(192 days)
The i-STAT Celite Activated Clotting Time (ACT) test cartridge is an in vitro diagnostic test used to monitor moderate- and high-level hevarin therapy through analysis of arterial and venous whole blood samples. The cartridge is to be used with the i-STAT System 200 model analyzer.
As part of the i-STAT System, the Celite ACT test cartridge is to be used by trained and certified health care professionals in accordance with a facility's policies and procedures.
The i-STAT Celite ACT test is useful for monitoring patients receiving heparin for treatment of pulmonary embolism or venous thrombosis, and for monitoring anticoagulation therapy in patients undergoing medical procedures such as catheterization, cardiac surgery, surgery, organ transplant and dialysis.
The i-STAT Celite ACT test is contained in a single test cartridge. In use, approximately 40 microliters of fresh whole blood are placed in the cartridge as described below. The cartridge is inserted into the thermally controlled i-STAT Model 200 Portable Clinical Analytical steps are performed automatically. Patient and user information may be entered into the analyzer via a keypad during the automated analysis cycle.
In the i-STAT ACT test the endpoint is indicated by the appearance of an electroactive marker generated by the thrombin-mediated conversion of a synthetic substrate included in the reagent. Detection of the marker indicates generation of thrombin and therefore complete activation of the coagulation cascade. The reported result is calculated from the time and rate of the substrate conversion and is given in seconds. The reported result correlates to the result of a traditional ACT in which the endpoint is indicated by physical clot formation.
The ACT cartridge is assembled from plastic components that provide the conduits for fluid handling and house the sensor chips. The coagulation test is identified to the user through the name and color code on the cartridge label and by the analyzer through features integral to the cartridge.
In the ACT cartridge the sensor comprises a gold film patterned on a silicon/silicon dioxide substrate.
During the test the blood sample is mixed with reagents which are coated on the cartridge cover in a segment of the sensor channel. The reagent layer includes an activating agent, a thrombin substrate, and inert matrix components. These reagents allow activation of the coagulation cascade and detection of clot formation.
Whole blood is introduced into the sample well of the cartridge at the sample port and the cartridge is closed and inserted into the analyzer. Insertion of the cartridge initiates a controlled and monitored sequence of steps in the instrument. These are:
- Electrical contact is made between the analyzer electronic input circuits and the cartridge. The analyzer identifies the type of cartridge being used and the tests contained in the cartridge.
- The dry chips and sensor channel are heated to 37C.
- The blood is then moved forward. Feedback from the fluid position sensor is used to allow controlled oscillation of the blood segment resulting in dissolution of the reagent layer.
- Following mixing, a count up time is displayed.
- During the course of testing, the position of the blood segment is actively controlled to maintain the length of the blood containing the reagent coincident with the endpoint detector.
- Calculation of sample clot time is performed and displayed.
The provided 510(k) summary describes the i-STAT Celite ACT test and its comparison to a predicate device, the Hemochron Systems Activated Clotting Time. The document focuses on demonstrating substantial equivalence, not on pre-defined acceptance criteria in the way AI/ML devices typically present them. However, we can extract performance metrics and the study design to infer the criteria being met.
Here's an analysis based on the provided text, structured to align with your request for acceptance criteria and study details:
Acceptance Criteria and Device Performance
The acceptance criteria here are implicitly derived from demonstrating substantial equivalence to the predicate device, the Hemochron Systems Activated Clotting Time. The study's goal was to show that the i-STAT Celite ACT test performs comparably to the predicate device in various clinical settings.
