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The NOVEOS Specific IgE Assay is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum. NOVEOS Specific IgE Assay is to be used with the NOVEOS Immunoassay Analyzer. It is intended for use as an in vitro diagnostic aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings and is to be used in clinical laboratories.

The NOVEOS Specific IgE Assay is an immunometric, chemiluminescent procedure for the quantitative determination of IgE of known specificity in human serum samples. It employs fluorescent labelled magnetic, streptavidin coated microparticles which are incubated with a biotinylated allergenic capture reagent, patient sample and monoclonal anti‐human IgE antibody: horseradish peroxidase conjugate. If present in the sample, IgE binds to the biotinylated allergen captured to the streptavidin‐coated microparticles to form a complex. After a final wash, the resulting complex is incubated with the enzyme substrate and a chemiluminescent signal is generated, the magnitude of which is proportional to the concentration of IgE in the patient sample. The concentration of allergen‐specific IgE is determined from a standard curve, which is traceable to the World Health Organization (WHO) reference reagent serum Immunoglobulin E (IgE) 11/234.

The provided FDA 510(k) clearance letter and summary for the NOVEOS Specific IgE (sIgE) Assay outlines the device's performance, but it does NOT describe "acceptance criteria" in an explicit, quantifiable manner that is typically found in a clinical study report. Instead, the document presents study results and compares them to a predicate device (ImmunoCAP Specific IgE) to demonstrate substantial equivalence, and also to clinical diagnosis of allergic status. The closest approximations to acceptance criteria are implicit in the performance metrics presented (e.g., target ranges for sensitivity, specificity, agreement, precision, linearity).

This device is an in vitro diagnostic (IVD) assay, not an AI/ML-based diagnostic imaging or analysis system. Therefore, the concepts of "human readers improve with AI vs without AI assistance," "standalone (algorithm only) performance," "number of experts," "adjudication method," and "training set ground truth establishment" do not directly apply in the same way they would for AI-powered diagnostic imaging devices. The "ground truth" for this IVD device is established through reference methods (Skin Prick Test, Oral Food Challenge, ImmunoCAP predicate device) or established clinical diagnosis.

Here's a breakdown of the information that is provided and how it relates to the requested points, with interpretations where necessary for IVD context:

1. Table of Acceptance Criteria and Reported Device Performance

As mentioned, explicit acceptance criteria are not stated. However, the performance data presented effectively serves as the "reported device performance" that presumably met the FDA's requirements for substantial equivalence. I will present the key performance metrics from the document.

Key Performance Metrics (Implicit Acceptance Criteria)

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

• Clinical Performance Study (Clinical Sensitivity & Specificity):

  • Sample Size: Ranges from 102 to 228 patients overall, depending on the specific allergen.
    • "Atopic" (positive) samples: 32 to 88 samples confirmed by skin-prick testing or oral food challenge.
    • "Non-Atopic" (negative) samples: 53 to 146 samples deemed negative by ImmunoCAP testing (result <0.35 kU/L).
  • Data Provenance: Not explicitly stated (e.g., country of origin). The study is described as a "clinical study," which implies real-world patient samples. It's unclear if the study was retrospective or prospective, but the description of "confirmed by skin-prick testing or oral food challenge" suggests a direct clinical evaluation.

• Method Comparison to ImmunoCAP:

  • Sample Size: Ranges from 175 to 268 patient samples, depending on the specific allergen.
  • Data Provenance: Not explicitly stated (e.g., country of origin). These are "patient samples," implying clinical origins. Retrospective or prospective nature is not specified.

• Precision/Reproducibility:

  • Sample Size: 80-86 replicates per sample for within-laboratory precision (4-5 samples per allergen).
  • Sample Size: 50-240 replicates per sample for lot-to-lot imprecision (4 samples per allergen).

• Linearity:

  • Sample Size: Three sets of serially diluted human serum samples (low, mid, high concentration) for each allergen. Dilutions created up to 1/32.

3. Number of Experts and Qualifications for Ground Truth

For an IVD device like this, "experts" in the sense of radiologists interpreting images are not directly involved in setting the ground truth for the device's output. The ground truth is laboratory or clinical reference standards.

• Clinical Study Ground Truth: "Allergic status (atopic) was confirmed by skin-prick testing or oral food challenge, and the other 53 to 146 samples were deemed negative (non‐atopic) by ImmunoCAP testing (result <0.35 kU/L)."

  • Number of Experts: Not specified. Skin-prick testing and oral food challenges are clinical procedures typically performed and interpreted by allergists or clinicians skilled in allergy diagnosis. ImmunoCAP testing is a laboratory-based method.
  • Qualifications of Experts: Implied to be medical professionals (allergists/clinicians) and laboratory personnel capable of performing and interpreting these established diagnostic tests. No specific "years of experience" or board certifications are mentioned.

• Method Comparison Ground Truth: The ImmunoCAP Specific IgE Assay (K051218) is used as the comparative "ground truth." This is a legally marketed predicate device.

4. Adjudication Method for the Test Set

• Adjudication Method: Not applicable for this type of IVD device. The ground truth is based on established clinical diagnostic procedures (skin-prick test, oral food challenge) and a comparative predicate laboratory assay (ImmunoCAP), not on multiple human interpretations requiring adjudication.

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

• MRMC Study: No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for diagnostic imaging devices where human readers interpret medical images, often with and without AI assistance. This device is an in vitro diagnostic assay that directly measures a biomarker in serum.

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

• Standalone Performance: The reported performance of the NOVEOS sIgE Assay (clinical sensitivity/specificity, agreement with ImmunoCAP, precision, linearity, etc.) is the standalone performance of the assay system. It operates automatically to measure allergen-specific IgE levels. There isn't a "human-in-the-loop" aspect to its direct output generation; it provides a quantitative result. The interpretation of that result for clinical diagnosis happens after the device provides its measurement, "in conjunction with other clinical findings."

7. Type of Ground Truth Used

• Clinical Study Ground Truth:

  • Clinical Diagnosis: Allergic status was confirmed by skin-prick testing or oral food challenge (for atopic individuals). These are considered definitive clinical methods for allergy diagnosis.
  • Predicate Device Result: Samples deemed non-atopic were confirmed by ImmunoCAP testing (result <0.35 kU/L).

• Method Comparison Study Ground Truth:

  • Predicate Device Result: The ImmunoCAP Specific IgE Assay results were used as the comparator.

8. Sample Size for the Training Set

• Training Set: This device is a quantitative in vitro diagnostic immunoassay, not a machine learning or AI algorithm in the traditional sense that requires distinct "training" datasets for model development. The development of such assays involves extensive analytical validation (e.g., reagent optimization, calibration curve establishment, linearity, precision) using various characterized samples and controls, but this is different from an AI model's "training set." The document describes various validation studies, but does not refer to a "training set" for an algorithm.

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

• Ground Truth Establishment for Training Set: Not applicable as described above. The assay's performance characteristics (e.g., calibration, measurement range) are established through a rigorous and well-defined analytical validation process, typically using reference materials, characterized control samples, and patient samples with known concentrations/statuses, rather than through ground truth established for an AI "training set." The calibrators are traceable to the World Health Organization (WHO) reference reagent serum Immunoglobulin E (IgE) 11/234, which serves as a fundamental "truth" reference for IgE measurement.

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ImmunoCAP Specific IgE is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum or plasma (EDTA or Na-Heparin). It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings, and is to be used in clinical laboratories. ImmunoCAP Specific IgE is to be used with the instruments Phadia 1000, Phadia 2500 and Phadia 5000.

ImmunoCAP Specific IgE reagents are modular in concept and are available individually. For a complete listing of reagents needed to perform the Phadia ImmunoCAP Specific IgE assay, please consult the ImmunoCAP Specific IgE Conjugate Directions for Use.

