(268 days)
The i-STAT hs-Tnl cartridge with the i-STAT 1 System is in the in vitro quantification of cardiac troponin I (cTnl) in whole blood or plasma samples in point of care or clinical laboratory settings.
The i-STAT hs-Tnl cartridge with the i-STAT 1 System is intended to be used as an aid in the diagnosis of myocardial infarction (MI).
The i-STAT hs-TnI cartridge is an in vitro diagnostic test for the quantitative measurement of cardiac troponin I (cTnI) in whole blood or plasma samples using the i-STAT 1 analyzer in point of care or clinical laboratory settings.
The i-STAT hs-TnI test uses an enzyme-linked immunosorbent assay (ELISA) method with electrochemical detection of the resulting enzyme signal. The test reports a quantitative measurement of the sample concentration of cTnI in units of ng/L in approximately 15 minutes.
The i-STAT hs-TnI immunoassay test method uses anti-cTnI antibodies for labeling and capture. The capture antibodies are coated on para-magnetic microparticles. Both label and capture antibodies are contained within the cartridge on a biosensor chip. The ELISA is initiated when the test cartridge is inserted into the analyzer. The sample is positioned over the biosensor chip to dissolve the reagents. This forms the ELISA sandwich (detection antibodylabel/antigen/capture antibody). The sample and excess antibody-conjugate are then washed off the sensors. An enzyme within the ELISA sandwich generates an electrochemically detectable product. The biosensor chip measures the enzyme product which is proportional to the concentration of cTnI within the sample.
The i-STAT hs-TnI cartridge is a single use test cartridge. The cartridge contains a biosensor chip and all reagents required to execute the test cycle. All fluid movements within the cartridge (test sample or reagent) are automatically controlled by the i-STAT 1 analyzer by electromechanical interaction with the cartridge. The analyzer executes the test cycle, acquires and processes the electrical sensor signals converting the signals into quantitative results. These functions are controlled by a microprocessor.
The i-STAT 1 System is comprised of the i-STAT 1 analyzer and accessories (i-STAT 1 Downloader/Recharger, i-STAT Electronic Simulator, i-STAT Printer and i-STAT 1 9V NiMH Rechargeable Battery).
Assay quality control materials are also available for use with the i-STAT hs-TnI cartridge and include i-STAT hs-TnI Control Level 1. i-STAT hs-TnI Control Level 2. i-STAT hs-TnI Control Level 3, and the i-STAT hs-TnI Calibration Verification Levels 1-3.
Acceptance Criteria and Device Performance for i-STAT hs-TnI Cartridge with i-STAT 1 System
This response outlines the acceptance criteria and the study that demonstrates the i-STAT hs-TnI Cartridge with the i-STAT 1 System meets these criteria, based on the provided FDA 510(k) summary.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document doesn't explicitly list "acceptance criteria" in a single, consolidated table with pass/fail remarks. Instead, it presents performance characteristics and states whether the results "met the acceptance criteria" or "demonstrated acceptable performance." Based on this, the table below synthesizes the reported performance against inferred acceptance criteria.
