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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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EliA Celikey IgG is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to tissue transglutaminase (tTG) in human serum and EDTA-plasma. EliA Celikey IgG is based on recombinant human tissue transglutaminase as antigen and is useful as an aid in the clinical diagnosis of patients with celiac disease in conjunction with other laboratory and clinical findings. EliA Celikey IgG uses the EliA IgG method on the instrument Phadia 2500/5000.

EliA GliadinDP IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to gliadin in human serum or plasma (Li-heparin, EDTA) to aid in the diagnosis of celiac disease in conjunction with other laboratory and clinical findings. EliA GliadinDP IgA uses the EliA IgA method on the instrument Phadia 2500/5000.

EliA GliadinDP IgG is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to gliadin in human serum or plasma (Li-heparin, EDTA) to aid in the diagnosis of celiac disease in conjunction with other laboratory and clinical findings. EliA GliadinDP IgG uses the EliA IgG method on the instrument Phadia 2500/5000.

The method-specific reagents are identical with K062583 (EliA Celikey IgG) and K093459 (EliA Gliadin® IgA and EliA Gliadin® IgG), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of: Test Wells (EliA Celikey IgG Wells, EliA GliadinDP IgA Wells, EliA GliadinDP IgG Wells), EliA Sample Diluent, EliA IgG reagents (EliA IgG Conjugate, EliA IgG Calibrator Strips, EliA IgG Curve Control Strips, EliA IgG Calibrator Well), and EliA IgA reagents (EliA IgA Conjugate, EliA IgA Calibrator Strips, EliA IgA Curve Control Strips, EliA IgA Calibrator Well). The Phadia EliA Immunodiagnostic System is an automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages are required to carry out EliA Celikey IgG and EliA GliadinDP IgA and EliA GliadinDP IgG tests.

The provided document is a 510(k) Premarket Notification from the FDA, detailing the substantial equivalence determination for the Phadia AB EliA Immunoassays (Celikey IgG, GliadinDP IgA, GliadinDP IgG) for use on the Phadia 2500/5000 instrument. The document primarily focuses on demonstrating that the performance of these assays on the new instrument platform is substantially equivalent to their performance on a previously cleared instrument (Phadia 250).

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

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

The document does not explicitly present a single table outlining "acceptance criteria" alongside "reported device performance" for the overall substantial equivalence determination. Instead, it details performance characteristics for various analytical aspects, and the acceptance criteria are implied by the ranges and thresholds specified for these studies. The primary "acceptance criteria" for the overall submission appear to be demonstrating equivalence to the predicate device and meeting specific statistical thresholds for precision and linearity.

However, based on the sections "M. Performance Characteristics (if/when applicable)" and "2. Comparison studies: - Instrument comparison C.", we can construct a table for the analytical performance and comparative study results:

Table: Acceptance Criteria (Implied) and Reported Device Performance

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

• Precision Test Set: The study used "a total of 21 runs (3 instruments x 7 runs)". Each sample was tested in "four replicates/run giving in total 84 replicates per sample." The number of distinct samples for precision is not explicitly stated, but multiple samples covering various concentrations are typically used (e.g., 5 samples in the EliA Celikey IgG table).
• Linearity Test Set: "Four patient serum samples (five for Celikey IgG)" were diluted and tested.
• Detection Limit Test Set: "One blank sample and three low level samples were measured in thirty-three and eleven replicates, respectively, in each of two runs." For Celikey IgG LoD, "6 low level samples and a total of 132 determinations" were used. For LoQ, "66 determinations of 3 low level samples."
• Method Comparison Test Set: "More than 100 samples (≥20% of the samples within ±25% of the medical decision point)" were run for each of the three EliA tests.
• Expected Values/Reference Range: 400 "apparently healthy subjects ... from a Caucasian population obtained from a blood bank."

Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. It is a 510(k) submission for a device, and the focus is on analytical performance and comparison to a predicate device, not primary clinical trial data of patient outcomes. The "Expected Values/Reference Range" suggests the use of existing blood bank samples, which typically implies retrospective use of collected samples.

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

This information is not applicable to this type of device and study. The EliA Immunoassays measure specific antibodies (tTG IgG, Gliadin IgA, Gliadin IgG) in patient samples. The "ground truth" for the analytical studies (precision, linearity, detection limits, method comparison) is based on the quantitative concentration of these analytes as measured by the predicate device or a reference method, rather than subjective expert interpretation (like in imaging studies). For the reference range, the "ground truth" is simply the measured values in a defined healthy population.