Phadia 250, Phadia 1000, Phadia 2500 and Phadia 5000 instrument systems, and associated software, processes all steps of the assay and calculates results automatically after the assay is completed. Analytical and clinical validation of these components were performed on the representative instrument Phadia 250 and Phadia 1000.

Here's a breakdown of the acceptance criteria and study details for the ImmunoCAP Allergen Components, 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 single summary table, but rather presents the results of studies supporting the device's performance. The implied acceptance criteria for most analytical studies would be that the results achieved demonstrate suitable performance for the intended use (e.g., low imprecision, good linearity, sufficient detection limits, absence of significant interference, and adequate stability).

For the purpose of this summary, I'll extract the key performance metrics and the reported results from the provided text.

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

• Precision/Reproducibility:
  • Within-laboratory: 5 or 6 positive samples tested in 4 replicates per day for 20 days (total 80 replicates per sample), except for one sample with 3 replicates for 11 runs over 20 days (33 replicates).
  • Lot-to-lot: 4 or 5 positive samples and 1 negative sample. Each lot (3 lots total) tested with 12 replicates per sample in one run.
  • Provenance: Not explicitly stated, but clinical and non-clinical samples are mentioned in other studies suggesting human samples.
• Linearity: 3 or 4 positive samples, each diluted to generate at least six 2-fold consecutive dilutions. Samples tested with a minimum of 4 replicates in one run.
  • Provenance: Not explicitly stated, but clinical/patient samples are implied.
• Detection Limit: 5 blank samples (for LoB) and 5 low positive samples (for LoD). Blank samples determined in 3 runs with 5 replicates per run. Low positive samples measured in 15 replicates.
  • Provenance: Not stated.
• Analytical Specificity (Inhibition Studies): One positive sample for each ImmunoCAP Allergen component.
  • Provenance: Not stated, implied human.
• Interference (Endogenous Substance): Three samples (two positive and one negative) for each ImmunoCAP Allergen component.
  • Provenance: Not stated, implied human.
• Stability: Three lots of each ImmunoCAP Allergen component. The accelerated stability study for rSes i 1 (f449) used two positive and one negative sample across three lots.
  • Provenance: Not stated.
• Method Comparison Study (vs. Predicate):
  • f433, rTri a 14: 33 positive clinical samples, 10 positive non-clinical samples, 100 negative samples. Total = 143.
  • f416, rTri a 19: 34 positive clinical samples, 14 positive non-clinical samples, 100 negative samples. Total = 148.
  • f449, rSes i 1: 32 positive clinical samples, 30 positive non-clinical samples, 100 negative samples. Total = 162.
  • Provenance: Samples from individuals with clinical history of allergy-like symptoms, sensitized individuals without documented clinical history, and healthy non-atopic donors. The location or retrospective/prospective nature is not specified, but it implies a mix of historical and presumably current clinical samples.
• Clinical Sensitivity and Specificity:
  • f433, rTri a 14: 133 atopic (clinical history of allergy-like symptoms upon exposure to wheat, physician-diagnosed) and 100 non-atopic (healthy, no reported clinical reaction to allergen) samples. Total = 233.
  • f416, rTri a 19: 129 atopic and 100 non-atopic samples. Total = 229.
  • f449, rSes i 1: 35 atopic and 100 non-atopic samples. Total = 135.
  • Provenance: "Selected samples from individuals with a clinical history of allergy-like symptoms upon exposure to wheat/sesame, as diagnosed by a physician" and "samples from healthy subjects with no reported clinical reaction." Location and retrospective/prospective nature not explicitly stated.

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

• For the Clinical Sensitivity and Specificity studies, the ground truth for "atopic" cases was established by "clinical diagnosis of allergy" by a "physician." The specific number or qualifications of these physicians are not detailed in the document. For "non-atopic" cases, it relied on "no reported clinical reaction to the allergen."

4. Adjudication Method for the Test Set

• The document does not describe any formal adjudication method (e.g., 2+1, 3+1) for establishing the clinical diagnosis (ground truth) in the clinical studies. The mention of "diagnosed by a physician" suggests individual physician diagnoses were used.

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

• No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) assay that measures allergen-specific IgE levels, not an imaging device or AI-assisted diagnostic tool for human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.

6. 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 the assay itself provides quantitative results for specific IgE antibodies. The performance characteristics described (precision, linearity, detection limit, analytical specificity, interference, stability, method comparison, and clinical sensitivity/specificity) are all "algorithm only" or device-only performance measures. The "human-in-the-loop" aspect comes in the interpretation of these quantitative results by a clinician in conjunction with other clinical findings, as stated in the Indications for Use. The clinical studies evaluate how well the device's output correlates with a clinical diagnosis, not how well humans perform with or without the device.

7. The Type of Ground Truth Used

• Clinical Diagnosis (by a physician) / Reported Clinical Reaction: For the clinical sensitivity and specificity studies, the ground truth was based on a "clinical diagnosis of allergy" by a physician for atopic individuals and "no reported clinical reaction" for non-atopic individuals.
• Absence of IgE Antibodies / Healthy Non-atopic Donors: For the method comparison study, "healthy, non-atopic donors" and "undetectable levels of specific IgE antibodies" (<0.1 kUX/L) served as ground truth for negative cases.
• Expected Results: For linearity studies, a calculated "expected result" based on dilution served as the ground truth.
• Defined Concentrations: For precision and detection limit studies, defined concentrations of IgE (or blank samples) were used as a reference.

8. The Sample Size for the Training Set

• The document does not explicitly mention a "training set" in the context of device development or machine learning. This is an IVD assay, not an AI/ML device that typically involves a separate training phase with a distinct dataset. The performance data presented are for validation and verification of the device's analytical and clinical performance.

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

• As a "training set" is not explicitly described or applicable in the AI/ML sense for this type of IVD, this question is not directly answered by the document. The "ground truth" used in the various performance studies (as described in point 7) was established through clinical diagnosis, reference methods, or known sample characteristics.

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The NOVEOS Specific IgE Assay is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum. NOVEOS Specific IgE Assay is to be used with the NOVEOS Immunoassay Analyzer. It is intended for use as an in vitro diagnostic aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings and is to be used in clinical laboratories.

The NOVEOS Specific IgE Assay is an immunometric, chemiluminescent procedure for the quantitative determination of IgE of known specificity in human serum samples. It employs fluorescent labelled magnetic, streptavidin coated microparticles which are incubated with a biotinylated allergenic capture reagent, patient sample and monoclonal anti-human IgE antibody: horseradish peroxidase conjugate. If present in the sample, IgE binds to the biotinylated allergen captured to the streptavidin-coated microparticles to form a complex. After a final wash, the resulting complex is incubated with the enzyme substrate and a chemiluminescent signal is generated, the magnitude of which is proportional to the concentration of IgE in the patient sample.

The concentration of allergen-specific IgE is determined from a standard curve, which is traceable to the World Health Organization (WHO) reference reagent serum Immunoglobulin E (IgE) 11/234.

Here's a breakdown of the acceptance criteria and the study information for the NOVEOS Specific IgE (sIgE) Assay, Capture Reagent M006, Alternaria alternata, based on the provided text:

Acceptance Criteria and Reported Device Performance

Study Information

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

• Clinical Performance Comparison to ImmunoCAP:

  • Sample Size: 257 samples
  • Data Provenance: Not explicitly stated (e.g., country of origin), but implies laboratory testing of human serum samples. The study is presented as part of a 510(k) submission, typically indicating data relevant for regulatory approval.
  • Retrospective/Prospective: Not explicitly stated.

