(892 days)
The Hipro® Glycosylated Hemoglobin (HbA1c) Test System comprised of the Hipro Glycosylated hemoglobin (HbA1c) test kit and the HP-AFS/1 automatic immunoassay analyzer is used as an aid in diagnosis of diabetes mellitus, as an aid to identify patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. It is an in vitro diagnostics reagent system intended for quantitative determination of % hemoglobin A1c (DCCT/NGSP) in venous whole blood.
The Hipro® Glycosylated hemoglobin (HbA1c) test system is intended for quantitative determination of % hemoglobin A 1c (DCCT/NGSP) in venous whole blood. It is composed of Glycosylated hemoglobin (HbA1c) test kit and automatic immunoassay analyzer. Glycosylated hemoglobin (HbA1c) test kit consists of two reagents R1 and R2, which are liquid and ready to use. Reagent R1 contains glycine buffer and latex, and reagent R2 contains glycine buffer and two types of antibodies, Goat anti-mouse IgG, mouse anti-human HbAlc monoclonal antibody.
HP-AFS/1 Automatic Immunoassay Analyzer is made up of light absorption test module, scattered light test module, fluorescence test module, press components, data transmission interface and printer. And the absorption test module is made up of absorption light path unit, and lightabsorption sensor part. The scattered light test module is made up of scattered light path unit and scattered light sensor part.
Here's a breakdown of the acceptance criteria and the study details for the Hipro® Glycosylated Hemoglobin (HbA1c) Test System:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria values for most tests. Instead, it describes performing studies and concluding whether "All acceptance criteria were met" or providing summary statistics. For the purpose of this table, I will infer relevant criteria based on common industry standards for diagnostic devices and the structure of the reported results. For Method Comparison, Total Error, and Linearity, the reported results are directly in line with typical performance metrics. For Interference and Hemoglobin Variants, "met acceptance criteria" and specific thresholds are mentioned.
| Performance Characteristic | Acceptance Criterion (Inferred/Stated) | Reported Device Performance |
|---|---|---|
| Precision (Total %CV) | Not explicitly stated. Implied to be within acceptable clinical limits. | For HbA1c concentrations ranging from 5.2% to 12.3%, Total %CV ranged from 1.5% to 2.7% across multiple analyzers and lots. For controls (6%, 11%), Total %CV was 3.0% and 1.6% respectively. |
| Method Comparison (Mean Bias) | Not explicitly stated. Implied to show good agreement. | Mean bias vs. NGSP Bio-Rad: -0.0148. |
| 95% CI for mean bias: -0.0470 to 0.0174. | ||
| Bias at Specific Concentrations | Not explicitly stated. | -0.5% at 5.23% HbA1c, -0.26% at 6.34%, -0.02% at 8.03%, 0.31% at 12.53%. |
| Total Error (%TE) | Not explicitly stated. Implied to be within acceptable clinical limits. | %TE ranged from 3.3% to 5.5% for HbA1c concentrations 5.23% to 12.53%. |
| Linearity (R value) | Not explicitly stated. Implied to be high (close to 1). | R = 0.999 |
| Linearity (Range) | Not explicitly stated. | 4.3% - 14% HbA1c |
| Endogenous Interference (Deviation) | >7% deviation in % HbA1c considered significant interference. | All tested substances (Lipemia, Unconjugated Bilirubin, Conjugated Bilirubin, Glucose, Rheumatoid Factor, Total Protein) showed no significant interference at the highest tested concentrations. |
| Drug Interference (Deviation) | >7% deviation from reference value considered significant interference. | All 16 commonly used drugs tested showed no significant interference. |
| Cross-reactivity | Not explicitly stated. Implied no significant cross-reactivity. | Studies performed for Hb A0, Labile Hb A1c, Carbamylated Hb, Acetylated Hb, Glycated Albumin, Hb A1a+b. Results not detailed, but implied acceptance. |
| Hemoglobin Variants (Interference) | Not explicitly stated. Implied to be minimal or within acceptable clinical limits. Interference with HbF > 8% was observed. | Average bias for HbC: -0.17 at ~6.5% HbA1c, 2.27 at ~9.0% HbA1c. |
| Average bias for HbD: 1.67 at ~6.5% HbA1c, 2.10 at ~9.0% HbA1c. | ||
| Average bias for HbE: 1.58 at ~6.5% HbA1c, 1.38 at ~9.0% HbA1c. | ||
| Interference was observed when the concentration of HbF is > 8%. | ||
| Average bias for HbS: 1.69 at ~6.5% HbA1c, 1.20 at ~9.0% HbA1c. | ||
| Average bias for HbA2: 1.57 at ~6.5% HbA1c, -0.51 at ~9.0% HbA1c. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision: Four EDTA K2 whole blood samples with targeted HbA1c concentrations (5.2%, 6.4%, 8.0% and 12.3%) and two controls (6% and 11%). Each sample was analyzed in duplicate per run, two runs per day for 20 days on three analyzers (total of 240 measurements per sample/control).
