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Binding assay for the in vitro quantitative determination of folate in erythrocytes (red blood cells, RBC). Folate measurements are used in the diagnosis and treatment of anemia. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

Elecsys Folate III is a binding assay that makes use of a competitive test principle using a ruthenium labeled folate-binding assay.
Elecsys Folate III is a binding assay for the in vitro quantitative determination of folate in erythrocytes (red blood cells, RBC). Folate measurements are used in the diagnosis and treatment of anemia. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
Whole blood treated with anticoagulants (heparin or EDTA) is mixed with ascorbic acid solution and incubated for approximately 90 minutes at 20-25 °C. Lysis of the erythrocytes takes place, with liberation and stabilization of the intracellular folate. The resulting hemolysate sample is then used for subsequent measurement.
Results are determined via a calibration curve, which is instrument-specifically generated by 2point calibration, and a master curve provided via the cobas link.

Here's a summary of the acceptance criteria and study details for the Elecsys Folate III device, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Sizes and Data Provenance

• Precision (Repeatability & Intermediate Precision): Not explicitly stated, but typically involves multiple replicates over several days/runs with multiple instruments. Specific sample types are "Hemolysate 1" to "Hemolysate 5".
• Lot-to-lot Reproducibility: "three reagent lots" were used.
• Analytical Sensitivity (LoB, LoD, LoQ): Not explicitly stated, but determined according to CLSI EP17-A2, which involves specific numbers of blank and low-concentration samples.
• Linearity and Dilution: "At least seven concentrations using hemolysate samples" for linearity. Dilution study used "high concentration hemolysate samples".
• Endogenous Interferences: Not explicitly stated, but "various endogenous substances" were evaluated.
• Analytical Specificity/Cross-Reactivity: Not explicitly stated.
• Exogenous Interferences: "17 commonly and 1 specially used pharmaceutical" compounds.
• Sample Matrix Comparison: "Whole blood samples were drawn into Na-Heparin and K3-EDTA tubes." (Number not specified).
• Method Comparison to Predicate: 119 samples with concentrations between 132 and 618 ng/mL.
• Reagent Stability (On-board), Lot Calibration Stability, On-board Calibration Stability: Tested on "one cobas e 801 analyzer".

Data Provenance: The document states "NON-CLINICAL PERFORMANCE EVALUATION" and refers to CLSI (Clinical and Laboratory Standards Institute) guidelines, which are standard for in-vitro diagnostic device performance studies. The data is internal to Roche Diagnostics, a company with global operations. The specific country of origin for the studies is not stated, but given the submission is to the U.S. FDA, the studies are expected to meet international and U.S. regulatory standards. These are retrospective studies in the context of device development and validation.

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

This device is an in-vitro diagnostic (IVD) assay that produces quantitative measurements of folate. It does not involve human interpretation of images or other subjective data. Therefore, the "ground truth" for its performance is established by reference methods, calibrated standards, and accurate measurement principles, rather than human expert consensus. No human experts were used to establish ground truth in the way one would for an AI imaging device.

4. Adjudication Method (Test Set)

Not applicable, as this is an IVD device producing quantitative results, not an AI imaging device requiring expert adjudication.

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

Not applicable. This is an in-vitro diagnostic device, not an AI device assisting human readers with interpreting cases.

6. Standalone (Algorithm Only) Performance

Yes, the studies described are standalone performance evaluations of the Elecsys Folate III assay (the "algorithm" in a broad sense for an IVD) without human intervention in the measurement process. The device performs the quantitative determination of folate using its defined binding assay and electrochemiluminescence immunoassay (ECLIA) method.

7. Type of Ground Truth Used

The ground truth for evaluating the Elecsys Folate III's performance is established through:

• Reference materials/standards: For analytical sensitivity (LoB, LoD, LoQ) and linearity, where known concentrations are used.
• Performance against a predicate method: For method comparison, the results are compared to a previously cleared, established method (Elecsys Folate RBC).
• CLSI guidelines: Adherence to established scientific and statistical methodologies for validating assay performance, implying well-defined benchmarks for accuracy, precision, and interference.

8. Sample Size for the Training Set

Not explicitly stated. For an IVD like the Elecsys Folate III, a traditional "training set" as understood in machine learning is not directly applicable. The "training" for such a system would involve the development and optimization of the reagent formulations, assay parameters, and calibration curve algorithms, using various samples and experiments during the research and development phase. However, a specific training set size with corresponding ground truths is not documented in the same way as an AI algorithm.

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

As above, a formal "training set ground truth" isn't directly applicable in the machine learning sense. The "ground truth" during the development and optimization (analogous to training) would have been established through:

• Known concentrations: Using purified folate standards or spiked samples.
• Reference methods: Comparing early-stage assay performance against established, often more labor-intensive or gold-standard methods for folate determination.
• Clinical correlation: (Though "clinical testing" is marked Not Applicable for this 510(k), early development might involve correlation with clinical status or outcomes).
• Statistical optimization: Adjusting reagent ratios, incubation times, and instrument settings to achieve optimal analytical performance characteristics (sensitivity, specificity, precision, linearity) based on these known values and reference method comparisons.

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The Access Folate assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of folic acid levels in human serum, lithium heparin plasma, and red blood cells using the Access Immunoassay Systems. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia.

Folate levels in serum, lithium heparin plasma, and red blood cells are used to assess folate status. The serum folate levels is an indicator of recent folate intake. A low RBC folate value can indicate a prolonged folate deficiency.

The Access Folate assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of folic acid levels in human serum and lithium heparin plasma or red blood cells using the Access Immunoassay Systems.