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

This information is not applicable. Adjudication methods (like 2+1 or 3+1 for resolving discrepancies) are typically used in clinical studies where expert readers independently interpret data (e.g., medical images) and their interpretations need to be reconciled to establish a "ground truth" or reference standard. This document describes analytical and comparative studies for an in vitro diagnostic immunoassay, where quantitative measurements are the primary data.

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 information is not applicable. MRMC studies are primarily relevant for AI-powered diagnostic devices, particularly in medical imaging, where multiple human readers interpret cases, and the AI's impact on their diagnostic performance is assessed. This document pertains to an in vitro diagnostic immunoassay, not an AI-assisted diagnostic tool that aids human "readers."

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

Yes, this can be considered a standalone performance evaluation in the context of an immunoassay. The device (EliA Immunoassays on Phadia 2500/5000) operates as an automated system to semi-quantitatively measure antibody levels. The analytical performance studies (precision, linearity, LoD/LoQ) and the instrument comparison are essentially the "standalone" performance of the assay on the new platform. It's not an "algorithm only" in the sense of a software-only device, but the analytical steps are automated, and the reported values are direct outputs of the system. Human intervention relates to sample loading and equipment maintenance, not interpretation of raw data for diagnosis.

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

The "ground truth" for the performance studies described is primarily:

• Quantitative Analytical Values: For precision, linearity, LoD/LoQ, the ground truth is derived from the inherent nature of the samples at known or measured concentrations, often established by reference methods or highly characterized materials.
• Predicate Device Measurements: For the "Instrument Comparison," the results obtained from the previously cleared Phadia 250 instrument serve as the reference or "ground truth" against which the new Phadia 2500/5000 is compared to demonstrate substantial equivalence.
• Clinically Defined Healthy Population: For "Expected Values/Reference Range," the ground truth is simply the distribution of the analyte in a healthy population.

It's important to note that this 510(k) is for "adding previously cleared assays on a new instrument platform." This means the clinical utility and diagnostic performance (e.g., clinical sensitivity/specificity for celiac disease) of the assays themselves were already established and reviewed in the original 510(k) clearances (K062583 and K093459). The current submission leverages that prior clinical validation by demonstrating that the new instrument maintains equivalent analytical performance. Thus, the "clinical ground truth" for celiac disease diagnosis (e.g., biopsy confirmation, clinical outcomes) was established in those prior studies, not detailed here. The current submission's focus is on bridging the analytical performance to the new instrument.

8. The sample size for the training set

This document describes a 510(k) submission for an IVD immunoassay, not a machine learning or AI model. Therefore, there is no "training set" in the context of artificial intelligence/machine learning. The assays are based on established biochemical principles (antigen-antibody reactions, fluorescence detection), not on training data to learn patterns or parameters.

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

As there is no "training set" for an AI/ML model, this question is not applicable. The methods for establishing the performance characteristics are described in point 7 above.

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The Anti-tissue Transglutaminase ELISA (IgA) test kit is intended for the qualitative determination of IgA class antibodies against tissue transglutaminase in human serum and EDTA plasma (K3-EDTA, Lit-heparin, Na+citrate). It is used as an aid in the diagnosis of gluten-sensitive enteropathy (celiac disease) and dermatitis herpetiformis Duhring, in conjunction with other laboratory and clinical findings.

The Anti-tissue Transglutaminase ELISA (IgG) test kit is intended for the qualitative determination of IgC class antibodies against tissue transglutaminase in human serum and EDTA plasma (K3-EDTA, Li+-citrate). It is used as an aid in the diagnosis of gluten-sensitive enteropathy (celiac disease), in conjunction with other laboratory and clinical findings.

Not Found

This document is a 510(k) clearance letter from the FDA for an In Vitro Diagnostic (IVD) device, specifically an ELISA test for anti-tissue transglutaminase antibodies. These types of regulatory documents typically do not contain the detailed study information (acceptance criteria, specific performance metrics, sample sizes, expert qualifications, etc.) that would be found in a clinical trial report or a submission summary.

The letter explicitly states: "We have reviewed your Section 510(k) premarket notification... and have determined the device is substantially equivalent...". This determination of substantial equivalence relies on the manufacturer providing adequate data, but the letter itself does not present that data in a public-facing way.

