Search Results

The Alere NT-proBNP for Alinity i assay is a chemiluminescent microparticle immunoassay (CMIA) used for the in vitro quantitative determination of N-terminal pro B-type natriuretic peptide (NT-proBNP) in human serum and plasma on the Alinity i system.

In the emergency department, measurements of NT-proBNP are used as an aid in the diagnosis of heart failure (HF) in patients with clinical suspicion of new onset or worsening HF.

The Alere NT-proBNP for Alinity i assay is an automated, two-step immunoassay for the in vitro quantitative determination of NT-proBNP in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology. Sample and anti-NT-proBNP coated paramagnetic microparticles are combined and incubated. The NT-proBNP present in the sample binds to the anti-NT-proBNP coated microparticles. The mixture is washed. Anti-NT-proBNP acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added. The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a direct relationship between the amount of NT-proBNP in the sample and the RLU detected by the system optics.

Despite the request for acceptance criteria and study proving the device meets said criteria, the provided document is a 510(k) summary for a diagnostic test (Alere NT-proBNP for Alinity i Reagent Kit). This type of document focuses on demonstrating substantial equivalence to a predicate device, and thus does not explicitly list "acceptance criteria" for performance in the same way one might find for a new medical device claiming superiority or non-inferiority.

Instead, the document details various performance characteristics of the device, comparing them to relevant standards (CLSI guidelines) and providing statistical data. It aims to show that the new device performs acceptably and similarly to a previously cleared device.

Therefore, I cannot extract a table of "acceptance criteria" as such a table is not explicitly presented. However, I can infer the implied acceptance criteria from the reported performance, specifically from the "No Significant Interference" and "within acceptable performance" statements in the nonclinical performance section, and the effectiveness of the cutoffs for diagnosis in the clinical performance. The "reported device performance" will be the actual numbers provided in the document.

Here's a summary of the available information, structured to address your points as much as possible given the document type:

Implied Acceptance Criteria and Reported Device Performance

As this is a 510(k) submission, explicit quantitative acceptance criteria are not stated in a dedicated table format. Instead, the device's performance characteristics are presented as evidence of substantial equivalence to a predicate device and adherence to recognized standards. The implied acceptance criteria are that the device demonstrates acceptable accuracy, precision, and clinical utility for its stated indications for use.

Here's a table summarizing key performance indicators that would implicitly serve as acceptance criteria given standard diagnostic device requirements:

Study Details:

1. Sample sizes used for the test set and the data provenance:

   • Clinical Performance Study (test set): 2127 Emergency Department (ED) subjects.
     • Provenance: Multi-center prospective study across 17 collection sites in the US.
     • Demographics: 1030 (48.4%) female, 1097 (51.6%) male, age 19-97 years. Predominantly White (53.1%) and Black/African American (39.5%). 90.9% non-Hispanic/Latino.
   • Nonclinical Performance (examples):
     • Within-Laboratory Precision: 240 replicates (controls/panels).
     • Reproducibility: 360 replicates (controls/panels) per assay (across 3 sites).
     • Lower Limits of Measurement: n ≥ 60 replicates for LoB, LoD, LoQ.
     • Analytical Specificity/Interference: Each substance tested at 2 analyte levels (approximately 125 pg/mL and 2000 pg/mL).

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The ground truth for the clinical study was an "adjudicated diagnosis" determined by a panel of board-certified cardiologists. The exact number of cardiologists on the panel is not specified in the provided text.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

   • The document states "An adjudicated diagnosis was determined by a panel of board-certified cardiologists." It does not specify the exact adjudication method (e.g., majority vote, sequential review, etc.).

4. 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, this document describes the validation of a quantitative in vitro diagnostic (IVD) reagent kit for measuring NT-proBNP levels using an automated chemiluminescent immunoassay (CMIA) system. It is not an AI-assisted diagnostic imaging device, so an MRMC study is not relevant to this submission. The "readers" are the automated analyzers and laboratory personnel interpreting numerical results.

5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

   • This device is a standalone diagnostic test in the sense that it provides a quantitative NT-proBNP result. The assay itself is a fully automated process on the Alinity i system. The performance data presented (precision, linearity, limits, specificity, clinical performance tables) represent the performance of the device "standalone" in generating these quantitative results, which are then used by clinicians as an "aid in diagnosis." There isn't a "human-in-the-loop" component to the measurement itself, though medical professionals interpret the results in a clinical context.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • For the clinical performance study, the ground truth for Heart Failure (HF) diagnosis was established by expert consensus (adjudicated diagnosis by a panel of board-certified cardiologists).

