(205 days)
ST AIA-PACK HbA1c is designed for In Vitro Diagnostic Use Only for the quantitative measurement for percent concentration of Hemoglobin A1c (HbA1c) in EDTA whole blood on Tosoh AIA System Analyzer. HbA1c measurement is used in the management and treatment of diabetes.
The ST AIA-PACK HbA1c is an enzyme immunoassay which, after pretreatment, is performed entirely in ST AIA-PACK HbA1c test cups. The whole blood sample must first be pretreated prior to immunocomplex formation between HbA1c and sheep anti-HbA1c polyclonal antibody. Sample pretreatment is performed to achieve complete hemolysis of erythrocytes and to expose carbohydrate part of HbA1c in the whole blood sample using ST AIA-PACK HbA1c PRETREATMENT SOLUTION (40 °C, 20 minutes). HbA1c present in the pretreated test sample is captured on the magnetic beads along with hemoglobin and bound with enzyme-labeled sheep anti-HbA1c polyclonal antibody in the AIA-PACK test cup. The beads are washed to remove the unbound materials and are then incubated with a fluorogenic substrate, 4-methylumbelliferyl phosphate (4MUP). The amount of enzyme-labeled polyclonal antibody that binds to the beads is directly proportional to the HbA1c concentration in the test sample. A standard curve using a range of known standard percent concentrations aligned to NGSP % is constructed and unknown HbA1c percent concentrations are calculated using this curve.
Here's an analysis of the acceptance criteria and the study data provided for the ST AIA-PACK HbA1c device:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the studies performed and the comparison to the predicate device. Based on the provided text, the key performance characteristics evaluated and their results are:
| Acceptance Criteria (Implied) | Device Performance (ST AIA-PACK HbA1c) |
|---|---|
| Correlation with Predicate Device | |
| Slope (Deming Regression) | 1.027 (95% CI: 1.006 to 1.047) |
| Intercept (Deming Regression) | -0.168 (95% CI: -0.326 to -0.011) |
| Correlation Coefficient (R) | 0.99 |
| Bias | 0.025 |
| Recovery | -4.9% to 2.2% (within a measuring range of 3-14% HbA1c) |
| Within-Run Precision (CV%) | 1.1% to 1.9% |
| Total Precision (CV%) | 1.9% to 4.0% |
| Assay Range | 3.0 to 14% |
| Cross-reactivity with HbF | >10% (comparable to predicate's 15%) |
| Cross-reactivity with HbS | 1 out of 5 variant HbS specimens was outside +/- 10% recovery (Predicate had "NO" cross-reactivity) |
Note on Acceptance Criteria: The document implies that these performance metrics, particularly the correlation and precision values, were considered acceptable as part of demonstrating substantial equivalence to the predicate device. Specific numerical acceptance ranges for each metric are not explicitly stated in the provided text as "acceptance criteria." However, the strong correlation (R=0.99), small bias, and reported precision values are generally considered indicative of acceptable performance for diagnostic devices. The deviations in HbS cross-reactivity are noted, but the conclusion of substantial equivalence suggests it was deemed acceptable in the overall context.
2. Sample Size Used for the Test Set and Data Provenance
- Correlation Study (Test Set): 126 patient specimens.
- Precision Study (Test Set): Three levels of unaltered EDTA whole blood specimens. Each level was assayed with 2 replicates, 2 times a day for 20 non-consecutive days, resulting in 40 runs and 80 determinants per specimen level.
- Recovery Study (Test Set): The exact number of samples for the recovery study is not explicitly stated, but it involved "high sample and low sample" with similar hemoglobin concentrations.
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It refers to "patient specimens" and "unaltered Human EDTA Whole Blood Specimen," suggesting human samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The provided text describes analytical performance studies (correlation, recovery, precision) comparing the device to a predicate device or evaluating its inherent performance characteristics. There is no mention of "experts" in the traditional sense (e.g., radiologists interpreting images) for establishing ground truth in this context.
For this type of in vitro diagnostic device, the "ground truth" for comparative effectiveness is established by the reference method (the predicate device, Tosoh Automated Glycohemoglobin Analyzer HLC-723G7, which uses an HPLC method) or by the inherent properties of the samples themselves when evaluating precision and recovery. The predicate device's HbA1c values are used as the reference for the correlation study.
4. Adjudication Method for the Test Set
Not applicable. As described in point 3, this is an analytical device comparison, not a study involving human interpretation with adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This type of study (MRMC, human readers with/without AI assistance) is typically performed for imaging diagnostics or other devices where human interpretation is a primary component of diagnosis. The ST AIA-PACK HbA1c is an in vitro diagnostic assay, and its performance is evaluated analytically, not through human reader performance.
6. Standalone (Algorithm Only Without Human-in-the-Loop) Performance
Yes, the studies reported (correlation, recovery, precision) represent the standalone performance of the ST AIA-PACK HbA1c device. It's an automated assay system; therefore, the reported performance metrics reflect the algorithm's and instrument's capabilities without human intervention influencing the measurement process itself.
7. Type of Ground Truth Used
- Correlation Study: The ground truth was established by the predicate device, the Tosoh Automated Glycohemoglobin Analyzer HLC-723G7, which uses an HPLC method for HbA1c measurement. This is a recognized reference method.
- Recovery Study: The ground truth for expected values was based on the prepared concentrations of high and low samples.
- Precision Study: The ground truth for the mean HbA1c values was derived from the measurements of unaltered EDTA whole blood specimens themselves using the device over multiple runs, reflecting the inherent variability of the assay.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set." This device is an enzyme immunoassay with a predefined chemical and instrumental methodology, not a machine learning or AI model that typically requires a separate training set. Its calibration uses a "ST AIA-PACK HbA1c CALIBRATOR SET" (6 points aligned to IFCC and NGSP), which serves a similar function to training in establishing the measurement curve but is not a "training set" in the machine learning sense.
9. How the Ground Truth for the Training Set Was Established
As noted above, there isn't a "training set" in the machine learning context. The calibration curve for the assay is established using the ST AIA-PACK HbA1c CALIBRATOR SET. These calibrators are described as "6 point aligned to IFCC and NGSP," meaning their HbA1c values are traceable to internationally recognized standards (International Federation of Clinical Chemistry and Laboratory Medicine) and reference methods (National Glycohemoglobin Standardization Program). This ensures the accuracy and standardization of the assay's measurements.
§ 864.7470 Glycosylated hemoglobin assay.
(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).