Therefore, I cannot extract the requested information from the provided text. The document is an FDA clearance letter and not a detailed clinical study report.

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The Ig plex Celiac DGP Panel is an in vitro diagnostic test for the semi-quantitative detection of the IgA and IgG immunoglobulin classes of antibodies to deamidated gliadin peptide (DGP) and tissue transglutaminase (TG) in human serum. The test is intended for use in clinical laboratories as an aid in the disease in conjunction with other laboratory and clinical findings, and requires the sqid-X system.

The Ig plex Celiac DGP Panel is a consumable reagent kit. It is designed to run on the sqid-X system. The kit includes a microarray plate, reporter mix, standards, controls, sample diluents, wash buffer concentrates and a CD-ROM.

The assay detects the presences of the IgA and IgG classes of antibody, and the IgA and lgG classes of anti-tissue transglutaminase antibody. This is performed in an integrated fashion on the sqid-X system that reports all analytes simultaneously to aid in the diagnosis of celiac disease.

The system is a multiplex immunoassay analyzer that semi-automates the protocol of a specific lg plex assay from plate washing to reporting of all assay markers for each individual patient sample. The system combines manual liquid handling (samples and reagents) with automated steps for washing, scanning, data analyses and reporting. Results for each patient sample are obtained simultaneously for each of the four markers using the results from one well containing one aliquot of the patient's serum. Results are reported independently.

Here's a summary of the acceptance criteria and study findings for the Ig plex Celiac DGP Panel, based on the provided document:

1. Table of Acceptance Criteria & Reported Device Performance

The document does not explicitly state formal "acceptance criteria" in a go/no-go fashion with numerical targets for all performance metrics. However, it presents various performance results without indicating that they failed to meet any internal or regulatory thresholds. The following table summarizes what can be inferred as the expected performance based on the reported study results:

The concluding statement, "the lg_plex Celiac DGP Panel demonstrated performance, safety and effectiveness equivalent or superior to its predicates," implies that the reported performance met or exceeded the expected standards set by the predicate devices.

2. Sample Size and Data Provenance

• Sensitivity and Specificity (Test Set): 378 samples
  • 128 celiac biopsy-confirmed samples.
  • 250 samples from other autoimmune diseases (rheumatic and infectious diseases).
  • No specific country of origin is mentioned, nor is it explicitly stated whether the data is retrospective or prospective. Given the nature of these studies, it's highly likely to be retrospective, utilizing banked samples.
• Method Comparison: 379 samples
  • 229 positive celiac patient samples.
  • 132 presumptively normal samples.
  • 18 other autoimmune disease samples.
• Expected Values/Cut-off Determination: 292 specimens
  • 126 presumed normal.
  • 56 other autoimmune disease.
  • 110 celiac patient specimens.
• Reference Range Determination: 328 presumptively normal donors.
  • 167 males (age 19-90 years).
  • 161 females (age 18-66 years).
• Analytical Interference: 3 samples (2 celiac diagnosed, 1 negative).
• Precision and Reproducibility: Various replicates (e.g., replicates of two for 20 days for inter-assay, replicates of five per kit for lot-to-lot and multi-instrument studies). The total number of unique samples for these studies is not clearly aggregated but involves multiple runs and sites.

3. Number of Experts and Qualifications for Ground Truth

• The document does not mention the use of experts to establish ground truth for the test set.
• For the "celiac biopsy confirmed samples," the ground truth is implied to be established by the biopsy itself, which would typically be interpreted by pathologists. No number or specific qualifications of these pathologists are provided.
• For "other autoimmune diseases," the diagnosis is implied as existing, but the means of diagnosis or qualifications of those who made the diagnoses are not described.

4. Adjudication Method

• No adjudication method (e.g., 2+1, 3+1) is described for establishing the ground truth of the test set. The ground truth seems to be based on pre-existing diagnoses (biopsy, clinical diagnosis).

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

• No MRMC comparative effectiveness study is mentioned. This device is an in vitro diagnostic (IVD) assay designed for laboratory use, not typically requiring human reader interpretation in the same way as an imaging AI device would. It provides numerical results for analytes.