The provided text describes the Beckman Coulter Access Folate Assay, a chemiluminescent immunoassay for the quantitative determination of folic acid levels. The submission is a 510(k) premarket notification for demonstrating substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and supporting studies based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Method Comparison: 123 samples. Data provenance is not specified (e.g., country of origin, retrospective/prospective).
• Linearity: The number of samples/levels used is not explicitly stated, but it's a verification study.
• Serum Imprecision: 5 serum samples with varying concentrations. Each sample was assayed in duplicate with two runs per day, over 20-22 days, meeting a minimum requirement of 80 replicates per sample on each instrument and reagent lot combination. This implies a total of (5 samples * 80 replicates/sample) = 400 replicates (for one instrument and reagent lot combination, multiplied by 3 instruments and 3 reagent lots, so 3600 replicates in total across all combinations). Data provenance is not specified.
• RBC Imprecision: 6 whole blood hemolysate samples with varying concentrations. For each sample, N=80 replicates were collected for imprecision calculations. Data provenance is not specified.
• LoB/LoD/LoQ: Verification studies were performed but sample sizes are not explicitly stated, though CLSI EP17-A2 is mentioned as the protocol, which specifies methodologies for determining these limits.

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

Not applicable. This is a laboratory diagnostic assay for measuring analyte concentrations, not an interpretation task typically requiring expert consensus on ground truth like image analysis. The "ground truth" for method comparison and imprecision studies typically refers to the reference method (predicate device) results and the true concentration of controls/samples, respectively.

4. Adjudication Method for the Test Set

Not applicable. As this is a quantitative laboratory assay, there is no expert adjudication process in the traditional sense. The comparisons are against the predicate device or established analytical performance criteria.

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

No. This is an in-vitro diagnostic device (IVD) that quantitatively measures a biomarker (folic acid). MRMC studies are typically performed for devices that involve human interpretation, such as imaging devices, to evaluate the impact of AI assistance on reader performance.

6. Standalone Performance (Algorithm Only without Human-in-the-Loop Performance)

Yes, the studies described (Method Comparison, Linearity, Imprecision, LoB/LoD/LoQ) demonstrate the standalone performance of the Access Folate Assay on the DxI 9000 Access Immunoassay Analyzer. This device is an automated immunoassay system; its output is a quantitative measurement, not an interpretation that involves human-in-the-loop interaction in the same way as, for example, an AI-powered diagnostic imaging tool. The "performance" refers to the analytical accuracy, precision, and range of the automated system itself.

7. Type of Ground Truth Used

• Method Comparison: The predicate device's results (Access Folate assay on Access 2 Instrument) served as the comparator for showing substantial equivalence.
• Linearity, Imprecision, LoB/LoD/LoQ: The "true" concentrations of control materials and samples, as determined by highly controlled experimental conditions and accepted statistical methods (e.g., CLSI guidelines), serve as the basis for evaluating performance against pre-defined analytical criteria.

8. Sample Size for the Training Set

The document does not provide information about a "training set." This type of IVD, an immunoassay, is typically developed and characterized through analytical verification and validation studies rather than machine learning training sets. While there is an "algorithm" (the immunoassay process), it's based on chemical reactions and detection, not a learned model from a large dataset. Therefore, the concept of a training set as used in AI/ML is not directly applicable here.

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

Not applicable, as a training set, in the machine learning sense, is not described for this device.

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The DiaSorin LIAISON® Folate assay uses chemiluminescent immunoassay (CLIA) technology for the quantitative determination of Folic acid in human serum. Folic acid measurements are used in the diagnosis and treatment of anemias. Assay results should be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions.

The assay must be performed on the LIAISON® XL Analyzer.

The LIAISON® Folate assay is a competitive chemiluminescence immunoassay (CLIA) for quantitative determination of Folic acid in serum. During the first incubation, Folic acid is dissociated from its binding protein. After five (5) minutes, a high pH buffer is added to prevent re-association to the binding protein. After five (5) minutes, Folic acid binds to a Folate Binding Protein on the solid phase, which competes with a Folic acid linked to an isoluminol derivative. After a third incubation, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added to initiate a flash chemiluminescent reaction. The light signal is measured by a photomultiplier as relative light units (RLU) and is inversely proportional to the concentration of Folic acid present in calibrators, controls, or samples.

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

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" for each performance characteristic in a pass/fail format. Instead, it presents study results which implicitly demonstrate the device's acceptable performance. For clarity, I've inferred common acceptance standards for such in vitro diagnostic assays where explicit criteria aren't given and formatted the reported performance against these.

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

• Test Set (Method Comparison): 157 human serum samples, spanning the assay range.
• Test Set (Expected Values/Reference Range): 166 prospectively collected serum samples from apparently healthy U.S. adults (21-59 years old) of mixed ethnic backgrounds (30% Caucasian, 32% African American, 38% Hispanic).
• Data Provenance: The method comparison study and the expected value study used human serum samples. The expected values study explicitly mentions "United States" for its population, implying the data is from the US and prospectively collected. The nature of the other analytical performance studies (precision, linearity, recovery, etc.) generally involves contrived or spiked samples and do not typically draw from specific patient populations or geographical locations.

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

• General Context: For an in vitro diagnostic (IVD) device like the LIAISON® Folate assay, the "ground truth" for the test set is established by the predicate device (Abbott Laboratories, ARCHITECT Folate, K092740) for method comparison, or by the inherent concentration of the analyte in the samples for analytical performance characteristics (like precision, linearity, etc.).
• No human "experts" established ground truth for the test set in the way radiologists might agree on an image diagnosis. Instead, the predicate device (an established, cleared medical device) serves as the reference standard for comparative effectiveness.

4. Adjudication Method for the Test Set:

• This is not applicable to the analytical performance studies of an in vitro diagnostic assay. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies, particularly for diagnostic imaging or pathology, where human interpretation of results is involved and consensus among experts is needed to define the "true" diagnosis or finding for a given sample/case. Here, the comparison is against an instrument's measurement (predicate device) or against known concentrations.

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:

• This question is not applicable to this type of device. The LIAISON® Folate assay is an automated in vitro diagnostic device, not an AI-assisted diagnostic tool that humans interpret. There are no "human readers" involved in interpreting the results from this specific device.

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

• Yes, this entire submission describes the standalone performance of the LIAISON® Folate assay. It is an automated chemiluminescent immunoassay (CLIA) system (LIAISON® XL Analyzer) that quantitatively determines Folic acid in human serum. Its performance characteristics (precision, linearity, accuracy, etc.) are evaluated intrinsically as a standalone device, without human intervention in the result determination process once the sample is loaded.

