(57 days)
The Total Bilirubin assay is used for the quantitation of total bilirubin in human serum and plasma. Measurement of total bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.
Total Bilirubin is an in vitro diagnostic assay for the quantitative determination of total bilirubin in human serum and plasma. Total (conjugated and unconjugated) bilirubin couples with the diazo reagent in the presence of a surfactant to form azobilirubin. The increase in absorbance at 548 nm due to azobilirubin formation is directly proportional to the total bilirubin concentration.
Here's an analysis of the provided 510(k) summary regarding the Total Bilirubin assay, structured to address your questions.
1. Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a numerical target format (e.g., "correlation coefficient must be >=X"). Instead, it demonstrates substantial equivalence by showing that the new device's performance characteristics are "similar" and "acceptable" when compared to a legally marketed predicate device. The implied acceptance is that the correlation and precision results are sufficiently close to generally accepted standards for a diagnostic assay and comparable to the predicate.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (AEROSET® System) | Reported Device Performance (ARCHITECT® c8000™ System) |
|---|---|---|---|
| Method Comparison/Correlation | High correlation with predicate device (Roche Total Bilirubin) | Correlation coefficient = 0.999 | Correlation coefficient = 0.999 |
| Slope | Close to 1.0 (indicating proportional agreement) | Slope = 0.93 | Slope = 0.93 |
| Y-intercept | Close to 0.0 (indicating minimal constant bias) | Y-intercept = 0.16 mg/dL | Y-intercept = 0.15 mg/dL |
| Precision (Total %CV) Level 1 | Low %CV, generally acceptable for clinical assays | 2.5 to 4.6% | 2.2 to 3.4% |
| Precision (Total %CV) Level 2 | Low %CV, generally acceptable for clinical assays | 1.0 to 1.9% | 1.1 to 1.2% |
| Precision (Total %CV) Level 3 | Low %CV, generally acceptable for clinical assays | 0.9 to 1.3% | 0.7 to 0.9% |
| Precision (Total %CV) Level 4 | Low %CV, generally acceptable for clinical assays | 0.9 to 1.2% | 0.6 to 0.9% |
| Assay Range | Appropriate for clinical use | 0.1 to 35.7 mg/dL | 0.1 to 35.7 mg/dL |
| Limit of Quantitation (Sensitivity) | Clinically appropriate low detection | 0.03 mg/dL | 0.08 mg/dL |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size for Test Set: The document does not explicitly state the number of samples used for the comparative performance studies (method comparison). For precision studies, four levels of control material were used, but the number of replicates per level is not specified.
- Data Provenance: Not specified. It's common for such studies to use a mix of patient samples and spiked controls to cover the assay range, but the origin (e.g., country, specific populations) and whether they were retrospective or prospective are not mentioned. Given the date of submission (2002), it's highly likely these were retrospective samples or controlled proficiency testing samples.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
Not applicable. This is an in vitro diagnostic (IVD) assay for a quantitative measurement (total bilirubin). The "ground truth" for method comparison studies in IVDs is typically established by comparing the new device's results to a legally marketed predicate device (the Roche Total Bilirubin assay in this case), often itself validated against a reference method. It does not involve human expert interpretation of images or clinical findings.
4. Adjudication Method for the Test Set:
Not applicable for a quantitative IVD assay. Adjudication methods (like 2+1, 3+1) are common in studies involving subjective interpretation (e.g., radiology, pathology) to reach a consensus ground truth. For this device, the "truth" is the measured concentration.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
No, an MRMC study was not done. MRMC studies are used to evaluate the impact of a system (often AI) on human reader performance, typically in diagnostic imaging. This device is a standalone quantitative lab assay.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the performance characteristics described (correlation, precision, assay range, sensitivity) represent the standalone performance of the Total Bilirubin assay itself on the specified automated systems (AEROSET and ARCHITECT c8000), without human interpretation as part of the primary measurement.
7. The Type of Ground Truth Used:
The primary "ground truth" for the comparative performance study was the results obtained from the legally marketed predicate device, the Roche Total Bilirubin assay on the Hitachi 717 Analyzer, combined with established analytical methods for precision and sensitivity. For IVD assays, predicate comparison is a common method for demonstrating substantial equivalence.
8. The Sample Size for the Training Set:
Not applicable. This is a traditional IVD assay, not an AI/ML algorithm that requires a "training set" in the computational sense. The assay is based on a well-established chemical reaction (diazo reagent coupling) rather than a learned model from data.
9. How the Ground Truth for the Training Set Was Established:
Not applicable. As mentioned, there is no "training set" in the context of an AI/ML algorithm for this type of device. The assay's performance is driven by its chemical formulation and instrument calibration.
§ 862.1110 Bilirubin (total or direct) test system.
(a)
Identification. A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.(b)
Classification. Class II.