Table: Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Inferred Acceptance Criteria (e.g., Target Range, Deviation Limit, "Acceptable Performance") | Reported Device Performance |
|---|---|---|
| Analytical Performance | ||
| 20-Day Precision (Plasma) | Results within acceptance criteria for all levels (e.g., CV% within specified limits, not explicitly stated as numerical values but implied by "demonstrated acceptable performance"). | All levels demonstrated acceptable performance, with Within-Laboratory CV% ranging from 3.68% to 15.89%. One outlier (0.07%) was excluded. |
| Whole Blood Precision | Within-site precision acceptable for all levels for each specimen type at each site (e.g., CV% within specified limits, not explicitly stated as numerical values but implied by "demonstrated to be acceptable"). | All levels and sites demonstrated acceptable performance. Within-Site CV% for whole blood ranged from 3.09% to 9.93%. |
| Plasma Precision | Within-site precision acceptable for all levels for each specimen type at each site (e.g., CV% within specified limits, not explicitly stated as numerical values but implied by "demonstrated to be acceptable"). | All levels and sites demonstrated acceptable performance. Within-Site CV% for plasma ranged from 2.57% to 12.80%. One outlier (0.38%) was excluded. |
| Precision in Control Materials | Results demonstrate acceptable precision (e.g., CV% within specified limits, not explicitly stated as numerical values but implied by "acceptable"). | Within-Laboratory CV% ranged from 3.25% to 7.45%. |
| Multi-site Multi-Day Precision | Reproducibility within acceptable limits (e.g., CV% within specified limits, not explicitly stated as numerical values but implied by "acceptable"). | All levels demonstrated acceptable reproducibility. Reproducibility CV% ranged from 3.54% to 4.71%. |
| Linearity | Demonstrated linearity over the reportable range (2.9 – 1000.0 ng/L) with a slope close to 1 and R^2 close to 1, meeting acceptance criteria (not explicitly stated as numerical range, but implied). | Whole Blood: Slope = 1.025, Intercept = 0.183, R^2 = 0.9990. Plasma: Slope = 1.043, Intercept = -0.171, R^2 = 0.9993. Both met acceptance criteria over the reportable range. |
| Sample Type Comparison (WB vs. Plasma) | Slope close to 1, Intercept close to 0, and high correlation (r) indicating equivalence. | Slope = 1.01, Intercept = 0.603, r = 0.99. |
| High Dose Hook Effect | No hook effect observed up to 500,000 ng/L. | No hook effect was observed for whole blood and plasma samples with cTnI concentrations up to 500,000 ng/L. |
| Limit of Blank (LoB) | Determined from study results, ensuring minimal false positives. | Whole Blood LoB: 0.78 ng/L; Plasma LoB: 0.57 ng/L. |
| Limit of Detection (LoD) | Determined from study results, ensuring minimal false negatives. | Whole Blood LoD: 1.61 ng/L; Plasma LoD: 1.05 ng/L. |
| Limit of Quantitation (LoQ) | LoQ determined as 20% CV concentration using a precision profile method, with lower limit of reportable range set to the greater of WB and Plasma LoQ. | Whole Blood LoQ: 2.90 ng/L. Lower limit of reportable range set to 2.9 ng/L. |
| Analytical Specificity (Interference) | Difference between control and test samples within a pre-determined acceptable range (not explicitly quantified but implied by "No interference"). | Bilirubin (Unconjugated) showed decreased results > 85.5 µmol/L (5 mg/dL). Cefoxitin showed decreased results > 6564 µmol/L (295 mg/dL) in plasma. Fibrinogen showed decreased results > 0.4 g/dL in plasma. Rheumatoid Factor (RF) showed decreased results > 350 IU/mL in plasma. Total Protein showed decreased results ≥ 8.5 g/dL in plasma. All other listed substances showed no interference. |
| Analytical Specificity (Cross-reactivity) | No cross-reactivity observed at specified concentrations. | None of the nine substances tested (e.g., cTnT, CK-MB, Myoglobin, sTnI) were found to cross-react. |
| Hematocrit Sensitivity | Imprecision not exceeding 10% and bias not exceeding ±10% for whole blood samples. | Increased imprecision exceeding 10% for whole blood with hematocrit > 57 %PCV and increased bias exceeding ±10% for whole blood with hematocrit > 55 %PCV. |
| Altitude Performance | Equivalent performance (slope close to 1, high correlation r) between simulated altitude (7,500 ft and 10,000 ft) and sea level. | All conditions demonstrated equivalent performance: 7,500 ft (WB r=1.00, Plasma r=1.00), 10,000 ft (WB r=1.00, Plasma r=1.00) with slopes close to 1. |
