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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.

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The ADVIA Centaur® Erythropoietin (EPO) assay is for in the quantitative measurement of exythropoitin in pediatric and adult human serum or plasma (K2-EDTA, lithium heparin) using the ADVIA Centaur XP system. Measurement of erythropoietin is used as an aid in the diagnosis of anemias and polycythemias.

The ADVIA Centaur EPO assay is a fully automated, one-step sandwich immunoassay using direct chemiluminescent technology. The assay utilizes an acridinium-ester-labeled monoclonal mouse anti-EPO antibody in the Lite Reagent. The Solid Phase consists of mouse anti-EPO monoclonal antibody-coated paramagnetic microparticles.

Here's an analysis of the provided text to extract the acceptance criteria and study details for the ADVIA Centaur Erythropoietin (EPO) assay:

1. Table of Acceptance Criteria and Reported Device Performance

This table compiles information primarily from the "Summary of Non-Clinical Performance" and "Summary of Clinical Performance" sections.

2. Sample Size Used for the Test Set and Data Provenance

• Linearity: Not specified, but involved three high EPO samples mixed with low EPO human serum.
• Dilution Recovery: 10 samples (containing high EPO levels: 618.63-986.07 mIU/mL).
• Detection Capability (LoD): 323 determinations using 10 low-level samples.
• Cross-reactivity: Not explicitly stated as a "sample size," but involved numerous cross-reactants (e.g., various plasma proteins, epoetin alfa, darbepoetin alfa).
• Interference: Not explicitly stated as a specific "sample size" for each interferent, but involved various substances tested at different concentrations.
• Precision: 7 pooled serum samples. For each sample, there were 80 observations (replicates of 2, in 2 runs/day, over 20 days).
• Specimen Collection Comparison: 65 samples (serum EPO values ranging from 4.39 - 707.81 mIU/mL).
• Method Comparison:
  • Study 1: 216 human serum samples (range: 3.29 – 691.60 mIU/mL).
  • Study 2: 100 human serum samples from US population (range: 4.45 - 407.74 mIU/mL).
  • Study 3 (Multi-site): 327 human serum samples (range: 3.55 - 596.81 mIU/mL), with ≥ 100 samples per site.
• Expected Values (Adult): 251 apparently healthy subjects (128 males, 123 females), older than 21 years of age.
• Expected Values (Pediatric): 266 apparently healthy children (2 to <13 years) and adolescents (13 to <22 years).

Data Provenance:
The document does not explicitly state the country of origin for all data sets, but mentions:

• Method Comparison Study 2: "100 human serum samples from US population".
• Method Comparison Study 3: "3 sites, 2 within Europe and 1 within the US".
• Most studies imply retrospective (samples collected before the study) or prospective (samples collected during the study for specific evaluation), but this is not consistently specified for each study. For establishing expected values, samples were collected prospectively following specific criteria (e.g., healthy subjects, specific age ranges, exclusion criteria).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

• This device is an in vitro diagnostic assay that measures erythropoietin levels. The "ground truth" for such assays typically comes from the actual concentration of the analyte in the biological sample, often confirmed by a reference method or standardized preparations.
• The document describes traceability to World Health Organization (WHO) International Reference Preparations and Standards (NIBSC codes 67/343 and 11/170). These international standards are established through collaborative studies involving multiple expert laboratories and scientists, but the immediate "ground truth" for the test samples in this submission would be their assigned values based on these standards or the results from the predicate device.
• No "experts" in the sense of radiologists or other clinicians interpreting images or assessments are directly involved in establishing the ground truth for individual test samples for this type of device. The ground truth is biochemical measurement.

4. Adjudication Method for the Test Set

• Not applicable. This is a quantitative diagnostic assay. "Adjudication" typically refers to resolving discrepancies between multiple human readers in diagnostic imaging or clinical assessment studies. For an immunoassay, the "ground truth" is a measured concentration.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

• Not applicable. This is an immunoassay, not an AI-assisted diagnostic imaging or clinical decision support device involving human readers.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

• Yes, the performance studies described (Linearity, Dilution Recovery, Measuring Interval, Detection Capability, High Dose Hook, Cross-reactivity, Interference, Precision, Specimen Collection Comparison, Method Comparison, Expected Values) represent the standalone performance of the ADVIA Centaur Erythropoietin (EPO) assay itself, meaning the algorithm/instrument's measurement capabilities without direct human interpretation of the final measurement result for diagnostic purposes. The device directly produces a quantitative EPO value.

7. The Type of Ground Truth Used

• Reference materials/standards: The assay is traceable to WHO International Reference Preparations/Standards for Erythropoietin.
• Predicate device comparison: For method comparison studies, the results from the legally marketed predicate device (Beckman Coulter Access EPO Assay) serve as a comparative "ground truth" to demonstrate substantial equivalence.
• Expert consensus (indirectly): The establishment of reference intervals (expected values) involved defining "healthy" populations based on standard medical criteria, which would implicitly rely on shared medical understanding and the consensus of medical professionals. The CLSI protocols referenced (e.g., EP28-A3) also represent a form of expert consensus on how to establish such values.
• Biochemical measurement: The fundamental ground truth is the actual concentration of EPO in the samples, determined through rigorous biochemical methods and validated against international standards.

