(319 days)
The i-STAT Kaolin Activated Clotting Time (ACT) test is an in vitro diagnostic test which uses fresh whole blood to monitor high-dose heparin anticoaqulation frequently associated with cardiovascular surgery. The test is to be used with the i-STAT Portable Clinical Analyzer (Models 200 and 300), but not the Philips Medical Systems (formerly Agilent Technologies) Blood Analysis Module (BAM). As part of the i-STAT System, the Kaolin ACT test is to be used by trained and certified health care professionals in accordance with a facility's policies and procedures.
The i-STAT Kaolin ACT test is contained in a single test cartridge. In use, approximately 40 microliters of fresh whole blood are placed in the cartridge is inserted into the thermally controlled i-STAT Model 200 or Model 300 Portable Clinical Analyzer, and all analytical steps are performed automatically. Patient and user information may be entered into the analyzer via a keypad during the automated analysis cycle. 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. 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 provided text describes the i-STAT Kaolin ACT test and its comparison to the predicate device, the Hemochron ACT test.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. A table of acceptance criteria and the reported device performance
The document doesn't explicitly state "acceptance criteria" with numerical targets for each performance metric. Instead, it presents the results of a comparison study against a predicate device and concludes that the i-STAT Kaolin ACT test shows "acceptable correlation" and "comparable" performance to the predicate. Based on the "Summary of Clinical Test Performance," we can infer the implied acceptance criteria were related to achieving a strong correlation and similar bias to the predicate device.
| Performance Metric | Implied Acceptance Criteria (relative to predicate) | Reported Device Performance (mean across 3 sites) |
|---|---|---|
| Correlation (r) | High correlation (e.g., >0.90) | 0.906, 0.940, 0.971 (Average: 0.939) |
| Slope (y vs x) | Close to 1.0 | 0.962, 1.051, 0.962 (Average: 0.992) |
| Bias at 480 seconds | Low bias (e.g., within a clinically acceptable range, ideally near 0) | 30, -11, -47 (Average: -9.3) |
| Relative within sample imprecision of test method (Syy%) | Acceptable imprecision (comparable or better than predicate) | 3.6%, 4.0%, 3.6% (Average: 3.7%) |
| Relative within sample imprecision of comparative method (Sxx%) | (Provided for context of predicate's performance) | 9.1%, 6.8%, 7.6% (Average: 7.8%) |
| Precision (plasma controls) | Adequate precision for normal and prolonged clot times | Level 1: 168 ± 4 seconds (2.1% C.V.) |
| Level 2: 407 ± 20 seconds (4.8% C.V.) | ||
| Linearity to heparin concentration | Linear response across reportable range | Responds linearly from 50 to 1000 seconds. Sensitivity: 73 seconds / U/mL heparin (equivalent to predicate). |
| Insensitivity to pre-analytical sample temperature | Insensitive to pre-analytical temperature | Insensitive to the effect of pre-analytical sample temperature. |
| Sensitivity to fibrinogen levels | Comparable sensitivity to predicate | Comparable sensitivity to fibrinogen levels from 105 - 514 mg/dL as the Hemochron. |
| Response to platelet inhibition/removal | Equivalent response to predicate | Equivalent response to the Hemochron. |
| Response to aprotinin | Comparable or better than predicate | Approximately half the extension of the Hemochron system to the effect of added aprotinin. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size:
- Site 1: 311 patient samples
- Site 2: 352 patient samples
- Site 3: 313 patient samples
- Total Clinical Samples: 976 patient samples
- Data Provenance: The studies were conducted at "three external sites" and used "samples taken during cardiovascular surgery procedures." This indicates a prospective collection of real-world patient samples. The document does not specify the country of origin, but given the submission is to the FDA (U.S.), it is highly probable the studies were conducted in the U.S.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This is not applicable as the "ground truth" for this device is a quantitative measurement (Activated Clotting Time), not an interpretation by experts. The comparison is against a predicate device, which itself measures ACT.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable. The study involves direct comparison of numerical results from two analytical devices, not subjective expert interpretations that would require adjudication.
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
Not applicable. This is not an AI-assisted diagnostic device, but an in vitro diagnostic test for measuring Activated Clotting Time. No human readers or AI assistance are involved in the measurement process.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are effectively standalone performance studies for the i-STAT Kaolin ACT test. The device automatically performs the analysis once the blood sample is introduced into the cartridge and inserted into the analyzer. There is no human intervention in the result generation process itself, and the study compares the results generated by the i-STAT system directly against those of the predicate device.
7. The type of ground truth used (expert concensus, pathology, outcomes data, etc)
The "ground truth" in this context is the measurement provided by the predicate device, the Hemochron® Activated Whole Blood Clotting Time (Hemochron KACT). The study aimed to demonstrate that the i-STAT device's measurements are substantially equivalent to those of a legally marketed, established device.
8. The sample size for the training set
The document does not explicitly mention a "training set" for the device itself. Medical devices like this typically undergo a development and calibration phase, which involves extensive testing, but the term "training set" as understood in machine learning (where the algorithm learns from data) is not directly applicable here. The non-clinical studies (imprecision, linearity, sensitivity tests) represent development and validation data, but not a distinct "training set" in the AI sense.
9. How the ground truth for the training set was established
Not applicable (see point 8). For the non-clinical studies, "ground truth" would generally refer to known control values, known heparin concentrations, or comparison to established laboratory methods for determining fibrinogen levels, etc.
§ 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).