• Clinical Performance (vs. Clinical Diagnosis):

  • Sample Size: 182 patients (65 with allergic status confirmed by skin-prick testing and clinical history, 117 from healthy, non-atopic donors).
  • Data Provenance: Not explicitly stated (e.g., country of origin).
  • Retrospective/Prospective: Not explicitly stated.

• Precision/Reproducibility:

  • Sample Size: Six samples (1 negative, 3 positive patient samples, 2 controls), each assayed for 80 replicates total (2 runs/day for 20 days, duplicate replicates).
  • Data Provenance: Not explicitly stated.
  • Retrospective/Prospective: Not explicitly stated, likely prospective laboratory testing.

• Lot-to-Lot Imprecision:

  • Sample Size: Six samples, each assayed for 240 replicates total (3 different lots, 2 replicates/run, 2 runs/day for 20 days).
  • Data Provenance: Not explicitly stated.
  • Retrospective/Prospective: Not explicitly stated, likely prospective laboratory testing.

• Site-to-Site Reproducibility:

  • Sample Size: 6 samples (4 patient pools and 2 controls), each tested for 75 replicates total (5 replicates/run, 1 run/day for 5 days, across 3 sites).
  • Data Provenance: Not explicitly stated.
  • Retrospective/Prospective: Not explicitly stated, likely prospective laboratory testing.

• Linearity:

  • Sample Size: Dilutions of M006 specific IgE samples with analyte concentrations from 0.17 to 41.9 kU/L. The number of individual samples/dilutions used for the regression is not explicitly stated, but the range is.
  • Data Provenance: Not explicitly stated.
  • Retrospective/Prospective: Not explicitly stated, likely prospective laboratory testing.

• Detection Limit (LoB, LoD, LoQ):

  • Sample Size: 60 replicates of analyte-free samples, 300 replicates of low IgE samples (for LoB/LoD). For LoQ, a panel of seven low analyte samples was assayed in 80 replicates total (replicates of two, 2 runs/day for 20 days).
  • Data Provenance: Not explicitly stated.
  • Retrospective/Prospective: Not explicitly stated, likely prospective laboratory testing.

• Reference Range:

  • Sample Size: 127 apparently healthy subjects.
  • Data Provenance: Not explicitly stated.
  • Retrospective/Prospective: Not explicitly stated.

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

• For the Clinical Performance vs. Clinical Diagnosis study: The allergic status of 65 samples was confirmed by "skin-prick testing and clinical history." This implies that the ground truth was established by medical professionals (allergy specialists, physicians) who conduct these tests and histories, but the number and specific qualifications of these experts are not mentioned.
• For other studies (e.g., ImmunoCAP comparison, precision, linearity), the ground truth is based on the performance of the predicate device, or established values in quality control materials, or analytical measurements, rather than expert interpretation of individual cases.

4. Adjudication method for the test set:

• For the Clinical Performance vs. Clinical Diagnosis study: The text states "allergic status was confirmed by skin-prick testing and clinical history." This suggests a consensus-based approach by the clinicians involved in the diagnosis, but no formal adjudication method (e.g., 2+1, 3+1) is described.
• For the ImmunoCAP comparison study, the "ground truth" is the result from the ImmunoCAP predicate device. No expert adjudication is applicable in this context.

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 MRMC comparative effectiveness study was done. This device is an in-vitro diagnostic (IVD) immunoassay for quantitative measurement of IgE, not an AI-powered image analysis or diagnostic assist device where human readers would be involved in interpreting results in combination with the device's output. The device produces quantitative values directly.

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

• Yes, this is a standalone device in the context of its intended use. The NOVEOS Specific IgE Assay, used with the NOVEOS Immunoassay Analyzer, is an automated system that "automatically generate results" for allergen-specific IgE levels. It directly provides a quantitative measurement. While the interpretation of these results for clinical diagnosis requires a trained clinician ("in conjunction with other clinical findings"), the device itself operates as a standalone analytical tool.

7. The type of ground truth used:

• Clinical Performance vs. ImmunoCAP: The ground truth was the results from the legally marketed predicate device (ImmunoCAP Specific IgE).
• Clinical Performance vs. Clinical Diagnosis: The ground truth was established by expert clinical diagnosis based on "skin-prick testing and clinical history."
• Precision/Reproducibility: The ground truth is inherent in the known values of controls and patient samples for measuring variability.
• Linearity/Detection Limits: The ground truth is based on analytically determined concentrations/dilutions of samples.
• Reference Range: The ground truth for healthy individuals was defined by testing samples from "apparently healthy subjects" to establish expected physiological levels.
• Interference/Cross-Reactivity/Competitive Inhibition: Ground truth derived from known concentrations of interfering substances or related/unrelated allergens to assess their impact on assay performance.

8. The sample size for the training set:

• The document describes performance studies for a diagnostic assay, not a machine learning algorithm that typically requires a large training set. Therefore, there is no "training set" in the sense of an ML model being trained on data. The studies and samples described are for validation and verification of the assay's analytical and clinical performance.

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

• As indicated in point 8, there isn't a "training set" in the conventional machine learning sense for this type of IVD immunoassay. The device's underlying principles are based on established immunometric and chemiluminescent assay technologies, not a data-driven learning algorithm. The "ground truth" for calibrators and controls used in the analytical process is established through rigorous laboratory methods, often traceable to international reference standards like the World Health Organization (WHO) reference reagent serum Immunoglobulin E (IgE) 11/234, as mentioned in the "Calibrator Traceability" section.

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The OPTIGEN® Allergen-Specific IgE Assay 12 Allergen Bundle A is an in vitro test for use in the semi-quantitative determination of circulating allergen specific IgE concentrations in human serum. OPTIGEN® Allergen-Specific IgE assays are meant to be included in panel tests to be used with the AP3600™ instrument. Each assay is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergenic disorders in conjunction with other clinical findings and are to be used in clinical laboratories.

The OPTIGEN® 12 Allergen Bundle A includes Almond (f20), Bermuda Grass (g2), Cashew (f207), Crab (f23), Hazelnut (Food) (f17), Oak, White (f7), Salmon (f41), Sesame Seed (f10), Shrimp (f24), Tuna (f40), and Walnut (Food) (f256).

Not Found

This document is a marketing authorization letter for a device, not a study report. It does not contain information about acceptance criteria or a study proving the device meets those criteria.

Therefore, I cannot provide the requested information. The document focuses on the regulatory clearance of a device based on its substantial equivalence to previously marketed devices, not on the presentation of performance data from a specific study against predefined acceptance criteria.

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The Aptiva Celiac Disease IgG Reagent is an immunoassay utilizing particle-based multi-analyte technology for the semiquantitative determination of anti-tissue transglutaminase IgG autoantibodies and anti-deamidated gliadin peptide IgG autoantibodies in human serum. The presence of these antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of celiac disease and dermatitis herpetiformis, particularly in patients with selective IgA deficiency.

The Aptiva Celiac Disease IgG Reagent is intended for use with the Inova Diagnostics Aptiva System.

The Aptiva Celiac Disease IgG reagent utilizes particle based multi-analyte technology (PMAT) in a cartridge format. Each analyte (tissue transglutaminase [tTG] and deamidated gliadin peptide [DGP]) in the Aptiva Celiac Disease IgG reagent is a solid phase immunoassay utilizing fluorescent microparticles. This technology allows each of the two analytes, along with a human IgG capture antibody (IgG Control Microparticle), to be coated onto three uniquely recognizable paramagnetic microparticles, which are combined into one tube.

The Aptiva instrument is a fully automated, random access analyzer. This platform is a closed system with continuous load and random-access capabilities that processes the samples, runs the reagent and reports results. It includes liquid handling hardware, optical module (OM), and integrated computer with proprietary software and touch screen user interface.