8. The Sample Size for the Training Set

• For an immunoassay like this, there isn't a "training set" in the machine learning sense. The device is not learning from data in the same way an AI algorithm would. Instead, the assay's reagents, calibration curves, and analytical procedures are developed and optimized through extensive R&D and internal validation studies. The studies described in the 510(k) are primarily for verification and validation (V&V) of the final device's performance characteristics. Therefore, a specific "training set sample size" as might be provided for an AI/ML device is not applicable or provided.

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

• As above, the concept of a "training set" and its "ground truth" in the context of machine learning is not directly applicable to an immunoassay. The development of the assay involves extensive characterization of reagents, optimization of reaction conditions, and establishment of calibration curves using purified EPO standards of known concentrations, which are themselves traceable to international standards. The "ground truth" during this development phase would be the known concentrations of these standards.

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The ADVIA Centaur® Calcitonin (CALCT) assay is for in vitro diagnostic use in the quantitative measuremt of calcitonin in human serum using the ADVIA Centaur XP system. Calcitonin measurement is used as an aid in the diagnosis and treatment of diseases involving the thyroid and parathyroid glands, including carcinoma and hyperparathyroidism.

The ADVIA Centaur CALCT Assay Kit (100-Tests) consists of 1 ReadyPack containing ADVIA Centaur CALCT Lite Reagent and Solid Phase reagent, and one set of Calibrators (1 vial each of Low and High, with fill volume of 2 mL each). ADVIA Centaur CALCT Calibrator Assigned Value Card and barcode labels and ADVIA Centaur CALCT Master Curve Card are also included in the kit. The ADVIA Centaur CALCT assay is a fully automated, two-step immunoassay using direct chemiluminescent technology. The assay utilizes an acridinium- ester-labeled recombinant antibody as the Lite Reagent. The Solid phase consists of anti-calcitonin mouse monoclonal antibody-coated paramagnetic microparticles.

Here's a summary of the acceptance criteria and study information for the ADVIA Centaur® Calcitonin (CALCT) assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

2. Sample size used for the test set and the data provenance:

• Linearity: Not explicitly stated as a "test set" in the context of patients, but rather an analytical study using two samples containing high levels of calcitonin mixed with analyte-free human serum. The number of measurements performed for linearity or dilution recovery is not explicitly stated.
• Dilution Recovery: Fourteen samples containing high levels of calcitonin.
• Detection Capability (LoD): 125 determinations using 6 low-level samples.
• Precision: Five pooled serum samples, tested in replicates of 2, in 2 runs per day, over 20 days, yielding 80 observations per sample (400 total observations for the 5 samples).
• Cross-reactivity: Tested with individual cross-reactants. Number of samples per reactant not specified.
• Interference: Tested using two levels of calcitonin with various interfering substances. Number of samples not specified. For biotin, samples containing different calcitonin levels were tested.
• Specimen Collection Comparison: 60 samples.
• Method Comparison: 97 human serum samples.
• Expected Values (Reference Intervals): 240 apparently healthy subjects (120 males, 120 females), age range 22-79 years.

Data Provenance: The document generally describes these as studies performed by the manufacturer, Axis-Shield Diagnostics Limited, in support of their 510(k) submission. It does not provide specific country of origin for the patient/human serum samples, nor explicitly state if they are retrospective or prospective. However, based on the nature of these analytical and clinical validation studies for a diagnostic device, they are typically conducted prospectively to evaluate the device's performance.

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

This is an in vitro diagnostic (IVD) device designed for quantitative measurement of calcitonin. The "ground truth" for such devices is established through laboratory methods and standards (e.g., traceable reference materials, expert consensus on method accuracy, or clinical outcomes for reference ranges).

• For analytical performance (linearity, detection capability, precision, etc.): Ground truth is established by the analytical reference methods, international standards (e.g., WHO 2nd IRP 89/620), and carefully prepared samples with known concentrations. No "experts" in the sense of clinicians or radiologists are typically involved in establishing this type of ground truth.
• For expected values/reference intervals: While derived from human subjects, the calculation of reference intervals is a statistical process (97.5th percentiles) rather than an "expert" adjudication of individual cases. The "apparently healthy subjects" serve as the basis for this ground truth.

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

Not applicable. This is not an image-based diagnostic or clinical decision support AI where human experts adjudicate classifications. The device measures a biomarker quantitatively.

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 in vitro diagnostic assay, not an AI-assisted diagnostic device for human readers/clinicians reading images or other complex data.

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

Yes, the studies described (linearity, precision, detection capability, interference, method comparison) are all standalone performance evaluations of the ADVIA Centaur CALCT assay. The device provides a quantitative measurement of calcitonin from a human serum sample without human interpretation or intervention in the measurement process itself. The "algorithm" here refers to the immunoassay's measurement and calculation protocols.

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

• Analytical Performance: Primarily analytical standards (e.g., CLSI protocols EP06-A, EP17-A2, EP05-A3, EP07-A2), international reference materials (WHO 2nd IRP 89/620), and known concentrations in spiked or diluted samples.
• Expected Values (Reference Intervals): Derived from samples from a population of apparently healthy subjects, with the normal range defined statistically (97.5th percentiles).
• Method Comparison: Comparison against a "comparable method" (the Roche Elecsys/Cobas® Calcitonin assay, which is the predicate device), where the predicate serves as the comparative "ground truth" for demonstrating equivalence.

8. The sample size for the training set:

Not explicitly stated. For an IVD such as this, the development ("training") of the assay involves various stages of optimization and formulation. The provided document focuses on the validation or test data used to demonstrate performance for regulatory purposes. The term "training set" is more commonly used in machine learning. However, if interpreted as samples used during the development phase to establish assay parameters, that information is not detailed in this summary.

