(270 days)
The i-STAT G cartridge with the i-STAT 1 System is intended for use in the in vitro quantification of glucose in arterial. venous or capillary whole blood in point of care or clinical laboratory settings.
Glucose measurements are used in the diagnosis, monitoring, and treatment of carbohydrate metabolism disorders including, but not limited to, diabetes mellitus, neonatal hypoglycemia, and pancreatic islet cell carcinoma.
The i-STAT G cartridge is used with the i-STAT 1 analyzer as part of the i-STAT 1 System to measure glucose in arterial, venous, or capillary whole blood for the diagnosis, monitoring, and treatment of metabolism disorders including, but not limited to, diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and pancreatic islet cell carcinoma.
The i-STAT 1 System is an in vitro diagnostic (IVD) medical device intended for the quantitative determination of various clinical chemistry tests contained within i-STAT cartridges using whole blood. The i-STAT 1 System consists of a portable blood analyzer (i-STAT 1 analyzer), single-use disposable test cartridges (i-STAT cartridges), liquid quality control and calibration verification materials, and accessories (i-STAT 1 Downloader/Recharger, i-STAT Electronic Simulator and i-STAT 1 Printer). The i-STAT 1 Sustem, including the i-STAT G cartridge, is designed for use by trained medical professionals in point of care or clinical laboratory settings and is for prescription use only.
The i-STAT G cartridge contains the required sensors and a fluid pack (calibrant pouch), a sample entry well and closure, fluid channels, waste chamber, and the necessary mechanical features for controlled fluid movement within the cartridge. The test is contained in a single-use, disposable cartridge. All the test steps and fluid movements occur within the i-STAT G cartridge. Cartridges require two to three drops of whole blood applied to the cartridge using a transfer device, by the trained user before the cartridge is placed within the analyzer.
The i-STAT 1 analyzer is a handheld, in vitro diagnostic analytical device designed to run only i-STAT test cartridges. The analyzer interacts with the cartridge to move fluid across the sensors and generate a quantitative result (within approximately 2 minutes).
Here's a breakdown of the acceptance criteria and the study details for the i-STAT G cartridge with the i-STAT 1 System, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" for each performance characteristic in a summarized table within the 510(k) summary. However, it indicates that the studies "met acceptance criteria" or "demonstrated equivalency" to a predicate device or allowable error.
For several tests (e.g., precision, linearity), the results are presented, and the implicit acceptance criterion is that these results fall within acceptable clinical or statistical limits, or demonstrate substantial equivalence to the predicate device.
For the purpose of this response, I will infer the acceptance criteria from the context of how the results are presented and the FDA's ultimate determination of "substantially equivalent."
| Acceptance Criteria (Inferred) | Reported Device Performance (Summary from Tables) |
|---|---|
| Precision | |
| 20-Day Precision (Aqueous Materials): Within laboratory precision (Total SD and %CV) within acceptable limits for a clinical glucose test. | CV L1 (25.0 mg/dL): SD 0.55, %CV 2.19 |
| CV L2 (38.5 mg/dL): SD 0.49, %CV 1.27 | |
| CV L3 (119.1 mg/dL): SD 0.78, %CV 0.66 | |
| CV L4 (272.2 mg/dL): SD 1.66, %CV 0.61 | |
| CV L5 (565.5 mg/dL): SD 5.41, %CV 0.96 (Table 1) | |
| Multi-site/Operator Precision (Aqueous Materials): Overall precision (SD and %CV) within acceptable limits across multiple sites and operators. | CV L1 (573.1 mg/dL): SD 2.89, %CV 0.50 |
| CV L2 (266.3 mg/dL): SD 0.82, %CV 0.31 | |
| CV L3 (133.7 mg/dL): SD 0.61, %CV 0.46 | |
| CV L4 (46.1 mg/dL): SD 0.48, %CV 1.04 | |
| CV L5 (33.7 mg/dL): SD 0.58, %CV 1.73 (Table 2) | |
