIII | Coefficient of Correlation (r) | 0.990 | CA-6000 | Total %CV | 3.6 - 4.6 |
| Antithrombin III | Coefficient of Correlation (r) | 0.998 | BCT | Total %CV | 4.8 - 8.1 |
2. Sample Sizes Used for the Test Set and Data Provenance
The "test set" in this context refers to the samples used in the clinical correlation (method comparison) studies and precision studies.
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Clinical Correlation (Method Comparison) Studies:
- Sample sizes ranged from 66 to 165 samples, depending on the specific test.
- Data Provenance: The specimens were evaluated from "apparently healthy individuals and from patients with different pathological conditions." The country of origin is not explicitly stated, but Dade Behring Inc. is based in Miami, FL, and Sysmex Corporation in Kobe, Japan. Given the submission is to the FDA, it is most likely that at least some, if not all, of the clinical correlation studies were performed using data from the US, or globally applicable data following international standards. The studies appear to be prospective in the sense that they were conducted for the purpose of this submission (as clinical correlation studies comparing the new device to predicates).
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Precision Studies:
- For all precision studies, the sample size (N) was 40. Note: For precision, N refers to the number of replicates or measurements taken, not necessarily unique patient samples.
- Data Provenance: The study utilized "Control Level" samples, specifically "CPN" (Control Plasma Normal) and either "Path. Pool" (Pathological Pool) or "CPP" (Control Plasma Pathological). These are likely commercially prepared quality control materials or pooled patient samples designed for assay validation. The provenance (country, retrospective/prospective) for these specific control materials is not detailed.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
This type of submission (510(k) for an automated coagulation analyzer) does not involve human expert interpretation of images or clinical findings to establish a "ground truth" in the way medical imaging AI devices do.
Instead, the "ground truth" for the test set is established by the predicate devices (Sysmex® Automated Coagulation Analyzer CA-6000 and Behring Coagulation Timer (BCT)), which are legally marketed and accepted devices for performing these coagulation tests. The new device's results are compared to the predicate device's results.
Therefore, there were no human experts establishing ground truth in the typical sense for this device. The 'gold standard' is the measurement provided by the established predicate device and associated reference methods/standards for coagulation assays.
4. Adjudication Method for the Test Set
As explained above, there isn't an "adjudication method" involving human experts in the context of this device. The comparison is between the quantitative results of the proposed device and the predicate device. If discrepancies were observed, standard laboratory procedures for investigating outliers or re-running samples would be employed, but not a panel of experts adjudicating a "truth."
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are typically used for diagnostic imaging devices where human readers interpret medical images, and the AI's impact on their performance (e.g., accuracy, efficiency) is measured. This submission is for an automated laboratory analyzer, which produces quantitative results directly, not interpretations by human readers in the same way.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the provided studies are for standalone performance. The Sysmex® Automated Coagulation Analyzer CA-1500 is an in vitro diagnostic (IVD) device designed to perform coagulation tests automatically. The method comparison and precision studies directly evaluate the performance of this analyzer (the "algorithm/device only") without human intervention during the measurement process, beyond loading samples and reagents. The results presented (correlation coefficients, %CV) represent the inherent analytical performance of the device itself.
7. The Type of Ground Truth Used
The "ground truth" for the method comparison studies was established by the measurements obtained from the legally marketed predicate devices (Sysmex® CA-6000 and Behring Coagulation Timer (BCT)). For precision studies, the ground truth refers to the expected or consensus values for the control materials used. This is a form of reference method/predicate device comparison rather than pathology, expert consensus, or outcomes data in the traditional sense.
8. The Sample Size for the Training Set
The document does not mention a "training set" in the context of machine learning or AI models, as this is a traditional IVD device. The device's operation is based on established electrochemical/optical principles and pre-programmed algorithms for signal processing and calculation, not on a machine learning model that requires a distinct training phase with labeled data.
9. How the Ground Truth for the Training Set Was Established
As there is no mention of a "training set" for an AI model, this question is not applicable to the provided document. The device's operational parameters and algorithms would have been developed and validated internally by the manufacturer through engineering design, laboratory testing, and adherence to performance specifications, rather than through an AI training paradigm.
§ 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.