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

Not explicitly stated. Similar to point 8, this refers to assay development. Ground truth during development would typically involve using highly characterized samples, reference materials, and comparing results to established methods to refine the assay's chemical and procedural parameters.

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The ADVIA Centaur Active-B12 (Holotranscobalamin)(AB12) assay is for in vitro diagnostic use in the quantitative measurement of holotranscobalamin (holoTC) in human serum using the ADVIA Centaur XP system. Active-B12 (holotranscobalamin) is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.

The ADVIA Centaur AB12 assay is a fully automated, two-step direct immunoassay using chemiluminescent technology. The assay utilizes an acridinium ester-labeled anti-transcobalamin antibody as the Lite Reagent. The Solid Phase consists of biotinylated anti-holotranscobalamin antibody coupled to streptavidin-coated magnetic latex microparticles.

Here's an analysis of the provided text regarding the ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) assay, structured to address your specific questions about acceptance criteria and the supporting study:

It's important to note that this document is a 510(k) summary, which is a high-level overview. It describes a modification to an already cleared device (K160757), primarily focusing on a change in calibration traceability. Therefore, detailed study protocols and raw data are not typically included in this summary. The summary focuses on demonstrating that the modified device is substantially equivalent to the predicate device and that the modification did not negatively impact its performance.

Since this is a summary of a modification intended to show substantial equivalence, the "acceptance criteria" discussed are largely in the context of ensuring the modification did not degrade performance.

1. Table of Acceptance Criteria and Reported Device Performance

The document states that "The device passed all of the tests based on pre-determined Pass/Fail criteria." However, the specific numerical acceptance criteria for each test are not explicitly provided in this 510(k) summary. It lists the types of tests performed and implies that the results were satisfactory.

2. Sample Size Used for the Test Set and Data Provenance

The summary does not explicitly state the sample sizes used for the various validation tests (Accuracy, Linearity, Precision, Detection Limits, Recovery, Proficiency, or Reference Range).

• Data Provenance: Not explicitly stated, but the reference range study provides a mean and 95% central reference interval for an "asymptomatic population," implying human serum samples. The device itself is for in vitro diagnostic use in human serum. The data would have been collected in the course of validating the device. The manufacturer is Axis-Shield Diagnostics Ltd. in Scotland, UK, so it's plausible the data collection occurred there or in other regions where they conducted studies. The study is retrospective in the sense that these tests are performed after the device (or its modification) has been developed, but the sample collection itself for the reference range could be prospective.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts

This type of information is not applicable and not provided in the context of this device. This is an in vitro diagnostic (IVD) assay that measures a biomarker (holotranscobalamin) directly. The "ground truth" for the test set is established by the analytical reference methods or reference materials (like the WHO International Standard), not by human experts interpreting images or complex clinical scenarios.

4. Adjudication Method for the Test Set

This is not applicable for this type of IVD device. Adjudication methods (like 2+1, 3+1) are typically used in studies involving human interpretation of medical images or clinical data where there might be inter-reader variability. For an IVD assay, the result is a quantitative measurement, and the "ground truth" is based on the accuracy and precision of the analytical measurement itself, often against a validated reference method or material.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is for evaluating human performance, often with and without AI assistance, especially in radiology or pathology. This device is an automated IVD assay, not an AI-assisted human interpretation tool.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This device is a standalone algorithm/assay in the sense that it performs the measurement automatically without human intervention during the measurement process. The "performance" mentioned (accuracy, linearity, precision, etc.) are all standalone performance metrics of the assay itself. There is no "human-in-the-loop" once the sample is loaded onto the ADVIA Centaur XP system for this specific measurement.

7. The Type of Ground Truth Used

The ground truth for evaluating the performance of this IVD assay is primarily based on:

• Reference Materials: Specifically, the WHO International Standard for Holotranscobalamin (NIBSC Code 03/178) is highlighted as the new traceability standard for calibration. This serves as a primary ground truth for accurate measurement.
• Comparative Methods: The "Accuracy by correlation" likely involved comparing results from the modified device with those obtained using a reference method or the predicate device.
• Defined Concentrations: For tests like dilution linearity, precision, and detection capability, samples with precisely known or established concentrations of holotranscobalamin are used.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" sample size as this is not a machine learning or AI algorithm in the contemporary sense that would require a separate training phase with a distinct dataset for model building. The calibration process implicitly "trains" the device to measure correctly against known standards. The calibration itself uses "2-point Calibration using 2 level calibrators" (Low – 19 pmol/L, High - 121 pmol/L). However, this is not a "training set" in the context of complex ML models.

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

Given that there isn't a traditional "training set" for a machine learning model, the "ground truth" for the calibration materials (which serve a similar function of establishing correct performance parameters) is established through:

• Reference to the WHO International Standard (NIBSC Code 03/178): The primary modification in this 510(k) is to make the calibration traceable to this international standard. This standard itself would have been value-assigned through a rigorous international collaborative study.
• Internal Reference Material: The predicate device used an "Internal reference material; recombinant holotranscobalamin and phosphate buffer with protein (bovine) stabilizers." This internal standard would have been characterized and assigned values through the manufacturer's own internal assay development and validation processes, likely against an existing recognized reference method or material.

