(49 days)
For in vitro diagnostic use with the CARESIDE Analyzer™ to measure direct bilirubin from whole blood, serum or plasma specimens to aid in the diagnosis and treatment of patients with hepatic, hemolytic hematologic, and metabolic diseases, including hepatitis and gall bladder blockage.
CARESIDE™ Direct Bilirubin cartridges are used with the CARESIDE Analyzer™ to measure direct bilirubin in whole blood, plasma or serum specimens. The CARESIDE™ Direct Bilirubin cartridge, a single use disposable in vitro diagnostic test cartridge, delivers a measured volume of plasma or serum to a dry film to initiate the measurement of direct bilirubin. The film cartidge (patent pending) contains all reagents necessary to measure direct bilirubin. Each CARESIDE™ Direct Bilirubin cartridge consists of a direct bilirubin-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the specimen into the cartridge Sample Well, closes the lid and inserts the cartridge into the CARESIDE Analyzer™. Once loaded, the CARESIDE Analyzer™ scans the cartridge barcode, brings the cartridge and the contained specimen to 37℃, and spins the cartridge to move the sample from the Sample Well into the cartridge channels and chambers. 8.5 microliters of sample remains in the metering passage. Any excess sample flows into an overflow well. The 8.5 microliters of sample is automatically dispensed onto the multi-layer reagent film. The spreading layer distributes the specimen uniformly before it passes through to the absorption layer. The color intensity of the resulting bluish dye, as measured by the amount of reflected light at 570 nanometers, directly relates to the direct bilirubin concentration of the specimen.
Here's a breakdown of the acceptance criteria and the study details for the CARESIDE™ Direct Bilirubin device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied through the comparison with the predicate device and the stated performance characteristics.
| Acceptance Criterion | Predicate Device Performance (Trace Direct Bilirubin) | CARESIDE™ Direct Bilirubin Performance |
|---|---|---|
| Intended Use | To aid in the diagnosis and treatment of patients with hepatic, hemolytic hematological, and metabolic disease, including hepatitis and gall bladder blockage. | Same (Substantially Equivalent) |
| Indications | For in vitro diagnostic use | For in vitro diagnostic use, For point of care use |
| Measurement | Quantitative | Quantitative (Substantially Equivalent) |
| Method Principle | Acid diazo method | Dry film, diazo method |
| Materials | Sulphanilic acid, sodium nitrite | Sulfanilic acid, sodium nitrite (Substantially Equivalent) |
| Detection Limit | Depends on instrumentation | 0.2 mg/dL |
| Reportable Range | Up to 20 mg/dL | 0.1 to 16 mg/dL |
| Accuracy | Not provided | Mean recovery 97% |
| Precision | Total CV, 1.2 mg/dL, 8.7% | Total CV, 2.2 mg/dL, 3.1% |
| Linearity | Linear up to 20 mg/dL | Linear up to 16 mg/dL |
| Interference | No reported interference | No significant interference observed at tested concentrations (Ascorbic Acid, Hemoglobin, Total Protein, Triglycerides) |
| Test time | 10 minutes | Approx. 4 minute warm-up + 5 minute test time |
| Sample Type | Serum | Anti-coagulated whole blood, plasma, or serum plasma. |
| Specimen volume | 10 µl | 8.5 µl test volume (90 ± 10 µl applied volume) |
Notes on Acceptance Criteria:
- The document doesn't explicitly state "acceptance criteria" but rather presents a comparative performance table against a legally marketed predicate device. The underlying assumption is that the CARESIDE™ device must perform as well as or better than the predicate for these parameters to be considered substantially equivalent.
- For "Reportable Range," the CARESIDE™ device has a slightly lower upper limit (16 mg/dL vs 20 mg/dL) but this is still within clinically relevant ranges and the overall performance is deemed equivalent.
- For "Precision," the CARESIDE™ device demonstrates better precision (3.1% vs 8.7% CV).
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective). It only provides the performance characteristics determined from studies.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This information is not provided in the document. The type of device (in vitro diagnostic for bilirubin) suggests that the ground truth would likely be established through a reference method or laboratory standard, rather than expert consensus on interpretation.
4. Adjudication Method for the Test Set
This information is not applicable/provided as the "test set" and "ground truth establishment" would refer to analytical performance studies, not human expert interpretation of images or other subjective data.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
This information is not applicable/provided. The CARESIDE™ Direct Bilirubin is an in vitro diagnostic device, operating independently to measure a biomarker. It does not involve human readers interpreting output that would be assisted by AI.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
The entire study described is essentially a standalone (algorithm only) performance assessment, as the device directly measures bilirubin concentration without requiring human subjective interpretation during the measurement process. The device's performance characteristics (detection limit, reportable range, accuracy, precision, linearity, interference) are all measures of its standalone analytical capability.
7. Type of Ground Truth Used
The ground truth for this type of in vitro diagnostic device would be established by:
- Method Comparison: Comparing the CARESIDE™ device's results against a well-established, legally marketed predicate device (BM/Hitachi 902 Direct Bilirubin) or a recognized reference method. The document states:
- "CARESIDETM = 0.99 (BM/Hitachi 902 Direct Bilirubin) + 0.019 mg/dL, r = 0.997"
- Reference Standards/Calibrators: For accuracy, linearity, and detection limits, the performance would be verified against known concentrations of bilirubin in control materials or calibrators.
8. Sample Size for the Training Set
This information is not provided in the document. For an in vitro diagnostic device like this, "training set" doesn't typically apply in the same way it would for an AI/machine learning algorithm that learns from data. Device development involves establishing reagent formulations, reaction kinetics, and optical measurement parameters, which are validated through analytical studies.
9. How the Ground Truth for the Training Set Was Established
Since a "training set" in the machine learning sense is not applicable here, the question of how its ground truth was established is also not applicable. The underlying chemical reactions and spectrophotometric measurements are based on established scientific principles. The "calibration information bar-coded on each cartridge" and the "lot-specific standard curve" mentioned in the device description imply that internal reference materials and procedures are used to establish the device's measurement accuracy for each manufacturing lot.
§ 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.