| Whole Blood Precision: %CVs for different sample types (Venous, Arterial, Capillary) across various glucose ranges within acceptable clinical limits. | Venous (20-700 mg/dL): %CVs 0.32-2.01 |
| Arterial (20-700 mg/dL): %CVs 0.26-0.46 | |
| Capillary (20-700 mg/dL): %CVs 1.38-2.71 (Table 3) | |
| Linearity/Reportable Range | |
| Linearity: Slope ~1, Intercept ~0, R2 ~1 over the reportable range (20-700 mg/dL). | Slope 1.002, Intercept -1.258, R2 0.999 for reportable range 20-700 mg/dL (Table 4). |
| LoQ: LoQ value must be less than or equal to the lower limit of the reportable range (20 mg/dL). | LoQ for Glucose: 14 mg/dL. This is below the lower limit of the reportable range of 20 mg/dL (Table 5). |
| LoB/LoD: LoB and LoD values should be sufficiently low, ideally near zero, for a glucose test. | LoB for Glucose: 0 mg/dL |
| LoD for Glucose: 0.7 mg/dL (Table 6) | |
| Analytical Specificity (Interference): Difference in means (or medians) between control and test samples for potentially interfering substances within allowable error (±Ea). | Most tested substances showed "No" interference. Identified interferents (Bromide, Hydroxyurea, Isoniazid) resulted in a comment to "Use another method" or noted increased results (Table 7). This implies the device performed as expected by identifying interferents, potentially leading to warnings for users. |
| Oxygen Sensitivity: 95% confidence interval (CI) of the difference in means (or medians) between high and low oxygen conditions within the allowable error (±Ea). | Insensitive to oxygen levels between 21 and 515 mmHg. |
| Hematocrit Sensitivity: Difference between low/high and mid hematocrit levels within the allowable error (±Ea). | Insensitive to hematocrit levels between 15% to 75% packed cell volume (PCV). |
| Altitude: Correlation coefficient (r) and slope met acceptance criteria when compared to a comparator device at altitude. | At approximately 10,000 feet above sea level, r = 0.97 (CI 0.964 to 0.972) and Slope = 1.00 (CI 1.000 to 1.000) (Table 8), demonstrating equivalent performance. |
| Method Comparison (vs. Comparator Device): Passing-Bablok regression with slope ~1, intercept ~0, and high correlation (r ~1). | Arterial/Venous vs. i-STAT CHEM8+: N=571, Slope 1.00, Intercept 1.85, r 1.00 (Table 9) |
| Capillary vs. epoc Blood Analysis System: Included in the pooled data above. (Table 9) | |
| By sample type: |
- Arterial vs. i-STAT CHEM8+: N=173, Slope 1.00, Intercept 1.00, r 1.00
- Venous vs. i-STAT CHEM8+: N=164, Slope 1.00, Intercept 1.50, r 1.00
- Capillary vs. epoc Blood Analysis System: N=234, Slope 1.00, Intercept 2.00, r 1.00 (Table 10) |
| Matrix Equivalence: Passing-Bablok regression (non-anticoagulated vs. heparinized) with slope ~1, intercept ~0, and high correlation (r ~1). | N=158, r 1.00, Slope 1.00, Intercept 0.00 (Table 11). |
| EDTA Matrix Equivalence: Passing-Bablok regression (K2EDTA/K3EDTA vs. lithium heparin) with slope ~1, intercept ~0, and high correlation (r ~1). | K2EDTA vs. LiHep: N=43, r 1.00, Slope 1.03, Intercept -1.037 (Table 12)
K3EDTA vs. LiHep: N=43, r 1.00, Slope 1.03, Intercept 0.015 (Table 13) |
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision (20-day, aqueous materials): N=80 for each of 5 fluid levels.
- Precision (Multi-site and operator-to-operator, aqueous materials): N=89-90 for each of 5 fluid levels.
- Precision (whole blood):
- Venous whole blood: N=38 (20-90 mg/dL), N=67 (>90-150 mg/dL), N=32 (>150-250 mg/dL), N=15 (>250-400 mg/dL), N=12 (>400-700 mg/dL).
- Arterial whole blood: N=9 (20-90 mg/dL), N=94 (>90-150 mg/dL), N=64 (>150-250 mg/dL), N=6 (>250-700 mg/dL).
- Capillary whole blood: N=33 (20-90 mg/dL), N=53 (>90-150 mg/dL), N=37 (>150-250 mg/dL), N=16 (>250-700 mg/dL).
- Linearity: Whole blood samples of varying glucose levels across the reportable range.
- Limit of Quantitation (LoQ): Whole blood "altered to a low glucose level."
- Limit of Blank/Detection (LoB/LoD): Whole blood "altered to a blank glucose level" and "two (2) low glucose levels."
- Interference: Whole blood samples at low and high glucose levels.
- Oxygen Sensitivity: Whole blood samples "altered to four (4) glucose levels."