6. Standalone Performance

• Yes, the studies described are standalone performance studies. The device (Ig plex Celiac DGP Panel on the sqid-X system) is evaluated on its own ability to accurately measure the target analytes and to classify samples as positive or negative for celiac disease markers based on objective cut-off values. There is no human-in-the-loop component for the performance metrics measured here (sensitivity, specificity, agreement, precision).

7. Type of Ground Truth Used

• The primary ground truth used is biopsy confirmation for celiac disease (specifically, "celiac biopsy confirmed samples").
• For other conditions, it relies on existing clinical diagnoses of "other autoimmune diseases."

8. Sample Size for the Training Set

• The document does not explicitly state a separate "training set" for the algorithm. For IVD diagnostic tests, the "training" equivalent often involves the development and optimization of the assay itself, selection of reagents, and establishment of cut-off values using reference populations.
• The "Expected Values" section mentions that 126 presumed normal, 56 other autoimmune disease, and 110 celiac patient specimens (total 292 samples) were "evaluated for accurate determination of each analyte's cut-off." This process is analogous to defining thresholds, which could be considered part of the development/training phase for the diagnostic interpretation.

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

• As mentioned above, if the "Expected Values" samples were used for cut-off determination (a form of "training" or optimization), the ground truth for these samples would likely be established in the same way as the test set: through biopsy confirmation for celiac patients and clinical diagnosis for other conditions/normal individuals. However, the document does not elaborate further on the process for these specific sets of samples beyond their use for cut-off determination.

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Enzyme linked immunoassay (ELISA) for the qualitative or semi-quantitative detection of IgA and IgG antibodies to synthetic human tissue transglutaminase (1TG) and deamidated gliadin peptide (DGP) in human serum to aid in the diagnosis of celiae disease (CD) in conjunction with other laboratory tests and clinical findings.

Enzyme linked immunoassay (ELISA)

The provided text details the FDA's clearance of the ImmuLisa Enhanced Celiac Fusion (tTG/DGP) IgA/IgG Antibody ELISA for aiding in the diagnosis of celiac disease. However, the document does not contain specific acceptance criteria or a study summary that details the device's performance against such criteria. The document is primarily an FDA clearance letter and an "Indications for Use" statement.

Therefore, I cannot provide the requested information from the given text.

To address the prompt fully, I would need a study report or a different document detailing the performance evaluation of the ImmuLisa Enhanced Celiac Fusion ELISA.

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The BioPlex 2200 Celiac IgA kit is an in vitro multiplex flow immunoassay intended for the semi-quantitative detection of IgA autoantibodies to deamidated gliadin peptide (DGP) and tissue Transglutaminase (tTG) in human serum. In conjunction with clinical findings and other diagnostic tests, the test system is used as an aid in the diagnosis of Celiac Disease (gluten-sensitive enteropathy). The BioPlex 2200 Celiac IgA kit is intended for use with the Bio-Rad BioPlex 2200 System.

The BioPlex 2200 Celiac IgG kit is an in vitro multiplex flow immunoassay intended for the semi-quantitative detection of IgG autoantibodies to deamidated gliadin peptide (DGP) and tissue Transglutaminase (tTG) in human serum. In conjunction with clinical findings and other diagnostic tests, the test system is used as an aid in the diagnosis of Celiac Disease (gluten-sensitive enteropathy). The BioPlex 2200 Celiac IgG kit is intended for use with the Bio-Rad BioPlex 2200 System.

The BioPlex 2200 Celiac IgA Calibrator Set is intended for the calibration of the BioPlex 2200 Celiac IgA Reagent Pack.

The BioPlex 2200 Celiac IgG Calibrator Set is intended for the calibration of the BioPlex 2200 Celiac IgG Reagent Pack.

The BioPlex 2200 Celiac IgA Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 Instrument and BioPlex 2200 Celiac IgA Reagent Pack in the clinical laboratory. The performance of the BioPlex Celiac IgA Control Set has not been established with any other antitissue Transglutaminase (tTG) and anti-Deamidated Gliadin Peptide IgA assays.

The BioPlex 2200 Celiac IgG Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 Instrument and BioPlex 2200 Celiac IgG Reagent Pack in the clinical laboratory. The performance of the BioPlex Celiac IgG Control Set has not been established with any other antitissue Transglutaminase (tTG) and anti-Deamidated Gliadin Peptide IgG assays.

