(270 days)
The ATAC Direct Bilirubin Reagent Kit, which contains both reagent and calibrator, is intended for use with the ATAC 8000 Random Access Chemistry System as a system for the quantitative determination of conjugated bilirubin in serum and plasma. Conjugated bilirubin results are used for the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.
This reagent is intended to be used by trained personnel in a professional setting and is not intended for home use.
The ATAC Direct Bilirubin Reagent Kit, which contains both reagent and calibrator, is substantially equivalent to the Trace Direct Bilirubin Reagent, product UG38 (Trace Scientific, Ltd. of Melbourne, Australia) calibrated with the Sigma Bilirubin Calibrator, Total and Direct, product no. B8652 (Sigma Diagnostics, Inc. St. Louis, MO). The effectiveness of ATAC Direct Bilirubin Reagent Kit on the ATAC 8000 Random Access Chemistry System is shown in the following studies.
The ATAC Direct Bilirubin Reagent determines conjugated bilirubin through its reaction with diazotized sulfanilic acid to form a red-purple complex. The resulting increase in absorbance at 546 nm is proportional to the direct bilirubin concentration in the sample.
This document describes the acceptance criteria and performance of the ATAC Direct Bilirubin Reagent Kit, a device intended for the quantitative determination of conjugated bilirubin in serum and plasma.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct pass/fail thresholds in the provided text. However, the reported device performance demonstrates the device's characteristics, which would implicitly meet internal acceptance based on established analytical standards for diagnostic reagents. We can infer the "acceptance" by the fact that these results are presented as evidence of the device's effectiveness and substantial equivalence.
| Acceptance Criteria (Inferred from reported performance) | Reported Device Performance (ATAC Direct Bilirubin Reagent Kit) |
|---|---|
| Linearity Range | Linear from 0.1 to 20 mg/dL |
| Linearity Regression (Correlation Coefficient) | r = 0.999 |
| Linearity Regression (Sy.x) | 0.29 mg/dL |
| Within Run Precision (Serum 1, 0.9 mg/dL) | 0.10 1SD, 10.3% CV |
| Within Run Precision (Serum 2, 3.8 mg/dL) | 0.11 1SD, 3.0% CV |
| Within Run Precision (Serum 3, 6.7 mg/dL) | 0.12 1SD, 1.9% CV |
| Total Precision (Serum 1, 0.9 mg/dL) | 0.09 1SD, 9.2% CV |
| Total Precision (Serum 2, 3.8 mg/dL) | 0.13 1SD, 3.4% CV |
| Total Precision (Serum 3, 6.7 mg/dL) | 0.18 1SD, 2.7% CV |
| Method Comparison (Deming Regression Slope) | 1.143 |
| Method Comparison (Deming Regression Intercept) | -0.10 mg/dL |
| Method Comparison (Sy.x) | 0.32 mg/dL |
| Detection Limit | 0.1 mg/dL |
| Onboard Reagent/Calibration Stability (Imprecision) | Less than 0.15 mg/dL or 3% over 5 days |
| Reconstituted Stability (Shift) | Less than 0.1 mg/dL or 6% over 14 days |
2. Sample Size for the Test Set and Data Provenance
- Sample Size for Linearity: n = 18 (for standard factor recoveries).
- Sample Size for Precision: n = 60 for each of the three control serum levels (total 180 assays)
- Sample Size for Method Comparison: n = 96 (after exclusions).
- Sample Size for Detection Limit: 125 results over 25 runs.
- Data Provenance: The document states that mixed serum and plasma specimens were collected from adult patients. The country of origin is not explicitly stated, but the predicate device is from Trace Scientific, Ltd. of Melbourne, Australia, and Sigma Diagnostics, Inc. St. Louis, MO, for the calibrator, suggesting a US/Australian context. The study appears to be prospective in nature, as indicated by the collection of patient specimens for the method comparison and repeated assays for precision and detection limit.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of those Experts
This device is an in vitro diagnostic reagent kit for quantitative determination of a biomarker (conjugated bilirubin). The "ground truth" for such devices is typically established through reference methods or highly accurate analytical techniques, not through expert human interpretation of images or clinical cases. Therefore:
- Number of Experts: Not applicable in the context of this type of diagnostic device.
- Qualifications of Experts: Not applicable.
4. Adjudication Method for the Test Set
Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies involving subjective interpretations (e.g., imaging studies where multiple readers interpret results and discrepancies need to be resolved). For a quantitative chemical assay, the "adjudication" is inherent in the analytical methodology itself, such as repeat measurements, statistical analysis, and comparison to a predicate device or reference method.
- Adjudication Method: Not applicable in the traditional sense. The method comparison study involved comparing the ATAC 8000 results with those from another commercially available method, and statistical analysis (Deming regression) was used to assess agreement. Outliers were excluded based on statistical criteria (poor reproducibility and residuals exceeding 6 standard errors).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Was an MRMC study done? No. This type of study is relevant for devices involving human interpretation of results, such as imaging diagnostics. This is a quantitative chemical assay that provides a numerical output.
- Effect size of human readers improve with AI vs without AI assistance: Not applicable.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- Was a standalone study done? Yes, the entire evaluation presented (linearity, precision, method comparison, detection limit, stability) represents the standalone performance of the ATAC Direct Bilirubin Reagent Kit on the ATAC 8000 Random Access Chemistry System. This is an automated system; once the sample is loaded, the measurement is performed by the instrument and reagents without real-time human intervention in the result generation process.
7. The Type of Ground Truth Used
- Ground Truth Type:
- Reference Standards: For linearity, the ground truth was established by "standard values" which are specific concentrations of conjugated bilirubin used for calibration curves.
- Commercially Available Control Serum: For precision, the ground truth was the expected range of values for these control sera.
- Comparison to a Predicate Device/Method: For method comparison, the ground truth was established by "another commercially available method" (the "Competitive Reagent"). This approach demonstrates substantial equivalence, where the predicate serves as the de facto "ground truth" for comparative performance.
- Diluted Serum Pool: For the detection limit, the ground truth involved a diluted serum pool to assess the lowest measurable concentration.
8. The Sample Size for the Training Set
This document describes the validation of a chemical reagent kit, not a machine learning or AI-based algorithm that typically uses "training sets." The linearity standards, control sera, and patient samples used in the performance studies are for validation/testing, not for "training" the reagent itself.
- Sample Size for the Training Set: Not applicable.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the context of this device, this question is not applicable. The device's operational parameters (e.g., absorbance at 546 nm proportional to concentration) are based on established chemical principles, not on a trained algorithm.
§ 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.