(259 days)
The Creatine Kinase-MB assay is an in-vitro test for the quantitative determination of the catalytic activity of creatine kinase MB subunit (CK-MB) in human serum and plasma on Roche/Hitachi cobas c systems.
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.
The Creatine Kinase-MB assay is a two reagent assay for the quantitative determination of creatine kinase-MB (CK-MB) in human serum and plasma on automated clinical chemistry analyzers. The rate of the NADPH formation is directly proportional to the catalytic CK-MB activity. It is determined by measuring the increase in absorbance photometrically.
This document is a 510(k) summary for a medical device called "Creatine Kinase-MB" by Roche Diagnostics. It describes the device, its intended use, technological characteristics, and performance evaluation data.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Key Takeaway: This document is about a clinical chemistry assay (an in-vitro diagnostic test), not an AI/ML device. Therefore, many of the typical AI/ML study components (like multi-reader multi-case studies, expert adjudication, or separate training/test sets for AI models) are not applicable to this type of device. The "ground truth" here is the reference measurement method or the expected concentration of the analyte.
1. Table of Acceptance Criteria and Reported Device Performance
Since this is an in-vitro diagnostic test and not an AI/ML device, the acceptance criteria are not typically expressed as sensitivity/specificity in an MRMC study for diagnostic imaging. Instead, the acceptance criteria relate to analytical performance characteristics. The document presents the performance data against established analytical standards (CLSI guidelines) and comparisons to a predicate device.
| Acceptance Criterion Category | Specific Criterion (Implicit/Explicit from CLSI Guidelines/Industry Standards) | Reported Device Performance |
|---|---|---|
| Precision | Repeatability (Within-run precision): Acceptable CV/SD for varying analyte concentrations. | Human Serum 1 (17.9 U/L): SD 0.4 U/L, CV 2.2% |
| Human Serum 2 (29.1 U/L): SD 0.4 U/L, CV 1.2% | ||
| Human Serum 3 (524 U/L): SD 2.5 U/L, CV 0.5% | ||
| Human Serum 4 (1040 U/L): SD 4.9 U/L, CV 0.5% | ||
| Human Serum 5 (1826 U/L): SD 25 U/L, CV 1.3% | ||
| Intermediate Precision (Within-lab precision): Acceptable CV/SD for varying analyte concentrations. | Human Serum 1 (17.8 U/L): SD 0.5 U/L, CV 2.8% | |
| Human Serum 2 (29.0 U/L): SD 0.6 U/L, CV 1.9% | ||
| Human Serum 3 (531 U/L): SD 4.4 U/L, CV 0.8% | ||
| Human Serum 4 (1040 U/L): SD 8.4 U/L, CV 0.8% | ||
| Human Serum 5 (1851 U/L): SD 42 U/L, CV 2.3% | ||
| Analytical Sensitivity | Limit of Blank (LoB): Should be below claimed limit of quantitation. | Result: 0.3 U/L, Claim: 3 U/L |
| Limit of Detection (LoD): Should be below claimed limit of quantitation and above LoB. | Result: 1.0 U/L, Claim: 3 U/L | |
| Limit of Quantitation (LoQ): The lowest concentration at which quantitative results can be reported with acceptable precision and accuracy. | Result: 1.9 U/L, Claim: 10 U/L | |
| Linearity/Assay Reportable Range | Measurements across the claimed measuring range should be linear with a high correlation coefficient (R2). | Plasma: y=0.969x + 0.210, R2=0.9996 |
| Serum: y=0.992x + 0.306, R2=0.9999 | ||
| Endogenous Interferences | No significant interference from common interferents up to specified levels. | Conjugated Bilirubin: No significant interference up to 60 I Index (approx. 1026 µmol/L or 60 mg/dL). |
| Lipemia: No significant interference up to 500 L Index. | ||
| Hemolysis: Interferes, hemolyzed samples should not be used. | ||
| Exogenous Interferences (Drugs) | No significant interference from common drugs at therapeutic concentrations. | No interference with common drug panels, except Cyanokit (Hydroxocobalamin) and Cefoxitin. |
| Method Comparison to Predicate | Results should be comparable to the legally marketed predicate device (e.g., strong correlation, slope near 1, intercept near 0). | Regression: y = 0.977x + 1.12, r = 0.968 (105 human serum samples plus 4 spiked samples). |
| Matrix Comparison (Anticoagulants) | Different sample matrices (serum vs. various plasma types) should yield comparable results. | Serum vs. Serum Gel Separation: y = 0.996x + 0.804, r = 1.00 |
| Serum vs. Li-heparin: y = 1.00x - 0.616, r = 0.999 | ||
| Serum vs. K2-EDTA: y = 1.00x - 0.717, r = 0.999 | ||
| Serum vs. K3-EDTA: y = 0.995x - 0.062, r = 1.00 |
Study Details:
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision (Repeatability & Intermediate Precision):
- 5 human serum samples and 2 control samples.
