(482 days)
PATHFAST® cTnl-II test is an in vitro diagnostic test for the quantitative measurement of cardiac Troponin I (cTn!) in heparinized or EDTA whole blood and plasma. Measurements of cardiac Troponin I are used as an aid in the diagnosis of acute myocardial infarction. This method is for use in clinical laboratory or point of care (POC) settings.
The PATHFAST® cTnl Calibrators are for calibration of the PATHFAST® system when used for the quantitative determination of cardiac Troponin I in human heparinized or EDTA whole blood and plasma.
The PATHFAST cTnl-II assay is for the quantitative measurement of human cardiac troponin I in heparinized or EDTA whole blood or plasma. The assay is designed for use on the PATHFAST instrument.
The PATHFAST cTnl-II test is a chemiluminescent enzyme immunoassay performed on the PATHFAST instrument. Patient samples, whole blood or plasma, are dispensed by the operator into the designated area on the reagent cartridge. The instrument combines the patient sample, the antibody coated magnetic particles, and the alkaline phosphatase conjugate and incubates the mixture for 5 minutes at 37°C. During this incubation, the analyte in the patient sample binds to the antibody on the coated particles, and the alkaline phosphatase conjugate binds to the analyteantibody-coated particle.
After the incubation, the instrument performs Bound/Free (B/F) separation using Magtration® technology to remove any excess unbound reagents. The chemiluminescent substrate is then added. The substrate is catalyzed by the bound alkaline phosphatase, which results in emission of photons.
The photo-multiplier tube in the PATHFAST instrument detects the photons that are emitted during the reaction. The chemiluminescent count is converted to analyte concentration values by the instrument based on the master calibration curve for the reagent lot.
Here's a detailed breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
The core purpose of the PATHFAST® cTnI-II test is to aid in the diagnosis of acute myocardial infarction (AMI) by quantitatively measuring cardiac Troponin I (cTnI). The acceptance criteria are implicitly defined by the clinical sensitivity and specificity targets presented in the study.
Table of Acceptance Criteria and Reported Device Performance
The device performance is evaluated at two different cutoffs: the 99th percentile cutoff (0.029 ng/mL) and an ROC cutoff (0.264 ng/mL). The study describes the performance across three time intervals for sample collection relative to presentation at the Emergency Room (ER): 0-2 hours, 2-6 hours, and 6-12 hours.
| Cutoff | Time Interval | Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|---|---|
| 0.029 ng/mL | 0 to 2 h | Clinical Sensitivity | (Not explicitly stated, but generally high for AMI diagnosis) | 73.6% (95% CI: 61.9% - 83.3%) |
| Clinical Specificity | (Not explicitly stated, but generally high for AMI diagnosis) | 92.7% (95% CI: 88.9% - 95.6%) | ||
| 2 to 6 h | Clinical Sensitivity | (Not explicitly stated, but generally high for AMI diagnosis) | 93.1% (95% CI: 84.5% - 97.7%) | |
| Clinical Specificity | (Not explicitly stated, but generally high for AMI diagnosis) | 93.1% (95% CI: 89.3% - 95.9%) | ||
| 6 to 12 h | Clinical Sensitivity | (Not explicitly stated, but generally high for AMI diagnosis) | 91.7% (95% CI: 82.7% - 96.9%) | |
| Clinical Specificity | (Not explicitly stated, but generally high for AMI diagnosis) | 91.6% (95% CI: 87.5% - 94.6%) | ||
| 0.264 ng/mL | 0 to 2 h | Clinical Sensitivity | (Not explicitly stated, but generally high for AMI diagnosis) | 23.6% (95% CI: 14.4% - 35.1%) |
| Clinical Specificity | (Not explicitly stated, but generally high for AMI diagnosis) | 99.2% (95% CI: 97.3% - 99.9%) | ||
| 2 to 6 h | Clinical Sensitivity | (Not explicitly stated, but generally high for AMI diagnosis) | 62.5% (95% CI: 50.3% - 73.6%) | |
| Clinical Specificity | (Not explicitly stated, but generally high for AMI diagnosis) | 98.1% (95% CI: 95.6% - 99.4%) | ||
| 6 to 12 h | Clinical Sensitivity | (Not explicitly stated, but generally high for AMI diagnosis) | 80.6% (95% CI: 69.5% - 88.9%) | |
| Clinical Specificity | (Not explicitly stated, but generally high for AMI diagnosis) | 97.7% (95% CI: 95.1% - 99.2%) |
Note on "Acceptance Criteria (Implied)": The document doesn't explicitly state numerical acceptance thresholds for sensitivity and specificity. Instead, it presents the device's performance, implying these are acceptable for the intended use as an aid in AMI diagnosis. The fact that the device was cleared suggests these performance metrics met the FDA's requirements for substantial equivalence.
Study Details
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Sample size used for the test set and the data provenance:
- Sample Size: 333 consecutively eligible consented patients.
- 72 patients diagnosed with MI
- 261 patients diagnosed as non-MI
- Data Provenance: Prospectively collected banked serial plasma samples (heparin anticoagulant). The country of origin is not explicitly stated in the provided text.
- Sample Size: 333 consecutively eligible consented patients.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Number of experts: An "adjudication panel" was used. The exact number of experts is not specified.
- Qualifications of those experts: The qualifications are not explicitly stated, but the panel followed "ESC/ACCF/AHA/WHF 2007 guidelines" for diagnosing MI, implying expertise in cardiology and clinical diagnosis of MI.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Adjudication Method: "The clinical diagnosis of MI was performed by an adjudication panel according to ESC/ACCF/AHA/WHF 2007 guidelines." This indicates a consensus-based approach guided by established clinical guidelines. Specific voting rules (like 2+1) are not detailed.
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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:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study with human readers and AI assistance was not described. This study focuses on the standalone performance of the PATHFAST® cTnI-II test.
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If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, a standalone study was done. The reported clinical sensitivity and specificity describe the performance of the PATHFAST® cTnI-II test (algorithm/device only) in distinguishing MI from non-MI based on cTnI levels, without human interpretation of the test results themselves as part of the primary analysis. The ground truth, however, was human-adjudicated.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Ground Truth Type: Expert consensus based on "existing clinical data including ECG and other clinical information" and adherence to "ESC/ACCF/AHA/WHF 2007 guidelines." Notably, the panel explicitly "did not use the final discharge diagnosis or the PATHFAST cTnI-II Test results" to avoid bias. This is a form of expert consensus based on comprehensive clinical information.
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The sample size for the training set:
- The document primarily describes a clinical validation study and does not explicitly state a separate "training set" for the clinical performance evaluation of the PATHFAST® cTnI-II test in the context of MI diagnosis. The device's internal calibration and analytical performance were likely developed using other sample sets, but these are not detailed as "training sets" for the clinical sensitivity/specificity study. The data referenced for the 99th percentile cutoff (0.029 ng/mL) was derived from "490 heparinized plasma samples from apparently healthy individuals," which could be considered a reference sample set used in establishing normative values rather than a "training set" for a diagnostic algorithm.
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How the ground truth for the training set was established:
- As no explicit "training set" for the clinical performance study (diagnosis of AMI - serial samples) is detailed, the method for establishing its ground truth is not applicable in this context. For the 99th percentile reference interval determination, the ground truth was "apparently healthy individuals," implying a healthy cohort without MI.
§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.
(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.