(17 days)
The VARIANT™ II Hemoglobin A1c Program is intended for the determination of hemoglobin A1c in human whole blood using ion-exchange high performance liquid chromatography (HPLC).
The VARIANT™ II Hemoglobin A1c Program is intended for use only with the Bio-Rad VARIANT™ II Hemoglobin Testing System.
For in vitro diagnostic use only.
The VARIANT™ II Hemoglobin A1c Program is based on chromatographic separation of HbA1c on a cation exchange cartridge. The analytical system of instrument and reagent kit provides a means of measuring Hemoglobin A1c, formed by the non-enzymatic attachment of circulating blood glucose to the N terminal valine of the B-chain of the hemoglobin molecule (HbAo). Attachment of glucose to hemoglobin is achieved in a two step process. The first step is the formation of an unstable aldimine (Schiff base, labile, or pre-A1c), a reversible reaction between the carbonyl group of glucose and the N terminal valine of the ß-chain of hemoglobin. The amount of Schiff base formed is directly proportional to the blood glucose concentration. The second step is the much slower and irreversible conversion of the Schiff base intermediate to the stable "ketoamine" product (Hemoglobin A1c). The percentage of Hemoglobin A1c in whole blood is dependent on the level of sustained blood glucose and indicative of mean blood glucose over the lifetime of red blood cells (~ 120 days).
The VARIANT™ II HbA1c Program has added front end automation and Clinical Data Management Software capabilities. The front end automation allows sampling from primary sample tubes. The predicate used a hemolysis reagent during sample preparation to remove Schiff base. The VARIANT™ II HbA1c Program separates Schiff base from HbA1c in the analysis step.
Here's a breakdown of the acceptance criteria and study information for the Bio-Rad VARIANT™ II HbA1c Program, based on the provided text:
Acceptance Criteria and Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Precision | |
| Within-run %CV (low patient sample) | 1.51% |
| Within-run %CV (medium patient sample) | 1.93% |
| Within-run %CV (high patient sample) | 1.04% |
| Between-run %CV (low patient sample) | 2.40% |
| Between-run %CV (medium patient sample) | 2.01% |
| Between-run %CV (high patient sample) | 0.92% |
| Total Precision (low patient sample) | 4.10% |
| Total Precision (medium patient sample) | 3.36% |
| Total Precision (high patient sample) | 2.00% |
| Correlation with Predicate Device | r² = 0.9885 |
| National Glycohemoglobin Standardization Program (NGSP) Precision Requirements | Met |
Study Information:
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Sample Size Used for the Test Set and Data Provenance:
- Precision Study: Low, medium, and high patient whole blood samples were used. The exact number of samples or runs is not specified, but the study implies multiple measurements for within-run and between-run variability.
- Correlation Study: The document does not specify the exact sample size for the correlation study against the VARIANT™ HbA1c Program.
- Data Provenance: Not specified, but generally, clinical validations for these types of devices in the US would use samples from the US or a similar regulatory environment. The document is for a US FDA submission.
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Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- This device is an in vitro diagnostic (IVD) for quantitative measurement of HbA1c. The "ground truth" for such devices is typically established through reference methods or comparison to a predicate device, rather than expert consensus on image interpretation or similar qualitative assessments. For the precision studies, the device measures the HbA1c values directly. For accuracy, it's compared to another device. Therefore, no "experts" in the sense of clinical reviewers are explicitly mentioned for establishing ground truth.
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Adjudication Method:
- Not applicable as the "ground truth" for this quantitative IVD is based on direct measurement or comparison to a predicate device, not qualitative assessments requiring adjudication.
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Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No. This is an In Vitro Diagnostic (IVD) device that performs a biochemical assay. MRMC studies are typically for imaging devices where human readers interpret results, often with and without AI assistance. This device provides a quantitative numerical output, not an image for human interpretation.
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Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:
- Yes, implicitly. The performance data presented (precision, correlation) are measurements of the device's analytical performance on its own, without direct human intervention in the result generation beyond operating the instrument and loading samples.
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Type of Ground Truth Used:
- For precision, the ground truth is the inherent variability of the assay itself when measuring known samples (low, medium, high patient whole blood).
- For accuracy/correlation, the ground truth is considered to be the results obtained from the predicate device, VARIANT™ HbA1c Program (K926469).
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Sample Size for the Training Set:
- This is an IVD device, not a machine learning algorithm in the typical sense that would have a "training set" for model development. The "training" for this device involves analytical method development and optimization, and subsequent validation using characterized samples. No specific "training set" relevant to AI/ML is mentioned or applicable here.
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How the Ground Truth for the Training Set was Established:
- As explained above, the concept of a "training set" and its ground truth in the context of AI/ML does not directly apply to this traditional IVD device. The development process would involve extensive analytical testing and optimization using characterized biological samples and controls, but this is distinct from the training of a machine learning model.
§ 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).