(322 days)
The Quantech CK-MB Assay is intended to be used as an aid in diagnosing myocardial infarction in patients exhibiting chest pain. It is intended to be used in conjunction with EKG, and physician examination, as well as possibly other biochemical blood tests to rule in or out origin of the chest pain.
The Quantech CK-MB Assay is intended to be used for the quantitative determination of the cardiac isoenzyme CK-MB, in order to assist in the diagnosis of acute myocardial infarction.
The Quantech CK-MB assay is based on the principle of two site, or sandwich immunoassav in combination with SPR surface mass measurement. Each test module contains a solid phase anti-CK-MB monoclonal antibody immobilized onto a gold surface. An anti-CK-MB polyclonal antibody, used to enhance the specific detection of the isoenzyme is introduced sequentially.
The Quantech assay utilizes CK-MB-specific antibody to capture the CK-MB in the sample. This is followed by a quantitation of the surface mass increase using surface plasmon resonance (SPR), to measure the CK-MB in plasma.
The provided text describes the Quantech CK-MB Assay, an in vitro immunological assay for the quantitative measurement of human CK-MB, intended to aid in diagnosing myocardial infarction. The submission seeks substantial equivalence to the AxSYM® CK-MB assay.
Here's an analysis of the acceptance criteria and study data based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria values in a table. Instead, it presents performance data and concludes that the device's performance is "acceptable" or "demonstrates essential equivalence" to the predicate device. The "accepted value for cardiac damage" is mentioned as "greater than 7.0 ng/mL CK-MB", which can be considered a clinical threshold, but not a specific acceptance criterion for the device's technical performance.
Here's a summary of the reported device performance:
| Performance Metric | Reported Device Performance (Quantech CK-MB Assay) |
|---|---|
| Dilution Linearity/Parallelism | Average percent of expected: 118% (deemed acceptable) |
| Recovery | Average recovery: 103% (corrected for endogenous analyte; deemed acceptable) |
| Analytical Sensitivity | 0.3 ng/mL |
| Precision (INTERASSAY) | Low pool (37.5 ng/mL): 9.4% CV; Medium pool (83.1 ng/mL): 4.8% CV; High pool (149 ng/mL): 7.0% CV |
| TOTAL IMPRECISION | Low pool (37.5 ng/mL): 13.3% CV; Medium pool (83.1 ng/mL): 9.1% CV; High pool (149 ng/mL): 10.1% CV |
| Interfering Substances | Percent recovery of CK-MB determined to be acceptable in all three solutions (hemoglobin, bilirubin, triglycerides); no interference noted. |
| Hook Effect | No high dose hook effect observed up to at least 5,000 ng/mL. |
| Normal Range (vs. predicate) | Performs similarly at and below 7.0 ng/mL CK-MB. 95% limit of normals: 4.2 ng/mL (vs. predicate's 3.8 - 6.5 ng/mL). No false positives. |
| Patient Sample Correlation | Correlation coefficient: 0.95 (slope = 0.81, y-intercept = 0.37 ng/mL) with a commercially available method (fluorogenic ELISA). |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: The document does not explicitly state the exact sample size for the clinical test sets.
- For the "Normal Range" study, it mentions "Testing of apparently healthy individuals" and "samples containing high levels of either RF or HAMA". The specific number of individuals or samples is not provided.
- For "Patient Sample Correlation", it mentions "Results from human samples with values distributed throughout the quantitative range". The specific number of human samples is not provided.
- Data Provenance: The document does not specify the country of origin of the data. It implies the data is retrospective as it compares the new device with an existing "predicate device" (AxSYM® CK-MB assay marketed by Abbott Laboratories since 1993) and a "commercially available method (fluorogenic ELISA)".
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable. This device is an in vitro diagnostic (IVD) assay for measuring a biochemical marker (CK-MB levels). The "ground truth" for the test set is the actual CK-MB concentration in the samples, determined by reference methods or the predicate device, not by expert interpretation of images or clinical data.
4. Adjudication Method for the Test Set
Not Applicable. As an IVD assay, the ground truth is established by the concentration of the analyte, not by expert consensus requiring adjudication. Comparisons are made against the predicate device or a reference method.
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 is an IVD assay, not an AI-assisted diagnostic imaging or clinical decision support tool that involves human readers. Therefore, an MRMC study and effect size on human readers are not relevant.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are standalone performance evaluations of the Quantech CK-MB Assay itself. The performance data (linearity, recovery, sensitivity, precision, interference, hook effect, normal range comparison, and patient sample correlation) all represent the direct output of the algorithm/device without explicit human intervention in the result generation or interpretation phase beyond standard laboratory procedures for operating the instrument and collecting samples.
7. The Type of Ground Truth Used
The ground truth for the performance studies was:
- Reference measurements/Predicate Device: For "Normal Range" and "Patient Sample Correlation," the Quantech CK-MB Assay's results were compared against the AxSYM® CK-MB assay (predicate device) and a "commercially available method (fluorogenic ELISA)". The predicate device's established values and the results from the alternative commercial method served as the comparative "truth".
- Known Spiked Concentrations: For "Dilution Linearity/Parallelism" and "Recovery", samples were "spiked with CK-MB" at known concentrations.
- Stripped Plasma: For "Analytical Sensitivity", "zero samples (stripped plasma)" were used to determine the minimum detectable quantity, implying a known absence of the analyte.
- Physiological Interference: For "Interfering Substances", known levels of interferents (hemoglobin, bilirubin, triglycerides) were added to CK-MB samples.
8. The Sample Size for the Training Set
The document does not provide information on a specific "training set" or its sample size. This type of regulatory submission for an IVD assay typically focuses on validation and verification studies rather than machine learning model training. The assay relies on established immunoassay principles, not a learnable algorithm that requires a separate training set.
9. How the Ground Truth for the Training Set was Established
Not applicable, as a distinct "training set" for a machine learning algorithm is not described or implied for this device. The development of the assay itself would have involved internal optimization and calibration using reference materials and characterized samples, but this is distinct from a machine learning training 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.