The two analyte microparticles, along with the control microparticle, are stored in the reagent cartridge under conditions that preserve the proteins in their reactive states. When the assay cartridge is ready to be used for the first time, the reagent tube seals are pierced using the cartridge lid. The reagent cartridge is then loaded onto the Aptiva instrument, where the microparticles are automatically rehydrated using buffer located within the cartridge.

A patient's serum is diluted 1:23 with Aptiva system rinse by the instrument in a disposable cuvette. A small amount of the diluted sample is combined with assay buffer and the microparticle suspension in a second cuvette, and mixed (final serum dilution: 1:230). This reaction cuvette is incubated for 9 ½ minutes at 37°C. The cuvette is then exposed to a small magnet that holds the microparticles in place. The liquid is aspirated, and the microparticles are resuspended as system rinse is added to the cuvette and the magnet is removed. This wash cycle is repeated one more time. During the third wash, no system rinse is added after the aspiration step. After the third wash, phycoerythrin conjugated polyclonal anti-human lgG (known as PE Tracer IgG) is added to the microparticles in the cuvette, and mixed. Again, the cuvette is incubated for 9 ½ minutes at 37℃. Three wash steps, as described above, are performed on the microparticles. Following the wash steps, the microparticles are transferred to the of the instrument, where a charge coupled device (CCD) camera takes multiple images in order to identify and count the three unique microparticle regions, as well as determine the amount of conjugate on the microparticles. The control microparticle, a third particle, coated with goat anti-human IgG, is included in the reagent in as a control to flag low concentrations of IgG the patient serum sample as an assay verification step. The median fluorescent intensity (MFI) is proportional to the amount of PE Tracer that is bound to the human IgG, which is proportional to the amount of IgG antibodies bound to the corresponding microparticle regions.

For quantitation, the DGP IgG and tTG IgG assays (together as part of the Aptiva Celiac Disease IgG Reagent) each utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge RFID tag. Every new lot of reagent cartridge must be calibrated before first use with the reagent specific calibrators. Based on the results obtained with the calibrators included in the Aptiva Celiac Disease IgG Calibrator kit (sold separately), an instrument specific Working Curve is created for each assay, which is used to calculate reported fluorescent light units (FLU) from the median fluorescent intensity (MFI) instrument signal obtained for each sample, on each of the two assays within the reagent.

Aptiva Celiac Disease IgG Calibrators and Aptiva Celiac Disease IgG Controls are sold separately.

The Aptiva Celiac Disease IgG Reagent kit contains the following materials:

One (1) Aptiva Celiac Disease IgG Reagent Cartridge, containing the following reagents for 200 determinations:

• a. Aptiva Celiac Disease IgG microparticle containing 3 unique microparticle regions coated with recombinant tissue transglutaminase, deamidated gliadin peptide, or goat antihuman IgG antibody.
• b. Assay buffer - colored pink, containing protein stabilizers and preservatives.
• C. PE Tracer IgG - phycoerythrin (PE) labeled anti-human IgG antibody, containing buffer, protein stabilizers and preservative.
• ð. Rehydration Buffer - containing protein stabilizers and preservatives.

This document describes the analytical and clinical performance of the Aptiva Celiac Disease IgG Reagent, an immunoassay for the semi-quantitative determination of anti-tissue transglutaminase IgG autoantibodies (tTG IgG) and anti-deamidated gliadin peptide IgG autoantibodies (DGP IgG) in human serum. This device is intended as an aid in the diagnosis of celiac disease and dermatitis herpetiformis.

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

1. Acceptance Criteria and Reported Device Performance

The document presents several analytical performance characteristics and their corresponding acceptance criteria, along with the reported performance values. The primary clinical acceptance criteria are related to sensitivity and specificity, and the agreement with a predicate device.

2. Sample Sizes and Data Provenance

• Test Set (Clinical Validation Set): A total of 515 characterized samples.
  • 171 samples from celiac disease patients.
  • 20 samples from patients with IgA deficient celiac disease.
  • 34 dermatitis herpetiformis patients.
  • 290 control samples from patients with various types of autoimmune and infectious diseases.
• Data Provenance: The document does not explicitly state the country of origin. Given it's an FDA submission, it's typically a mix of US and possibly international data, but this is not specified. The studies are retrospective as they use "characterized samples" from a "cohort."
• Precision and Reproducibility Studies: Between 75 to 80 replicates per sample for repeatability/precision and reproducibility studies. These numbers are for analytical performance, not clinical.
• LoB, LoD, LoQ: 120 data points were generated for each assay on each reagent lot for LoB and LoD studies. For LoQ, 120 data points per assay per reagent lot.
• Linearity: The number of dilutions and duplicates used is stated (e.g., 4 human serum samples for DGP IgG and 3 for tTG IgG serially diluted, assayed in duplicates).
• Interference: 3 human serum specimens (one positive, one near cut-off, one negative) were tested for each assay.
• Sample Stability: 6 samples for DGP IgG, 7 for tTG IgG (tested in duplicates).
• Reagent Stability: 3 lots of microparticle beads and 3 lots of PE Tracer IgG for accelerated stability. Real-time stability data from 2 different lots.
• Reference Range/Cut-off Establishment:
  • Reference Population: 192 subjects from various autoimmune/infectious disease groups (e.g., Crohn's Disease, Autoimmune Thyroid Disease, Rheumatoid Arthritis).
  • Celiac Disease Patients: 11 diagnosed celiac disease (CD) patient specimens were assayed to aid in cut-off determination.
  • Apparently Healthy Donors (Expected Values): 120 blood donors.

3. Number of Experts and Qualifications

• The document does not mention the number of experts used to establish the ground truth for the test set, nor their specific qualifications. It refers to "characterized samples" and "diagnosed celiac disease (CD) patient specimens," implying a pre-existing clinical diagnosis, but the process of how these characterizations were definitively made (e.g., biopsy confirmation, clinical consensus, expert review) is not detailed for the test set.

4. Adjudication Method

• The document does not describe any specific adjudication method for the test set. The samples are described as "characterized," suggesting that their disease status was already established prior to their use in the study, likely through standard clinical diagnostic procedures, but no expert review or consensus process for this specific study's set is detailed.

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

• Not Applicable. This is an in-vitro diagnostic (IVD) device, specifically an immunoassay for determining autoantibodies in serum. MRMC studies are typically performed for imaging diagnostic devices (e.g., AI for radiology) where human readers (e.g., radiologists) interpret images with and without AI assistance. This document describes the performance of a lab test that outputs a quantitative result (FLU) and a qualitative interpretation (positive/negative) and does not involve human interpretation of complex data in the same way an imaging AI device would.

6. Standalone Performance

• Yes, standalone performance was done. The entire study report describes the standalone performance of the Aptiva Celiac Disease IgG Reagent without human intervention beyond performing the test and interpreting the quantitative results per the device's defined cut-offs. The sensitivity, specificity, and agreement with predicate devices are measures of its standalone performance.

7. Type of Ground Truth Used

• The ground truth for the clinical validation was based on clinical diagnosis/characterization of the patient samples.
  • For celiac disease and dermatitis herpetiformis patients, they were "diagnosed" or "characterized." While not explicitly stated, the gold standard for celiac disease diagnosis usually involves intestinal biopsy with characteristic changes, alongside clinical symptoms and serology.
  • For the control group, patients were characterized with "various types of autoimmune and infectious diseases," implying a clinical diagnosis for these conditions to confirm they are not celiac disease.
  • For the cut-off determination, "diagnosed celiac disease (CD) patient specimens" were used in conjunction with a reference population.