BioPlex® 2200 Celiac IgA and IgG kits include the following components:
One (1) 10 mL vial of Bead Set, containing dyed beads coated with recombinant antigens; an Internal Standard bead (ISB), a Serum Verification bead (SVB) and IgA Verification Bead (AVB) (in Celiac IgA only), in MOPS (3-[N-Morpholino] propanesulfonic acid) buffer supplemented with Glycerol and protein stabilizer (bovine and porcine). ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (< 0.1%) are added as preservatives.
One (1) 5 mL vial of Conjugate, containing phycoerythrin conjugated murine monoclonal anti-human IgA or IgG and phycoerythrin conjugated sheep anti-human FXIII in MOPS (3-N-Morpholino] propanesulfonic acid) buffer supplemented with bovine protein stabilizers. ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (< 0.1%) are added as preservatives.
One (1) 10 mL vial of Sample Diluent, containing bovine and murine protein stabilizers in triethanolamine buffer. ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (< 0.1%) are added as preservatives.

BioPlex 2200 Celiac IgA and IgG Calibrator Sets contain nine (9) 0.5 mL vials of human antibodies to tTG and DGP in a buffer supplemented with protein stabilizer (porcine for IgA and porcine/human for IgG) with ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (< 0.1%) as preservatives.

BioPlex 2200 Celiac IgA and IgG Control Sets contain four (4) 1.5 mL vials of Positive Controls of human antibodies to tTG or DGP and two vials of Negative Controls in a human serum matrix made from defibrinated plasma; and, in a human serum matrix made from defibrinated plasma with ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (< 0.1%) as preservatives.

Additional materials required but not supplied include BioPlex 2200 Sheath Fluid containing Phosphate Buffered Saline (PBS) with ProClin 300 (<0.03%), and sodium azide (<0.1%) as preservatives; and BioPlex 2200 Wash Solution containing Phosphate Buffered Saline (PBS) and Tween 20 with ProClin 300 (≤0.03%) and sodium azide (<0.1%) as preservatives.

Here's an analysis of the acceptance criteria and study findings for the BioPlex® 2200 Celiac IgA and IgG kits, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state numerical acceptance criteria in a dedicated section with pass/fail thresholds. Instead, it presents performance characteristics from various studies. For this table, I will present the reported performance, which implicitly serves as the evidence that the device meets acceptable levels for these metrics. The "Target Performance" column will reflect typical expectations for such assays or the performance shown by the predicate devices where applicable.

Performance Characteristics for BioPlex® 2200 Celiac IgA and IgG Kits

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

• Precision/Reproducibility:

  • CLSI EP5-A2: 24 samples (serum panel consisting of samples spanning the measuring range), tested in replicate twice daily over 20 days (n=80 replicates per sample type).
  • CLSI EP15-A2: 12 samples (serum panel consisting of samples spanning the measuring range), tested in 4 replicates per run, one run per day over 5 days (n=20 replicates per sample type).
  • Lot-to-lot Reproducibility: Unspecified number of serum samples covering the assay range, tested with three reagent lots on three instruments, 10 replicates for two runs per lot (60 points per sample ID for calculation).

• Linearity/Reportable Range: 3 low positive and 3 high positive patient serum samples for each antibody (anti-tTG IgA/IgG, anti-DGP IgA/IgG).

• Analytical Specificity (Interference): Test substances (e.g., Hemolysate, Bilirubin, Triglycerides). No specific number of samples given for the interference study, but the substances were tested at specified concentrations.

• Analytical Specificity (Cross-Reactivity): 244 samples from individuals with various disease states (e.g., Chronic Active Hepatitis, Crohn's Disease, Diabetes Mellitus Type 1, Rheumatoid Arthritis). The number of samples for each disease state ranged from 6 to 30.

• Assay Cut-off Determination: 123 samples from patients with diagnosed celiac disease and 112 from non-celiac/rheumatic disease control donors. Confirmed with 298 samples from apparently healthy donors.

• Method Comparison with Predicate Device:

  • All samples: 156 patients with celiac disease, 163 patients with other rheumatic or non-CD disease control, 11 celiac IgA deficient patients, and 16 Dermatitis Herpetiformis (DH) patients. Total: 346-347 samples (1 sample excluded in some analyses).
  • Samples within measuring range (and 10% diluted): Varying totals per assay, e.g., anti-tTG IgA (211), anti-DGP IgA (310), anti-tTG IgG (288), anti-DGP IgG (248).

