(28 days)
The Bayer ADVIA IMS BNP method is for in vitro diagnostic use in the quantitative determination of B-type Natriuretic Peptide (BNP) in human plasma using the ADVIA IMS® System. This assay is indicated for the measurement of plasma BNP as an aid in the diagnosis and assessment of the severity of heart failure. In patients with acute coronary syndromes (ACS), this test, in conjunction with other known risk factors, can also be used to predict survival as well as to predict the likelihood of future heart failure. This assay is not intended for use on any other system.
The ADVIA IMS BNP Assay is an in vitro immunoassay intended for the quantitative measurement of b-type natriuretic peptide (BNP) in human EDTA plasma covering the analytical range of 10 to approximately 6,000 pg/mL. The assay is a heterogeneous sandwich immunoassay using magnetic separation. Reagony a a freel genedus monoclonal antibody to BNP labeled with FITC and Reagent 2 (R2) contains the second monoclonal antibody to BNP (F(ab)2) conjugated to the enzyme /kaline phosphatase (ALP). The monoclonal antibodies used in the ADVIA IMS BNP assay are identical to those used in the ADVIA Centaur assay. The sandwich complex formed by the modite and the antibody conjugates is captured by the magnetic particles so that the BNP concentration in the sample can be measured in terms of enzyme activity. The substrate used for this assay is a dioxetane phosphate derivative, which is dephosphorylated by ALP resulting in photon emission. Luminescence is measured by a photomultiplier tube. The dose response curve is proportional to the analyte concentration in sample.
The provided text describes the 510(k) Summary of Safety and Effectiveness for the BNP Assay for Bayer ADVIA® Integrated Modular System (IMS). This is a diagnostic device, and the acceptance criteria and study detailed are centered on its analytical performance and equivalence to a predicate device, not on clinical effectiveness in human readers or pathology.
Here's a breakdown of the requested information based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" as a separate, pre-defined set of values that the new device must meet to be considered effective. Instead, it presents performance characteristics of the new device (ADVIA IMS BNP assay) and compares them directly to the predicate device (ADVIA Centaur BNP assay) to demonstrate substantial equivalence. The implication is that performance comparable to the predicate device is the de-facto acceptance criterion.
| Performance Metric | Acceptance Criteria (Implied: Comparable to Predicate) | Reported Device Performance (ADVIA IMS) | Predicate Device Performance (ADVIA Centaur) |
|---|---|---|---|
| Imprecision (CV%) | Comparable to Predicate device | Level 71 pg/mL: 4.1% | |
| Level 716 pg/mL: 1.9% | |||
| Level 2660 pg/mL: 1.8% | Level 48.5 pg/mL: 3.5% | ||
| Level 458 pg/mL: 2.8% | |||
| Level 1736 pg/mL: 2.9% | |||
| Correlation (Spearman R) | Close to 1 (indicating high correlation) | 0.992 | Not directly stated for comparison, but the new device is correlated against it. |
| Correlation (Regression Equation Y=ADVIA IMS, X=ADVIA Centaur) | Y ≈ X | $0.990 * X + 4.37$ | N/A (It is the comparison system) |
| Interfering Substances (% Deviation in Recovery) | Generally within acceptable biological variation (e.g., 100 pg/mL)** | Comparable to predicate device clinical studies results | 72.6% (All), 43.1% (NYHA I), 95.8% (NYHA IV) |
2. Sample sized used for the test set and the data provenance
- Imprecision Study: Not explicitly stated, but typically involves repeated measurements of control samples or patient pools across multiple runs and days. The levels (71 pg/mL, 716 pg/mL, 2660 pg/mL) indicate different concentrations of BNP tested.
- Correlation Study:
- Sample Size: N = 360 EDTA Plasma specimens.
- Data Provenance: Not explicitly stated (e.g., country of origin). The study is described as a comparison of the new device (ADVIA IMS) against the predicate device (ADVIA Centaur) using patient samples, implying it is retrospective or a prospective collection for analytical validation.
- Interfering Substances Study: Not explicitly stated, but involves testing samples spiked with various interfering substances at different BNP concentrations (e.g., 145.3 pg/mL and 407.5 pg/mL for Albumin).