8. Sample Size for the Training Set

• The document does not specify a separate "training set" in the context of an AI/machine learning model. This device is an immunoassay, which relies on chemical reactions and optical detection, not on a machine learning algorithm trained on large datasets in the conventional sense. The "training" in this context refers to the development and optimization of the assay's reagents and parameters, and the establishment of master curves and cut-offs. The data used for calibration and master curve generation (e.g., "in-house Master Curve Standards with assigned FLU values run multiple times," "Calibrators included in the Aptiva Celiac Disease IgG Calibrator kit") effectively serve a similar purpose to training/calibration data in general analytical chemistry.

9. How Ground Truth for Training Set was Established

• Given this is an immunoassay, the concept of "ground truth" for a training set (as defined for AI/ML) is not directly applicable. Instead, the assay's performance and "ground truth" are established through:
  • Calibration: Using Master Curve Standards with "assigned FLU values" (likely determined through extensive in-house characterization and reference methods).
  • Controls: Using Aptiva Celiac Disease IgG Controls with "lot specific values assigned."
  • Reference Materials: The development of the assay's antigens (recombinant tTG and deamidated gliadin peptide) and antibodies would have involved rigorous characterization against known reference materials and clinical samples during the assay development stages to ensure they correctly bind to their target autoantibodies.
  • Cut-off determination: As mentioned in point 7, this involved a reference population of 192 subjects and 11 diagnosed celiac disease patients to establish the 5.00 FLU cut-off.

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The Aptiva Celiac Disease IgA Reagent is an immunoassay utilizing particle-based multi-analyte technology for the semiquantitative determination of anti-tissue transglutaminase IgA autoantibodies and anti-deamidated gliadin peptide IgA autoantibodies in human serum. The presence of these autoantibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of celiac disease and dermatitis herpetiformis. The Aptiva Celiac Disease IgA Reagent is intended for use with the Inova Diagnostics Aptiva System.

The Aptiva Celiac Disease IgA reagent utilizes particle based multi-analyte technology (PMAT) in a cartridge format. Each analyte (tissue transglutaminase [tTG] and deamidated gliadin peptide [DGP]) in the Aptiva Celiac Disease IgA reagent is a solid phase immunoassay utilizing fluorescent microparticles. This technology allows each of the two analytes, along with a human IgA capture antibody (IgA Control Microparticle), to be coated onto three uniquely recognizable paramagnetic microparticles, which are combined into one tube.

The Aptiva instrument is a fully automated, random access analyzer. This platform is a closed system with continuous load and random-access capabilities that processes the samples, runs the reagent and reports results. It includes liquid handling hardware, optical module (OM), and integrated computer with proprietary software and touch screen user interface.

The two analyte microparticles, along with the control microparticle, are stored in the reagent cartridge under conditions that preserve the proteins in their reactive states. When the assay cartridge is ready to be used for the first time, the reagent tube seals are pierced using the cartridge lid. The reagent cartridge is then loaded onto the Aptiva instrument, where the microparticles are automatically rehydrated using buffer located within the cartridge.

A patient's serum is diluted 1:46 with Aptiva system rinse by the instrument in a disposable cuvette. A small amount of the diluted sample is combined with assay buffer and the microparticle suspension in a second cuvette, and mixed (final serum dilution: 1:230). This reaction cuvette is incubated for 9 ½ minutes at 37°C. The cuvette is then exposed to a small magnet that holds the microparticles in place. The liquid is aspirated, and the microparticles are resuspended as system rinse is added to the cuvette and the magnet is removed. This wash cycle is repeated one more time. During the third wash, no system rinse is added after the aspiration step. After the third wash, phycoerythrin conjugated polyclonal anti-human IgA (known as PE Tracer IgA) is added to the microparticles in the cuvette, and mixed. Again, the cuvette is incubated for 9 ½ minutes at 37℃. Three wash steps, as described above, are performed on the microparticles. Following the wash steps, the microparticles are transferred to the of the instrument, where a charge coupled device (CCD) camera takes multiple images in order to identify and count the three unique microparticle regions, as well as determine the amount of conjugate on the microparticles. A third particle, coated with goat antibodies, is present in the reagent as a control to flag low concentrations of IgA in the sample as an assay verification step. The median fluorescent intensity (MFI) is proportional to the amount of PE Tracer that is bound to the human IgA, which is proportional to the amount of IgA antibodies bound to the corresponding microparticle regions.

For quantitation, the DGP IgA and tTG IgA assays (together as part of the Aptiva Celiac Disease IgA Reagent) each utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge RFID tag. Every new lot of reagent cartridge must be calibrated before first use with the reagent specific calibrators. Based on the results obtained with the calibrators included in the Aptiva Celiac Disease IgA Calibrator kit (sold separately), an instrument specific Working Curve is created for each assay, which is used to calculate reported fluorescent light units (FLU) from the median fluorescent intensity (MFI) instrument signal obtained for each sample, on each of the two assays within the reagent.

Aptiva Celiac Disease IgA Calibrators and Aptiva Celiac Disease IgA Controls are sold separately.

The Aptiva Celiac Disease IgA Reagent kit contains the following materials:

One (1) Aptiva Celiac Disease IgA Reagent Cartridge, containing the following reagents for 250 determinations:

• a. Aptiva Celiac IgA microparticle containing 3 unique microparticle regions coated with recombinant tissue transglutaminase, deamidated gliadin peptide, or goat anti-human IgA antibody.
• b. Assay buffer - colored pink, containing protein stabilizers and preservatives.
• PE Tracer IgA phycoerythrin (PE) labeled anti-human IgA antibody, containing buffer, C. protein stabilizers and preservative.
• d. Rehydration Buffer - containing protein stabilizers and preservatives.

The provided text is a 510(k) Summary for the Aptiva Celiac Disease IgA Reagent, an in vitro diagnostic device. It describes the analytical and clinical performance of the device to demonstrate its substantial equivalence to predicate devices. It does not describe an AI/ML-based device, a comparative effectiveness study with human readers, or the establishment of ground truth by expert consensus. Therefore, most of the requested information cannot be extracted from this document as it pertains to AI/ML device studies.

However, I can extract the acceptance criteria and reported performance for analytical aspects of this specific in vitro diagnostic device, as well as details regarding sample size, data provenance, and the type of ground truth used for performance evaluation.

Acceptance Criteria and Reported Device Performance

The device under review is an in vitro diagnostic (IVD) test, not an AI/ML-based medical imaging device. As such, the acceptance criteria and performance evaluation are based on typical analytical validation parameters for immunological assays, such as precision, limit of detection, linearity, interference, and clinical sensitivity/specificity against established reference methods or patient diagnoses.

Table of Acceptance Criteria and Reported Device Performance:

Study Details:

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

   • Precision: 9 samples for DGP IgA, 10 samples for tTG IgA (run in duplicates, twice a day, for 20 days).
   • Reproducibility (Between Sites): 7 samples for DGP IgA and 6 samples for tTG IgA.
   • Reproducibility (Between Lots): 6 samples for DGP IgA and 6 samples for tTG IgA.
   • LoB, LoD, LoQ:
     • LoB: 8 blank samples. For each assay (DGP IgA & tTG IgA), on two reagent lots, run in replicates of 5, once per day for 3 days (120 data points per lot).
     • LoD & LoQ: 4 low-level samples for each assay (DGP IgA & tTG IgA). For each assay, on two reagent lots, run in replicates of 5, twice per day for 3 days (120 data points per assay per lot).
   • Linearity: 4 human serum samples for each assay, serially diluted and assayed in duplicates.
   • Interference: 3 human serum specimens (one positive, one near cutoff, one negative).
   • Sample Stability: 8 test samples for DGP IgA, 6 test samples for tTG IgA.
   • Clinical Performance (Validation Set): A total of 495 characterized samples.
     • 171 samples from celiac disease patients.
     • 34 dermatitis herpetiformis patients.
     • 290 control samples from patients with various types of autoimmune and infectious diseases (e.g., Rheumatoid Arthritis, Ulcerative Colitis, Crohn's Disease, Hepatitis C/B, Syphilis, Sjögren's Syndrome, Systemic Sclerosis, Autoimmune Gastritis, HIV, Systemic Lupus Erythematosus, Epstein-Barr Virus).
     • The document does not explicitly state the country of origin but implies data collection from clinical settings. It describes the use of "characterized samples" and "diagnosed celiac disease (CD) patient specimens," indicating that this was likely a retrospective collection of samples with established diagnoses.
   • Expected Values (Normal Population): 120 apparently healthy blood donors.
   • Method Comparison: All 495 samples from the clinical validation study were also used for method comparison against the predicate devices.