- Method Comparison: One hundred and twenty (120) samples.
- Linearity: One dilution series consisting of 9 levels. Each level measured in triplicate.
- Endogenous Interference: Pooled whole blood samples with two HbA1c levels, spiked with 5 interferents (10 spiked samples), and one unspiked pool. A 10-level dilution series was created for each. Tested ten-fold.
- Drug Interference: Native patient samples at 2 different HbA1c levels, spiked with 16 drugs at two defined concentrations. Measured ten-fold.
- Hemoglobin Variants: 20 samples for each variant (HbC, HbD, HbE, HbF, HbS, HbA2) for a total of 120 samples. Each sample was tested twice.
Data Provenance:
- Method Comparison: The 120 samples were obtained from the NGSP reference laboratory.
- General: The document does not explicitly state the country of origin or whether samples were retrospective or prospective, but the reliance on the NGSP reference laboratory suggests a standardized, potentially retrospective, approach for the method comparison component. The use of "native patient samples" for drug interference suggests clinical sources.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The establishment of ground truth is primarily through a traceable reference method and a standardization program.
- Method Comparison: The test system was compared against the Bio-Rad Hemoglobin Testing System which was certified by the National Glycohemoglobin Standardization Program (NGSP). The NGSP is a program that standardizes HbA1c results to align with the results of the Diabetes Control and Complications Trial (DCCT). This implies that the 'ground truth' is established by the NGSP's reference methods and processes, rather than individual experts adjudicating each case. The document specifies that the NGSP reference laboratory measured the "X axis" samples.
The document does not specify a number of "experts" in the traditional sense of clinicians or radiologists adjudicating individual cases.
4. Adjudication Method for the Test Set
Not applicable. This is not a study requiring human adjudication of imaging or clinical cases. The "ground truth" is established by a reference laboratory measurement (NGSP Bio-Rad Hemoglobin Testing System) for chemical analysis.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) test system for quantitative determination of HbA1c, not a diagnostic imaging or AI-assisted interpretation device that involves human readers.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies described are standalone performance evaluations of the Hipro® Glycosylated Hemoglobin (HbA1c) Test System (the automatic immunoassay analyzer and test kit) without human intervention in the measurement process. The system quantifies HbA1c levels directly.
7. The Type of Ground Truth Used
- Reference Method: For method comparison, the ground truth was established by the NGSP (National Glycohemoglobin Standardization Program) Bio-Rad Hemoglobin Testing System. The device is certified with NGSP.
- Reference Materials: For precision, linearity, interference, and hemoglobin variant studies, the ground truth for HbA1c concentrations was established using characterized samples (e.g., targeted HbA1c concentrations, spiked samples, varying hemoglobin variant concentrations) which would derive their values from established reference methods or known preparations.
8. The Sample Size for the Training Set
The document does not mention a separate "training set" in the context of an AI/ML algorithm that is trained. This device is a chemical assay system, not an AI/ML-based diagnostic. The described studies are all for performance evaluation (test set) of the final device.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no specific "training set" for an AI/ML algorithm mentioned for this device.
§ 862.1373 Hemoglobin A1c test system.
(a)
Identification. A hemoglobin A1c test system is a device used to measure the percentage concentration of hemoglobin A1c in blood. Measurement of hemoglobin A1c is used as an aid in the diagnosis of diabetes mellitus and as an aid in the identification of patients at risk for developing diabetes mellitus.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device must have initial and annual standardization verification by a certifying glycohemoglobin standardization organization deemed acceptable by FDA.
(2) The premarket notification submission must include performance testing to evaluate precision, accuracy, linearity, and interference, including the following:
(i) Performance testing of device precision must, at a minimum, use blood samples with concentrations near 5.0 percent, 6.5 percent, 8.0 percent, and 12 percent hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least three lots of the device and three instruments, as applicable.
(ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the device and compare results of the new device to results of a standardized test method. Results must demonstrate little or no bias versus the standardized method.
(iii) Total error of the new device must be evaluated using single measurements by the new device compared to results of the standardized test method, and this evaluation must demonstrate a total error less than or equal to 6 percent.
(iv) Performance testing must demonstrate that there is little to no interference from common hemoglobin variants, including Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2, and Hemoglobin S.
(3) When assay interference from Hemoglobin F or interference with other hemoglobin variants with low frequency in the population is observed, a warning statement must be placed in a black box and must appear in all labeling material for these devices describing the interference and any affected populations.