7. The Type of Ground Truth Used:

• Method Comparison: The "ground truth" was established by measurements from the predicate device, the Abbott Laboratories, ARCHITECT Folate (K092740).
• Other Analytical Performance (e.g., Precision, Linearity, Recovery, Specificity): The "ground truth" was established internally through various experimental designs:
  • Precision: By repeated measurements of samples with known or target concentrations.
  • Linearity: By testing serial dilutions from a high-concentration sample, where the "expected" concentration is mathematically derived from the initial concentration and dilution factor.
  • Recovery: By comparing measured concentrations of diluted samples to their calculated expected concentrations.
  • Analytical Specificity: By comparing results of samples spiked with potential interferents/cross-reactants to unspiked samples.
  • Limits (LoB, LoD, LoQ): Through statistical analysis of repeated measurements of blank and low-level samples.

8. The Sample Size for the Training Set:

• For an IVD like the LIAISON® Folate assay, there isn't a "training set" in the context of machine learning. The technology is based on established biochemical principles (chemiluminescence immunoassay) and reagents, rather than an AI/ML algorithm that learns from data. Therefore, this question is not applicable.

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

• As mentioned above, there is no "training set" for this type of device. The design and validation are based on chemical and biological principles and rigorous experimental testing, not machine learning model training.

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The Atellica™ Folate assay is for in vitro diagnostic use in the quantitative determination of folate in serum or red blood cells using the Atellica IM Analyzer. Folic acid measurements are used in the diagnosis and treatment of anemias.

The Atellica™ IM Folate Assay is an immunoassay with the following components: Atellica™ IM Folate Primary Reagent ReadyPack (including Lite Reagent, Solid Phase Reagent, and Folate Binding Protein), Atellica™ IM Folate Calibrator (including Low and High Calibrators), Atellica IM Folate DTT/Releasing Agent (sold separately, including Dithiothreitol and Sodium hydroxide), and Atellica IM RBC Folate (sold separately, including Lyophilized ascorbic acid and RBC Folate Ascorbic Acid Diluent).

The provided text is a 510(k) summary for an in vitro diagnostic device (Atellica™ IM Folate Assay), not an AI/ML medical device. Therefore, much of the requested information regarding AI/ML device acceptance criteria and study design (such as multi-reader multi-case studies, expert adjudication, training set ground truth, etc.) is not applicable to this document.

However, I can extract information related to the acceptance criteria for this diagnostic assay and how its performance was proven.

Here's a summary based on the provided document, addressing the applicable points:

Device Name: Atellica™ IM Folate Assay

Indications for Use: For in vitro diagnostic use in the quantitative determination of folate in serum or red blood cells using the Atellica IM Analyzer. Folic acid measurements are used in the diagnosis and treatment of anemias.

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a singular table, but rather presents performance characteristics of the device, implying that the observed performance met internal or regulatory (CLSI) standards. The predicate device (ADVIA Centaur Folate Assay, K010050) serves as the benchmark for substantial equivalence.

Here's a compilation of key performance characteristics, acting as de-facto acceptance criteria for a new in vitro diagnostic assay, and the reported performance. The "Acceptance Criteria" here are implicitly derived from CLSI guidelines and comparison to the predicate.

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

• Precision Study:
  • Serum: 4 human serum samples + 2 control levels. Tested 80 times each (N=80).
  • Whole Blood: 5 whole blood samples + 2 control levels. Tested 80 times each (N=80).
  • Provenance: Not explicitly stated, but typically clinical samples from a diverse patient population within the manufacturer's operational regions (often global or US/EU). Implied to be retrospective for the testing as the samples are "tested".
• Linearity Study:
  • Serum: 9 samples (prepared from high and low human serum pools). Each tested in triplicate.
  • RBC: 11 samples (prepared from previously cleared device's values).
• Dilution Recovery: 5 human serum samples. Each run in triplicate.
• Spiking Recovery: 5 samples (human serum pools with added folate stock).
• Method Comparison:
  • Human Serum: 105 samples.
  • Human Whole Blood: 100 samples.
  • Provenance: Not explicitly stated, but clinical samples.
• Collection Tube Comparison: 90 samples (K2 EDTA Whole Blood vs. Lithium Heparin Whole Blood).
• Reference Intervals Verification:
  • Serum: 30 serum samples from apparently healthy individuals.
  • RBC: 25 RBC samples (whole blood with tested percent hematocrit) from apparently healthy individuals.
• Detection Limits: Not specified as a sample size, but uses CLSI EP17-A2 protocol, which involves multiple replicates of blank, low-concentration, and standard samples.
• Interference: Two human sample pools (one approx. 4.0 ng/mL Folate, second approx. 12.0 ng/mL Folate). Both spiked with potential interferents.
• Cross-Reactivity: Normal human serum sample and blank assay diluent for each test compound. Multiple replicates processed.

Data Provenance: Not explicitly stated as "country of origin," but given it's a Siemens Healthcare Diagnostics product, it's likely multi-site clinical samples, possibly from North America and/or Europe. The studies are described as lab-based performance studies using human samples, fitting a retrospective data collection model for the test set.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This section is not applicable as this is an in vitro diagnostic assay for quantitative determination of an analyte (folate) using chemical/immunological reactions, not an AI/ML device requiring interpretation of complex images or data by human experts. The "ground truth" for this device is the actual concentration of folate in the samples, determined either by highly accurate reference methods or by comparison to an established, legally marketed predicate device (ADVIA Centaur Folate assay).

4. Adjudication Method for the Test Set

Not applicable. As a quantitative in vitro diagnostic device, there is no need for expert adjudication. The result is a numerical concentration.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

Not applicable. MRMC studies are specific to AI/ML devices that assist human readers in interpreting medical images or other complex data. This is a lab-based immunoassay.

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

Applicable, but in a different context. The "standalone" performance for this device refers to the ability of the Atellica IM Analyzer and reagents to accurately and precisely measure folate concentration without human intervention influencing the measurement itself (beyond loading samples and initiating tests). The performance characteristics listed (precision, linearity, detection limits, etc.) are all measures of the standalone analytical performance of the device.