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

   • This is an IVD device, not an AI/ML imaging device. The "ground truth" for the test set (clinical validation cohort) was based on patient diagnoses (e.g., "celiac disease patients," "dermatitis herpetiformis," "control samples from patients with various types of autoimmune and infectious diseases"). Therefore, the ground truth was established by clinical diagnosis, which would typically be made by medical doctors/specialists based on relevant clinical findings and other laboratory tests, rather than by a specific number of experts reviewing image data. The document does not specify the number or qualifications of clinicians involved in establishing these diagnoses.

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

   • Not applicable, as this is an IVD test assessing biochemical markers, not an imaging device requiring expert adjudication of interpretations. The "ground truth" is the established clinical diagnosis of the patient.

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 not an AI/ML imaging device, and no MRMC study was performed or is relevant to this type of IVD test.

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

   • The "standalone performance" of this device is represented by its analytical performance characteristics (precision, linearity, LoD, etc.) and its clinical sensitivity and specificity, where the device provides a quantitative result (FLU) to aid in diagnosis. There is no "human-in-the-loop" aspect to the performance of the device itself (it's an automated analyzer), though clinicians interpret its results in conjunction with other clinical findings.

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

   • The primary ground truth for the clinical performance evaluation was established clinical diagnoses of patients ("celiac disease patients," "dermatitis herpetiformis patients," and "control samples from patients with various types of autoimmune and infectious diseases"). This implicitly relies on a combination of clinical findings, potentially other laboratory tests, and possibly biopsy results (pathology) for definitive diagnoses like celiac disease. The document states, "The presence of these autoantibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of celiac disease and dermatitis herpetiformis."

7. The sample size for the training set:

   • This device is an immunoassay (particle-based multi-analyte technology) operating on predefined Master Curves and calibrations. It does not use a "training set" in the sense of machine learning algorithms. The Master Curves and calibrations are established by the manufacturer through runs of precisely quantified standards (e.g., "in-house Master Curve Standards," "reagent specific calibrators"). The section "Quantitation and units of measure" describes how these curves are generated. For example, "Aptiva Celiac Disease IgA Master Curve Standards - DGP IgA" lists 6 standards with assigned FLU values. While these could be seen as "training data" for the device's internal quantitation function, it's not a machine learning model.

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

   • Not applicable in an AI/ML context. For this IVD device, the "ground truth" for its internal calibration (analogous to a training set for an AI model) is based on manufacturer-defined standards with assigned known values ("in-house Master Curve Standards with assigned FLU values"). These standards are run multiple times to generate the 4-parameter logistic (4PL) curve that quantifies the analyte concentration.

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The NOVEOS Specific IgE Assay is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum. NOVEOS Specific IgE Assay is to be used with the NOVEOS Immunoassay Analyzer. It is intended for use as an in vitro diagnostic aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings and is to be used in clinical laboratories.

The NOVEOS Specific IgE Assay is an immunometric, chemilyminescent procedure for the quantitative determination of IgE of known specificity in human serum samples. It employs fluorescent labelled magnetic, streptavidin coated microparticles which are incubated with a biotinylated allergenic capture reagent, patient sample and monoclonal anti-human IgE antibody: horseradish peroxidase conjugate. After a final wash, the resulting complex is incubated with the enzyme substrate and a chemiluminescent signal is generated, the magnitude of which is proportional to the concentration of IgE in the patient sample. The concentration of allergen-specific IgE is determined from a standard curve, which is traceable to the World Health Organization (WHO) reference reagent serum Immunoglobulin E (IqE) 11/234.

This document describes the validation of the NOVEOS Specific IgE (sIgE) assays for Cat Dander (E001, Felis domesticus) and Timothy Grass (G006, Phleum pratense). This is a quantitative in vitro diagnostic device, not an AI/ML powered device. Therefore, many of the typical acceptance criteria for AI models, such as MRMC studies, ground truth establishment by experts, and training set details, are not applicable.

The acceptance criteria for this device are based on its analytical and clinical performance when compared to a legally marketed predicate device (ImmunoCAP Specific IgE Assay) and clinical diagnosis.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the performance metrics reported and the statistical analysis acceptable for FDA clearance of an in vitro diagnostic device of this type. The key performance indicators for a quantitative assay would typically include linearity, precision (imprecision/reproducibility), agreement with a predicate device, and clinical concordance (sensitivity and specificity).

Performance Table for NOVEOS Specific IgE (sIgE) Assays

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

The document describes several test sets for different performance evaluations.

• Agreement with Predicate Device (Comparative Study):
  • E001: 242 clinical samples.
  • G006: 238 clinical samples.
  • Data Provenance: The document does not explicitly state the country of origin. It refers to "clinical samples" and "patient samples" without further geographical details. The studies are assumed to be retrospective as they involve collecting and testing existing clinical samples.
• Clinical Performance Study:
  • E001: 200 samples (70 samples with allergic status confirmed by skin-prick testing and clinical history, and 130 samples from healthy, non-atopic donors with no reported allergy).
  • G006: 188 samples (63 samples with allergic status confirmed by skin-prick testing and clinical history, and 125 samples from healthy, non-atopic donors with no reported allergy).
  • Data Provenance: Similar to the predicate comparison, the country of origin is not specified, and the studies appear to be retrospective.
• Reference Range Verification:
  • E001: 132 apparently healthy subjects.
  • G006: 127 apparently healthy subjects.

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

For this type of in vitro diagnostic device, "experts" in the context of AI models (e.g., radiologists interpreting images) are not directly applicable.

• For Agreement with Predicate: The ground truth is the result obtained from the predicate device (ImmunoCAP Specific IgE Assay), which is a previously FDA-cleared and legally marketed device.
• For Clinical Performance: The ground truth for the clinical study was established by "skin-prick testing and clinical history". This implies that clinical professionals (e.g., allergists, physicians) made the diagnosis of "allergic status" or "non-atopic" based on standard medical procedures and patient history, rather than experts reviewing data specifically for the study.

The number and qualifications of these clinical professionals are not specified in the document, as it's a standard clinical diagnostic process rather than a specific panel of experts assembled for ground truth annotation.

4. Adjudication Method for the Test Set

Adjudication methods like 2+1 or 3+1 are typically used for subjective assessments (e.g., image interpretation by multiple human readers). For this quantitative in vitro diagnostic device:

• For Agreement with Predicate: There is no specific "adjudication" in the sense of reconciling differing expert opinions. The comparison is directly between the quantitative results of the new device and the predicate device.
• For Clinical Performance: The "allergic status" or "non-atopic" ground truth was established by clinical diagnosis (skin-prick testing and clinical history). While clinical diagnosis often involves physician judgment, the document does not describe a formal multi-reader adjudication process; it refers to the standard clinical standard of care.

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

No, an MRMC comparative effectiveness study was not done. This is an in vitro diagnostic assay (a laboratory test) that measures a biomarker (specific IgE) in human serum. It is not an AI-powered image analysis device or a device that directly assists human readers in interpreting complex visual data. Therefore, the concept of human readers improving with AI assistance is not applicable.