- Hematocrit Sensitivity: Whole blood samples at "three (3) hematocrit levels...at four (4) glucose levels."
- Altitude: Whole blood samples "across the reportable range."
- Method Comparison:
-
Arterial/Venous: N=571 (pooled data for i-STAT CHEM8+ comparison)
-
Arterial: N=173 (vs. i-STAT CHEM8+)
-
Venous: N=164 (vs. i-STAT CHEM8+)
-
Capillary: N=234 (vs. epoc Blood Analysis System)
-
- Matrix Equivalence (non-anticoagulated vs. heparinized): N=158
- EDTA Matrix Equivalence: N=43 for K2EDTA vs LiHep, N=43 for K3EDTA vs LiHep.
Data Provenance:
- Retrospective/Prospective: Primarily involves prospective testing of samples (aqueous materials, whole blood) under controlled conditions, or collection of patient samples for method comparisons.
- Country of Origin: Not specified in the provided text, but implied to be within the scope of where Abbott Point of Care (US company) conducts its clinical evaluations, likely the US or other regions following CLSI guidelines.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not detailed in the provided document. The ground truth for analytical performance studies on diagnostic devices like this often relies on:
- Reference methods using highly accurate laboratory analyzers.
- Certified reference materials (like NIST SRM 965 mentioned for traceability).
- Clinically established ranges and allowable errors.
- The "experts" are primarily the laboratory scientists and statisticians who conduct and analyze the studies according to CLSI guidelines.
For method comparison studies, the "ground truth" is typically the result from a legally marketed predicate device (i-STAT CHEM8+ cartridge) or a well-established laboratory reference method (epoc Blood Analysis System). The document does not mention human expert annotation of samples for establishing ground truth, as it's an in-vitro diagnostic device not directly involving image interpretation or clinical decision-making by human experts for the output itself.
4. Adjudication Method for the Test Set
This information is not applicable in the traditional sense for an in-vitro diagnostic glucose test. Adjudication methods (like 2+1 or 3+1) are typically used in clinical studies where human readers or interpreters make subjective assessments that might differ, and a consensus or adjudication process is needed to establish a definitive ground truth. For quantitative measurements like glucose, the "adjudication" is inherent in the analytical process:
- Reference methods provide the comparative "true" value.
- Statistical analyses (e.g., Passing-Bablok regression, precision calculations) determine if the device's results are sufficiently close to this reference or internally consistent.
- Discrepancies would be investigated through quality control and root cause analysis, not expert adjudication of contradictory readings from the device itself.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done. This type of study (comparing human readers with and without AI assistance on multiple cases) is relevant for AI-powered diagnostic imaging devices where human interpretation is a key component. The i-STAT G cartridge is an in-vitro diagnostic device that directly measures glucose levels, not an AI assistance tool for human interpretation.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are essentially "standalone" performance evaluations. The i-STAT G cartridge with the i-STAT 1 System functions as an automated system for quantifying glucose. The performance data presented (precision, linearity, LoQ, LoB/LoD, interference, sensitivity, altitude, method comparison, and matrix equivalence) are all evaluations of the device's analytical performance on its own, without direct real-time human interpretation of the glucose value itself as the primary output to be compared. Human involvement is for sample collection, device operation, and quality control, but the reported glucose value is generated by the "algorithm" (the device's embedded processes).
7. The Type of Ground Truth Used
The ground truth used for performance validation includes:
- Reference methods: For method comparison studies, the i-STAT CHEM8+ cartridge on the i-STAT 1 System (predicate device) and the epoc Blood Analysis System served as comparative methods to establish ground truth or reference values.
- Certified reference materials/Calibrators: Mention of NIST SRM 965 for traceability and "i-STAT Calibration Verification set" for precision studies indicates the use of highly accurate, traceable materials.
- Spiked samples: For linearity, LoQ, LoB/LoD, and interference studies, samples were "altered" or "spiked" to known concentrations of glucose or interfering substances.
- Statistical models and clinical thresholds: The "allowable error (±Ea)" indicates that performance is judged against pre-defined clinical or statistical acceptance limits.
8. The Sample Size for the Training Set
This information is not provided in the document. The document describes performance validation studies (test sets). For an IVD device like this, the "training set" would refer to data used during the development and optimization phases before the formal validation for regulatory submission. Details on development-stage datasets are generally not included in 510(k) summaries.
9. How the Ground Truth for the Training Set was Established
This information is not provided for the same reasons as point 8.
§ 862.1345 Glucose test system.
(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.