(12 days)
The ACCESS® Troponin I assay is a paramagnetic-particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I levels in human serum and plasma (EDTA), using the ACCESS® Immunoassay System.
The ACCESS® Troponin I assay is a paramagnetic-particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I levels in human serum and plasma (EDTA), using the ACCESS® Immunoassay System.
The ACCESS® Troponin I assay is a chemiluminescent immunoassay designed for the quantitative determination of cardiac troponin I levels in human serum and plasma. The study aimed to establish the clinical performance characteristics of the device and demonstrate its substantial equivalence to a previously cleared troponin I assay (Baxter Stratus® Cardiac Troponin-I) and CK-MB, which was considered the "gold standard" biochemical marker at the time.
Here's a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Metric | Acceptance Criterion (Implicit) | Reported Device Performance |
|---|---|---|---|
| Analytical Performance | Precision | Acceptable CV range | 5.97% CV (high control) to 13.53% CV (low control) |
| Dilution Recovery | Average recovery close to 100% | 93.5% average recovery | |
| Correlation with Predicate Device (Stratus®) | Strong correlation (r) | r = 0.87, y = 0.136x -0.088 (189 samples) | |
| Analytical Sensitivity | Low detectable level | 0.03 ng/ml (95% confidence) | |
| Clinical Performance | Optimal Cutoff for AMI | Clinically relevant cutoff | 0.15 ng/ml |
| Clinical Sensitivity (at cutoff 0.15 ng/ml) | High sensitivity for AMI | 89% | |
| Clinical Specificity (at cutoff 0.15 ng/ml) | High specificity for AMI | 91% | |
| Concordance with Predicate Device (Stratus®) | High concordance | 90% (201 patients) | |
| Concordance with Gold Standard (CK-MB) | High concordance | 90% (208 subjects) | |
| Specificity in Skeletal Muscle Injury | High specificity | 86% (58 patients) | |
| Specificity in Renal Disease | High specificity | 96% (81 subjects) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size:
- Clinical Performance Study: 289 subjects presenting to the emergency department with chest pain.
- 45 subjects were ruled-in for Acute Myocardial Infarction (AMI).
- Correlation with Stratus® (clinical): 201 patients.
- Concordance with CK-MB (clinical): 208 subjects.
- Specificity in Skeletal Muscle Injury: 58 patients.
- Specificity in Renal Disease: 81 subjects.
- Correlation with Stratus® (analytical): 189 samples.
- Clinical Performance Study: 289 subjects presenting to the emergency department with chest pain.
- Data Provenance: The study was described as a "multi-site prospective study." The country of origin is not explicitly stated, but given the 510(k) submission to the FDA, it is highly probable the data was collected within the United States.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not specify the number of experts or their qualifications used to establish the ground truth for the clinical diagnosis of AMI (rule-in/rule-out). However, the "gold standard biochemical marker, CK-MB" was used as a comparative measure, suggesting that a combination of clinical assessment and established biochemical markers (like CK-MB) likely formed the basis for the ground truth determination rather than solely expert consensus on imaging or other modalities.
4. Adjudication Method for the Test Set
The document does not explicitly state an adjudication method (e.g., 2+1, 3+1). The diagnosis of AMI was established by following subjects serially (minimum of two serum samples) to "rule-in or rule-out AMI," implying a standard clinical diagnostic process was followed rather than a specific expert adjudication process for the test results themselves.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This study is for an in-vitro diagnostic (IVD) assay that measures a biomarker, not an imaging device or AI-assisted diagnostic tool that would typically involve human readers. Therefore, there is no effect size reported for human readers improving with or without AI assistance.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the primary clinical performance (sensitivity, specificity, concordance) was assessed for the ACCESS® Troponin I assay as a standalone device (i.e., algorithm only if you consider the "algorithm" to be the assay's chemical reaction and measurement process). There is no mention of a human-in-the-loop component for the performance evaluation itself. The device provides a quantitative measurement, and a cutoff is applied to this measurement for clinical interpretation.
7. The Type of Ground Truth Used
The ground truth for the clinical performance assessment of AMI (rule-in/rule-out) was based on:
- Clinical diagnosis of AMI: This would typically involve a combination of patient symptoms (chest pain of 20 minutes duration), serial measurements of cardiac markers, and potentially ECG findings.
- Comparison to a "gold standard biochemical marker, CK-MB": This served as a key reference for determining the clinical accuracy of the Troponin I assay.
8. The Sample Size for the Training Set
The document does not explicitly state the sample size for a "training set." This type of IVD device typically undergoes extensive analytical validation (precision, linearity, sensitivity) and then clinical validation. The "optimal cutoff of 0.15 ng/ml" was determined from ROC curve analysis on "all subject results" (which included the 289 subjects in the multi-site prospective study), suggesting that the clinical validation set was also used for defining this cutoff rather than a separate, explicitly defined "training set" in the machine learning sense.
9. How the Ground Truth for the Training Set Was Established
As noted above, a distinct "training set" in the machine learning sense is not explicitly described. However, if the determination of the "optimal cutoff of 0.15 ng/ml" is considered part of a "training" or optimization process, then the ground truth for this optimization was established using the clinical diagnosis of AMI (rule-in or rule-out) for the 289 subjects in the prospective study. This clinical diagnosis would have been based on standard medical criteria at the time.
§ 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.