| Acceptance Criterion (Inferred from Predicate Equivalence) | Reported Device Performance (i-STAT Celite ACT vs. Hemochron ACT) |
|---|---|
| Linearity to Heparin Concentration: Device should respond linearly to heparin across its reportable range, similar to the predicate. | Responds linearly in the range of 50 to 1000 seconds. Average sensitivity across multiple donors is 77 seconds / U/ml heparin, "equivalent to the sensitivity of the Hemochron System Activated Celite Clotting Time test." |
| Within-Sample Reproducibility/Precision (whole blood): Imprecision should be comparable or better than the predicate device. | 5.6% within-sample reproducibility across the reportable range. (Predicate: 8.8%) |
| Imprecision (plasma controls - Level 1): Imprecision should be acceptable for plasma controls. | 221 ± 19 seconds (8.4% C.V.). (Predicate: 6.5% for whole blood controls) |
| Imprecision (plasma controls - Level 2): Imprecision should be acceptable for plasma controls. | 456 ± 22 seconds (4.8% C.V.). (Predicate: 5.3% for whole blood controls) |
| Clinical Correlation (Cardiac Catheterization/Bypass Procedures) - Sample Size (N): Adequate number of samples for comparison. | Site 1: 118; Site 2: 74; Site 3: 101 |
| Clinical Correlation (Cardiac Catheterization/Bypass Procedures) - Correlation Coefficient: High correlation between the two methods. | Site 1: 0.949; Site 2: 0.923; Site 3: 0.949 |
| Clinical Correlation (Cardiac Catheterization/Bypass Procedures) - Slope: Slope close to 1.0. | Site 1: 1.00; Site 2: 0.951; Site 3: 0.902 |
| Clinical Correlation (Cardiac Catheterization/Bypass Procedures) - Intercept: Intercept close to 0. | Site 1: 0; Site 2: 25; Site 3: 24 |
| Clinical Correlation (Cardiac Catheterization/Bypass Procedures) - Relative Standard Error of the Estimate (Syx %): Acceptable error between methods. | Site 1: 15.9%; Site 2: 15.7%; Site 3: 12.6% |
| Clinical Comparison (Hemodialysis/ECMO) - Mean Bias: Acceptable average bias between the methods. | Site 1: -24; Site 2: -24 |
| Insensitivity to Interfering Factors: | Not affected by hematocrit (20-70%), fibrinogen (100-500 mg/dL), or sample temperature (15-37°C). |
Note: The document does not explicitly state numerical "acceptance criteria" but presents performance data to demonstrate "substantial equivalence" to the predicate device, which is the regulatory standard for 510(k) clearance. The favorable comparisons above (e.g., better precision, high correlation) implicitly meet these unstated criteria.
Study Details:
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Sample sizes used for the test set and the data provenance:
- Cardiac Catheterization and Bypass Procedures:
- Site 1: 118 patient samples
- Site 2: 74 patient samples
- Site 3: 101 patient samples
- Hemodialysis and Extra-corporeal Membrane Oxygenation:
- Site 1: 52 patient samples
- Site 2: 14 patient samples
- Data Provenance: The studies were conducted at "three external sites" and "two sites" for different patient populations. The samples were "fresh whole blood samples" from patients undergoing the described procedures. The data is prospective in the sense that samples were collected and tested on both devices concurrently. Location (country of origin) is not explicitly stated but implies clinical sites within the same regulatory jurisdiction as the submission (likely USA).
- Cardiac Catheterization and Bypass Procedures:
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable in the typical sense for an AI/ML device. For this in vitro diagnostic device, "ground truth" for the clinical studies was established by the predicate device (Hemochron® Systems Activated Clotting Time). The goal was to show correlation and agreement with an existing, legally marketed device, not to establish a new gold standard. Therefore, no "experts" for ground truth adjudication are described.
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Adjudication method for the test set:
- Not applicable as the "ground truth" was the measurement from the predicate device. The identical sample was tested on both the i-STAT device and the predicate device. Statistical comparisons (least squares regression, average bias) were then performed.
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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:
- Not applicable. This is an in vitro diagnostic device, not an AI/ML medical imaging device that requires human reader interpretation. The device provides a quantitative measurement (Activated Clotting Time).
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, implicitly. The performance data presented (linearity, precision, clinical correlation) represents the performance of the i-STAT device itself in generating an ACT result, compared to the predicate device. The i-STAT system automatically performs the analytical steps and calculates the result, so this is a standalone performance assessment in its context.
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The type of ground truth used:
- For the clinical correlation studies, the "ground truth" was effectively the measurement obtained from the predicate device (Hemochron® Systems Activated Clotting Time). The internal studies for linearity and precision used established methods for determining heparin concentration and control material values.
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The sample size for the training set:
- Not applicable. This device is not an AI/ML algorithm that requires a "training set" in the conventional sense. Its underlying principles are electrochemical detection and established chemical reactions, not machine learning from a dataset. The development likely involved internal validation and calibration using various samples, but this is not generally referred to as a "training set" for such a device.
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How the ground truth for the training set was established:
- Not applicable, as there is no traditional "training set" for this type of medical device. The "ground truth" for method development would be based on established analytical standards, reference methods, and gravimetric/volumetric preparations for control materials.
§ 864.7140 Activated whole blood clotting time tests.
(a)
Identification. An activated whole blood clotting time tests is a device, used to monitor heparin therapy for the treatment of venous thrombosis or pulmonary embolism by measuring the coagulation time of whole blood.(b)
Classification. Class II (performance standards).