(266 days)
Access hsTnI is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnI) levels in human serum and plasma using the Access 2 Immunoassay Analyzers to aid in the diagnosis of myocardial infarction (MI).
The Access hsTnI assay is a two–site immunoenzymatic ("sandwich") assay. Monoclonal anti–cTnI antibody conjugated to alkaline phosphatase is added to a reaction vessel along with a surfactant–containing buffer and sample. After a short incubation, paramagnetic particles coated with monoclonal anti–cTnI antibody are added. The human cTnI binds to the anti–cTnI antibody on the solid phase, while the anti–cTnI antibody–alkaline phosphatase conjugate reacts with different antigenic sites on the cTnI molecules. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of analyte in the sample. Analyte concentration is automatically determined from a stored calibration.
The provided text describes the 510(k) clearance for the Beckman Coulter Access hsTnI device, specifically focusing on demonstrating its equivalence when run on the DxC 500i Clinical Analyzer compared to the previously cleared Access 2 Immunoassay System. The "acceptance criteria" and "study that proves the device meets the acceptance criteria" in this context refer to the analytical performance characteristics required to show substantial equivalence between the new platform (DxC 500i) and the cleared predicate platform (Access 2) for the Access hsTnI assay.
Here's a breakdown of the requested information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Parameter | Acceptance Criteria (New DxC 500i vs. Predicate Access 2 for Access hsTnI) | Reported Device Performance (Access hsTnI on DxC 500i) |
|---|---|---|
| Platform Equivalency (Method Comparison - Serum) | ||
| Slope (Passing-Bablok) | Slope 1.00 ± 0.10 | 1.001 |
| Platform Equivalency (Method Comparison - Serum) | ||
| Slope 95% CI | N/A (implied by slope criteria) | 0.976 – 1.020 |
| Platform Equivalency (Method Comparison - Serum) | ||
| Intercept (pg/mL) | N/A | -0.184 |
| Platform Equivalency (Method Comparison - Serum) | ||
| Correlation Coefficient (r) | N/A (implied by clinical performance criteria for r) | 0.999 |
| Platform Equivalency (Method Comparison - Plasma) | ||
| Slope (Passing-Bablok) | Slope 1.00 ± 0.10 | 0.997 |
| Platform Equivalency (Method Comparison - Plasma) | ||
| Slope 95% CI | N/A (implied by slope criteria) | 0.978 – 1.016 |
| Platform Equivalency (Method Comparison - Plasma) | ||
| Intercept (pg/mL) | N/A | 0.560 |
| Platform Equivalency (Method Comparison - Plasma) | ||
| Correlation Coefficient (r) | N/A (implied by clinical performance criteria for r) | 0.999 |
| Clinical Performance (Method Comparison) | ||
| Slope | 1.00 ± 0.10 | Met the acceptance criteria (specific value not reported, but stated to be within range) |
| Clinical Performance (Method Comparison) | ||
| Correlation Coefficient (r) | ≥ 0.90 | Met the acceptance criteria (specific value not reported, but stated to be within range) |
| **Imprecision (Total within-laboratory) for levels 1,000,000 pg/mL sample |
Note: The acceptance criteria for the "Platform Equivalency" and "Clinical Performance" studies are largely the same (slope 1.00 ± 0.10 and r ≥ 0.90), indicating the central intent was to show the DxC 500i performs equivalently to the Access 2 for this assay.
2. Sample Size Used for the Test Set and Data Provenance
- Platform Equivalency Study (Method Comparison - Representative) Sample Size:
- Serum: N = 106
- Plasma: N = 122
- Clinical Performance (Method Comparison) Sample Size:
- "More than 200 discrete lithium heparin plasma samples" per site for a total of three sites (2 external, 1 internal). This implies a total sample size of >600 for this specific study.
- Imprecision, Linearity, Detection Capability, and Carryover studies: Sample sizes are not explicitly stated for these, but they are implied to be sufficient for the CLSI standards cited (EP05-A3, EP06-2nd Edition, EP17-A2).
- Data Provenance: The studies were conducted at "two external tests sites and one internal test site." The specific country of origin is not mentioned, but "Beckman Coulter, Inc." is based in California, USA. The data is prospective as it involves controlled studies and analyses to demonstrate performance on the new platform.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This section is Not Applicable to this device. The Access hsTnI assay is an in vitro diagnostic (IVD) test that quantitatively measures a biomarker (cardiac troponin I). The "ground truth" for method comparison and analytical performance studies of IVDs is typically established by comparative analysis against a reference method or a legally marketed predicate device, as seen here. It does not involve human expert interpretation of images or signals that would require expert consensus for ground truth.
4. Adjudication Method for the Test Set
This section is Not Applicable. As stated above, this is an IVD device for quantitative measurement. The "test set" in this context refers to patient samples with varying concentrations of the analyte, measured by both the candidate and predicate devices. There is no human interpretation or subjective assessment that would require adjudication.
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
This section is Not Applicable. The device is a quantitative immunoassay, not an AI-powered diagnostic imaging or interpretation tool that assists human readers. Therefore, an MRMC study is not relevant.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
This section is Not Applicable in the context of an "algorithm only" being evaluated for standalone performance. The Access hsTnI device on the DxC 500i is a laboratory instrument system performing a chemical assay. Its "performance" is inherently "standalone" in the sense that the instrument provides a quantitative result without immediate human-in-the-loop assistance for that specific measurement. The "comparison testing" essentially evaluates its standalone performance against a predicate standalone device.
7. The Type of Ground Truth Used
The "ground truth" for the test set was essentially:
- Measurement by the legally marketed predicate device (Access hsTnI on Access 2 Immunoassay System): This is the gold standard against which the performance of the Access hsTnI on the DxC 500i Clinical Analyzer is compared to demonstrate substantial equivalence.
- Definitions within CLSI guidelines: For parameters like precision, linearity, and detection capability, the "ground truth" is adherence to statistical and analytical performance models defined by the specified CLSI (Clinical and Laboratory Standards Institute) guidelines.
8. The Sample Size for the Training Set
This section is Not Applicable. The Access hsTnI is a reagent and instrument system for an immunoassay. It is not an AI/ML algorithm that requires "training data" in the typical sense. The term "training set" is usually associated with machine learning models. The development and validation of such IVD assays involve extensive R&D, method development, and verification on an internal set of samples, but these are not referred to as a "training set" in the context of AI.
9. How the Ground Truth for the Training Set was Established
This section is Not Applicable for the reasons stated in point 8.
§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.
(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.