- Expected Results (Reference Group):
- Sample Size: 1521 individuals without heart failure (785 women and 736 men).
- Data Provenance: Not explicitly stated. The text notes these values are "representative of the results obtained from clinical studies" and were derived from the predicate device's clinical studies. This suggests the data is retrospective and likely US-based, though not explicitly stated.
- Expected Results (Heart Failure Group):
- Sample Size: 722 patients diagnosed with heart failure (264 women and 458 men).
- Data Provenance: Not explicitly stated. Similar to the reference group, these values are "representative of the results obtained from clinical studies" for the predicate device. This suggests the data is retrospective and likely US-based, though not explicitly stated.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This document describes the analytical performance and clinical utility of an in vitro diagnostic assay, not the performance of human experts interpreting images or complex data. Therefore, the concept of "experts" establishing ground truth in the traditional sense (e.g., radiologists interpreting images) does not directly apply here.
The "ground truth" for the analytical performance studies (imprecision, correlation, interfering substances, analytical range, MDC) is the actual measured concentration of BNP in the samples, as determined by a well-controlled laboratory method (often the predicate device itself or a reference method).
For the "Expected Results" sections, the ground truth for patient classification (heart failure vs. no heart failure, and NYHA functional class) would have been established by clinical diagnosis. This would involve qualified medical professionals (e.g., cardiologists, physicians) using a combination of patient history, physical examination, imaging (e.g., echocardiography), and other clinical tests to make these diagnoses. The number and specific qualifications of these clinicians are not provided in this summary.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
Not applicable. This is an analytical performance study for an in vitro diagnostic device, not a study involving human reader agreement or adjudication of results.
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 analytical comparison of two automated IVD assays, not an MRMC study involving human readers or AI assistance.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented (imprecision, correlation, interfering substances, analytical range, minimum detectable concentration) are all standalone performance evaluations of the ADVIA IMS BNP assay device itself. The "Expected Results" sections describe how the device performs in clinically defined patient populations, again, as a standalone measurement device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- Analytical Ground Truth: For the analytical performance characteristics (imprecision, correlation, interfering substances, analytical range, MDC), the ground truth is based on the quantified concentration of BNP in the samples. In the correlation study, the predicate device (ADVIA Centaur BNP assay) served as the comparator or reference method for the new device.
- Clinical Ground Truth (for Expected Results): For the reference and heart failure population data, the ground truth for classifying patients as "without heart failure" or "with heart failure" (and their NYHA functional class) was based on clinical diagnosis, which would typically include outcomes data, physical examinations, and other diagnostic tests, as determined by qualified medical professionals.
8. The sample size for the training set
This document does not describe a "training set" in the context of machine learning or AI. It describes the validation of a new in vitro diagnostic assay. The equivalent concept would be the development of the assay itself and the establishment of its calibration curves and internal parameters. The text indicates that the ADVIA IMS assay uses identical monoclonal antibodies to the predicate ADVIA Centaur assay and uses the Centaur BNP Master Curve Material (MCM) as calibrators. This implies that the underlying "training" for the assay's fundamental chemistry and measurement principles was established during the development of the predicate device and is being adapted or confirmed for the new platform. No specific "training set" sample size for this development is provided.
9. How the ground truth for the training set was established
As noted above, the concept of a "training set" in this context is primarily related to the development and calibration of the assay. The ground truth for developing and calibrating such an immunoassay typically involves:
- Known concentrations of BNP: Precisely quantified BNP standards are used to establish the dose-response relationship and build the master curve.
- Replicate measurements: Numerous measurements of these standards and various patient samples are performed to optimize assay parameters, ensure linearity, and define the analytical range.
The document indicates that the calibrators used for the ADVIA IMS BNP assay are the same as those used for the ADVIA Centaur assay (Centaur BNP Master Curve Material). This means the "ground truth" for the calibration of this new assay directly relies on the established and validated calibration from the predicate device. Details of how the predicate device's master curve ground truth was established are not provided here.
§ 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.”