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

Yes, the primary performance evaluation of this device is standalone. The NOVEOS Specific IgE assay is an automated in vitro diagnostic test performed on the NOVEOS Immunoassay Analyzer. Its performance (quantitative measurement of IgE) is assessed directly through analytical studies (linearity, imprecision, detection limits, interference, cross-reactivity) and comparison to a predicate device/clinical diagnosis, without human intervention in the measurement process itself. The result is a quantitative value used by clinicians in conjunction with other findings.

7. The Type of Ground Truth Used

• For Agreement with Predicate: The ground truth was based on the results obtained from the legally marketed predicate device (ImmunoCAP Specific IgE Assay). This is a common approach for establishing substantial equivalence for new IVD assays.
• For Clinical Performance: The ground truth for allergic status was established by clinical diagnosis, specifically "skin-prick testing and clinical history." This is considered an objective clinical standard for diagnosing allergic disorders.

8. The Sample Size for the Training Set

This document describes the validation of an immunoassay, not an AI/ML model that requires "training sets" in the conventional sense. The device is a chemical/biological assay system. Therefore, there is no "training set" in the context of machine learning.

The studies described are for validation/testing of the already developed assay.

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

As stated above, there is no "training set" for an AI/ML model for this type of device. The assay's "performance characteristics" (e.g., reagent formulations, assay parameters) would have been optimized during the device development phase, which is an engineering/chemistry process, not an AI model training process that uses labeled ground truth data.

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ImmunoCAP Allergen o215, Component nGal-alpha-1,3-Gal (alpha-Gal) Thyroglobulin, bovine, is intended for in vitro diagnostic use, in human serum or EDTA plasma, as an aid in the diagnosis of IgE mediated mammalian (red) meat hypersensitivity, due to alpha-Gal sensitization, and to be used in conjunction with other clinical findings. This test is not to be the sole criterion for diagnosing allergy to alpha-Gal. It is a quantitative test to be used in clinical laboratories. ImmunoCAP Allergen 0215, alpha-Gal is to be used with the ImmunoCAP Specific IgE assay on the instrument Phadia™ 250.

ImmunoCAP Allergen o215, Component nGal-alpha-1,3-Gal (alpha-Gal) Thyroglobulin, bovine, is a component of, and is designed to be used with, the ImmunoCAP Specific IgE assay, previously cleared under K051218. The test has the same overall design as all other ImmunoCAP Allergen components and uses identical assay and system specific reagents, instruments and software.

This document describes the performance characteristics and acceptance criteria for the ImmunoCAP Allergen o215, Component nGal-alpha-1,3-Gal (alpha-Gal) Thyroglobulin, bovine test, which is intended to aid in the diagnosis of IgE mediated mammalian (red) meat hypersensitivity.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document describes both analytical and clinical performance studies, but directly states acceptance criteria only for analytical performance implicitly through the successful completion of the studies. For clinical performance, it discusses the study design and patient numbers, from which performance can be inferred.

Analytical Performance Characteristics:
The document states that analytical performance characteristics were established by studies of:

• Precision
• Lot-to-Lot Reproducibility
• Linearity
• Limit of Quantitation
• Sample Matrix Equivalency
• Interference
• Inhibition
• Stability

While specific numerical acceptance criteria for each of these analytical characteristics are not explicitly listed in the provided text, the overall conclusion is that the device's analytical performance was verified and supports its substantial equivalence. The document concludes: "Analytical performance characteristics for the new ImmunoCAP Allergen Components were established by studies of Precision, Lot-to-Lot Reproducibility, Linearity, Limit of Quantitation, Sample Matrix equivalency, Interference, Inhibition and Stability." This implies that the device met the pre-defined acceptance criteria for these analytical aspects.

Clinical Performance Characteristics:
For clinical performance, a retrospective study was conducted. The document does not explicitly present a table of acceptance criteria (e.g., minimum sensitivity, specificity) against which the device's performance was measured for clinical use. Instead, it describes the study design, and the implied acceptance is that the device demonstrated sufficient performance to be considered an "aid in the diagnosis."

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

• Test Set Sample Size: The clinical performance was evaluated using samples from 200 subjects with a case history of mammalian meat hypersensitivity (cases) and 110 control subjects.
• Data Provenance: The study was a retrospective study. The country of origin of the data is not specified in the provided text.

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

The document does not specify the number of experts used to establish the ground truth for the test set, nor does it detail their specific qualifications (e.g., "radiologist with 10 years of experience"). It mentions that the 200 subjects had a "case history of mammalian meat hypersensitivity," implying that their status was established through clinical diagnosis, likely by medical professionals.

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) used for establishing the ground truth for the test set.

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

No MRMC comparative effectiveness study was reported in which human readers' improvement with AI vs. without AI assistance was assessed. This device is an in-vitro diagnostic assay, not an AI-assisted imaging device, so such a study would not be applicable.

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

This device is an in-vitro diagnostic test kit that provides quantitative measurements of IgE antibodies. Its performance, as described, is inherently "standalone" in the sense that the test itself generates a result without direct human interpretation influencing the measurement, though human interpretation is required for the final diagnostic aid. The "performance characteristics" detailed refer to the analytical and clinical performance of the assay itself, which is analogous to a standalone performance evaluation in the context of an IVD.

7. Type of Ground Truth Used

The ground truth for the clinical study was based on a "case history of mammalian meat hypersensitivity" for the 200 subjects and "control subjects" for the 110 individuals. This suggests that the ground truth was established by clinical diagnosis and patient history, rather than a specific expert consensus on images, pathology, or outcomes data from a prospective study directly.

8. Sample Size for the Training Set

The document does not mention a separate "training set" or its sample size. This is typical for an IVD assay, where performance is established through validation studies rather than machine learning model training. The development process for such an assay would involve internal development and optimization, but not typically in the sense of a machine learning training set with a distinct ground truth establishment process as described for AI models.

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

Since no distinct "training set" is mentioned in the context of this device's validation, the method for establishing its ground truth is not applicable. The development of an IVD assay involves extensive R&D, but the concept of "ground truth for a training set" usually applies to machine learning algorithms.

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The NOVEOS Specific IgE Assay is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum. NOVEOS Specific IgE Assay is to be used with the NOVEOS Immunoassay Analyzer. It is intended for use as an in vitro diagnostic aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings and is to be used in clinical laboratories.

The NOVEOS™ Specific IgE Assay is an immunometric, chemiluminescent procedure for the quantitative determination of IgE of known specificity in human serum samples. It employs fluorescent labelled magnetic, streptavidin coated microparticles which are incubated with a biotinylated allergenic capture reagent, patient sample and monoclonal anti-human IgE antibody: horseradish peroxidase conjugate. After a final wash, the resulting complex is incubated with the enzyme substrate and a chemiluminescent signal is generated, the magnitude of which is proportional to the concentration of IgE in the patient sample.

The provided document describes the analytical and clinical performance of the NOVEOS Specific IgE (sIgE) Assay for Dermatophagoides farinae (D002), an in vitro diagnostic device. It does not describe a study involving human readers assisting with AI, but rather a laboratory-based immunoassay. Therefore, information related to "Number of experts used to establish the ground truth for the test set," "Adjudication method," and "MRMC comparative effectiveness study" is not applicable for this type of device and study.

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

1. Table of Acceptance Criteria and Reported Device Performance

Since this is an in vitro diagnostic assay, typical acceptance criteria would involve analytical performance metrics like accuracy (compared to a predicate or clinical diagnosis), precision (reproducibility), linearity, detection limits, and interference. The document presents these results rather than explicit "acceptance criteria" tables. However, we can infer the implicit criteria from the reported data.

