(73 days)
This in vitro diagnostic procedure is a solid- phase enzyme immunoassay intended for the quantitative determination of Troponin I in human serum and plasma on the Bayer Immuno 1 system. When used in combination with other clinical data such as presenting symptoms and diagnostic procedures, measurement of Troponin I aids in the diagnosis of acute myocardial infarction.
The Baver Immuno 1 Troponin I™ assay is an enzyme label sandwich assay using a monoclonal and a polvclonal antibody. A Troponin I specific monoclonal antibody is labeled with fluorescein and a Troponin I specific goat affinity purified antibody is labeled with alkaline phosphatase (ALP). The solid phase consists of a suspension of magnetizable particles coated with antibody to fluorescein (mIMP reagent). Sample or cailbrator, R1 reagent containing fluorescein - antibody conjugate. R2 reagent containing ALP-antibody conjugate and mIMP reagent are mixed and incubated at 37°C. In the presence of Troponin I a (fluorescein-conjugate: Troponin I:ALPconjugate) complex is formed and captured by the anti fluorescein antibodies on the magnetic particles. The particles are washed and para-nitrophenvl phosphate solution is added. The ALP in the antibody conjugate reacts with the substrate to form para-nitrophenoxide and phosphate. Increasing absorbance due to the formation of para-nitrophenoxide is monitored at 405 nm and 450 nm. The dose response curve is directly proportional to the concentration of Troponin I in the sample. A linear point fit is used to construct the dose response curve. The Baver Immuno 1 Troponin ITM assay has a range of 0 to 200 ng/ml and liquid calibrators are provided with values of 0, 5, 10, 20, 60 and 200 ng/ml Troponin I. Bayer Immuno 1 Troponin I TEST point controls are provided with values of 3, 7, 50 ng/mL Troponin I.
Here's a breakdown of the acceptance criteria and study information for the Bayer Immuno 1™ System Troponin I method, based on the provided text:
Acceptance Criteria and Device Performance
The submission relies on demonstrating substantial equivalence to a predicate device, the Dade Stratus® Troponin I kit. Therefore, the "acceptance criteria" are implicitly defined by the performance characteristics of the predicate device and the new device's ability to demonstrate comparable performance. The key performance indicators evaluated are imprecision (precision), linearity (recovery), correlation with the predicate device, and minimum detectable concentration (detection limit).
| Performance Characteristic | Acceptance Criteria (Implicitly based on predicate/industry standards) | Reported Device Performance (Bayer Immuno 1™ Troponin I Method) |
|---|---|---|
| Imprecision (Total) | Not explicitly stated as a numerical criterion, but expected to be within acceptable limits for a quantitative assay. | Ranges from 4.3% (at 2.9 ng/mL Troponin I) to 2.1% (at 47.8 ng/mL Troponin I). |
| Linearity (Recovery) | Not explicitly stated as a numerical criterion, but expected to demonstrate accurate recovery across a range of concentrations. | Recoveries range from 88% to 110% when diluting human AMI patient pools with troponin I-free normal human serum. Recoveries average 97.9% (range 85% to 116%) with Immuno 1 Sample diluent B. |
| Correlation | Strong correlation (e.g., r > 0.95) with the predicate device. | r = 0.98 with the Dade Stratus® Troponin I method. |
| Minimum Detectable Concentration | Expected to be sufficiently low for clinical utility. | 0.1 ng/mL. |
| Cross Reactivity | Minimal or undetectable cross-reactivity with related substances. | Minimal or undetectable with human cardiac Troponin T, human cardiac Troponin C, human skeletal Troponin I, human skeletal Troponin T, bovine actin, and bovine tropomyosin. |
| Expected Values (Normal Population) | Results in healthy individuals should be below the detection limit. | 197 healthy Red Cross blood donors all showed results below 0.1 ng/mL. |
| Expected Values (Angina Patients) | Majority of angina patients should have results below detection limit or slightly elevated. | 60 out of 64 angina patients had results below 0.1 ng/mL; 4 had results between 0.2 and 0.6 ng/mL. |
| Expected Values (AMI Patients) | AMI patients should show elevated Troponin I levels. | 41 hospitalized AMI patients all had results greater than or equal to 0.9 ng/mL. |
Study Details
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Sample sizes used for the test set and the data provenance:
- Imprecision: Human serum samples were analyzed. The number of samples is not explicitly stated, but the analysis involved duplicate measurements on two instruments over 18 days. This suggests a total of 18 days * X samples/day (where X is at least 1) * 2 duplicates * 2 instruments = at least 72 measurements (if only one sample type was used per run).
- Linearity: Human AMI patient pools. The number of pools or individual samples is not specified.
- Correlation: 279 patient samples.
- Expected Values:
- Healthy Red Cross blood donors: 197 specimens.
- Angina patients: 64 specimens.
- AMI patients: 41 specimens.
- Data Provenance: Not explicitly stated, but likely retrospective as it involves analyzing "patient samples" and "specimens." The mention of "clinical trial sites" for the correlation study suggests multi-site data collection, but specific countries are not mentioned.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- For expected values in different patient populations (healthy, angina, AMI), the "clinical diagnosis of angina" and "clinical diagnosis of AMI" serve as the ground truth. The number and qualifications of clinicians making these diagnoses are not specified.
- For the correlation study, the "Dade Stratus® Troponin I method" is used as a reference for the Troponin I values in the patient samples, rather than an expert panel.
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Adjudication method for the test set:
- No adjudication method (e.g., 2+1, 3+1) is mentioned, as the study primarily relies on quantitative measurements and comparison to a predicate device or predefined clinical diagnoses.
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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:
- No MRMC study was done. This submission is for an in-vitro diagnostic (IVD) assay which provides a quantitative measurement, not an AI-assisted diagnostic imaging or interpretation device that would involve human "readers."
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- This is an in-vitro diagnostic assay, which by nature operates as a standalone system to measure analyte concentration. The performance characteristics described are "algorithm only" in the sense that they represent the performance of the assay itself in generating a quantitative result. There is no human "in-the-loop" once the sample is processed by the Immuno 1 system.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For correlation: The predicate device's measurements (Dade Stratus® Troponin I method) served as the comparative "ground truth" for the new device's measurements.
- For expected values: Clinical diagnoses (e.g., "clinical diagnosis of angina," "clinical diagnosis of AMI") were used to categorize patients for expected value determination.
- For linearity and imprecision: Ground truth is established by the known concentrations in engineered samples (calibrators, controls, diluted pools) or by statistical analysis of repeat measurements.
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The sample size for the training set:
- This submission describes performance characteristics and validation studies. No specific "training set" for an algorithm is mentioned, as the device is a chemical immunoassay, not a machine learning model.
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How the ground truth for the training set was established:
- As there is no distinct "training set" for an algorithm in this context, this question is not applicable. The assay itself involved development and optimization, but standard laboratory practices and known concentrations in controls and calibrators would have guided this, rather than a formal "ground truth for a training set" as understood in AI/ML contexts.
§ 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.