7. The Type of Ground Truth Used

The ground truth for this in vitro diagnostic device is established using:

• Reference Methods/Internal Standards: Traceability is stated as being to an "internal standard manufactured using highly purified material (N-5-methyl tetrahydrofolate)." Calibrator values are traceable to this standardization.
• Comparison to a Legally Marketed Predicate Device: The primary method for demonstrating substantial equivalence is by comparing performance (method comparison studies) to the existing, FDA-cleared ADVIA Centaur Folate Assay (K010050). The predicate's results serve as a de-facto "ground truth" for demonstrating equivalence in clinical performance.
• Known Concentrations: For studies like linearity, dilution, spiking, and detection limits, samples with pre-defined or precisely measured concentrations are used as ground truth.
• Clinically Defined Samples: Healthy donor samples for reference interval verification.

8. The Sample Size for the Training Set

Not applicable in the AI/ML context. This is not an AI/ML device that undergoes a "training" phase with a dataset. The "training" for such an in vitro diagnostic device involves the manufacturer's internal development and optimization of the assay formulation, reagents, and instrument parameters to achieve desired performance, not data-driven model training.

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

Not applicable for an AI/ML training set. For the development of the assay itself, the ground truth for optimizing the assay would involve various analytical chemistry techniques and reference materials to ensure the assay accurately measures folate, coupled with comparison to existing validated methods or the predicate device during development phases.

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The Diazyme Folate Assay is a homogeneous enzyme immunoassay intended for use in the quantitative analysis of folate in human serum. Folic acid measurements are used in the diagnosis and treatment of anemias. For in-vitro diagnostic use only.

The Diazyme Folate Calibrator Set is intended for use in the calibration of the Diazyme Folate Assay. For in vitro diagnostic use only.

The Diazyme Folate Control Set is intended for use as quality controls for the Diazyme Folate Assay. For in vitro diagnostic use only.

Not Found

The provided text describes the FDA 510(k) clearance for the Diazyme Folate Assay, Diazyme Folate Calibrator Set, and Diazyme Folate Control Set. It focuses on the regulatory approval process and includes an "Indications for Use" statement.

Crucially, the document is a regulatory approval letter and not a study report. Therefore, it does not contain the detailed performance data, study design, or methodology information required to answer most of your questions about acceptance criteria verification and study details.

The information provided only allows for a very limited and generic answer:

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

• Acceptance Criteria (Implied): The device must be "substantially equivalent" to legally marketed predicate devices for the stated indications for use.
• Reported Device Performance: The FDA determined that the device is "substantially equivalent" to legally marketed predicate devices.

2. Sample size used for the test set and the data provenance
NOT PROVIDED IN THE DOCUMENT. This document does not detail the specific performance studies that Diazyme Laboratories conducted to demonstrate substantial equivalence.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
NOT PROVIDED IN THE DOCUMENT.

4. Adjudication method for the test set
NOT PROVIDED IN THE DOCUMENT.

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 (IVD) assay for measuring folate levels, not an AI-assisted diagnostic imaging device. Therefore, MRMC studies and human reader improvement with AI are not relevant.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
NOT APPLICABLE. As an IVD assay, its performance is inherently "standalone" in a laboratory setting, meaning it measures a biomarker without human interpretation of complex images or AI algorithms. However, the document does not contain the specific performance data (e.g., accuracy, precision, linearity) that would typically be generated in such a study.

7. The type of ground truth used
NOT PROVIDED IN THE DOCUMENT. For an IVD assay, ground truth would typically be established through reference methods, clinical diagnosis, or patient outcomes for the condition being diagnosed/monitored (anemia in this case).

8. The sample size for the training set
NOT PROVIDED IN THE DOCUMENT.

9. How the ground truth for the training set was established
NOT PROVIDED IN THE DOCUMENT.

In summary, the provided FDA 510(k) clearance letter confirms regulatory approval based on substantial equivalence but does not contain the detailed study data, methodologies, or acceptance criteria that would typically be found in a clinical study report or a 510(k) submission's performance section. To answer your questions comprehensively, you would need to review the actual 510(k) submission materials, which are not included in this document.

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Binding assay for the in vitro quantitative determination of folate in human serum. The binding assay is intended for use on Elecsys and cobas e immunoassay analyzers. Folic acid measurements are used in the diagnosis and treatment of anemias.

The Folate III Assay employs a competitive test principle using natural folate binding protein (FBP) specific for folate. Folate in the sample competes with the added folate (labeled with biotin) for the binding sites on FBP (labeled with a ruthenium complex). Results are determined using a calibration curve that is generated specifically on each instrument by a 2 point calibration and a master curve (5-point-calibration) provided with the reagent bar code.

Roche Diagnostics' Elecsys Folate III Assay is a quantitative in vitro diagnostic device designed for measuring folate levels in human serum, primarily for the diagnosis and treatment of anemias. The following outlines its acceptance criteria and the studies performed to demonstrate its performance.

Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Elecsys Folate III Assay are primarily established through comparison to a predicate device, the Roche Elecsys Folate III (K082340). The device demonstrates comparable or improved analytical performance characteristics.

Study Details

The provided document describes a premarket notification (510(k)) to demonstrate substantial equivalence to a legally marketed predicate device (Roche Elecsys Folate III, K082340). The studies conducted are analytical performance studies.

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

   • Precision (Repeatability/Intermediate): Human serum (HS) samples (5 levels) and PreciControl Varia (PCV) control levels (2 levels) were used. The document lists mean, SD, and CV values, which are derived from repeated measurements of these samples. The exact number of individual patient samples in the precision study is not explicitly stated, but typically these studies involve multiple runs over several days.
   • Analytical Specificity (Cross-reactivity): Specific cross-reactants (Amethopterin, Aminopterin, Folonic acid) were tested at concentrations of 1500 ng/mL.
   • Limitations (Interference): Bilirubin (< 29 mg/dL), Lipemia (< 1500 mg/dL), Biotin (< 21 ng/mL), Rheumatoid factors (< 1000 IU/mL), IgG (< 1.6 g/dL), IgM (< 1.0 g/dL), IgA (< 0.4 g/dL) were tested. Also, 16 commonly used pharmaceuticals and human erythropoietin were tested. The number of samples for each interference test is not specified.
   • Reference Range Study:
     • Predicate Device: N = 261 subjects from USA.
     • Candidate Device: N = 214 subjects from USA.
     • Provenance: All reference range data is from the USA. These appear to be prospective studies to establish healthy reference ranges.
   • Method Comparison: n = 106 patient samples were used, with folate concentrations ranging from 2.08 ng/mL to 19.6 ng/mL.
     • Provenance: Not explicitly stated, but typically these are retrospective or prospectively collected clinical samples.