In summary, this 510(k) pertains to a minor modification (calibration traceability) of an existing in vitro diagnostic test. The evaluation focuses on ensuring the modification did not alter the fundamental performance characteristics, and the "acceptance criteria" are implied to be that the modified device performs comparably to the predicate and meets standard analytical performance requirements for IVDs. The "study" refers to a series of analytical verification and validation tests rather than clinical trials with human readers or AI algorithms.

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The ADVIA Centaur® anti-CCP IgG (aCCP) assay is for in vitro diagnostic use in the semi-quantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum or plasma (K2-EDTA and lithium heparin) using the ADVIA Centaur XP system. Detection of anti-CCP antibodies is used as an aid in the diagnosis of Rheumatoid Arthritis (RA) and should be used in conjunction with other clinical information. Autoantibody levels represent one parameter in a multi-criteria diagnostic process, encompassing both clinical and laboratory-based assessments.

Quality Control:
The ADVIA Centaur® Anti-CCP IgG (aCCP) quality control material is for in vitro diagnostic use to monitor the precision and accuracy of the ADVIA Centaur aCCP assay using the ADVIA Centaur systems.

Master Curve Material (MCM):
The ADVIA Centaur® Anti-CCP IgG (aCCP) Master Curve Material (MCM) is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur aCCP assay.

The ADVIA Centaur aCCP assay is a fully automated, two-step immunoassay using chemiluminescent technology. The assay utilizes an acridinium ester-labeled anti-human lgG as the Lite Reagent. The Solid Phase consists of biotinylated CCP coupled to streptavidin which is then coated onto magnetic latex microparticles.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Device Name: ADVIA Centaur® Anti-CCP IgG (aCCP) Assay

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" as a separate, quantitative table derived from a pre-defined standard (like a predicate device's performance). Instead, it compares the performance of the new device (ADVIA Centaur aCCP assay) to a predicate device (ARCHITECT Anti-CCP Assay) for several characteristics and implies that similar performance constitutes meeting the criteria for substantial equivalence. I will reconstruct a table showing the implied acceptance criteria (based on the predicate's performance or general expectations for such an assay) and the reported performance.

2. Sample Sizes and Data Provenance:

• Test Set (Clinical Performance):
  • Method Comparison Study: 253 samples (143 confirmed positive for RA, and 110 samples where other auto-antibodies may be present). Data provenance not explicitly stated (e.g., country of origin, retrospective/prospective), but it is a clinical study.
  • Clinical Sensitivity and Specificity Study: 767 patient samples.
    • 307 confirmed-positive RA subjects.
    • 460 non-RA subjects with potentially cross-reacting conditions (22 subgroups).
    • Data provenance not explicitly stated (e.g., country of origin, retrospective/prospective).
• Training Set: Not explicitly mentioned for this type of in vitro diagnostic assay. Immunoassays are generally calibrated and validated, not "trained" in the machine learning sense. The "training" in this context would likely refer to the development and optimization of the assay reagents and parameters.

3. Number of Experts and Qualifications for Ground Truth (Test Set):

• For RA Confirmation: "307 confirmed-positive RA subjects that were classified according to the American College of Rheumatology criteria." This implies expert clinical diagnosis based on established criteria, but the specific number and qualifications of individuals making these diagnoses are not provided.
• For Non-RA Subjects: "22 subgroups of non-RA subjects (n=460) with potentially cross-reacting conditions." This also implies clinical diagnosis by experts, but details are not provided.
• For Autoantibody Presence (Method Comparison): "110 samples where other auto-antibodies may be present." This suggests expert determination of autoantibody status, but details are not given.

4. Adjudication Method for the Test Set:

Not applicable or explicitly stated as this is an immunoassay, not an imaging device requiring expert adjudication of reader interpretations. The ground truth for clinical sensitivity and specificity is based on clinical diagnosis (American College of Rheumatology criteria for RA).

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

No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for imaging devices or AI tools that assist human readers in interpretation. The ADVIA Centaur anti-CCP IgG assay is a standalone diagnostic laboratory test.

6. Standalone Performance:

Yes, standalone performance was done. The entire document describes the standalone performance of the ADVIA Centaur aCCP assay in various analytical and clinical studies (linearity, dilution linearity, detection capability, high dose hook, cross-reactivity, interference, precision, specimen collection comparison, clinical concordance with a predicate, and clinical sensitivity/specificity against clinical diagnosis). The results presented are solely the performance of the algorithm/assay without human intervention in the result determination.

7. Type of Ground Truth Used:

• Analytical Performance: Based on reference materials, spiked samples with known concentrations, or established analytical methods.
• Clinical Performance (Sensitivity/Specificity):
  • RA Diagnosis: American College of Rheumatology criteria (clinical diagnosis) for RA.
  • Non-RA Status: Clinical diagnosis of various conditions (22 subgroups).
• Method Comparison: The predicate device (ARCHITECT Anti-CCP Assay) results were used as a reference point for agreement.

8. Sample Size for the Training Set:

Not applicable in the machine learning sense. For an immunoassay, "training" is typically assay development, which involves optimizing reagents and parameters. The document doesn't specify sample sizes used during the development phase.

9. How the Ground Truth for the Training Set Was Established:

Not applicable. For an immunoassay, ground truth during development would involve well-characterized samples (e.g., confirmed positive/negative for CCP antibodies, known concentrations) to optimize the assay's performance characteristics. Specific details on this are not provided in the summary.

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The ADVIA Centaur® Active-B12 (Holotranscobalamin)(AB12) assay is for in vitro diagnostic use in the quantitative measurement of holotranscobalamin (holoTC) in human serum using the ADVIA Centaur XP system. Active-B12 (holotranscobalamin) is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.

