Search Results

The i-STAT TBI test is a panel of in vitro diagnostic immunoassays for the quantitative measurements of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) in whole blood and a semi-quantitative interpretation of test results derived from these measurements, using the i-STAT Alinity instrument. The interpretation of test results is used, in conjunction with other clinical information, to aid in the evaluation of patients, 18 years of age or older, presenting with suspected mild traumatic brain injury (Glasgow Coma Scale score 13-15), which may include one of the following four clinical criteria: 1) any period of loss of consciousness, 2) any loss of memory for events immediately before and after the accident, 3) any alteration in mental state at the time of accident, and/or 4) focal neurological deficits, within 24 hours of injury, to assist in determining the need for a CT (computed tomography) scan of the head. A 'Not Elevated' test interpretation is associated with the absence of acute traumatic intracranial lesions visualized on a head CT scan.

The test is to be used with venous whole blood collected with EDTA anticoagulant in point of care or clinical laboratory settings by a healthcare professional.

The i-STAT TBI cartridge is a multiplex immunoassay that contains assays for both ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP). The assays test for the presence of these biomarkers in a whole blood sample and vield a semi-quantitative test interpretation based on measurements of both UCH-L1 and GFAP in approximately 15 minutes. The i-STAT TBI cartridge is designed to be run only on the i-STAT Alinity instrument.

The i-STAT Alinity instrument is a handheld, in vitro diagnostic device. The instrument is the main user interface of the i-STAT Alinity System and functions as the electro-mechanical interface to the test cartridge. The instrument 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 Alinity System is comprised of the i-STAT Alinity instrument, the i-STAT test cartridges and accessories (i-STAT Alinity Base Station, Electronic Simulator and Printer).

Assaved quality control materials are also available for use with the i-STAT TBI cartridge and include i-STAT TBI Control Level 1, i-STAT TBI Control Level 2, and the i-STAT TBI Calibration Verification Levels 1-3.

The i-STAT TBI Controls are available to monitor the performance of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) assays on the i-STAT Alinity instrument.

The i-STAT TBI Calibration Verification Materials are available to verify the calibration of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) assays throughout the reportable range on the i-STAT Alinity instrument.

The provided text describes the analytical and clinical performance of the i-STAT TBI cartridge with the i-STAT Alinity System, which measures GFAP and UCH-L1 to aid in the evaluation of patients with suspected mild traumatic brain injury (TBI). The information is presented to support a 510(k) premarket notification for substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided document:

1. A Table of Acceptance Criteria (Implied) and Reported Device Performance

The document does not explicitly present a "table of acceptance criteria" with predefined thresholds. Instead, it describes performance characteristics that are presumably deemed acceptable for demonstrating substantial equivalence. The core clinical performance criterion for this device, a TBI assessment test, is its ability to correctly identify patients not needing a head CT scan, which translates to high sensitivity and negative predictive value (NPV) for the absence of acute intracranial lesions.

Here's a summary of the reported core performance:

Key Implied Acceptance Criteria based on Regulatory Context:

• High Clinical Sensitivity: The device must reliably identify patients with acute intracranial lesions, minimizing false negatives to ensure patient safety and avoid missing critical injuries. A 96.5% sensitivity is presented as acceptable.
• High Negative Predictive Value (NPV): Crucially, the device's main utility is to aid in determining the need for a CT scan. A high NPV means that a "Not Elevated" result reliably indicates the absence of acute traumatic intracranial lesions. The 96.5% NPV (and higher adjusted NPV) supports this.
• Acceptable False Negative Rate: The reported 3.5% false negative rate, with the additional detail that "None of these ten (10) subjects with false negative results required surgical intervention related to their head injury as no neurosurgical lesions were identified by CT scan in these subjects," addresses a critical safety aspect.
• Analytical Performance: The document provides extensive data on analytical precision (semi-quantitative and qualitative, 20-day and multi-site), linearity, hook effect, traceability, reference interval, detection limit, analytical specificity (interference, cross-reactivity, cross-talk), and hematocrit sensitivity. These are all standard analytical performance characteristics that would need to meet predefined criteria (often internal to the manufacturer or based on regulatory guidance) to ensure the assay's reliability and robustness. While specific numerical acceptance criteria for each are not stated (e.g., "CV must be <X%"), the presentation of the data implies these were within acceptable ranges.

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size for Clinical Performance (Test Set): 970 subjects were included in the clinical performance analysis.
• Data Provenance: The data was collected from a prospective, multi-center, observational study conducted at 20 external point-of-care clinical sites across the United States. The study was designed to evaluate the clinical performance in classifying the intended use population.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

• Number of Experts: At least two neuroradiologists interpreted the CT images for ground truth establishment.
• Qualifications of Experts: The experts were "neuroradiologists." No specific details on their years of experience or board certifications are provided in this summary, but being neuroradiologists implies specialized training in interpreting neurological imaging.

4. Adjudication Method for the Test Set

• Adjudication Method: The clinical outcome (ground truth) was based on the "consensus interpretation between two neurologists" (which appears to be a slight inconsistency as the previous sentence referred to neuroradiologists, but the intent is clear: expert consensus). This implies a method where if the initial two readers disagreed, they would discuss and reach a consensus. If they couldn't reach consensus, a third reader might be involved, though the document only explicitly mentions "consensus interpretation between two neurologists." "Procedures for scoring images were established before conducting image review," suggesting a structured approach to adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

• No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance was not reported. This device is an in-vitro diagnostic (IVD) blood test, not an imaging AI algorithm designed to assist human readers in interpreting images. Its function is to provide a biomarker-based "Elevated" or "Not Elevated" interpretation to aid in clinical decision-making regarding CT scans, rather than augment human image interpretation.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

• Yes, the clinical performance study evaluated the device in a standalone (algorithm only) manner. The i-STAT TBI cartridge provides a "semi-quantitative interpretation of test results" (Elevated/Not Elevated) based on measurements of GFAP and UCH-L1. This interpretation is then compared directly to the CT scan ground truth. While it's used in conjunction with other clinical information by healthcare professionals, the reported sensitivity, specificity, and NPV are measures of the device's inherent performance.

7. The Type of Ground Truth Used

• The ground truth used was based on the presence or absence of acute traumatic intracranial lesions visualized on a head CT scan, as determined by consensus interpretation of at least two neuroradiologists/neurologists. "Acute intracranial lesion was defined as any trauma induced or related finding visualized upon head CT scan." This is a form of imaging-based ground truth, established by expert consensus.

8. The Sample Size for the Training Set

• The training set for determining the assay cut-offs for GFAP and UCH-L1 involved 420 subjects (274 males and 146 females) with suspected mild traumatic brain injury (GCS 13-15).

9. How the Ground Truth for the Training Set Was Established

• The ground truth for the training set used to establish the cut-off values was based on CT scan determinations. "Subjects who had blood drawn within 12 hours of injury and a head CT scan determination, were included in the analysis." The process involved "Using a 10-fold cross validation and bootstrapping method" to select the cut-off values of 65 pg/mL (GFAP) and 360 pg/mL (UCH-L1), using a selection criteria of "adjusted NPV (to 10%) ≥98.5% and sensitivity ≥97%". This indicates the CT scan results served as the ground truth for optimizing these cut-off values during model development.

Ask a specific question about this device