(77 days)
for the quantitative determination of high-density lipoprotein Cholesterol (HDL-C) n human serum and plasma.
for in vitro diagnostic use.
for the calibration of the Liquid N-geneous HDL Cholesterol assay.
for in vitro diagnostic use.
The Genzyme Liquid N-geneous™ HDL Cholesterol Kit is a two-reagent homogeneous method for the direct quantitative determination of high density lipoprotein cholesterol (HDL-C) in human serum and plasma.
In both user settings, the principle of the test is based upon a unique detergent which selectively solubilizes only the HDL. This unique detergent also strongly inhibits the reaction of the enzymes with cholesterol contained in the low density lipoprotein (LDL), very low density lipoprotein (VLDL) and chylomicron particles. Consequently, only the cholesterol in the resultant micell complexes of the detergent and lipids is subject to the enzyme reactions, leading to the selective determination of HDL cholesterol.
This document describes the submission for the Genzyme Liquid N-geneous™ HDL Cholesterol Kit, a device designed for the quantitative determination of high-density lipoprotein cholesterol (HDL-C) in human serum and plasma. The study aims to demonstrate that the device is substantially equivalent to existing reference methods.
1. Table of Acceptance Criteria (Implied) and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" but rather presents comparative performance data against established reference methods. The implicit acceptance criteria are that the Genzyme Liquid N-geneous™ HDL Kit should perform comparably to these reference methods in terms of correlation, slope, intercept, and mean differences, as well as meeting NCEP precision goals.
| Performance Metric | Acceptance Criteria (Implied by Comparison) | Genzyme Liquid N-geneous™ HDL vs. Phosphotungstate (n=92) | Genzyme Liquid N-geneous™ HDL vs. CDC Method (n=54) | Precision: Within-Run %CV (Low/Mid/High) | Precision: Between-Run %CV (Low/Mid/High) | POL Study: Coeff. (r) vs. Reference Lab (Site 1/2/3) | POL Study: NCEP Goals Achieved |
|---|---|---|---|---|---|---|---|
| Slope | Close to 1.0 | 0.960 | 1.056 | N/A | N/A | 1.11 / 1.12 / 0.93 | N/A |
| Intercept (mg/dL) | Close to 0.0 | 3.97 | -0.736 | N/A | N/A | -1.44 / -5.90 / 1.25 | N/A |
| Correlation Coefficient (r) | High (e.g., >0.95) | 0.991 | 0.992 | N/A | N/A | 0.97 / 0.99 / 0.99 | N/A |
| Mean Difference (mg/dL) | Small | 2.0 | 2.2 | N/A | N/A | N/A | N/A |
| Mean Percent Difference (%) | Small | 4.7% | 4.1% | N/A | N/A | N/A | N/A |
| Within-Run %CV | Low; ≤6% (≥42mg/dL), ≤2.5mg/dL SD (200 mg/dL. |
* **N=40** serum samples for the Physician Office Laboratories (POL) comparative studies. These were "split samples" from the same 40 specimens, with a reference laboratory (Genzyme) also analyzing them.
- Data Provenance: The studies were conducted at Genzyme Corporation. The origin of the patient samples (e.g., country of origin) is not explicitly stated. The data is retrospective as it involves testing existing serum samples.
3. Number of Experts and Qualifications for Ground Truth:
- The document does not mention the use of "experts" in the traditional sense for establishing ground truth for individual cases. For this type of diagnostic test, the "ground truth" is provided by established, accepted reference methods rather than human interpretation.
4. Adjudication Method for the Test Set:
- Not applicable. As the ground truth is established by chemical/instrumental reference methods, there is no need for expert adjudication of results. The comparison is quantitative.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No. This is an in vitro diagnostic (IVD) device for chemical analysis (HDL-C measurement), not an imaging or interpretive device that would typically involve human readers. Therefore, an MRMC study is not relevant or performed.
6. Standalone (Algorithm Only) Performance Study:
- Yes, in essence. The comparative performance studies directly evaluate the Genzyme Liquid N-geneous™ HDL Cholesterol Kit (the "algorithm/device") against reference methods, operating without direct human interpretation influencing the numerical result. These studies are standalone in that they assess the device's accuracy in producing a quantitative value.
7. Type of Ground Truth Used:
- The ground truth was established by established reference methods for HDL cholesterol measurement:
- Sodium Phosphotungstate MgCl2 (PTA) method.
- Center for Disease Control (CDC) Designated Comparison Method (DCM).
- HDL reference method (ultracentrifugation, chemical precipitation, and Abell-Kendall) for samples with triglyceride levels >200 mg/dL.
- The selection of samples was based on the Lipid Research Clinics (LRC) population studies, using patient serum samples with HDL values between 27-91 mg/dL (5th and 95th percentile).
8. Sample Size for the Training Set:
- The document does not explicitly describe a separate "training set" in the context of machine learning. The Liquid N-geneous™ HDL Cholesterol Kit is a reagent kit based on a chemical principle rather than an AI/ML algorithm that requires a training phase.
9. How the Ground Truth for the Training Set Was Established:
- Not applicable. As the device is a chemical reagent kit and not an AI/ML system, a training set with established ground truth in the machine learning sense is not described or relevant for this type of submission. The development of the kit would rely on chemical principles and validation against known standards and reference methods during its R&D phase, rather than a "training set" for an algorithm.
§ 862.1475 Lipoprotein test system.
(a)
Identification. A lipoprotein test system is a device intended to measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.