(68 days)
The Hemoglobin A1c2 (HbA1c2) reagent kit, when used in conjunction with SYNCHRON LX® System(s) and SYNCHRON® Systems HbA1c2 Calibrators, is intended for the quantitative determination of hemoglobin A1c (HbA1c2) concentration as a percentage of total hemoglobin in human whole blood.
Measurement of hemoglobin A1c is accepted as a method to measure long-term glucose control in patients with diabetes mellitus (a chronic disorder associated with disturbances in carbohydrate, fat, and protein metabolism and characterized by hyperglycemia). Determination of hemoglobin A1c provides an important diagnostic tool for monitoring the efficiency of dietary control and therapy during treatment of diabetes mellitus.
The SYNCHRON LX® System(s) HbA1c2 reagent is designed for optimal performance on the SYNCHRON LX® System(s). The reagent kit contains two A1c2 80-test cartridges, one Hb2 160-test cartridge and one 2 mL bottle each of Hb/A1c2 Calibrator Level 2, A1c2 Calibrator Levels 3, 4 and 5.
The provided 510(k) summary for the SYNCHRON LX® Systems Hemoglobin A1c2 (HbA1c2) Reagent focuses on demonstrating substantial equivalence to a predicate device, as is customary for such submissions. It includes performance data, but the structure of a typical 510(k) does not usually detail acceptance criteria in the same way a clinical trial protocol would, nor does it typically involve the extensive expert consensus or MRMC studies for establishing ground truth as seen in medical imaging AI device submissions.
Here's an analysis of the available information based on your request, highlighting what is present and what is not typically found in this type of submission:
Acceptance Criteria and Device Performance
The acceptance criteria are not explicitly stated in a pass/fail format with numerical thresholds. Instead, substantial equivalence is demonstrated through comparative performance metrics against predicate devices and through internal validation studies (stability, linearity, imprecision). The "acceptance" is implicitly tied to demonstrating performance comparable to the predicate.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Method Comparison | Slope close to 1, Intercept close to 0, r (correlation) close to 1 when compared to predicate methods. | SYNCHRON HbA1c (Predicate): Slope = 0.911, Intercept = 0.46, r = 0.991 (N=80) |
| Tosoh A1c (Reference Method): Slope = 1.042, Intercept = -0.56, r = 0.994 (N=80) | ||
| Imprecision (Within-Run) | Low standard deviation (S.D.) and coefficient of variation (%C.V.) at different HbA1c levels. | Normal (5.5%): S.D. = 0.07%, %C.V. = 1.2% (N=80) |
| Abnormal (9.8%): S.D. = 0.09%, %C.V. = 1.0% (N=80) | ||
| Imprecision (Total) | Low standard deviation (S.D.) and coefficient of variation (%C.V.) at different HbA1c levels. | Normal (5.5%): S.D. = 0.14%, %C.V. = 2.6% (N=80) |
| Abnormal (9.8%): S.D. = 0.27%, %C.V. = 2.8% (N=80) |
Study Information
Due to the nature of this 510(k) submission for an in vitro diagnostic (IVD) reagent, many of the requested categories (especially those related to expert consensus, adjudication, and MRMC studies, which are common for AI/imaging devices) are not applicable or not detailed in this document.
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Sample Size used for the test set and the data provenance:
- Sample Size: 80 for each method comparison study (SYNCHRON HbA1c and Tosoh A1c). 80 for each imprecision study (within-run and total), for both normal and abnormal samples.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, given it's a submission by Beckman Coulter, Inc. in Brea, California, it's highly likely to be U.S. data, and typically, these studies are prospective validation studies conducted by the manufacturer.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is not applicable in the context of an IVD reagent seeking substantial equivalence. The "ground truth" for method comparison is established by comparison to recognized reference methods or predicate devices, which are themselves validated laboratory assays. It does not involve human expert interpretation of images or clinical data in the way AI/imaging devices do.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- None (not applicable). Adjudication protocols are primarily used when subjective human interpretation is involved in establishing ground truth, such as in clinical or imaging studies.
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If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No (not applicable). MRMC studies are specific to evaluating the impact of AI on human readers, typically in image interpretation. This device is an automated IVD reagent.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, implicitly. The device (reagent on the SYNCHRON LX System) performs the HbA1c concentration determination quantitatively and automatically. The method comparison and imprecision studies directly reflect the standalone performance of the algorithm/reagent system. There is no "human-in-the-loop" for performing the actual analyte measurement.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The "ground truth" (or reference standard) is established by comparison to a legally marketed predicate device (SYNCHRON HbA1c) and a recognized reference method (Tosoh A1c). These methods are themselves quantitative assays, providing a numerical concentration for HbA1c.
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The sample size for the training set:
- This document does not specify a separate training set size. For IVD reagents, the development process might involve numerous internal studies to optimize the reagent formulation and assay parameters. However, the 510(k) submission focuses on the validation of the final commercialized product, which is represented by the "test set" samples (80 for method comparison, 80 for imprecision). The concept of a distinct "training set" and "test set" as in machine learning is not typically used or reported in this manner for traditional IVD assays.
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How the ground truth for the training set was established:
- As a distinct "training set" is not explicitly defined or reported in the context of a machine learning model, this question is not applicable to this 510(k) submission. The development and optimization of the reagent assay itself would be based on established chemistry principles and analytical methods, with the "ground truth" for these internal development efforts likely coming from well-characterized samples and reference methods.
§ 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).