2. 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 is an in vitro diagnostic (IVD) device for quantitative measurement of an analyte (folate). "Ground truth" in this context refers to the concentration of folate in the samples, determined by a reference method or the predicate device, rather than expert interpretation of images or clinical outcomes. Therefore, no "experts" in the sense of medical specialists reviewing results are mentioned as establishing ground truth. The ground truth for method comparison is the result obtained from the predicate device (Abbott Architect Folate assay, K092740).

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
   Not applicable, as this is an IVD device for quantitative measurement, not an assessment of diagnostic performance based on human interpretation or consensus.

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:
   Not applicable. This is an IVD device, not an AI-assisted diagnostic imaging device that involves human readers.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
   Yes, the performance characteristics (e.g., precision, measuring range, analytical sensitivity, specificity) described are for the Elecsys Folate III Assay itself, operating as a standalone algorithm/device. The method comparison study directly compares the results of the candidate device with another established assay.

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

   • Analytical Performance: The ground truth for evaluating analytical performance parameters like LoB, LoD, LoQ, precision, and specificity is typically based on control materials, spiked samples, and established analytical methods.
   • Method Comparison: The ground truth for the method comparison study was the results obtained from the predicate device, the Abbott Architect Folate assay (K092740). The acceptance criteria for this comparison would be for the candidate device's results to closely agree with those of the predicate.
   • Reference Range: The reference range was established by testing samples from a healthy population in the USA (N=214).

7. The sample size for the training set:
   The document does not specify a "training set" in the context of statistical modeling or machine learning. This is an immunoassay device, and its calibration curve is generated using a "2 point calibration and a master curve (5-point-calibration) provided with the reagent bar code" (page 3). The master curve is based on internal validation data, but a specific "training set sample size" for model development is not provided.

8. How the ground truth for the training set was established:
   As above, the concept of a "training set" with established ground truth as in machine learning is not directly applicable to this immunoassay. The device's operational characteristics and performance are based on analytical validation following established guidelines (CLSI documents EP5-A2, EP17-A2, EP6-A, EP-09-A2-IR mentioned on page 12). The calibration curve, which is critical to the assay's function, is standardized with a master curve and a 2-point calibration, and the device is standardized against the WHO International Standard NIBSC code: 03/178 (page 7).

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(1) Elecsys Folate RBC Assay: Binding assay for the in vitro quantitative determination of folate erythrocytes (red blood cells, RBCs). The binding assay is intended for use on Elecsys and cobas e immunoassay analyzers. Measurements obtained by this assay are used in the diagnosis and treatment of anemias.
(2) Elecsys Folate RBC CalSet: The Elecsys Folate RBC CalSet is used for calibrating the quantitative Elecsys Folate RBC assay on the Elecsys and cobas e immunoassay analyzers.
(3) Elecsys Folate RBC CalCheck: Elecsys Folate RBC CalCheck is used for the verification of the calibration established by the Elecsys Folate RBC reagent on the indicated Elecsys and cobas e immunoassay analyzers. For in vitro diagnostic use.

(1) The Elecsys Folate RBC assay employs a competitive test principle using natural folate binding protein specific for folate. Manually prepared hemolysate samples are used with this assay. Folate in the sample competes with the added folate (labeled with biotin) for the binding sites on folate binding protein (labeled with ruthenium complex). Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent barcode encoded on the reagent packaging.
(2) The Elecsys Folate RBC CalSet is a lyophilized product consisting of human serum with folate in two concentration ranges. During manufacture, the analyte is spiked into the matrix. This calibrator is used to calibrate the Elecsys Folate RBC assay.
(3) The Elecsys Folate RBC CalCheck is a lyophilized product consisting of a hemolysate with folic acid. During manufacture, the analyte is spiked into the matrix. This solution is used to verify the calibration established with the Elecsys Folate RBC CalSet.

The provided text describes the Elecsys Folate RBC Test System, but it is a device for in vitro quantitative determination of folate in red blood cells and not an AI or imaging device. Therefore, many of the requested categories related to AI performance, such as MRMC studies, ground truth establishment by experts for image data, or training/test set sample sizes for AI models, are not applicable.

However, I can extract information related to the device's analytical performance and the studies conducted to demonstrate its substantial equivalence to a predicate device, focusing on the available information.

Here's the breakdown based on the provided text, adapted for a non-AI diagnostic device:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct pass/fail thresholds in a table format. Instead, the submission demonstrates substantial equivalence by comparing the performance characteristics of the new Elecsys Folate RBC Assay to the predicate device (Elecsys RBC Folate III Assay) in a feature-by-feature comparison. The reported performance of the new device is shown alongside the predicate's performance. The "acceptance criteria" here are implicitly the predicate device's performance, as the goal is to show substantial equivalence.

Study Proving Device Meets Acceptance Criteria:

The study proving the device meets the acceptance criteria is a substantial equivalence comparison study against a legally marketed predicate device, the Elecsys RBC Folate III Test System (K082340). This type of study demonstrates that the new device is as safe and effective as the predicate device by showing that it has similar technological characteristics and performance.

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

The document does not explicitly state a single "test set" sample size in the way an AI model validation might. Instead, it details various analytical performance studies with different "samples" for each attribute:

• Precision (Repeatability & Intermediate Precision): Tested on multiple "Hemolysate" or "Sample" controls at different concentration levels. For each level, measurements were taken to determine SD and CV. The exact number of replicates or runs is not specified in the summary but is typically substantial for precision studies (e.g., multiple runs over several days).
• Analytical Sensitivity (LoB, LoD, LoQ): Determined using analytical methods, likely involving dilutions of folate-containing samples. The specific sample count for these determinations is not provided.
• Interferences: Tested using various interfering substances and pharmaceuticals. The number of samples/donors tested for each interference is not specified, but typically involves spiking known concentrations into samples and assessing recovery.
• Expected Values: Determined from a "Whole Blood Folate (from hemolysate sample)" study and an "RBC Folate (folate in erythrocyte fraction)" study. The sample size for these population studies is not provided in the summary.

Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. For in vitro diagnostic device submissions, such data is typically generated in a controlled laboratory setting (prospective) and may involve samples from different geographical regions, but this is not specified here.

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

Not applicable. This is not an AI/imaging device where expert consensus is used to establish ground truth for a test set. This device quantifies a biomarker (folate in RBCs). The "ground truth" for its analytical performance is established through reference methods and internal validation procedures, not human interpretation or adjudication by experts.

4. Adjudication Method for the Test Set

Not applicable. As this device measures a quantitative biomarker, there is no "adjudication" in the sense of resolving discrepancies in human interpretation or labeling. Analytical performance is typically verified against established laboratory standards and reference methods.

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 not an AI device used for interpretation or diagnosis by human readers, so an MRMC study is irrelevant.

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

This is a standalone device performance study. The Elecsys Folate RBC Test System performs the quantitative measurement of folate in RBCs automatically on immunoassay analyzers (Elecsys and cobas e platforms) without human-in-the-loop interpretative performance. The performance metrics (measuring range, sensitivity, precision, interference) are all measures of the algorithm and system's analytical capability.

7. The Type of Ground Truth Used

The "ground truth" for this device's performance relies on analytical reference methods and established laboratory principles. For example:

• For analytical sensitivity (LoB, LoD, LoQ): Determined using standard statistical methods and known concentrations of analyte.
• For precision: Assessed by running replicate measurements on control samples.
• For accuracy/comparison to predicate: The predicate device itself (Elecsys RBC Folate III Assay) serves as the "reference" for demonstrating substantial equivalence. The traceability of the new device is stated as "Reference method is Folate III (Application on the E2010)", meaning its measurements are compared to the predicate's measurements. The predicate's traceability is to the "Elecsys Folate II assay."

8. The Sample Size for the Training Set

Not applicable. This is not an AI/machine learning device that requires a "training set." The system's underlying principles are based on known biochemistry (competitive binding assay using folate binding protein) and not data-driven learning from a training set.

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

Not applicable, as there is no training set for this type of in vitro diagnostic device.

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The ARCHITECT Folate assay is a chemiluminescent microparticle Folate Binding Protein assay for the quantitative determination of folate in human serum and plasma on the ARCHITECT i System. Folate measurements are used in the diagnosis and treatment of megaloblastic anemia.
The ARCHITECT Folate Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of folate in human serum and plasma.
The ARCHITECT Folate Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of folate in human serum and plasma.

The ARCHITECT Folate assay is a two-step assay for the quantitative determination of folate in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology. Two pre-treatment steps mediate the release of folate from endogenous folate binding protein.
In Pre-Treatment Step 1, the sample and Pre-treatment Reagent 2 (Dithiothreitol or DTT) are aspirated and dispensed into a reaction vessel (RV). In Pre-Treatment Step 2, an aliquot of sample/Pre-Treatment Reagent 2 mixture is aspirated and dispensed into a second RV. Pre-Treatment Reagent 1 (potassium hydroxide or KOH) is then added. An aliquot of the pre-treated sample is transferred into a third RV, followed by the addition of Folate Binding Protein (FBP) coated paramagnetic microparticles and assay specific diluent. Folate present in the sample binds to the FBP coated microparticles. After washing, pteroic acid-acridinium labeled conjugate is added and binds to unoccupied sites on the FBP coated microparticles. Pre-Trigger and Trigger Solutions are then added to the reaction mixture; the resulting chemiluminescent reaction is measured as relative light units (RLUs). An inverse relationship exists between the amount of folate in the sample and the RLUs detected by the ARCHITECT i optical system.

The provided text describes a 510(k) submission for the ARCHITECT Folate assay, a medical device for quantitatively determining folate in human serum and plasma. The study conducted is a non-clinical performance comparison between the new ARCHITECT Folate assay and its predicate device, the AxSYM Folate assay.

Here's an analysis of the acceptance criteria and study as requested:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document states "The ARCHITECT Folate assay demonstrated substantially equivalent performance to the AxSYM Folate assay with correlation coefficients of 0.898 for serum samples." The acceptance criteria for "substantially equivalent" in areas like precision, linearity, and interferences are not explicitly quantified with numerical thresholds in the provided text. They are implied by the claim of substantial equivalence to the predicate device.

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

The document does not explicitly state the sample size used for the test set in the comparison study.

The data provenance is not specified in terms of country of origin or whether it was retrospective or prospective. It is a non-clinical performance study.

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

This information is not applicable to this type of study. The ground truth for a quantitative diagnostic assay is typically established through a reference method or standardization to an internationally recognized standard. In this case, the investigational assay was standardized to the WHO Serum Folate International Standard (IS) 03/178. Human expert consensus is not the method for establishing ground truth for quantitative laboratory tests like this.

4. Adjudication Method for the Test Set

This information is not applicable to this type of study. Adjudication methods (like 2+1 or 3+1) are typically used in studies where human readers are interpreting images or making subjective diagnoses, which is not the case for a quantitative immunoassay comparison. The comparison is likely done statistically between measured values.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study is a non-clinical performance evaluation of a quantitative diagnostic assay, not an AI-assisted human reading study.

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

Yes, this was a standalone performance study of the ARCHITECT Folate assay. The document describes the assay's mechanism and then presents its performance characteristics (precision, linearity, interferences, method comparison) against a predicate device. There is no mention of human-in-the-loop performance testing.

7. The Type of Ground Truth Used

The ground truth for the investigational assay was established by standardization to the WHO Serum Folate International Standard (IS) 03/178. For the comparison with the predicate, the predicate device's results serve as a comparative "truth," which were themselves based on gravimetric preparations of folic acid.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning. This is a traditional immunoassay device, not an AI/ML-based device. Therefore, a training set as understood in AI/ML is not applicable. The assay is "standardized" rather than "trained."