The ADVIA Centaur® Active-B12 (AB12) quality control is for in vitro diagnostic use to monitor the precision and accuracy of the ADVIA Centaur AB12 (Holotranscobalamin) assay using the ADVIA Centaur systems.

The ADVIA Centaur® Active-B12 (AB12) Master Curve Material (MCM) is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur AB12 (Holotranscobalamin) assay using the ADVIA Centaur systems.

The ADVIA Centaur AB12 assay is a fully automated, two-step direct immunoassay using chemiluminescent technology. The assay utilizes an acridinium ester-labeled antitranscobalamin antibody as the Lite Reagent. The Solid Phase consists of biotinylated antiholotranscobalamin antibody coupled to streptavidin-coated magnetic latex microparticles.

This document describes the ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) assay, a device for in vitro diagnostic use in the quantitative measurement of holotranscobalamin (holoTC) in human serum to aid in the diagnosis and treatment of vitamin B12 deficiency.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. A table of acceptance criteria and the reported device performance:

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):

• Linearity: The number of samples used is not explicitly stated, but it involved "Two samples containing high levels of active-B12" mixed with "a pool of artificial serum matrix."
• Dilution Linearity: Five samples were used.
• Detection Capability (LoB, LoD, LoQ): The raw sample sizes for these determinations are not specified but are described as being determined according to CLSI Document EP17-A2, which typically involves multiple replicates and measurements.
• High Dose Hook: Patient samples with "active-B12 levels as high as 1867.80 pmol/L" were tested. The exact number of samples is not stated.
• Cross-reactivity: Populations evaluated included "other B12 proteins apotranscobalamin and haptocorrin" at two different concentrations each. The number of samples per concentration is not stated.
• Interference: The number of unique samples or runs for each interfering substance is not explicitly stated.
• Precision: Five serum precision panel members were used. Each sample was tested in replicates of 2 in two runs per day over 20 days, resulting in 80 observations per sample for each reagent lot.
• Method Comparison: 104 serum samples were used.
• Expected Values (Reference Range): 241 apparently healthy males (n = 103) and females (n = 138) were used. The age range was 21 - 67 years.

The document does not explicitly state the country of origin of the data or whether the studies were retrospective or prospective, beyond stating that the device is manufactured by Axis-Shield Diagnostics Ltd. in Scotland, UK. The reference range study involved "apparently healthy males and females," suggesting prospective collection for that specific study.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):

This device is an in-vitro diagnostic assay for quantitative measurement of holotranscobalamin. The "ground truth" for such assays is typically established by established reference methods, calibrated standards, or the concentration values determined by a legally marketed predicate device. Experts are not directly involved in establishing "ground truth" for individual test results in the same way they would be for image interpretation.

• For method comparison, the "ground truth" reference values were obtained from the ARCHITECT Active-B12 (Holotranscobalamin) assay (K112443), which is the legally marketed predicate device.
• For reference range establishment, the "ground truth" is derived from the statistical analysis of results from a healthy population, following established protocols (EP28-A3c).

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

Not applicable. This is not a study involving human interpretation or subjective assessment that would require adjudication. The performance is based on quantitative measurements.

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 in-vitro diagnostic device, not an AI-assisted diagnostic tool that involves human readers interpreting cases.

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 ADVIA Centaur Active-B12 assay. The performance characteristics (linearity, precision, detection capability, interference, cross-reactivity, method comparison) are intrinsic to the device and do not involve human intervention in the interpretive output generation. The assay quantitatively measures holotranscobalamin levels.

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

The ground truth used depends on the specific performance characteristic:

• Assay values for clinical samples: The ARCHITECT Active-B12 (Holotranscobalamin) assay (CMIA) was used as the comparator or "reference" for method comparison studies.
• Known concentrations: For studies like linearity, dilution linearity, detection capability, high dose hook, cross-reactivity, and interference, the "ground truth" is based on known spiked concentrations of substances or defined samples with expected values (e.g., precision panel members with established active-B12 concentrations).
• Population statistics: For expected values (reference range), the "ground truth" is derived from statistical analysis of a healthy reference population, following CLSI guidelines.

8. The sample size for the training set:

Not applicable. This device is an in-vitro diagnostic assay, not a machine learning or AI model that requires a distinct training set in the conventional sense. The "training" or development of such assays involves reagent formulation, optimization, and calibration based on known standards and samples, but not a "training set" like that used for algorithms.

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

Not applicable. As explained in point 8, there isn't a "training set" for an in-vitro diagnostic assay in the same way there is for an AI algorithm. The assay is developed and optimized using known standards and calibrated samples, where the "ground truth" for these is established through highly accurate reference methods or certified reference materials. The calibration of the device itself relies on "Master Curve Material" (MCM) with established values.

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The Afinion™ Lipid Panel is an in vitro diagnostic test for quantitative determination of total cholesterol (Chol), high-density lipoprotein (HDL) cholesterol and triglycerides (Trig) in serum. Values for low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol and Chol/HDL ratio are calculated by the Afinion™ AS100 Analyzer. Chol, HDL cholesterol, Trig, and calculated LDL cholesterol, non-HDL cholesterol and Chol/HDL ratio) are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism disorders.

Afinion™ Lipid Panel Control has been designed for use with the Afinion™ AS100 Analyzer and Afinion™ Lipid Panel. Afinion™ Lipid Panel Control is intended for use as assayed control material for total cholesterol (Chol), high-density lipoprotein (HDL) cholesterol and triglycerides (Trig). The controls should be used to confirm that the Afinion™ AS100 Analyzer System is working properly and provides reliable results.

