(118 days)
The NMR LipoProfile® test, when used with the NMR Profiler, an automated NMR spectrometer, measures lipoprotein particles to quantify LDL particle number (LDL-P), HDL cholesterol (HDL-C), and triglycerides in human serum and plasma using nuclear magnetic resonance (NMR) spectroscopy. LDL-P and these NMR-derived concentrations of HDL-C and triglycerides are used in conjunction with other lipid measurements and clinical evaluation to aid in the management of lipoprotein disorders associated with cardiovascular disease. This test is performed and provided as a service by LipoScience Laboratory.
The NMR LipoProfile® test and NMR Profiler involves measurement of the 400 MHz proton NMR spectrum of a plasma/serum sample, deconvolution of the composite signal at approximately 0.8 ppm to produce signal amplitudes of the lipoprotein subclasses that contribute to the composite plasma/serum signal, and conversion of these subclass signal amplitudes to lipoprotein subclass concentrations. The ~0.8 ppm plasma NMR signal arises from the methyl group protons of the lipids carried in the LDL, HDL and VLDL subclasses of varying diameters. The NMR signals from the various lipoprotein subclasses have unique and distinctive frequencies and lineshapes, each of which is accounted for in the deconvolution analysis model. Each subclass signal amplitude is proportional to the number of subclass particles emitting the signal, which enables subclass particle concentrations to be calculated from the subclass signal amplitudes derived from the spectral deconvolution analysis. LDL subclass particle concentrations, in units of nanomoles of particles per liter (nmol/L), are summed to give the reported total LDL particle concentration (LDL-P). By employing conversion factors assuming that the various lipoprotein subclass particles have cholesterol and triglyceride contents characteristic of normolipidemic individuals, HDL cholesterol and triglyceride concentrations are also derived.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
The provided document focuses on analytical performance rather than clinical acceptance criteria. The acceptance criteria for the analytical evaluation (sensitivity, precision, linearity, and method comparison) are largely implied through the reported performance metrics and the use of CLSI guidelines. The document does not explicitly state pre-defined acceptance criteria values for bias or CVs in a standalone table, but rather presents the reported performance data.
Table 1: Acceptance Criteria and Reported Device Performance (Analytical)
| Performance Metric | Analyte | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|---|
| Analytical Sensitivity (LOQ) | LDL-P | Lowest concentration with acceptable precision and accuracy (Total error ≤20%) | 300 nmol/L |
| HDL-C | Lowest concentration with acceptable precision and accuracy (Total error ≤20%) | 10 mg/dL | |
| Triglycerides | Lowest concentration with acceptable precision and accuracy (Total error ≤20%) | 25 mg/dL | |
| Within-run Precision (%CV) | LDL-P | (Not explicitly stated, but typical for diagnostic assays) | 3.7% - 5.0% |
| HDL-C | (Not explicitly stated) | 0.9% - 2.0% | |
| Triglycerides | (Not explicitly stated) | 1.3% - 2.6% | |
| Within-laboratory Precision (%CV) | LDL-P | (Not explicitly stated) | 4.3% - 7.7% |
| HDL-C | (Not explicitly stated) | 1.8% - 3.3% | |
| Triglycerides | (Not explicitly stated) | 2.5% - 3.6% | |
| Linearity (Measuring Range) | LDL-P | (Not explicitly stated, but implied to be within acceptable non-linearity goal) | 300-3500 nmol/L |
| HDL-C | (Not explicitly stated, but implied to be within acceptable non-linearity goal) | 7-140 mg/dL | |
| Triglycerides | (Not explicitly stated, but implied to be within acceptable non-linearity goal) | 5-1100 mg/dL | |
| Method Comparison (Correlation with Predicate) | LDL-P | Strong positive correlation (e.g., r > 0.95 or 0.97) | r = 0.970 |
| HDL-C | Strong positive correlation (e.g., r > 0.95 or 0.99) | r = 0.999 | |
| Triglycerides | Strong positive correlation (e.g., r > 0.95 or 0.99) | r = 1.00 | |
| Interfering Substances | Endogenous agents & exogenous drugs | No significant interference | Tested (results not detailed, but implied acceptable) |
Study Details
The provided text describes analytical performance studies designed to demonstrate substantial equivalence to a predicate device.
2. Sample size used for the test set and the data provenance:
- Analytical Sensitivity (LOQ): "20 replicates of each were analyzed" for serially diluted serum specimens with low concentrations. The number of unique patient samples used for initial dilution is not specified.
- Assay Precision:
- Within-run: 20 replicates of three patient serum pools.
- Within-laboratory: 20 different runs over 20 days using three patient serum pools (n=80 for each pool across runs).
- Linearity: Four replicates of each of eleven (for LDL-P) or twelve (for TG and HDL-C) different samples derived from three serum pools.
- Method Comparison:
- LDL-P: n=1555 serum samples
- HDL-C: n=1599 serum samples
- Triglycerides: n=1597 serum samples
- Interfering Substances: "Five endogenous agents and twenty two drugs were screened". No sample size for patient samples is given, but likely spiked samples.
Data Provenance: The document does not explicitly state the country of origin. The samples are described as "patient serum pools" and "serum samples," implying they are from human subjects, likely in a clinical laboratory setting. The terms "retrospective" or "prospective" are not used; these appear to be analytical validation studies on collected samples.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. The ground truth for these analytical studies is based on quantitative measurements (e.g., predicate device measurements for method comparison, or target values established through dilution for linearity and sensitivity). This is not an image-based or clinical diagnostic study requiring expert interpretation.
4. Adjudication method for the test set: Not applicable. These are quantitative analytical studies, not studies requiring expert adjudication of results.
5. 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: Not applicable. This is an analytical device for quantifying lipoprotein particles, not an AI-assisted diagnostic imaging device with human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Yes, the entire performance data section (Analytical Sensitivity, Assay Precision, Linearity, Interfering Substances, Method Comparison) represents standalone algorithm performance, as the device is an automated NMR spectrometer with deconvolution software. There is no human interpretation or intervention in the measurement process itself.
7. The type of ground truth used:
- Analytical Sensitivity (LOQ): Target values from serial dilution.
- Assay Precision: Mean values from repeated measurements of serum pools.
- Linearity: Expected target values derived from mixing and diluting serum pools.
- Method Comparison: Measurements from the legally marketed predicate device (NMR Profiler and NMR Lipoprofile Assay, K063841).
- Interfering Substances: Pre-established target concentrations of potential interferents.
8. The sample size for the training set: Not applicable. This is an analytical device validation, not a machine learning model that undergoes a distinct training phase in the context of this 510(k) submission. The underlying deconvolution software likely had development and calibration phases, but those are not described as a "training set" in this document.
9. How the ground truth for the training set was established: Not applicable, as no training set is explicitly described for this 510(k) submission.
§ 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.