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

As explained above, there is no "training set" in the machine learning sense for this device. The assay was standardized to accurately recover WHO Serum Folate International Standard (IS) 03/178. This standardization process involves calibrating the assay's response to known concentrations of the analyte based on this international standard.

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Tosoh AIA-PACK RBC FOLATE is designed for in vitro diagnostic use only for the quantitative measurement of red blood cell folate (RBC FOLATE) in whole blood (Heparin or EDTA) samples on TOSOH AIA system analyzer. Measurement of RBC Folate is used in the diagnosis and treatment of anemia.

The Tosoh AIA-PACK RBC FOLATE is a competitive enzyme immunoassay which, after sample hemolysis and sample pretreatment, is performed entirely within the AIA-PACK. First, sample hemolysis is performed to achieve complete hemolysis of erythrocytes and deconjugation to monoglutamate in the whole blood sample using sample hemolyzing reagents (containing ascorbic acid). After sample hemolysis, sample pretreatment is performed to release folate from endogenous binding proteins in the hemolysate sample using sample pretreatment reagents (containing sodium hydroxide and dithiothreitol). Folate present in the pretreated test sample competes with enzyme-labeled folate for a limited number of binding sites on a fluorescein labeled bovine folate binding protein which then binds to anti-FITC (fluorescein isothiocyanate) antibody immobilized on magnetic beads. The beads are washed to remove the unbound enzyme-labeled folate and are then incubated with a fluorogenic substrate, 4-methylumbelifery| phosphate (4MUP). The amount of enzyme labeled folate that binds to the beads is inversely proportional to the folate concentration in the test sample. A standard curve using a range of known standard concentrations is constructed and unknown folate concentrations are calculated using this curve.

The Tosoh AIA-PACK RBC FOLATE is a device designed for the quantitative measurement of red blood cell folate (RBC FOLATE) in whole blood samples, used in the diagnosis and treatment of anemia. The device's performance was evaluated through various studies to demonstrate substantial equivalence to a predicate device (Bayer K010050, ADVIA Centaur and ACS: 180 Folate Immunoassay).

The document provides performance data for several criteria: Recovery, Dilution, Linearity, Precision, Correlation, Specificity, and Limit of Detection (LoD)/Limit of Quantitation (LoQ). Acceptance criteria are not explicitly stated as distinct numerical targets but are implied by the reported performance and the overall conclusion of substantial equivalence based on established CLSI protocols.

Here's a breakdown of the acceptance criteria and the study results:

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Size and Data Provenance for Test Set:

• Recovery Study: 3 whole blood (EDTA) samples, each spiked at 3 different levels.
• Dilution Study: 3 whole blood (EDTA) samples.
• Precision Study: 3 commercially available controls and 1 whole blood (EDTA) control.
• Correlation (EDTA vs. Heparin) Study: 50 patient samples.
• Correlation (vs. Alternate Method) Study: 101 patient specimens.
• LoD/LoQ Study: Blank sample with 60 replicates; 7 low-level samples with 10 replicates each.

The document does not explicitly state the country of origin for the patient samples used in the correlation studies, nor does it specify whether the data was retrospective or prospective. Given the nature of an in vitro diagnostic device regulatory submission, it is typically presumed to be clinical samples, often from a diverse patient population, collected prospectively or obtained retrospectively under controlled conditions for the purpose of the study.

3. Number of Experts and Qualifications for Ground Truth:

The studies described are primarily analytical performance studies for an in vitro diagnostic (IVD) device, not directly involving human interpretation of results in a diagnostic setting (i.e., not an image-based AI device relying on expert radiologists for ground truth). Therefore, the concept of "experts establishing ground truth" in the manner requested is not applicable here.

• Ground truth for these studies is established through reference methods and known concentrations of analytes in controls and spiked samples, measured by established laboratory practices and instrumentation.
• The "experts" involved would be qualified laboratory personnel (e.g., clinical laboratory scientists, chemists) conducting the assays and analyzing data according to standard operating procedures and CLSI guidelines. Their qualifications are inherent in their ability to perform and interpret such analytical studies.

4. Adjudication Method for the Test Set:

Not applicable. As described above, the ground truth is based on quantitative analytical measurements, not on subjective expert consensus requiring adjudication.

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

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation (e.g., reading medical images) where the AI aids human performance. The AIA-PACK RBC FOLATE is an automated analytical assay, and its performance is evaluated directly against known analytical values or comparative analytical methods, not human readers.

6. Standalone (Algorithm Only) Performance:

Yes, the studies effectively demonstrate standalone performance. The "device" in this context is the AIA-PACK RBC FOLATE assay run on a Tosoh AIA system analyzer. All the reported performance data (Recovery, Dilution, Linearity, Precision, LoD/LoQ, Specificity) demonstrate the intrinsic analytical capabilities of the assay without direct human intervention in the interpretive phase. Human operators perform the sample preparation and run the analyzer, but the measurement and calculation of folate concentration is algorithmic within the system. The correlation studies compare this standalone analytical result to other analytical methods or sample types.

7. Type of Ground Truth Used:

The ground truth used for these studies includes:

• Known concentrations: For recovery and linearity studies, samples were spiked with known amounts of folate to determine expected values. Commercial controls with established target values were also used for precision.
• Reference methods/Comparison methods: For correlation studies, the device's measurements were compared against an "alternate method" (likely another legally marketed Folate immunoassay) and against each other (EDTA vs. Heparin whole blood) to establish agreement.
• Analytical measurement techniques: The core ground truth for an IVD kit is its ability to accurately and precisely measure the analyte (RBC Folate) based on its chemical and immunological principles.

8. Sample Size for the Training Set:

The document does not explicitly mention a "training set" in the context of machine learning. For an immunoassay, the "training" aspect refers to the development and optimization of the assay reagents, protocols, and standard curve generation. This typically involves extensive R&D work using numerous samples and iterations to establish the optimal conditions and calibration. The calibration process for this device uses a 6-point calibration curve. The specific sample size for developing these foundational elements is not detailed but would precede the formal validation studies presented.

