(181 days)
The Direct Bilirubin test system is a device intended for the quantitative in vitro determination of Direct Bilirubin in serum and plasma. Bilirubin measurements can be used in the diagnosis and treatment of liver, hematological and metabolic disorders including hepatitis and gall bladder block.
This device is for prescription use only.
The Randox Direct Bilirubin kit consists of ready to use reagent solutions.
CATALOGUE NUMBER: BR8308 COMPONENTS: R1. 4 x 20ml, R2. 4 x 8ml
REAGENT COMPOSITION
R1. Direct Bilirubin RI Tartrate buffer, pH2.9 Detergent Antimicrobials and Preservatives Inhibitors Initial Concentration of Solutions 0.1 mol/L
R2. Direct Bilirubin R2 Phosphate buffer, pH 7.0 Sodium Metavanadate Initial Concentration of Solutions 10 mmol/L 4 mmol/L
Here's a breakdown of the acceptance criteria and the study details for the Randox Direct Bilirubin device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document provides performance characteristics but does not explicitly state "acceptance criteria" in a tabulated format derived from a regulatory body or a specific standard with pass/fail thresholds. Instead, it presents the results of various analytical performance studies. However, some sections imply acceptance criteria through their phrasing (e.g., "deviation from linearity is less than 5%" for linearity, "no significant interference" for specificity, and "≤20% CV imprecision" for LoQ).
Here's an interpretation of implied acceptance criteria and reported performance:
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Precision/Reproducibility: Repeatability and intermediate precision within acceptable limits. | Serum Pool 1 (Mean 0.65 mg/dl): Within Run CV: 3.0%, Among Run CV: 1.6%, Among Day CV: 2.4%, Total CV: 4.2% |
| Serum Pool 2 (Mean 2.31 mg/dl): Within Run CV: 3.1%, Among Run CV: 0.0%, Among Day CV: Not reported (likely very low, as next cell is blank), Total CV: 3.1% | |
| Serum Pool 4 (Mean 8.41 mg/dl): Within Run CV: 1.5%, Among Run CV: 0.8%, Among Day CV: 0.9%, Total CV: 1.9% | |
| Linearity/Reportable Range: Linear function to analyte concentration (deviation from linearity 12.6 mg/dl). | |
| Detection Limit (LoQ): Lowest concentration detectable with ≤20% CV imprecision. | LoD: 0.064 mg/dl |
| LoB: 0.006 mg/dl | |
| LoQ: 0.133 mg/dl (confirmed to be ≤20% CV imprecision). | |
| Analytical Specificity/Interference: No significant interference from common interferents at specified levels (Ac-ceptance Criteria: % of Control ± 10%). | Haemoglobin: No significant interference up to 1000 mg/dl |
| Triglycerides: No significant interference up to 750 mg/dl | |
| Intralipid®: No significant interference up to 1000 mg/dl | |
| Ascorbic Acid: No significant interference up to 25 mg/dl (This suggests the results fell within ± 10% of the control). | |
| Method Comparison with Predicate Device: Strong correlation with the predicate device. | Correlation Coefficient (r): 0.997 (for 103 serum patient samples spanning 0.123-12.46 mg/dl). |
| Regression Equation: Y = 1.01x + 0.01. | |
| Matrix Comparison: Agreement between serum and lithium heparin plasma samples. | Correlation Coefficient (r): 1.00 (for a minimum of 40 matched patient sample pairs spanning 0.091-12.48 mg/dl). |
| Regression Equation: Y = 0.99x + 0.01. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision/Reproducibility:
- Sample Size: Not explicitly stated as a number of samples but rather as "control material and unaltered human serum samples" divided into pools (Pool 1, 2, 4) and tested over 20 non-consecutive days with 2 replicates per run. This implies a significant number of measurements for each pool.
- Data Provenance: "unaltered human serum samples." The country of origin is not specified, but the submission is from the UK. The study is prospective in nature (testing conducted for the device).
- Linearity/Assay Reportable Range:
- Sample Size: Samples prepared at 11 levels. Each level run in replicates of five.
- Data Provenance: Not specified, but samples were prepared to cover a range of analyte concentrations. Prospective.
- Detection Limit:
- Sample Size: 240 determinations (for LoD) with 4 low-level samples.
- Data Provenance: Not specified. Prospective.
- Analytical Specificity/Interference:
- Sample Size: Not explicitly stated as a number of samples, but "the analytes detailed below were tested up to the levels indicated at Bilirubin concentrations of 0.14mg/dl and 5.03mg/dl."
- Data Provenance: Not specified. Prospective.
- Method Comparison with Predicate Device:
- Sample Size: 103 serum patient samples.
- Data Provenance: "patient samples." The country of origin is not specified. Likely retrospective, as existing patient samples were used, but the testing itself was prospective.
- Matrix Comparison:
- Sample Size: A minimum of 40 matched patient sample pairs.
- Data Provenance: "Patient samples." The country of origin is not specified. Likely retrospective, as existing patient samples were used, but the testing itself was prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This device is an in vitro diagnostic (IVD) test for quantitative determination of Direct Bilirubin. The "ground truth" for such devices is typically established through reference methods or established predicate devices, not through expert consensus in the same way an imaging or pathology AI might.
- Precision, Linearity, Detection Limit, Specificity: Ground truth is inherent in the analytical methods themselves (e.g., gravimetric dilutions for linearity, spiked samples, controlled interferent concentrations). No external experts are mentioned.
- Method Comparison and Matrix Comparison: The ground truth for these studies is the measurement obtained by the predicate device (Wako Direct Bilirubin V, K053132) or the matched serum/plasma results themselves. No external experts are described as establishing this "ground truth."
4. Adjudication Method for the Test Set
Not applicable for this type of IVD device. Adjudication is typically used in studies involving human interpretation (e.g., radiology reads) to resolve discrepancies.
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 automated in vitro diagnostic test, not an AI-assisted human reading device.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies presented are all standalone performance evaluations of the Randox Direct Bilirubin assay system, an automated IVD device. The results reported are directly from the instrument measurements.
7. The Type of Ground Truth Used
- For analytical performance studies (Precision, Linearity, Detection Limit, Specificity): The 'ground truth' is established through controlled laboratory preparations (e.g., known concentrations of analytes, spiked samples, dilutions) and comparisons to established analytical methods as described in CLSI guidelines.
- For method comparison: The 'ground truth' is the predicate FDA-cleared device (Wako Direct Bilirubin V, K053132).
- For matrix comparison: The 'ground truth' is the serum sample measurement when comparing to lithium heparin plasma.
8. The Sample Size for the Training Set
Not applicable. This is a chemical assay, not a machine learning model that requires a training set. The "development" or "optimization" phase of such an assay would involve internal R&D, but it's not a "training set" in the context of AI/ML.
9. How the Ground Truth for the Training Set Was Established
Not applicable. There is no training set for an IVD chemical assay as described here. Parameter settings and reagent formulations are determined through standard chemical and biochemical R&D processes, not through machine learning ground truth establishment.
§ 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.