(354 days)
The Quo-Test Alc System is intended for the in vitro quantitative determination of glycated hemoglobin (%HbA1c) levels in venous whole blood samples (using K2EDTA and lithium heparin anticoagulants). Measurement of percent glycated hemoglobin (%HbA1c) is effective for monitoring long-term glycemic control in individuals previously diagnosed with diabetes mellitus.
The Quo-Test A1c System is not intended for screening or diagnosis of diabetes or neonatal use. The device is intended for professional use in a clinical laboratory setting.
The Quo-Test Analyzer and A1c Test Kit (Quo-Test A1c System) are intended for the in-vitro quantitative determination of glycated hemoglobin in whole blood samples obtained from venous samples. The system contains a fluorimeter and two photometers to enable both fluorescent and photometric measurements to be made. The Quo-Test A1C Assay is calibrated by the manufacturer using European Reference Laboratory (ERL) calibrators. There are no user-serviceable parts in the analyzer. It has ports to support a printer and barcode scanner plus a USB port. It is powered by an AC/DC adapter plugged into a 100-240V AC outlet. The Quo-Test A1c Test Cartridge contains all the reagents, in a plastic cuvette, required to perform an HbA1c test on the Quo-Test Analyzer. The reagents consist of a lysing agent, buffer and a boronate fluorophore conjugate. A low level of sodium azide preservative is used to enhance the shelf life of the test cartridge. Each test cartridge is for single-use. The test cartridges are supplied in individual foil pouches and should be stored at 2 - 8°C.
This document describes the premarket notification (510(k)) for the Quo-Test A1c System, a device intended for the in vitro quantitative determination of glycated hemoglobin (%HbA1c) levels in venous whole blood samples for monitoring long-term glycemic control in individuals previously diagnosed with diabetes mellitus.
Here's an analysis of the acceptance criteria and the study proving the device meets them:
1. A Table of Acceptance Criteria and the Reported Device Performance
The acceptance criteria are generally implied by the performance characteristics demonstrated to be comparable (substantially equivalent) to the predicate device and compliant with relevant CLSI guidelines. While explicit "acceptance criteria" are not presented in a single table with pass/fail marks, the results provided in the analytical performance sections serve as the evidence that the criteria were met.
Here's a table summarizing the implicit acceptance criteria (based on common industry standards and the predicate device's performance, and supported by the study methodologies) and the reported performance:
| Performance Characteristic | Implicit Acceptance Criteria / Guideline | Reported Device Performance (Quo-Test A1c System) |
|---|---|---|
| Precision/Reproducibility | Imprecision ≤3 % CV (industry standard/predicate's expected performance); Evaluated per CLSI EP05-A3 | Whole blood samples: Total Precision CV % ranged from 1.00% to 1.79%. Controls: Total Precision CV % ranged from 1.00% to 1.11%. Conclusion: Supports claim of ≤3 % CV. |
| Linearity | $r^2 \geq 0.99$; Slope in the range 0.98 - 1.02; Intercept $\leq \pm 0.4 %A1c$; Evaluated per CLSI EP6-A | Achieved for all three cartridge lots: $r^2$ 0.999-1.000; Slope 0.9872-1.001; Intercept 0.05292-0.1983. Conclusion: Supports linear range of 4-15%A1c. |
| Traceability | Traceable to international standards (NGSP, IFCC) | Certified by NGSP and IFCC; Calibrated using ERL samples via NGSP network, traceable to IFCC reference method. |
| Stability (Reconstituted Controls) | Control results within allowable deviation to target value; CVs within acceptable limits. | Stable for 16 days when stored at 2-8°C; Single CVs ranged from 0.50% - 3.37%. |
| Stability (Cartridges - Shelf Life) | Performance maintained over claimed shelf life (25 months desired, 12 months minimum implied from predicate/typical IVD). | Confirmed shelf life of 12 months at 2-8°C; "still operational for at least three months after the expiry date." |
| Analytical Specificity (Interference) | No significant interference observed from common endogenous and exogenous substances at specified concentrations. | No interference observed at tested concentrations for Bilirubin, Creatinine, Triglycerides, Uric Acid, Ascorbic Acid, Glucose, Cholesterol, RF IgA/IgG/IgM, Acetaminophen, Caffeine, Dopamine, Glybenclamide, Hydroxyzine dihydrochloride, Ibuprofen, Metformin, Acetylsalicylic Acid, Salicylic Acid, Tetracycline, Tolazamide, Tolbutamide. |
| Analytical Specificity (Hemoglobin Variants) | No interference from specified common hemoglobin variants. | Unaffected by HbAS, HbAC, HbAD, HbAJ, HbDD, β-thalassemia, elevated fetal hemoglobin, labile glycated hemoglobin, and carbamylated hemoglobin. |
| Method Comparison (Correlation with Reference) | Strong correlation (e.g., high R^2$, slope near 1, intercept near 0) with NGSP-certified reference laboratory results. | For all subjects (n=423, K2EDTA): Slope 0.964, Intercept 0.084, R^2 0.993. For diabetes subjects (n=308, K2EDTA): Slope 0.959, Intercept 0.130, R^2 0.991. |
| Matrix Equivalence | K2EDTA and Heparin venous blood samples should be interchangeable. | Strong agreement (y = 0.9960x + 0.0408, R^2 = 0.9937, n=149); Conclusion: Interchangeable. |
2. Sample Size Used for the Test Set and the Data Provenance
- Precision Study (20-day precision):
- Sample Size: Three venous blood samples (High, Medium, Low A1C) and two control solutions. Each was tested in duplicate at two separate occasions per day over twenty days.
