(13 days)
The Bio-Rad VARIANT II TURBO Hemoglobin A1c Program is intended for the percent determination of hemoglobin A1c in human whole blood using ion-exchange high-performance liquid chromatography (HPLC).
The Bio-Rad VARIANT II TURBO Hemoglobin A1c Program is intended for Professional Use Only. For In Vitro Diagnostic Use.
Measurement of percent hemoglobin A1c is effective in monitoring long-term glucose control in individuals with diabetes mellitus.
The VARIANT II TURBO Hemoglobin Testing System uses the principles of high performance liquid chromatography (HPLC). The VARIANT II TURBO Hemoglobin A1c Program is based on chromatographic separation of Hemoglobin A1c on a cation exchange cartridge.
Acceptance Criteria and Device Performance Study for Bio-Rad VARIANT™ II TURBO Hemoglobin A1c Program
The Bio-Rad VARIANT™ II TURBO Hemoglobin A1c Program achieved substantial equivalence to its predicate device, the VARIANTTM II Hemoglobin A1c Program, based on testing evaluating accuracy, precision, and linearity, and comparison of interfering substances. The study provided data supporting these aspects.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific thresholds for accuracy, precision, or linearity that the new device must meet. Instead, the study's aim was to demonstrate "substantial equivalence" to the predicate device. Therefore, the "acceptance criteria" are implicitly derived from the performance of the predicate device. The "reported device performance" refers to that of the VARIANT™ II TURBO.
| Performance Metric | Acceptance Criteria (Implied from Predicate Performance) | Reported Device Performance (VARIANT™ II TURBO) |
|---|---|---|
| Accuracy (Method Correlation) | Linear Regression (vs. Predicate): Expect a strong linear relationship (similar slope, intercept, and correlation coefficient). | Slope: 1.006 |
| Intercept: -0.016% | ||
| Correlation Coefficient (r^2): 0.9997 | ||
| Range of samples: 3.9% to 17.5% HbA1c | ||
| Precision | Within Run CV: Similar to predicate device. | |
| Total Precision CV: Similar to predicate device. | Low Patient (HbA1c ~6.2%): Within run CV: 0.82%, Total Precision: 1.94% CV | |
| High Patient (HbA1c ~12.5%): Within run CV: 0.54%, Total Precision: 2.58% CV | ||
| (For comparison, Predicate Low Patient (HbA1c ~5.4%): Within run CV: 1.46%, Total Precision: 2.14% CV; Predicate High Patient (HbA1c ~13.7%): Within run CV: 0.65%, Total Precision: 1.68% CV) | ||
| Linearity | % Recovery: Similar to predicate device, maintaining recovery within acceptable limits across the assay range. | % Recovery: Ranged from 96.8% to 100% across theoretical HbA1c values from 3.8% to 17.3%. |
| Linear range as stated in Instruction for Use: 4.1 to 16.8% HbA1c. | ||
| Interfering Substances | Bilirubin: No interference up to 20 mg/dL. | |
| Lipids (Triglycerides): No interference up to 6000 mg/dL. | ||
| EDTA: No interference up to 11X EDTA. | Bilirubin: No interference up to 20 mg/dL | |
| Lipids (Triglycerides): No interference up to 5680 mg/dL | ||
| EDTA: No interference up to 11X EDTA |
2. Sample Size for Test Set and Data Provenance
- Accuracy (Method Correlation): 201 EDTA whole blood patient samples.
- Precision: 80 samples for the low patient HbA1c control and 80 samples for the high patient HbA1c control for each device (VARIANT II TURBO and VARIANT II). The wording "patient samples" suggests these were human whole blood samples.
- Linearity: Eight EDTA-based blood standards (n=2 for each standard) were used for comparison with the predicate. A separate study for the VARIANT II TURBO's stated linear range used seven standards (n=2 for each standard).
The data provenance is not explicitly stated in terms of country of origin. The samples were "EDTA whole blood patient samples" and "EDTA-based blood standards," implying they were clinical samples or derived from human blood. The studies appear to be prospective, specifically designed to compare the new device to the predicate.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This device is an in-vitro diagnostic (IVD) assay, not an AI/imaging device requiring expert interpretation for ground truth. The "ground truth" for this type of device is the measured value from the predicate device (VARIANT II Hemoglobin A1c Program) and, by extension, the established reference methods to which the predicate device is standardized (DCCT reference method, IFCC, and NGSP certification). No human experts were used to establish ground truth for individual test cases in the context of interpretation.
4. Adjudication Method for the Test Set
Not applicable. As an IVD assay measuring an analyte, there is no human adjudication process involved in confirming the output of the device. The comparison is quantitative between the new device and the predicate device's measurements.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is relevant for imaging or diagnostic interpretation tasks where human readers' performance is being evaluated, often with and without AI assistance. This document describes an IVD assay, not an AI-powered diagnostic interpretation tool.
6. Standalone (Algorithm Only) Performance
Yes, the studies evaluate the standalone performance of the VARIANT™ II TURBO Hemoglobin A1c Program by directly comparing its measurements to those of the predicate device (VARIANT™ II Hemoglobin A1c Program). The device itself is an automated HPLC system that provides a direct measurement, and its performance is assessed independently of human intervention during the measurement process, although it is intended for "Professional Use Only."
7. Type of Ground Truth Used
The ground truth used for comparisons was the measured values from the predicate device (VARIANT™ II Hemoglobin A1c Program). Both the predicate and the new device are standardized to recognized reference methods:
- Traceable to the Diabetes Control and Complications Trial (DCCT) reference method.
- Traceable to IFCC (International Federation of Clinical Chemistry and Laboratory Medicine).
- Certified via the National Glycohemoglobin Standardization Program (NGSP).
Therefore, the ground truth is based on a combination of established reference methods and direct comparison to a legally marketed equivalent device.
8. Sample Size for the Training Set
This document does not describe a machine learning or AI-based device that would typically have a "training set." The VARIANT™ II TURBO Hemoglobin A1c Program is an HPLC system. Therefore, the concept of a "training set" in the context of AI is not applicable here. The device's operational parameters and calibration would be established through internal development and validation, but not through an external "training set" of data in the AI sense.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the AI sense for this HPLC device.
§ 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).