(64 days)
The Dade Behring Dimension® Automated LDL Cholesterol Flex® reagent cartridge method is an in vitro diagnostic test intended for the quantitative determination of lowdensity lipoprotein cholesterol in human serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders and various liver and renal diseases.
The Dade Behring Dimension® Automated LDL Cholesterol Flex® reagent cartridge method is an in vitro diagnostic test that consists of prepackaged reagents in a flexible plastic cartridge for use on the Dimension® clinical chemistry system. The Dimension® Automated LDL Cholesterol Flex® reagent cartridge assay is a homogeneous method for directly measuring low-density lipoprotein cholesterol in human serum or plasma without the need for off-line pretreatment or centrifugation steps. The method is in a two reagent format and depends on the properties of detergent 1 which solubilizes only non- LDL particles. The cholesterol released is consumed by cholesterol esterase and cholesterol oxidase in a non-color forming reaction. Detergent 2 solubilizes the remaining LDL particles. The soluble LDL-C is then oxidized by the action of cholesterol esterase and cholesterol oxidase forming cholestenone and hydrogen peroxide (H2O2). The enzymatic action of peroxidase on H2O2 produces color in the presence of disodium salt (DSBmT) and 4-aminoantipyrine (4-AA) that is measured as a bichromatic endpoint technique at 540 nm and 700 nm. The color development is proportional to the amount of LDL-C present in the sample.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Dade Behring Dimension® Automated LDL Cholesterol Flex® reagent cartridge method:
General Statement: The document provided is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device rather than presenting a detailed study protocol and acceptance criteria in the manner one might find in an academic publication or a PMA submission. As such, the "acceptance criteria" are implicitly defined by the comparison to the predicate devices and the "study" is the comparative performance evaluation.
1. Table of Acceptance Criteria and Reported Device Performance
Given the nature of a 510(k) submission, explicit, pre-defined "acceptance criteria" are not stated as clear thresholds (e.g., "slope must be between 0.9 and 1.1"). Instead, the performance is demonstrated by comparison to legally marketed predicate devices, with the underlying "acceptance" being FDA's determination of substantial equivalence based on the presented data.
| Acceptance Criteria (Implicit) | Reported Device Performance (vs. Predicate) |
|---|---|
| Substantial Equivalence in Design and Performance to Legally Marketed Predicate Devices. This is demonstrated by: | - Intended Use: "in vitro use" (Matches predicate) |
- Sample Size: "3 uL" (Matches predicate)
- Measurement: "Direct LDL determination; Bichromatic endpoint; 540 nm and 700nm" (Similar to predicate's "Direct LDL determination; Bichromatic endpoint; 546 nm and 660 nm")
- Reagents: "Two-detergent Genzyme N-geneous™ LDL Cholesterol reagent set" (Matches predicate) |
| Strong Correlation and Agreement with Predicate Homogeneous LDL-C Assay. | Comparison to Genzyme N-geneous™ LDL Cholesterol assay: - Slope: 0.95
- Intercept: 4.7 mg/dL [0.12 mmol/L]
- Correlation Coefficient: 0.997 |
| Strong Correlation and Agreement with Beta-Quantification Reference Method (CRMLN), considered the gold standard for LDL-C. | Comparison to Beta-Quantification method (CRMLN): - Slope: 1.01
- Intercept: 3.3 mg/dL [0.08 mmol/L]
- Correlation Coefficient: 0.982 |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Versus Genzyme N-geneous™ LDL Cholesterol assay: 122 samples (n=122)
- Versus Beta-Quantification method (CRMLN): 49 samples (n=49)
- Data Provenance: Not explicitly stated in the document. It's common in such submissions to use samples from a clinical laboratory setting, potentially encompassing a range of patient demographics, but specific details like country of origin or whether the data was retrospective or prospective are not provided. Given the context of a comparative performance study for a new analyzer, it is highly likely these were prospective samples run concurrently on both the new device and the predicate/reference method.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The concept of "experts establishing ground truth" in the context of this device (an LDL cholesterol assay) is different from image-based diagnostics.
- For the Genzyme N-geneous™ LDL Cholesterol assay comparison: The "ground truth" was established by the predicate device itself. No human experts were involved in determining the "truth" for this comparison; it was an instrument-to-instrument comparison.
- For the Beta-Quantification method (CRMLN) comparison: The "ground truth" was established by the Cholesterol Reference Method Laboratory Network (CRMLN) Beta-Quantification reference method. This method is considered a highly accurate and standardized laboratory procedure for LDL-C determination. While this method is performed by highly qualified laboratory personnel, the document does not specify the "number of experts" or their individual qualifications. The "expertise" lies in the method's standardization and rigorous execution within a reference laboratory network.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are typically used in studies where human readers interpret results (e.g., radiology images) and disagreement needs to be resolved. This is not applicable here as the "test set" involves quantitative measurements from an automated clinical chemistry system. The "adjudication" is inherent in the comparison against established analytical methods, particularly the CRMLN Beta-Quantification reference method, which is itself a highly controlled and validated process.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done.
MRMC studies are relevant for diagnostic devices that involve human interpretation of outputs (e.g., radiologists reading images with or without AI assistance). This device is an automated in vitro diagnostic test that produces a quantitative numerical result for LDL-C, requiring no human interpretation for its primary output. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" does not apply.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, a standalone performance study was done. The entire premise of the submission is to demonstrate the performance of the device algorithm (the automated Flex® reagent cartridge method) by itself, producing an LDL-C value. The comparative studies describe its performance without human intervention in the analyte measurement process. The results (slope, intercept, correlation coefficient) directly reflect the algorithm's standalone analytical performance against other established methods.
7. The Type of Ground Truth Used
- For the comparison to the Genzyme N-geneous™ LDL Cholesterol assay: The ground truth was effectively the measurements from the predicate device. This is a common practice in 510(k) submissions to show equivalence.
- For the comparison to the Beta-Quantification method: The ground truth was the CRMLN Beta-Quantification reference method, which is considered a highly accurate and standardized analytical reference method. This is a gold standard for LDL-C measurement.
8. The Sample Size for the Training Set
The document does not provide information on a training set sample size. This is typical for a 510(k) summary for an in vitro diagnostic device, especially one involving chemical reagents and an automated system. Such devices are developed and optimized through internal R&D processes, but a distinct "training set" (as understood in machine learning) is not typically detailed or reported in regulatory submissions unless the device heavily relies on a data-driven model or AI component. The methods described are chemical reactions, not a machine learning algorithm that needs explicit training data.
9. How the Ground Truth for the Training Set Was Established
As no training set is explicitly mentioned or detailed in the document, the method for establishing its ground truth is not provided. The development of the assay itself would have involved extensive analytical chemistry, experimentation, and optimization using various known samples and reference materials, but these would be part of the product development process rather than a formalized "training set" as defined in studies for data-driven algorithms.
§ 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.