7. The sample size for the training set:

   • This document describes a 510(k) submission for an in vitro diagnostic reagent kit. Unlike AI/ML software, such devices typically undergo analytical and clinical validation studies with defined test sets but do not have a "training set" in the sense of machine learning algorithms. The development and optimization of the assay would have involved various internal samples and experiments, but these are not explicitly termed "training sets" and their size is not reported in this context.

8. How the ground truth for the training set was established:

   • As explained above, the concept of a "training set" with established ground truth, as typically applied to machine learning or AI models, does not directly apply to the regulatory submission type for this diagnostic reagent kit. The assay is based on chemical and biological principles (CMIA) rather than learned algorithms from large datasets.

Ask a specific question about this device

Immunoassay for the in vitro quantitative determination of N terminal pro Brain natriuretic peptide in human serum and plasma. This assay is used as an aid in the diagnosis of individuals suspected of having heart failure. The test is further indicated for the risk stratification of patients with acute coronary syndrome and 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 cobas e immunoassay analyzers.

Elecsys proBNP II (updated assay) is a second-generation assay by Roche Diagnostics for the in vitro quantitative determination of N-terminal pro-Brain natriuretic peptide (NT-proBNP) in human serum and plasma with increased biotin tolerance. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

The cobas e family of analyzers employs the electrochemiluminescence immunoassay "ECLIA" technology. The assays are an 18-minute (Elecsys proBNP II) and 9 minute (Elecsys proBNP II STAT) application following a sandwich principle using two monoclonal antibodies which are specifically directed against NT-proBNP.

Acceptance Criteria and Device Performance Study for Elecsys proBNP II and Elecsys proBNP II STAT Assays

The document describes the analytical performance studies conducted for the Elecsys proBNP II and Elecsys proBNP II STAT assays, which are in vitro diagnostic devices. These assays are intended for the quantitative determination of N-terminal pro-Brain natriuretic peptide (NT-proBNP) in human serum and plasma, aiding in the diagnosis of heart failure, risk stratification, and assessment of cardiovascular event risk. The assays have been modified to include increased biotin tolerance.

The studies aim to demonstrate that the updated assays meet predetermined acceptance criteria for various analytical parameters, ensuring their safety and effectiveness and substantial equivalence to their predicate devices.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly list "acceptance criteria" alongside "reported device performance" in a single, dedicated table for all parameters. However, the "Conclusion" sections for each analytical study implicitly state whether the acceptance criteria were met. Based on the provided text, a table can be constructed as follows:

2. Sample Sizes and Data Provenance

• Test Set Sample Sizes:

  • Precision (Repeatability & Intermediate): 8 human serum samples and 2 controls (n=10 total) for each assay, measured in 84 determinations over 21 operating days. The exact number of individual patient samples contained within the "8 human serum samples" is not specified but appears to be 8 distinct pools/matrices.
  • Precision (Inter-Instrument): 8 native human serum sample pools and 2 quality control levels (n=10 total) for each assay, with 75 determinations per sample/QC level (due to 5 days, 3 laboratories, 25 determinations/site, 5x5=25, 3 sites x 25 = 75 total reported).
  • Analytical Sensitivity (LoB): 60 determinations of an analyte-free sample.
  • Analytical Sensitivity (LoD): 5 low-level human serum samples, with 60 determinations per reagent lot.
  • Analytical Sensitivity (LoQ): 9 native, unaltered serum samples for Elecsys proBNP II and 10 native, unaltered serum samples for Elecsys proBNP II STAT, each tested with 25 measured values.
  • Linearity/Assay Reportable Range: One high analyte human, native serum sample diluted to 11 concentrations.
  • Endogenous Interference (Bilirubin, Hemoglobin, Lipemia, Biotin, Rheumatoid Factor, Albumin): Three different analyte concentration levels (low, medium, high) in human native serum samples. Specific number of samples at each level not explicitly stated but implied to be several.
  • Cross-Reactivity: Two human native serum samples (low and high analyte levels) spiked with potential cross-reactants.
  • Exogenous Interference (Drugs): Two human native serum samples (low and high analyte concentrations).
  • Matrix Comparisons: Single donor samples drawn into Serum (reference), Li-Heparin (98 pairs), and K2-EDTA plasma (111 pairs).
  • Method Comparison: 1928 subjects for Elecsys proBNP II STAT and 1940 subjects for Elecsys proBNP II.

• Data Provenance: The document generally refers to "human serum samples" and "native human serum samples" without specifying the country of origin. The studies are described as internal (e.g., "one internal site" for precision). There is no explicit mention of the data being retrospective or prospective, but the nature of in vitro diagnostic device performance studies (analytical validation) typically involves prospective testing of samples under controlled laboratory conditions, simulating diagnostic use.