For use in clinical laboratories and point of care laboratory settings.

For prescription use only.

Afinion™ Lipid Panel is a fully automated assay for quantitative determination of Chol. HDL and Trig in serum. LDL, non- HDL and Chol/HDL are calculated by the Afinion™ AS100 Analyzer.

The Afinion™ Lipid Panel Test Cartridge contains all reagents necessary for determination of Chol, HDL and Trig in serum. The sampling device integrated in the test cartridge is filled with sample material. The test cartridge is then placed in the Afinion™ AS100 Analyzer. The analyzer inspects the sampling device, and the sample is then diluted.

Total Cholesterol (Chol) is measured by an enzymatic colorimetric method.
Triglycerides (Trig) are measured by an enzymatic colorimetric method.
HDL cholesterol is measured by an enzymatic colorimetric method with direct determination of HDL by initial antibody blocking of apolipoprotein B (apo-B).
LDL cholesterol is calculated by use of the Friedwald formula: LDL (mg/dL) = Chol - HDL - Trig/5.
non-HDL cholesterol is calculated as total cholesterol minus HDL: non-HDL = Chol - HDL.
Chol/HDL ratio is calculated as Total Cholesterol/ HDL Cholesterol.

Acceptance Criteria and Device Performance for Afinion™ Lipid Panel

This document outlines the acceptance criteria and the study that demonstrates the Afinion™ Lipid Panel's performance, as derived from the provided 510(k) summary (K132031).

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state pre-defined acceptance criteria values for bias, precision (repeatability and within-device), or linearity. Instead, it presents the results of these studies and implies that these results were considered acceptable for demonstrating substantial equivalence to predicate devices. The reported device performance based on acceptable outcomes from comparison studies is presented below.

Interference: No significant interference (<10%) was observed from 26 common substances at specified concentrations. Limitations were noted for Calcium dobesilate, Methyldopa, Acetylcysteine, and Levodopa at certain levels.

Reporting Ranges (supported by linearity and LoQ studies):

Accuracy (Method Comparison with Predicate Devices):

Bias at Medical Decision Levels (Implied Acceptance: Low Bias):

Precision (Repeatability and Within-device %CV - Implied Acceptance: Low %CV):

Precision results are presented for control samples at two levels and one serum sample across three sites. The Coefficients of Variation (CV%) are generally low, indicating good precision. For example:

• Total Cholesterol: Repeatability CVs range from 1.7% to 3.5%, Within-device CVs range from 2.3% to 3.9%.
• HDL Cholesterol: Repeatability CVs range from 2.1% to 3.9%, Within-device CVs range from 2.6% to 4.9%.
• Triglycerides: Repeatability CVs range from 1.8% to 4.4%, Within-device CVs range from 2.2% to 4.9%.

2. Sample Sizes and Data Provenance

• Linearity Testing:

  • Test Set Sample Size: 11 concentration levels for each analyte, produced by intermixing one low and one high serum sample. Each level was measured in 4-6 replicates.
  • Data Provenance: Not explicitly stated, but the studies were performed by the manufacturer, Axis-Shield PoC AS (located in Oslo, Norway). The samples were described as "serum samples." It's retrospective in the sense that it's test data generated for regulatory submission, but the samples themselves could have been collected prospectively or retrospectively.

• Limits of Quantitation (LoQ) Testing:

  • Test Set Sample Size: 5 samples with concentrations near 0 mg/dL (LoB samples) and 5 low concentration samples (LoD samples). Each sample was measured in a total of 60 replicates (likely 12 replicates per sample, using 3 analyzers and 2 test cartridge lots).
  • Data Provenance: Not explicitly stated, but performed by the manufacturer. "Serum" is the sample type.

• Analytical Specificity (Interference) Testing:

  • Test Set Sample Size: "Samples covering two medical decision concentrations of each lipid analyte" were measured.
  • Data Provenance: Not explicitly stated, but performed by the manufacturer.

• Accuracy (Method Comparison) Testing:

  • Test Set Sample Size:
    • Cholesterol: 348 samples
    • Triglycerides: 246 samples
    • HDL: 251 samples
  • Data Provenance: The study was "performed at four point-of-care sites." No specific country of origin is mentioned, but the manufacturer is based in Norway. The samples were "serum." The nature of sample collection (retrospective or prospective) is not specified.

• Precision Testing:

  • Test Set Sample Size: Two control samples and one serum sample were tested. For each sample, 80 replicates were performed at each of the three point-of-care sites (2 replicates per run, 2 runs per day for 20 days).
  • Data Provenance: "Performed at three point-of-care sites." The origin of the control and serum samples is not detailed, but the study was conducted by the manufacturer.

3. Number of Experts and Qualifications for Ground Truth

This device is an in vitro diagnostic (IVD) for quantitative determination of analytes in serum. The ground truth for such devices is established by reference methods or highly accurate laboratory methods, not by expert interpretation of images or clinical assessments.

• Traceability:
  • Cholesterol (Chol) and HDL are traceable to the National Reference System for Cholesterol (NRS/CHOL).
  • Triglycerides (Trig) are traceable to a Centers for Disease Control and Prevention (CDC) reference method.
  • The device is CRMLN certified for Total Cholesterol and HDL Cholesterol, indicating its accuracy against reference measurement procedures.