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

• Accuracy (vs. Predicate): 234 samples (including 97 skin prick test positive samples). The provenance of these samples (country of origin, retrospective/prospective) is not explicitly stated, but they are implied to be clinical samples used for comparison.
• Clinical Performance: 187 samples (75 with allergic status confirmed by skin-prick testing and clinical history, 112 from healthy, non-atopic donors with no reported allergy). The provenance is not explicitly stated.
• Imprecision/Reproducibility:
  • Repeatability and within-laboratory precision: Samples assayed in duplicate in 2 runs per day for 20 days on 3 NOVEOS Immunoassay Analyzers (total of 80 replicates per sample evaluated for 7 different samples/controls).
  • Lot-to-lot imprecision: 8 serum samples (3 negative, 5 positive) tested in 2 replicates per run, 2 runs per day for 20 days (total of 240 replicates per sample) using 3 different reagent lots.
  • Site-to-site reproducibility: 4 patient pools and 2 controls tested in 5 replicates per run, 1 run per day for 5 days on 1 analyzer at each of 3 sites (total of 75 replicates per sample).
• Linearity: Samples with IgE concentrations from 0.04 to 126 kU/L were used. Number of distinct samples or dilution points not specified, but the range is.
• Interference & Cross-Reactivity: Not directly stated, but typically involves a panel of samples spiked with interfering substances or related analytes.
• Detection Limit: 90 replicates of analyte-free samples and 300 replicates of low IgE samples for LoB/LoD. For LoQ, low analyte samples assayed in replicates of five in 2 runs per day for 5 days (50 replicates total).
• Reference Range: 128 apparently healthy subjects.

The studies are described as analytical and clinical performance studies, implying they are a form of prospective data collection for regulatory submission. The country of origin for the data is not specified.

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

Not applicable for this in vitro diagnostic assay. The ground truth for clinical performance was established by "skin-prick testing and clinical history" for allergic status and "healthy, non-atopic donors with no reported allergy" for non-allergic status. These data are typically generated by allergists or clinicians, but the number and qualifications of those individuals are not specified.

4. Adjudication Method for the Test Set

Not applicable. This is not an image-based diagnosis or a study requiring human readers to adjudicate results. The device's results are quantitative and compared against established methods or clinical status.

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

No, this was not an MRMC study. This device is an automated laboratory immunoassay for quantitative measurement of IgE, not an AI assisting human readers with interpreting images or other data. Therefore, the concept of "effect size of how much human readers improve with AI vs. without AI assistance" is not relevant here.

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

Yes, the studies presented are all standalone performance evaluations of the NOVEOS Specific IgE Assay system. It is an automated in vitro diagnostic device, and its performance is assessed intrinsically, independent of human interpretive assistance during the measurement process. Human involvement occurs in sample collection and result interpretation in clinical context, but not in assisting the device's measurement.

7. The Type of Ground Truth Used

• For Accuracy (vs. Predicate): The "ground truth" was established by comparison with a legally marketed predicate device (ImmunoCAP d2) using a consistent cutoff value (0.35 kU/L).
• For Clinical Performance: The "ground truth" for allergic status was based on clinical diagnosis confirmed by skin-prick testing and clinical history for the allergic group, and "healthy, non-atopic donors with no reported allergy" for the non-atopic group. This represents a form of outcomes data/clinical findings consensus.
• For Analytical Performance (Precision, Linearity, Detection Limits, Interference, Cross-Reactivity): Ground truth is typically established by reference methods, gravimetric dilutions, or known concentrations of analytes/interferents. These are standard laboratory practices for validating assay performance.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of an machine learning or AI algorithm. This device is a quantitative immunoassay, not a machine learning model that needs training on data in the same way. Its parameters and calibration are established through standard assay development and validation protocols, which involve titrations, optimization, and establishment of calibration curves during the manufacturing process.

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

As explained above, the concept of a "training set" and associated "ground truth" for an AI model is not directly applicable to this traditional immunoassay device. The device's operational characteristics (e.g., calibration curve, reagent concentrations, reaction times) are determined through laboratory development and optimization, rather than machine learning training on a distinct dataset with "ground truth labels". The reference standard used for calibration is the "World Health Organization (WHO) reference reagent serum Immunoglobulin E (IgE) 11/234," which serves as the traceability standard for quantitative measurements.

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ImmunoCAP Specific IgE Assay is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum or plasma (EDTA or Na-Heparin). It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings, and is to be used in clinical laboratories. ImmunoCAP Specific IgE is to be used with the instrument Phadia 250, Phadia 1000, Phadia 2500 and Phadia 5000.

ImmunoCAP Specific IgE reagents are modular in concept and are available individually. For a complete listing of reagents needed to perform the Phadia ImmunoCAP Specific IgE assay, please consult the ImmunoCAP Specific IgE Conjugate Directions for Use.

Phadia 100, Phadia 250, Phadia 2500 and Phadia 5000 instrument systems, associated software, processes all steps of the assay and calculates results and a automatically after the assay is completed.

The allergen of interest, covalently coupled to ImmunoCAP, reacts with the specific IgE in the patient sample. After washing away non-specific IgE, enzyme labeled antibodies against IgE are added to form a complex. After incubation, unbound enzyme-anti-IgE is washed away and the bound complex is then incubated with a developing agent. After stopping the reaction, the fluorescence of the eluate is measured. The higher the response value, the more specific IgE is present in the specimen. To evaluate the test results, the responses for the patient samples are transformed to concentrations with the use of a calibration curve.

The provided text describes a 510(k) submission for new ImmunoCAP Allergen Components (rCan f 4 Dog, rCan f 6 Dog, rFel d 7 Cat) to an existing ImmunoCAP Specific IgE assay system. While it mentions performance characteristics studies, it does not provide a specific table of acceptance criteria or reported device performance for these new components. It primarily focuses on the regulatory submission and overall claims of performance.

However, based on the provided text, I can infer and summarize what information is available and what is missing regarding acceptance criteria and the study.

1. Table of Acceptance Criteria and Reported Device Performance

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

• Sample Size: The exact sample size for the "clinical positive samples" and "samples from healthy, nonatopic donors" is not provided.
• Data Provenance: The country of origin is not provided. The studies appear to be retrospective in nature, as they involve testing existing samples.

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

This type of information is not provided in the document. For immunoassays, ground truth is typically established by the clinical status of the patient (e.g., diagnosed allergy, physician assessment, other valid allergy tests) rather than expert review of images.

4. Adjudication method for the test set

This information is not applicable as it pertains to expert review of diagnostic results, which is not described for this type of immunoassay. The ground truth would be based on the clinical diagnosis or 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

• MRMC Study: This is not applicable. The device is an in vitro diagnostic immunoassay, 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

• Standalone Performance: The described studies (Precision, Reproducibility, Linearity, LOD, Stability, Clinical Comparison) all represent the standalone performance of the immunoassay system (device and instrument). There is no "human-in-the-loop" component for interpretation described beyond the overall clinical context for diagnosis.

7. The type of ground truth used

The ground truth for the clinical studies appears to be based on:

• Clinical Status: "clinical positive samples" imply patients with a diagnosed IgE-mediated allergic disorder related to the specific allergens.
• Absence of Allergy: "healthy, nonatopic donors" implies individuals without (or assumed to be without) IgE-mediated allergic disorders.
• Predicate Device Comparison: The new components were compared against an "extract based predicate device," which itself serves as a reference standard, implying its results are also part of the ground truth or a comparator for performance.

8. The sample size for the training set

This information is not applicable as the device is an immunoassay kit, not a machine learning or AI algorithm that requires a separate training set.

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

This information is not applicable for the same reason as above.

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