| Comparison Studies | ||
| Matrix Equivalence (Non-Anticoagulated WB vs. Li-Heparin WB) | Slope close to 1, Intercept close to 0, and high correlation (r) indicating equivalence. | r = 1.00, Slope = 1.04, Intercept = -0.01. Demonstrated to be equivalent. |
| Matrix Equivalence (Li-Heparin Tube with Separator Gel vs. Li-Heparin Tube) | Slope close to 1, Intercept close to 0, and high correlation (r) indicating equivalence for both whole blood and plasma. | Whole Blood: r = 1.00, Slope = 1.01, Intercept = -0.15. Plasma: r = 1.00, Slope = 1.01, Intercept = 0.04. Demonstrated to be equivalent. |
| Clinical Sensitivity (Overall 99th Percentile URL) | High sensitivity values, especially in later time points (>1 to 6 hours), with lower limits of 97.5% CI above specific thresholds (not numerically listed, but stated as a target for "acceptable performance"). | Female: 86.05% (0-1hr) to 95.71% (>3-6hr). Male: 83.08% (0-1hr) to 95.65% (>3-6hr). Plasma values were similar. |
| Clinical Specificity (Overall 99th Percentile URL) | High specificity values above specific thresholds (not numerically listed, but stated as a target for "acceptable performance"). Note: lower specificity in longer time points/lower MI prevalence areas is expected. | Female: 89.37% (0-1hr) to 65.91% (>6hr). Male: 78.33% (0-1hr) to 54.29% (>6hr). Plasma values were similar. |
| Clinical Sensitivity (Sex-Specific 99th Percentile URL) | High sensitivity values, especially in later time points (>1 to 6 hours), with lower limits of 97.5% CI above specific thresholds (not numerically listed, but stated as a target for "acceptable performance"). | Female: 91.47% (0-1hr) to 100.00% (>6hr). Male: 79.23% (0-1hr) to 94.20% (>3-6hr). Plasma values were similar. |
| Clinical Specificity (Sex-Specific 99th Percentile URL) | High specificity values above specific thresholds (not numerically listed, but stated as a target for "acceptable performance"). Note: lower specificity in longer time points/lower MI prevalence areas is expected. | Female: 83.23% (0-1hr) to 54.55% (>6hr). Male: 84.17% (0-1hr) to 57.14% (>6hr). Plasma values were similar. |
2. Sample Sizes and Data Provenance
-
Test Set Sample Size:
- 20-Day Precision: 240 replicates per level for 6 plasma samples (total 1440 tests across 3 cartridge lots, 20 days).
- Whole Blood and Plasma Precision: Min. 24 replicates per level (6 levels) per site (3 sites) for whole blood and plasma specimens. Total number of replicates for whole blood was 576, and for plasma was 576.
- Precision in Control Materials: 25 replicates per level (5 levels) for control materials.
- Multi-site Multi-Day Precision: 90 replicates per level (6 plasma samples) (total 540 tests across 3 sites, 5 days, 2 operators).
- Linearity: Not explicitly stated as a single number but implied by samples covering the reportable range.
- Sample Type Comparison (WB vs. Plasma): Not explicitly stated, implied by samples covering the reportable range.
- High Dose Hook Effect: Not explicitly stated.
- LoB/LoD: Not explicitly stated, but involved 4 healthy donors for each sample type and multiple cartridge lots.
- LoQ: Not explicitly stated, but involved a low-level cTnI whole blood and plasma samples and 4 cartridge lots.
- Interference: Tested at two cTnI levels using various interfering substances.
- Cross-reactivity: Tested at three cTnI concentrations for each cross-reactive substance.
- Hematocrit Sensitivity: Whole blood samples at two cTnI levels and seven hematocrit levels.
- Altitude: Not explicitly stated as a single number but involved whole blood and plasma samples at relevant cTnI levels.
- Matrix Equivalence (Non-Anticoagulated WB vs. Li-Heparin WB): 88 paired specimens (including 8 contrived).
- Matrix Equivalence (Li-Heparin Tube with Separator Gel vs. Li-Heparin Tube): 87 paired specimens (including 8 contrived).
- Clinical Sensitivity and Specificity: 3585 subjects presenting to the Emergency Department.
-
Data Provenance:
- Analytical Performance Studies (Precision, Linearity, Hook Effect, LoB/LoD/LoQ, Interference, Cross-reactivity, Hematocrit, Altitude): These studies used a combination of frozen plasma samples, native venous whole blood and plasma specimens (prospectively collected), whole blood/plasma samples altered via spiking, control materials, and healthy donor samples. The studies were conducted at various clinical sites and internally at Abbott Point of Care.