3. Number of Experts and Qualifications for Ground Truth

The document does not describe the use of human experts to establish "ground truth" for the test set in the context of diagnostic interpretation (e.g., radiologists, cardiologists). This document details the analytical performance of an in vitro diagnostic assay, not an AI/imaging diagnostic device that requires expert adjudication of images. The "ground truth" in this context refers to the true analytical concentration of NT-proBNP in the samples, established through well-defined laboratory methodologies and traceable standards, or comparison to a previously cleared predicate device.

4. Adjudication Method for the Test Set

Not applicable. As this is an analytical validation of an in vitro diagnostic assay, there is no "adjudication method" in the sense of multiple human readers or experts resolving discrepancies in diagnostic interpretation. The methods involve quantitative analytical measurements of biochemical markers.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Not applicable. This is not an imaging or AI-assisted diagnostic device that would typically undergo an MRMC study. The study focuses on the analytical performance of a laboratory immunoassay.

6. Standalone (Algorithm Only) Performance

Not applicable in the typical sense for medical imaging AI. The "algorithm" here is the chemical reaction and measurement process of the immunoassay itself. The analytical performance metrics (precision, sensitivity, linearity, interference, matrix comparison) are effectively the "standalone performance" of the device. The method comparison study directly compares the performance of the updated device against its predicate (older version) without human intervention in the result generation.

7. Type of Ground Truth Used

The ground truth used for these analytical studies is primarily measured analytical concentration, established through:

• Reference materials: Calibrators and controls with known concentrations.
• Spiking experiments: Adding known amounts of analyte or interfering substances to samples.
• Dilutions: Creating samples with predictable concentrations.
• Comparison to predicate device: The method comparison studies compare the new device's results against the results from the previously cleared Elecsys proBNP II and Elecsys proBNP II STAT (older versions) as the reference.
• Consensus laboratory methods/standards: Studies like LoB, LoD, LoQ, and precision follow CLSI (Clinical and Laboratory Standards Institute) guidelines, which are established consensus standards for analytical validation.

There is no mention of pathology, clinical outcomes data, or expert consensus interpretation of results as a primary ground truth in this analytical performance section.

8. Sample Size for the Training Set

Not applicable. This document describes the analytical validation of laboratory assays, not a machine learning model that requires a "training set" in the same sense. The assay works based on established biochemical principles (electrochemiluminescence immunoassay, ECLIA, utilizing specific antibodies) and wet-lab procedures, not on learned patterns from a large dataset. Reagent formulation and process optimization might involve internal development data, but it's not a "training set" in the AI/ML context.

9. How the Ground Truth for the Training Set was Established

Not applicable, as there is no "training set" for an AI/ML model in this context. The "ground truth" for the development of the assay itself would be based on fundamental analytical chemistry principles, extensive laboratory testing, control materials, and established reference methods for quantifying NT-proBNP.

Ask a specific question about this device

Immunoassay for the in vitro quantitative determination of digoxin in human serum and plasma. Measurements are used in the diagnosis and treatment of digoxin overlose and in monitoring levels of digoxin to ensure proper therapy. The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.

The Elecsys Digoxin assay employs a competitive test principle using a monoclonal antibody specifically directed against digoxin. Digoxin in the sample competes with the added digoxin derivative labeled with biotin for the binding sites on the ruthenylated antibody-complex. Results are determined via a calibration curve which is instrument- specifically generated by 2point calibration and a master curve provided via the reagent barcode. The reagent working solutions include: RackPack (kit placed on instrument) M: Streptavidin-coated microparticles, R1: Anti digoxin AbRu(bpy) 3+ and R2: Digoxin-derivativebiotin. PreciControl Cardiac II is a lyophilized control serum based on human serum in two concentration ranges. The controls are used for monitoring the accuracy and precision of the Elecsys CK MB, CK MB STAT, Myoglobin, Myoglobin STAT, proBNP II, proBNP II STAT, and Digoxin immunoassays.

The provided document is a 510(k) summary for the Elecsys Digoxin Immunoassay and Elecsys PreciControl Cardiac II. It describes the device, its intended use, and various performance evaluations conducted.

Here's a breakdown of the requested information based on the provided text:

1. Table of acceptance criteria and the reported device performance

The document lists performance characteristics in a comparative table (Table 1 and Table 2) between the "Predicate Device Elecsys Digoxin Immunoassay (K973112)" and the "Candidate Device Elecsys Digoxin Immunoassay." While specific acceptance criteria are not explicitly stated for each test, the reported performance data for the candidate device can be listed. The comparison to the predicate device implies that the candidate device's performance should be equivalent or better.

Ask a specific question about this device