Therefore, "experts" in the traditional sense (e.g., radiologists) are not used to establish ground truth for this type of device. The ground truth is established by recognized reference standards and methods in clinical chemistry.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are typically used in studies involving human interpretation or subjective assessments (e.g., image reading). This is a quantitative diagnostic device, and the ground truth is established by objective, highly accurate reference methods or laboratory instruments. Therefore, no "adjudication method" in this context is applicable or described.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that assist human readers in interpreting complex data (e.g., medical images). The Afinion™ Lipid Panel is a standalone quantitative measurement device, not an AI-assisted human reading system.

6. Standalone Performance Done

Yes, a standalone performance study was done. The studies detailed (linearity, limits of quantitation, analytical specificity, accuracy/method comparison, and precision) all represent the performance of the Afinion™ Lipid Panel device (algorithm only, without human-in-the-loop performance) in measuring lipid levels in serum samples.

7. Type of Ground Truth Used

The ground truth used is based on:

• Reference Methods: Specifically, the National Reference System for Cholesterol (NRS/CHOL) for Total Cholesterol and HDL Cholesterol, and a CDC reference method for Triglycerides.
• Comparison to Predicate Devices/Automated Laboratory Methods (CM): For accuracy evaluation, the Afinion™ Lipid Panel's results were compared against an "automated laboratory method (CM)" for Chol, Trig, and HDL, which are themselves established and validated lab instruments.

8. Sample Size for the Training Set

This document describes a 510(k) submission for an in vitro diagnostic device that measures specific analytes. It is highly unlikely that this device uses machine learning or AI models that require a "training set" in the conventional sense (i.e., iterative learning from labeled data). The device's operation is based on established enzymatic colorimetric methods and pre-programmed algorithms. Therefore, a "training set" size is not applicable or stated in this context.

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

As stated in point 8, a "training set" as understood in machine learning is not applicable to this type of IVD device. The methods for establishing the device's accuracy and performance are described under "Traceability" and "Accuracy" (method comparison with reference and predicate methods).

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The Axis-Shield Active-B12 (Holotranscobalamin) assay is an enzyme-immunoassay (EIA) for the quantitative determination of holotranscobalamin (HoloTC) in human serum. HoloTC (vitamin B12 bound to transcobalamin) is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.

The Axis-Shield Active-B12 (Holotranscobalamin) device contains the following components: a microtitre plate with 8 x 12-well breakapart strips coated with a anti-holotranscobalamin murine monoclonal antibody, in a resealable foil pack with desiccant; ready-to-use calibrators, low and high controls (phosphate buffer containing protein (bovine) stabiliser and sodium azide preservative with or without recombinant HoloTC); ready-to-use pre-treatment solution; murine anti-human transcobalamin alkaline phosphatase conjugate; para-NitroPhenyl Phosphate (pNPP) substrate; wash buffer (8x); ready-to-use stop solution.

Here is a breakdown of the acceptance criteria and study information for the Axis-Shield Active-B12 (Holotranscobalamin) device, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The acceptance criteria are largely derived from the performance claims of the predicate device, as the submission aims to demonstrate substantial equivalence to it. Where specific numerical "acceptance criteria" are not listed for the predicate, the comparison is made to the predicate's reported performance or general principles of equivalence. For interference, the "≤ 10% deviation" acts as an acceptance criterion for the subject device.

2. Sample size used for the test set and the data provenance

• Dilution Linearity: Not explicitly stated as a sample size, but linearity was demonstrated "across the measuring range of the assay from 5.3 to 156.0 pmol/L." This typically involves a series of dilutions of a high-concentration sample. Data provenance not specified but likely derived from lab studies.
• Analytical limits at low levels (Limit of Blank, Detection, Quantitation): No specific sample size provided, stated as "a representative study." Data provenance not specified, likely lab-generated.
• High Dose Hook: No sample size provided, determined by testing up to 2236 pmol/L Holotranscobalamin. Data provenance not specified, likely lab-generated.
• Cross-reactivity: No specific sample size provided, determined by testing in the presence of 500 pmol/L apotranscobalamin or 5000 pmol/L haptocorrin. Data provenance not specified, likely lab-generated.
• Interference: No specific sample size provided, determined by testing in the presence of various interfering compounds at specific concentrations. Data provenance not specified, likely lab-generated.
• Precision: 8 human serum samples were used, each assayed 80 times across 3 lots, 2 operators, and 5 days. This sums to 640 individual measurements (8 samples * 80 replicates) for the human serum samples, plus 80 replicates each for a low and a high control. Data provenance not specified, but the use of "human serum samples" suggests clinical samples, likely retrospective.
• Matrix Comparison: > 36 specimens were used for the correlation study comparing serum (clot) and serum separator (SST) tubes. Data provenance not specified, likely retrospective from a clinical setting.
• Method Comparison: 111 specimens from apparently healthy adults were used. Data provenance not specified, but the description "apparently healthy adults" suggests prospective collection or selection from a healthy cohort.

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

This device is an in-vitro diagnostic assay for quantitative determination of a biomarker (Holotranscobalamin). The ground truth for such assays is typically established through:

• Reference Methods: Comparison to established, clinically validated methods (like the predicate device) or gold standard analytical techniques.
• Known Concentrations: Use of samples with known, spiked concentrations for analytical performance validation (e.g., linearity, detection limits).
• Clinical Diagnosis: Correlating assay results with clinical diagnosis of B12 deficiency (though a direct study for this is not detailed for the subject device beyond the general "aid in diagnosis").