- Data Provenance: Internal evaluation by the manufacturer. Not specified if retrospective or prospective, but the design suggests a prospective, controlled laboratory study. Country of origin not explicitly stated for samples but manufacturer is Germany.
- Linearity Study:
- Sample Size: 11 patient samples (mixed in incremental amounts to generate a series of 11 samples over a broad HbA1c concentration range). All samples were analyzed fivefold.
- Data Provenance: Study carried out by Isala Ziekenhuis, Department of Clinical Chemistry, Zwolle, The Netherlands in August 2018. This was a prospective study using patient samples.
- Stability Study (Reconstituted Controls):
- Sample Size: Three EKF A1c Control Kits, each with a Normal Control. 4 bottles of each level (Normal/Abnormal) from each lot were pooled after reconstitution.
- Data Provenance: Internal testing (manufacturer or OEM). Prospective.
- Stability Study (Cartridges - Shelf Life):
- Sample Size: Three blood samples (covering the relevant clinical range 5-11% A1C) and the normal and abnormal kit controls. Each of five samples measured n=3 times on each of three Quo-Test analysers at five interval time points over a 15-month period.
- Data Provenance: Internal testing (manufacturer). Prospective, real-time study.
- Analytical Specificity (Interference):
- Sample Size: Not explicitly stated for the number of blood samples or replicates, but the study design evaluated the effects of various interfering substances.
- Data Provenance: Not specified, but likely internal laboratory testing.
- Analytical Specificity (Hemoglobin Variants):
- Sample Size: Venous whole blood samples collected in K2 EDTA tubes spread across the analytical measurement range (4.6-11.6 % HbA1c) for each variant.
- Data Provenance: Not specified, but likely internal laboratory testing.
- Method Comparison Studies:
- Sample Size: Total of 424 subjects across three clinical sites. 423 K2EDTA venous samples and 149 heparin venous samples. 115 normal subjects (27.1%) and 308 diabetes subjects. 209 male and 215 female subjects, ranging from 21 to 89 years of age.
- Data Provenance: Prospective study conducted at three clinical sites. IRB approval was obtained. Samples were sent to an NGSP-certified reference laboratory (Diabetes Diagnostic Laboratory, Columbia. MO). Country of origin for clinical sites/subjects is not specified, but the reference lab is in the US (Missouri).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
The concept of "experts" as human readers/interpreters establishing ground truth, as typically seen in AI/imaging studies, does not directly apply here. This is an in vitro diagnostic (IVD) device measuring a biochemical analyte.
- Ground Truth for Analytical Performance: Established by quantitative laboratory methods and reference standards.
- Precision/Linearity/Stability/Analytical Specificity: Ground truth is the quantitative value determined by the instrument/method under evaluation, compared against expected ranges or reference methods / defined mixtures. No human "experts" are adjudicating individual results in the sense of image interpretation.
- Traceability: The ground truth for calibration and methods is tied to IFCC reference methods and NGSP certification, which involve a network of reference laboratories and expert committees, not individual human readers.
- Ground Truth for Method Comparison: Established by a NGSP-certified reference laboratory using the Tosoh 8 analyzer. The NGSP certification process ensures that laboratories meet stringent criteria for accuracy and precision in HbA1c measurement. This is the gold standard for HbA1c testing.
4. Adjudication Method for the Test Set
Not applicable in the conventional sense of image interpretation or clinical diagnosis by multiple readers. The "ground truth" for the quantitative HbA1c measurements (analyte levels) is established by the NGSP-certified reference method, which is a highly standardized and validated laboratory process, not a subjective human interpretation requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
Not applicable. This is an in vitro diagnostic (IVD) device designed for direct quantitative measurement of HbA1c in blood, not an AI system assisting human readers in interpreting complex medical images or data. There are no "human readers" involved in interpreting the results of the Quo-Test A1c System in a manner that would necessitate an MRMC study.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies presented are standalone performance evaluations of the Quo-Test A1c System itself. The device is designed to provide a quantitative HbA1c result directly from a blood sample. Its output is a numerical value (%HbA1c), which is then used by laboratory professionals or clinicians for patient management. There is no "human-in-the-loop" interaction for interpreting the device's output in the way an AI imaging algorithm might require a radiologist's review. The device performs its measurement and calculation independently.
7. The Type of Ground Truth Used
- Analytical Performance (Precision, Linearity, Stability, Analytical Specificity): The ground truth is effectively the expected value or the reference method/instrument's value for the specific analyte concentration in control materials, spiked samples, or serially diluted/mixed patient samples. For traceabilty, the ground truth is established by the IFCC reference method and NGSP-certified standards.
- Method Comparison: The ground truth for patient samples was established by an NGSP-certified reference laboratory using the Tosoh 8 analyzer, which serves as the gold standard/reference method for HbA1c measurement.
8. The Sample Size for the Training Set
Not applicable in the context of an AI/machine learning model where a "training set" is used to develop the algorithm. The Quo-Test A1c system is a biochemical assay, not an AI algorithm trained on data. Its "training" or calibration is based on manufacturer's procedures using reference calibrators traceable to international standards (NGSP/IFCC), as described in the "Calibration" section.
9. How the Ground Truth for the Training Set Was Established
As explained above, there's no "training set" in the AI sense. For the calibration of the device and its cartridges:
- The Quo-Test A1C System is certified by the National Glycohemoglobin Standardization Program (NGSP) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).
- The Quo-Test Analyzer and A1C Test Cartridges have been calibrated using samples provided by the European Reference Laboratory (ERL) via the NGSP network.
- Results obtained using the Quo-Test A1C System are traceable to the IFCC reference method.
This means the ground truth for the device's calibration (which would be analogous to "training" in an ML context) is established by highly standardized and internationally recognized reference methods and laboratories.
§ 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).