(192 days)
For the in vitro quantitative determination of N-terminal proBrain natriuretic peptide in human serum and plasma. Elecsys proBNP is used as an aid in the diagnosis of individuals suspected of having congestive heart failure. The test is further indicated for the risk stratification of patients with acute coronary syndrome or congestive heart failure. The test may also serve as an aid in the assessment of increased risk of cardiovascular events and mortality in patients at risk for heart failure who have stable coronary artery disease. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010, Elecsys 2010 and MODULAR ANALYTICS E170 immunoassay analyzers.
A device for the measurement of human proBNP in serum or plasma.
Here's an analysis of the provided text regarding the Elecsys® proBNP Immunoassay's acceptance criteria and testing:
1. Table of Acceptance Criteria and Reported Device Performance:
The document primarily compares the expanded intended use device with a predicate device (K032646) which has the same core technology. The performance characteristics presented are more about consistency with the predicate rather than specific acceptance criteria against defined thresholds for new indications. However, implicit acceptance criteria can be inferred from the data provided demonstrating equivalent or better performance in the listed categories.
| Feature / Acceptance Criteria (Inferred) | Reported Device Performance (Elecsys proBNP Expanded Intended Use) |
|---|---|
| Precision | |
| E170 - Within run | 0.9%CV @ 474 pg/mL, 1.1%CV @ 8005 pg/mL, 0.9%CV @ 13682 pg/mL |
| E170 - Total | 5.8%CV @ 494 pg/mL, 4.1%CV @ 7827 pg/mL, 3.7%CV @ 13143 pg/mL |
| E1010/2010 – Within run | 2.7%CV @ 175 pg/mL, 2.4%CV @ 355 pg/mL, 1.9%CV @ 1068 pg/mL, 1.8%CV @ 4962 pg/mL |
| E1010/2010 – Total | 3.2%CV @ 175 pg/mL, 2.9%CV @ 355 pg/mL, 2.6%CV @ 1068 pg/mL, 2.3%CV @ 4962 pg/mL |
| Hook Effect | No effect up to 300,000 pg/ml |
| Analytical Sensitivity | 5 pg/mL |
| Interference (Limitations) | No interference from bilirubin up to 35 mg/dL, hemoglobin up to 1.4 g/dL, triglycerides up to 4000 mg/dL, biotin up to 30 ng/mL, rheumatoid factor up to 1500 IU/mL. Sample should not be taken until 8 hours after high biotin doses (>5 mg/dL). Rare interference from high titers of anti-streptavidin and ruthenium. |
| Measuring Range | 5-35,000 pg/mL |
| Result Interpretation | 125 pg/ml for patients younger than 75 years and 450 pg/ml for patients 75 years and older. |
The "study that proves the device meets the acceptance criteria" for the expanded indications primarily relies on three literature articles that support the clinical utility of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in the new indications (risk stratification in stable and unstable CAD, and assessment of increased risk of cardiovascular events/mortality in patients at risk for heart failure with stable CAD). The provided text confirms that the analytical performance characteristics (precision, hook effect, analytical sensitivity, limitations, measuring range, result interpretation) of the current device are the same as an existing predicate device (K032646), which presumably already met its own set of acceptance criteria. The submission is for an expanded intended use, implying the analytical performance itself is not a new challenge, but rather the clinical validation of the biomarker for additional conditions.
2. Sample Size Used for the Test Set and Data Provenance:
- Clinical Studies (Expanded Indications): The document does not explicitly state the sample size, provenance (country, retrospective/prospective), or specific details of the patient populations for the three literature articles cited. These are external peer-reviewed publications.
-
- Schnabel R, et al. (2005) - AtheroGene Study cohort.
-
- Kragelund C, et al. (2005) - Copenhagen.
-
- Ndrepepa G, et al. (2005) - Unknown.
-
- Analytical Performance Studies (Precision, Hook Effect, etc.): The sample sizes for the internal analytical performance studies are not provided. The text states "Elecsys proBNP (add'l indication)" and refers to the predicate device's performance, implying either that new studies for these parameters were performed and yielded identical results, or that the existing data for the predicate device is considered applicable due to the identical assay protocol, traceability, calibrator, controls, and instrument.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- Clinical Studies (Expanded Indications): This information would be within the cited literature articles, not directly in this 510(k) summary. These studies involve clinical endpoints and patient outcomes, which are not typically "expert-established ground truth" in the same way an image interpretation might be. The "ground truth" would be the observed clinical events (e.g., cardiovascular events, mortality) and patient diagnoses.
- Analytical Performance Studies: Not applicable. Ground truth for these studies relates to spiked samples or reference materials, not expert consensus.
4. Adjudication Method for the Test Set:
- Clinical Studies (Expanded Indications): This information would be within the cited literature articles. Clinical trials often have adjudication committees for endpoints, but the specific methods are not detailed here.
- Analytical Performance Studies: Not applicable.
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:
- No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) immunoassay, not an AI-assisted diagnostic imaging or interpretation device. Therefore, the concept of "human readers improving with AI assistance" is not applicable. The device provides a quantitative measurement of a biomarker.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, in a sense, a "standalone" performance was done for the analytical characteristics. The device itself provides a quantitative measurement (pg/mL) directly. The analytical performance metrics (precision, sensitivity, interference, hook effect, measuring range) are intrinsic to the device's function and were demonstrated without human intervention in the measurement process. The interpretation of these results for clinical decision-making is then done by a healthcare professional, but the measurement itself is automated.
7. The type of ground truth used:
- Clinical Studies (Expanded Indications):
- For the diagnosis of congestive heart failure and risk stratification of acute coronary syndrome/congestive heart failure: Presumed clinical diagnosis and patient outcomes/events (e.g., mortality, cardiovascular events) as defined and adjudicated within the cited clinical studies.
- For assessment of increased risk of cardiovascular events and mortality in patients at risk for heart failure with stable coronary artery disease: Presumed observed cardiovascular events and mortality over follow-up periods, as defined in the cited literature.
- Analytical Performance Studies: Presumed reference methods, defined concentrations in spiked samples, or reference materials for accuracy, precision, sensitivity, and interference studies.
8. The Sample Size for the Training Set:
- Not Applicable / Not Provided. For an immunoassay like this, there isn't typically a "training set" in the machine learning sense. The assay is built and validated based on biochemical principles, antibody specifications, and instrument calibration. The clinical utility is established in clinical trials, but these aren't "training sets" for an algorithm. If referring to assay development, that data is not provided.
9. How the Ground Truth for the Training Set was Established:
- Not Applicable / Not Provided. As mentioned above, "training set" is not a direct concept for this type of IVD. The development and validation of the immunoassay itself relies on established analytical chemistry and immunoassay principles, using characterized reagents and reference standards to establish the analytical performance.
§ 862.1117 B-type natriuretic peptide test system.
(a)
Identification. The B-type natriuretic peptide (BNP) test system is an in vitro diagnostic device intended to measure BNP in whole blood and plasma. Measurements of BNP are used as an aid in the diagnosis of patients with congestive heart failure.(b)
Classification. Class II (special controls). The special control is “Class II Special Control Guidance Document for B-Type Natriuretic Peptide Premarket Notifications; Final Guidance for Industry and FDA Reviewers.”