Thus, the ground truth is established through laboratory measurements and comparison to a legally marketed predicate device, rather than through expert consensus on diagnostic images or interpretations. Therefore, there were no human experts establishing the ground truth in the way described (e.g., radiologists interpreting images).

4. Adjudication method for the test set

Not applicable, as this is a quantitative diagnostic assay. Adjudication methods like 2+1 or 3+1 are typically used for qualitative or interpretive tasks, often in imaging, where human experts might disagree.

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 immunoassay device, not an AI-assisted diagnostic tool that aids human readers.

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

Yes, this device is a standalone (algorithm only) device if you consider the "algorithm" to be the immunoassay protocol and the detector quantifying the colored end-product. There is no human-in-the-loop for the final quantitative result generation from the assay. The intent is for the device to provide a direct quantitative holotranscobalamin level.

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

The ground truth used for demonstrating substantial equivalence and performance was primarily based on:

• Comparison to the predicate device: The ARCHITECT Active-B12 (Holotranscobalamin) assay served as the reference standard for the method comparison study. This implies the predicate's results were considered the "ground truth" for comparative purposes.
• Analytical validation standards: For metrics like linearity, detection limits, cross-reactivity, and interference, the ground truth is established by carefully prepared samples with known concentrations or compositions, following established analytical chemistry principles.
• Internal reference materials/controls: For precision studies, characterized control samples with established mean values are used.

8. The sample size for the training set

This device is a traditional immunoassay, not a machine learning or AI algorithm in the modern sense that requires a "training set" for model development. Therefore, there is no explicit training set as would be understood in AI/ML validation. The development and optimization of the assay would have involved various experimental batches and iterative improvements, but these do not constitute a formal "training set" in the context of AI regulatory submissions.

9. How the ground truth for the training set was established

Not applicable, as there is no formal "training set" in the AI/ML sense. The development of the assay involved standard biochemical and immunological research and development processes.

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Reagents: The ARCHITECT HbA1c assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of percent hemoglobin A1c (HbA1c) in human whole blood on the ARCHITECT i System. Percent HbA1c measurements are used for monitoring long term glycemic control in diabetic patients. Calibrators: The ARCHITECT HbA1c Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of percent haemoglobin A1c (HbA1c) in human whole blood.

The ARCHITECT HbA1c assay is a two-step pre-treatment immunoassay for the quantitative determination of percent haemoglobin A1c (% HbA1c) in human whole blood using CMIA technology, with flexible assay protocols, referred to as Chemiflex. Sample is incubated with pre-treatment reagent to lyse the red blood cells. Pre-treated sample is the incubated with magnetic microparticles with a silica surface. Hemaglobin and HbA1c in the sample bind to the silica surface of the microparticles. Following a wash cvcle, anti-HbA1c acridinium-labeled conjugate is added to create a reaction mixture. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). The haemoglobin and HbA1c that are bound to the surface of the microparticles represents the total percentage present in the sample however, only the HbA1c result is required to determine the % HbA1c in the sample. A direct relationship exists between the amount of HbA1c in the sample and the RLUs detected by the ARCHITECT i System optics.

The information provided describes the ARCHITECT HbA1c Reagents and ARCHITECT HbA1c Calibrators, an in-vitro diagnostic device. Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The submission focuses on establishing substantial equivalence to a predicate device (AxSYM HbA1c). Therefore, the "acceptance criteria" are implied to be performance comparable to the predicate device, demonstrated through specific statistical metrics.

2. Sample Size Used for the Test Set and Data Provenance

• Sample Size: 127 samples.
• Data Provenance: The document does not explicitly state the country of origin. It indicates the study was a "method comparison study" and does not specify if it was retrospective or prospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

This information is not provided in the document. For in-vitro diagnostic devices, the "ground truth" is typically established by comparative analysis against a recognized reference method or a legally marketed predicate device, rather than by human expert review of images or clinical cases.

4. Adjudication Method for the Test Set

This information is not applicable and not provided for this type of device and study. Adjudication methods like 2+1 or 3+1 are typically used in studies involving expert interpretation (e.g., radiology studies) to establish a consensus ground truth. Here, the comparison is between two quantitative assays.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study involves multiple human readers interpreting cases, often with and without AI assistance, and is relevant for devices that aid human interpretation (e.g., in medical imaging). This submission is for an in-vitro diagnostic assay that provides a direct quantitative measurement.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the performance described is a standalone (algorithm only) performance. The ARCHITECT HbA1c assay is an automated chemiluminescent microparticle immunoassay (CMIA) run on the ARCHITECT i System. The performance metrics presented (slope, intercept, correlation) compare the results obtained directly from this automated system against results from the predicate automated system, without any human-in-the-loop interpretation being evaluated.

7. The Type of Ground Truth Used

The "ground truth" in this context is the results obtained from the legally marketed predicate device (AxSYM HbA1c assay). The study is a method comparison, aiming to show that the new device produces results comparable to an already accepted method.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" or its sample size. For an in-vitro diagnostic assay like the ARCHITECT HbA1c, the development process likely involves internal validation and optimization, but the submission primarily details the performance evaluation study against the predicate device.

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

Since a dedicated "training set" with established ground truth as typically understood in AI/ML contexts is not explicitly mentioned, this information is not provided. The development of the assay itself would have involved establishing accurate calibrators and quality control materials, which form the basis for accurate measurement, but this is distinct from a "ground truth" used for training an AI algorithm.

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