- Reference Interval Study: United States (US) based general population, prospectively collected venous whole blood specimens from 895 apparently healthy subjects at 8 clinical sites.
- Matrix Equivalence Studies: Prospectively collected venous whole blood and plasma specimens from patients in point of care settings at two (2) clinical sites.
- Clinical Sensitivity and Specificity (Pivotal Study): Prospectively collected venous whole blood and plasma specimens at 28 clinical sites in the United States. These sites were geographically diverse EDs associated with acute care hospitals, medical centers, tertiary care facilities, and primary care clinics.
3. Number of Experts and Qualifications for Ground Truth
-
Clinical Sensitivity and Specificity Study (Pivotal Study):
- Number of Experts: Not explicitly stated as a specific number, but referred to as "board-certified cardiologists and/or emergency medicine physicians."
- Qualifications: Board-certified cardiologists and/or emergency medicine physicians. No specific years of experience are detailed.
- Role: Adjudicated subjects based on the fourth universal definition of MI.
-
Other Studies: The document does not indicate the involvement of external experts for establishing ground truth for other analytical performance or matrix equivalence studies. Ground truth for these was established through standard laboratory methods, spiked samples, and reference materials.
4. Adjudication Method for the Test Set
- Clinical Sensitivity and Specificity Study: The adjudication method for the clinical study involved "adjudication by board-certified cardiologists and/or emergency medicine physicians based on the fourth universal definition of MI." The adjudicators were blinded to the i-STAT hs-TnI test results, indicating an independent review process. The specific number of adjudicators per case (e.g., 2+1, 3+1) is not provided, but the mention of plural "physicians" suggests at least two.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- The document does not mention a multi-reader multi-case (MRMC) comparative effectiveness study to assess how much human readers improve with AI vs. without AI assistance. The device is an in vitro diagnostic test (IVD) for quantitative measurement of cTnI, not an imaging device or AI-powered diagnostic aide for human interpretation.
6. Standalone (Algorithm Only) Performance Study
- The performance studies described are inherently standalone for the device itself. The i-STAT hs-TnI cartridge with the i-STAT 1 System is a diagnostic test that provides a quantitative result. The clinical sensitivity and specificity are reported for the device's output (cTnI levels) as an aid in MI diagnosis, without human-in-the-loop interpretation of raw data from the device beyond reading the final numerical result.
7. Type of Ground Truth Used
- Clinical Sensitivity and Specificity Study: The ground truth for the diagnosis of MI was established by expert consensus (board-certified cardiologists and/or emergency medicine physicians) based on the fourth universal definition of MI. This is a clinical outcome/diagnostic ground truth.
- Analytical Studies:
- Precision, Linearity, Hook Effect, LoB/LoD/LoQ, Interference, Cross-reactivity, Hematocrit, Altitude, Matrix Equivalence: Ground truth was established using a combination of:
- Known concentrations in spiked samples.
- Reference methods/materials (e.g., NIST SRM2921 for traceability).
- Standard laboratory measurements and pre-defined expected values for linearity and comparison studies.
- Clinical classification based on robust biomarker criteria (for the reference interval study of healthy subjects).
- Precision, Linearity, Hook Effect, LoB/LoD/LoQ, Interference, Cross-reactivity, Hematocrit, Altitude, Matrix Equivalence: Ground truth was established using a combination of:
8. Sample Size for the Training Set
- The document describes performance evaluation studies and does not explicitly differentiate a "training set" for an AI/machine learning model. The i-STAT hs-TnI test is an immunoassay (ELISA method with electrochemical detection), not a device based on AI/ML. Therefore, the concept of a "training set" for an algorithm is not directly applicable in the context of this device description. The studies described are for analytical and clinical validation of the assay.
9. How the Ground Truth for the Training Set Was Established
- As stated in point 8, the device is an immunoassay, not an AI/ML system, so there isn't a "training set" in that conventional sense. The "ground truth" for the various analytical and clinical studies (which could be considered analogous to data used for establishing performance) was established as described in point 7.
§ 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.