(267 days)
The ATAC Total Bilirubin Reagent Kit is intended for use with the ATAC Calibrator and the ATAC 8000 Random Access Chemistry System as a system for the quantitative determination of total bilirubin in serum and plasma. Total bilirubin results are used for the diagnosis and treatment of liver, 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 Total Bilirubin Reagent determines total bilirubin through its reaction with diazotized sulfanilic acid in the presence of dimethylsulfoxide to form a red-purplex. The resulting increase in absorbance at 546 nm is proportional to the total bilirubin concentration in the sample.
The "ATAC Total Bilirubin Reagent Kit" is a device intended for the quantitative determination of total bilirubin in serum and plasma. The following information outlines its acceptance criteria and the studies performed to demonstrate its effectiveness.
1. Acceptance Criteria and Reported Device Performance
| Feature/Study | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Linearity/Recovery | Linear recovery across the usable range (0.1 to 25 mg/dL) with good correlation to standard values. | Recovery of linearity standards: (ATAC Recoveries) = 0.3 mg/dL + 0.87 x (Standard Factors), Sy.x = 0.28 mg/dL, r = 1.000, n = 18. This demonstrates linearity from 0.1 to 25 mg/dL. |
| Precision | Acceptable within-run and total precision for control serum. | Precision statistics (NCCLS Guideline EP3-T analogous method): |
| Serum 1 (mean 0.6 mg/dL): Within Run 1SD = 0.04 mg/dL (6.5%CV), Total 1SD = 0.10 mg/dL (16.3%CV)Serum 2 (mean 3.4 mg/dL): Within Run 1SD = 0.06 mg/dL (1.6%CV), Total 1SD = 0.11 mg/dL (3.1%CV)Serum 3 (mean 6.3 mg/dL): Within Run 1SD = 0.12 mg/dL (1.9%CV), Total 1SD = 0.17 mg/dL (2.7%CV) | ||
| Method Comparison | Good correlation and agreement with a commercially available comparative reagent. | Deming regression comparison with Competitive Reagent: ATAC 8000 = -0.05 mg/dL + 1.003 x Competitive Reagent, sy.x = 0.20 mg/dL, range = 0.2 - 25.7 mg/dL, n = 107. This shows excellent agreement. |
| Detection Limit | Quantifiable detection limit. | Detection limit: 0.1 mg/dL. Documented through repetitive assay of a diluted serum pool; observed standard deviation of a 30-replicate within-run precision study was 0.49 mg/dL. The detection limit is reported as the round-off error of the assay. |
| Onboard Reagent Stability | Stable for 5 days. | 5 day onboard reagent stability: Estimates of bilirubin recoveries over the test period are less than 0.15 mg/dL. |
| Calibration Stability | Stable for 24 hours. | 24 hour calibration stability: Observed shifts in recoveries over the 24-hour period average less than 0.1 mg/dL. |
| Reconstituted Stability | Stable for 14 days. | 14 day reconstituted stability: Observed shifts in recoveries over the 14-day period are less than 0.1 mg/dL or 2.5%. |
2. Sample Sizes and Data Provenance
- Test Set for Linearity: n = 18 (for the linear regression of standard factors). The data provenance is not explicitly stated as country of origin, but it is for "linearity standards," implying laboratory-prepared standards.
- Test Set for Precision: n = 36 for each of the three serum samples tested (total of 108 replicates). The data provenance is "commercially available control serum."
- Test Set for Method Comparison: n = 107. The data provenance is "Mixed serum and plasma specimens, collected from adult patients." The country of origin is not specified. It is likely prospective for the purpose of the study.
- Test Set for Detection Limit: 30 replicates of a diluted serum pool.
3. Number of Experts and Qualifications for Ground Truth
- This document describes the performance characteristics of an in-vitro diagnostic reagent kit (ATAC Total Bilirubin Reagent Kit) and does not involve image analysis or clinical interpretation by human experts to establish ground truth in the typical sense for a medical device that outputs diagnoses or classifications.
- The ground truth for the performance studies (linearity, precision, method comparison, detection limit, stability) is based on:
- Known concentrations for linearity standards.
- Assigned values for commercially available control serum.
- Results from a "commercially available method" (predicate device or similar) for method comparison.
- Therefore, the concept of "number of experts" and their "qualifications" for establishing ground truth as it applies to image interpretation or clinical diagnosis does not directly apply here. The "experts" are the analytical chemists and laboratory professionals who establish the values of standards and controls, and run the comparative assays.
4. Adjudication Method
- Adjudication methods like 2+1 or 3+1 are typically used in studies where there is subjective human interpretation involved (e.g., radiologists reviewing images).
- For the performance studies of this in-vitro diagnostic reagent, the "ground truth" or reference values are established through quantitative chemical analysis and metrological traceability. Therefore, an adjudication method in the human consensus sense is not applicable. Discrepancies would be resolved through re-testing, calibration verification, or investigation of analytical errors, not expert consensus.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- An MRMC study is not mentioned and is not applicable to the evaluation of an in-vitro diagnostic reagent kit like the ATAC Total Bilirubin Reagent Kit. These studies are relevant for devices that assist human readers in tasks like image interpretation or clinical decision-making.
6. Standalone Performance
- Yes, this document primarily reports on the standalone performance of the ATAC Total Bilirubin Reagent Kit when used with the ATAC 8000 Random Access Chemistry System. The results presented (linearity, precision, detection limit, stability) are measures of the algorithm's (reagent kit's) performance independent of human-in-the-loop diagnostic interpretation.
- The "method comparison" study essentially compares the standalone performance of the ATAC kit to another standalone, commercially available method.
7. Type of Ground Truth Used
The types of ground truth used are:
- Reference Standards/Known Concentrations: For linearity and stability studies, the performance is evaluated against solutions with established concentrations of total bilirubin.
- Assigned Values of Control Materials: For precision studies, the device's repeatability and reproducibility are measured against commercially available control sera with pre-determined mean values.
- Results from a Legally Marketed Predicate/Comparative Device: For method comparison, the results from the ATAC Total Bilirubin Reagent are compared against those obtained from the "Beckman Synchron Total Bilirubin Reagent, product 442745" or another "commercially available method," which serves as the reference ground truth for agreement.
8. Sample Size for the Training Set
- This document describes validation studies of a chemical reagent kit, not a machine learning or AI model. Therefore, the concept of a "training set" in the context of AI is not applicable. The development of the reagent itself would involve formulation, optimization, and initial testing, but these are not referred to as "training sets."
9. How the Ground Truth for the Training Set Was Established
- As the concept of a "training set" for an AI model is not applicable here, the question of how its ground truth was established is also not relevant. The studies focus on verifying the analytical performance of the finished reagent kit against established laboratory and regulatory standards.
§ 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.