(50 days)
The cassette COBAS INTEGRA LDL Direct (LDL-D) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative determination of LDL-cholesterol direct concentration in serum and plasma. Low density lipoprotein cholesterol measurement, in conjunction with other lipid determinations, has been shown to be useful in assessing the risk of coronary heart disease.
The Roche Calibrator LDL Direct is intended for use as calibrator in quantitative Low Density Lipoprotein cholesterol assays. It is recommended for use with LDL Direct reagents on COBAS® chemistry systems. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens.
The COBAS INTEGRA test applications contained in this submission are intended for use with the COBAS INTEGRA Analyzer, which is also known as the COBAS INTEGRA 700. The COBAS INTEGRA Analyzer and COBAS INTEGRA Reagent cassettes together provide an integrated system for in vitro diagnostic testing. The COBAS INTEGRA Analyzer utilizes three measuring principles, i.e., absorbance, fluorescence polarization and ion-selective electrodes. The analyzer has a throughput of up to 600 tests per hour with STAT samples prioritized and tested immediately. Random sample access, robotics and a user interface optimize time management and streamline workflow. The COBAS INTEGRA can store up to 68 COBAS INTEGRA Reagent Cassettes on board, 24 hours a day at 2-8°C. The COBAS INTEGRA Reagent Cassettes are compact and preparation-free with the added convenience of long term on-board stability. Barcode readers are used to identify newly loaded reagent cassettes, samples for patient identification, and rack inserts and to read calibration and control data from the cassette label. COBAS INTEGRA tests include chemistry, drugs of abuse, immunology, ion selective electrodes, therapeutic drug monitoring, and hematology reagents.
The cassette COBAS INTEGRA LDL Direct (LDL-D) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA 700 for the quantitative determination of LDL-cholesterol direct concentration in serum and plasma.
The Roche Calibrator LDL Direct is intended for use as calibrator in quantitative Low Density Lipoprotein cholesterol assays. It is recommended for use with LDL Direct reagents on COBAS® chemistry systems.
Here's a breakdown of the acceptance criteria and study information for the Roche COBAS® INTEGRA LDL Direct and Roche Calibrator LDL Direct, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" as a separate, pre-defined set of thresholds. Instead, it presents performance characteristics of the new device and compares them to those of predicate devices to demonstrate substantial equivalence. The implication is that if the new device's performance aligns with or is comparable to the predicate devices, it meets the "acceptance criteria" for substantial equivalence.
| Performance Characteristic | Acceptance Criteria (Implied by Predicate Performance) | Reported Device Performance (COBAS INTEGRA LDL Direct) |
|---|---|---|
| Intended Use (Reagent) | Quantitative determination of LDL-cholesterol direct concentration in serum or plasma, useful in assessing coronary heart disease risk. | Quantitative determination of LDL-cholesterol direct concentration in serum and plasma, useful in assessing coronary heart disease risk. |
| Intended Use (Calibrator) | Calibrator for quantitative Low Density Lipoprotein cholesterol assays. | Calibrator for quantitative Low Density Lipoprotein cholesterol assays on COBAS chemistry systems. |
| Matrix (Calibrator) | Human serum | Human serum |
| Approx. Value (Calibrator) | 51.4 mg/dL | 2.85 mmol/L (110 mg/dL) |
| Precision (Level 1 Mean) | Not explicitly stated (predicate data not available for direct comparison) | 2.72 mmol/L (105 mg/dL) |
| Precision (Level 1 Within Run CV) | Not explicitly stated | 1.4 |
| Precision (Level 1 Total CV) | Not explicitly stated | 1.9 |
| Precision (Level 2 Mean) | Not explicitly stated | 5.12 mmol/L (198 mg/dL) |
| Precision (Level 2 Within Run CV) | Not explicitly stated | 1.8 |
| Precision (Level 2 Total CV) | Not explicitly stated | 2.1 |
| Linearity | 500 mg/dL | 14.0 mmol/L (540 mg/dL) |
| Accuracy (Correlation Coefficient vs. COBAS MIRA) | Not explicitly stated (predicate comparison is to Beta-quantification or Friedewald) | 0.964 |
| Accuracy (Linear Regression vs. COBAS MIRA) | Not explicitly stated | y = 0.85x + 0.7 mmol/L |
Note: For accuracy, the new device is compared to COBAS MIRA, Beta-quantification, and Friedewald formula. The predicate device's accuracy is provided against Beta-quantification. The document implies that a strong correlation (e.g., r > 0.95) and a linear regression close to y=x would be acceptable for accuracy.
2. Sample Size Used for the Test Set and Data Provenance
The document refers to "clinical and nonclinical studies."
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Test Set Sample Size for Accuracy:
- Against COBAS MIRA: n = 276
- Against Beta-quantification: n = 150
- Against Friedewald formula: n = 276
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Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
This type of information is not provided in the document. For an in vitro diagnostic device like this, ground truth is typically established through reference methods or established laboratory procedures, not by human experts in the way it would be for an imaging AI.
4. Adjudication Method for the Test Set
This information is not applicable and therefore not provided. Adjudication methods (like 2+1, 3+1) are common in clinical trials involving subjective interpretations (e.g., imaging reads) to resolve discrepancies. For a quantitative diagnostic test like LDL-cholesterol, discrepancies would typically be resolved by retesting, using a definitive reference method, or investigating pre-analytical/analytical errors.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Readers Improvement with AI vs. Without AI Assistance
This information is not applicable and therefore not provided. MRMC studies are relevant for imaging devices or AI tools where human readers are interpreting data, and the AI's role is to assist or augment their performance. The Roche COBAS INTEGRA LDL Direct is a laboratory diagnostic assay, not one that involves human interpretation of "cases" in an MRMC context.
6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, this is essentially a standalone study. The document describes the performance of the COBAS INTEGRA LDL Direct system itself (the reagent cassette + analyzer) in measuring LDL-cholesterol directly. There isn't a human-in-the-loop component described for the function of this diagnostic device.
7. The Type of Ground Truth Used
The ground truth for the accuracy studies was established by comparing the COBAS INTEGRA LDL Direct results against:
- COBAS MIRA: Another automated chemistry analyzer, likely acting as a comparative reference method.
- Beta-quantification: A established reference method for lipoprotein analysis, considered highly accurate for LDL-cholesterol.
- Friedewald formula: A calculated estimate of LDL-cholesterol based on other lipid measurements (total cholesterol, HDL-cholesterol, triglycerides).
8. The Sample Size for the Training Set
The document does not mention a "training set". This is an in vitro diagnostic device, not an AI/machine learning algorithm in the typical sense that would require a distinct training set for model development. The development process for an IVD involves formulation, optimization, and verification, rather than "training" with a dataset for an algorithm.
9. How the Ground Truth for the Training Set Was Established
Since there is no "training set" mentioned or implied for this type of device, this information is not applicable.
§ 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.