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

As mentioned, "ground truth for a training set" is not directly applicable in the AI/ML sense for a traditional immunoassay. For an immunoassay, the "ground truth" for developing the assay and its calibration would be established through:

• Highly purified folate standards: Used to create the calibration curve and to spike samples for recovery and linearity.
• Reference materials: Certified reference materials or well-characterized patient samples with established folate concentrations from orthogonal or highly accurate methods.
• Methodology optimization: Iterative testing and adjustment of reagent concentrations, incubation times, antibody affinities, and detection limits to achieve the desired analytical performance.

The calibration curve itself (6-point calibration) serves as the "learned" relationship between signal and concentration, established using known folate standards.

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(1) Elecsys Folate III: Binding assay for the in vitro quantitative determination of folate in human serum and plasma. The binding assay is intended for use on Elecsys and cobas e immunoassay analyzers. Measurements obtained by these devices are used in the diagnosis and treatment of anemias. For in vitro diagnostic use.

(2) Elecsys RBC Folate Hemolyzing Reagent: Elecsys RBC Folate Hemolyzing Reagent is used together with the Elecsys Folate III assay for the quantitative determination of folate in erthrocytes (RBC (red blood cell) folate). Binding assay for the in vitro quantitative determination of folate in human serum and plasma. The binding assay is intended for use on Elecsys and cobas e immunoassay analyzers. Measurements obtained by these devices are used in the diagnosis and treatment of anemias.

(3) Elecsys Folate III CalSet: Elecsys Folate III CalSet is used for calibrating the quantitative Elecsys Folate III assay on the Elecsys and cobas e immunoassay analyzers.

(4) Elecsys Folate III CalCheck: Elecsys Folate III CalCheck is used for the verification of the calibration established by the Elecsys Folate III reagent on the indicated Elecsys and cobas e immunoassay analyzers.

(5) Elecsys PreciControl Anemia: Elecsys PreciControl Anemia is used for the quality control of specified Elecsys immunoassays on Elecsys and cobas e immunoassay analyzers.

(1) The Elecsys Folate III assay employs a competitive test principle using natural folate binding protein (FBP) specific for folate. Folate in the sample competes with the added folate (labeled with biotin) for the binding sites on FBP (labeled with ruthenium complex). Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent barcode.

(2) The Elecsys RBC Folate Hemolyzing Reagent is a 0.2% ascorbic acid solution with which whole blood treated with anticoagulants (heparin or EDTA) is diluted. After incubation the erythrocytes are lysed and intracellular folate is liberated and stabilized. The hemolysate is then used as a prediluted sample for subsequent measurement in the Elecsys Folate III assay.

(3) The Elecsys Folate III CalSet is a lyophilized product consisting of human serum with folic acid in two concentration ranges. During manufacture, the analyte is spiked into the matrix. This calibrator is used to calibrate the Elecsys Folate III assay.

(4) Elecsys Folate III CalCheck is a lyophilized product consisting of human serum with folic acid. During manufacture, the analyte is spiked into the matrix. This solution is used to verify the calibration established with the Elecsys Folate III CalSet.

(5) The Elecsys PreciControl Anemia is a lyophilized control serum based on human serum matrix in three concentration ranges. The controls are used for monitoring the accuracy and precision of the Elecsys Ferritin, Folate III, and Vitamin B12 immunoassays.

The Elecsys Folate III Test System, including Elecsys Folate III, Elecsys RBC Folate Hemolyzing Reagent, Elecsys Folate III CalSet, Elecsys Folate III CalCheck, and Elecsys PreciControl Anemia, is designed for the in vitro quantitative determination of folate in human serum, plasma, and erythrocytes. This system is intended for use in the diagnosis and treatment of anemias on Elecsys and cobas e immunoassay analyzers.

The acceptance criteria for the Elecsys Folate III and Elecsys RBC Folate Hemolyzing Reagent assays were established through comparison studies against their respective predicate devices (Elecsys Folate II Assay and Elecsys RBC Folate Hemolyzing Reagent (K051292)). The primary method for proving the device meets these criteria is through Method Comparison studies using Passing-Bablok and Linear Regression analysis.

Here's the breakdown of the acceptance criteria and performance:

Study Details:

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

   • Elecsys Folate III Assay (Method Comparison): N=98 samples. Sample concentrations were between approximately 1.76 and 15.9 ng/mL. The data provenance is not explicitly stated as retrospective or prospective, nor is the country of origin mentioned.
   • Elecsys RBC Folate Hemolyzing Reagent (Method Comparison): N=98 samples. Sample concentrations were between approximately 123 and 566 ng/mL. The data provenance is not explicitly stated as retrospective or prospective, nor is the country of origin mentioned.
   • Elecsys RBC Folate Hemolyzing Reagent (Expected Values): N=262 samples from a study in the USA. This suggests a prospective study for establishing typical ranges.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. This device is an in vitro diagnostic assay that measures a biochemical marker (folate concentration). Ground truth for measured analytes is typically established by reference methods or validated assays, not by expert consensus. The comparison is made against the predicate devices' measurements.

3. Adjudication method for the test set: Not applicable. The studies are method comparisons against a predicate device, not diagnostic performance studies requiring adjudication of disagreements among experts.

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: Not applicable. This is an in vitro diagnostic assay, not an imaging device or AI-assisted diagnostic tool that involves human reader interpretation.

5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: The device is a standalone immunoassay system (Elecsys Folate III assay run on Elecsys and cobas e immunoassay analyzers). The performance data presented (measuring range, precision, sensitivity, interferences, method comparison) reflects the standalone performance of the assay and the instrument system, without human intervention in the measurement process itself, beyond standard laboratory procedures for sample handling and instrument operation.

6. The type of ground truth used: For the method comparison studies, the "ground truth" was the measurements obtained by the predicate devices: Elecsys Folate II assay for serum folate and Elecsys RBC Folate Hemolyzing Reagent + Elecsys Folate II assay for RBC folate. This is a form of comparative reference standard.

7. The sample size for the training set: Not applicable. As an in vitro diagnostic assay, there is no "training set" in the context of machine learning or AI models. The assay performance is developed and validated through a series of analytical studies.

8. How the ground truth for the training set was established: Not applicable. See point 7.

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