- Measurements: Two aliquots per run, two runs per day for ≥ 21 days on the same analyzer using 3 lots of reagent.
- Data Provenance: Not explicitly stated (e.g., country of origin), but implies laboratory-based prospective testing as per CLSI guidelines.
- Analytical Sensitivity (LoB, LoD, LoQ):
- LoB: One analyte-free sample. Measured with three lots, 10-fold determination in 6 runs, over 3 days (60 measurements per lot).
- LoD: Five samples with low analyte concentration. Measured with three lots, twofold determination in 6 runs, over 3 days (60 measurements per lot).
- LoQ: 5 human serum samples diluted to low levels. Tested in 5 replicates per sample on 5 days, one run per day.
- Data Provenance: Implies laboratory-based prospective testing as per CLSI guidelines.
- Linearity:
- One serum pool and one plasma pool, diluted to 16 (serum) and 18 (plasma) concentrations.
- Measurements: Measured in triplicate.
- Data Provenance: Implies laboratory-based prospective testing.
- Endogenous Interferences:
- Pooled human serum samples spiked with varying levels of interferent.
- Measurements: Tested in triplicate.
- Data Provenance: Implies laboratory-based prospective testing.
- Exogenous Interferences (Drugs):
- Two sample pools (low and high CKMB concentration).
- Measurements: Aliquots spiked with drugs, determined in triplicate.
- Data Provenance: Implies laboratory-based prospective testing.
- Method Comparison to Predicate:
- 105 human serum samples (plus 4 spiked with CK MB rec human).
- Data Provenance: Not explicitly stated origins of human serum samples, but implies prospective collection for this comparison.
- Matrix Comparison (Anticoagulants):
- 31 Li Heparin tubes, 30 K2 EDTA tubes, 31 K3 EDTA tubes, and 31 Gel Separation tubes.
- Data Provenance: Implies prospective collection of samples drawn into different tubes.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
Not applicable. This is an analytical performance study for an in-vitro diagnostic assay. Ground truth is established by reference methods, known concentrations, or comparison to a predicate device, not by expert medical image interpretation.
4. Adjudication Method for the Test Set
Not applicable. There is no human interpretation or adjudication component in the analytical performance testing described for this device. Measurements are objective quantitative values.
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
Not applicable. This device is an in-vitro diagnostic test, not an AI-assisted diagnostic imaging tool or a device requiring human readers/interpreters in its primary use.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done
This is fundamentally a "standalone" device in the sense that its performance is measured analytically on its own, producing a quantitative result. There is no "human-in-the-loop" performance as would be relevant for an AI-powered diagnostic imaging tool. The device provides a direct measurement.
7. The Type of Ground Truth Used
The "ground truth" for this device's performance studies is based on:
- Reference Methods/Known Concentrations: For precision, linearity, and analytical sensitivity, samples with known or expected concentrations (e.g., controls, highly purified analytes, or diluted samples) are used.
- Comparison to a Legally Marketed Predicate Device: For method comparison, the results from the new device are compared to those obtained from the established predicate device, which serves as a de facto "truth" or reference standard for equivalence.
- CLSI Guidelines: The studies follow CLSI (Clinical and Laboratory Standards Institute) guidelines (e.g., EP5-A3, EP17-A2, EP6-A), which define how analytical performance characteristics should be determined using standard laboratory practices.
8. The Sample Size for the Training Set
Not applicable. This is not an AI/ML device, so there is no "training set" in the context of model development. The laboratory studies described are for system validation, not algorithm training.
9. How the Ground Truth for the Training Set Was Established
Not applicable. As there is no "training set" for an AI/ML model, there is no ground truth established for such a set.
§ 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.