• Clinical Studies (Sensitivity and Specificity): 319 serum specimens, including 163 non-Celiac disease control patients and 156 diagnosed Celiac disease patients.

• Expected Values/Reference Range: 300 serum samples from apparently healthy donors (139 males, 161 females, age <1 to 101).

Data Provenance (Retrospective/Prospective, Country of Origin):
The document states that the method comparison study used "all retrospective patient serum samples." Similarly, the clinical sensitivity and specificity study involved clinical diagnosis of Celiac patients and non-Celiac controls. For cross-reactivity and expected values, these also appear to be retrospective collections of patient/donor samples. There is no explicit mention of the country of origin for the data.

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

The document does not explicitly state the number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") for establishing the ground truth.

For the "clinical diagnosis," it refers to "patients previously diagnosed with celiac disease" and "non-Celiac disease control patients." This implies that the diagnosis was established through standard clinical practice by relevant healthcare professionals (e.g., gastroenterologists) using a combination of clinical findings, biopsy, and other diagnostic tests, which is a common approach for establishing ground truth in diagnostic assay validation. The specific expertise used for these previous diagnoses is not detailed.

4. Adjudication Method for the Test Set:

The document does not describe a specific adjudication method like "2+1" or "3+1" for determining ground truth in the patient samples. The ground truth appears to be based on "clinical diagnosis" or categorization of "apparently healthy donors" and specific disease states. While this is a form of ground truth, it wasn't established through a formal adjudication process (e.g., blinded review by multiple experts with a tie-breaker).

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. The device is an in vitro diagnostic immunoassay for semi-quantitative detection of antibodies, not an imaging device or AI system that assists human "readers" in interpreting images. Therefore, an MRMC study or an assessment of human reader improvement with AI assistance is not relevant to this product.

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

This question is not directly applicable in the typical sense of AI algorithms. The BioPlex® 2200 system performs the assay and provides numerical results (U/mL) without human interpretive input for the final measurement. The "standalone" performance is essentially the output of the instrument-reagent system. The "clinical sensitivity and specificity" study (Section 3) represents the standalone performance of the assay compared to clinical diagnosis.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.):

The ground truth used for performance evaluation can be categorized as:

• Clinical Diagnosis: For the clinical sensitivity and specificity studies, the ground truth for "Celiac disease patients" and "non-Celiac disease control patients" was based on their clinical diagnosis. This typically involves a combination of symptoms, serology, and duodenal biopsy.
• Predicate Device Results: For the method comparison study, the predicate immunoassay results served as the comparison point for agreement. While not a "true" ground truth in a clinical sense, it acts as a reference for establishing substantial equivalence.
• Disease State Classification: For cross-reactivity studies, samples were from individuals with "known disease states."
• Apparently Healthy Donors: For establishing expected values and confirming cut-offs, samples were from "apparently healthy donors."

8. The Sample Size for the Training Set:

The document does not explicitly describe a separate "training set" in the context of machine learning (AI). This is a diagnostic immunoassay system. The development of the assay (e.g., antigen selection, calibrator assignment, and establishment of linearity) inherently involves a "training" or development phase, but it's not described as a discrete "training set" in the AI sense.

However, the "Assay cut-off" section mentions that the cut-off values were determined using "123 samples from patients diagnosed with celiac disease and 112 from non-celiac or other rheumatic disease control donors." This set of samples was used to perform ROC analysis to establish the cut-off, which is a critical parameter for classifying results and could be considered analogous to a development or "training" set for defining the decision boundary of the assay. This was then "confirmed by testing 298 samples from apparently healthy donors."

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

As discussed in point 8, the "training set" for establishing the assay cut-off involved:

• Clinical Diagnosis: For the 123 celiac disease patients and 112 non-celiac/rheumatic disease control donors, the ground truth was their established clinical diagnosis. This implies diagnosis by medical professionals using standard diagnostic criteria.
• Healthy Status: For the 298 apparently healthy donors, the ground truth was their healthy status, likely determined through health screenings or self-reporting.

The specific "how" (e.g., detailed diagnostic reports, biopsy confirmation) and the expertise involved in these diagnoses are not explicitly detailed in the document beyond "clinically diagnosed."

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The IgX PLEX™ Celiac Qualitative Assay is an in vitro diagnostic test for the qualitative detection of the IgA and IgG immunoglobulin classes of anti-tissue transglutaminase antibody in serum. The test is intended for use in clinical laboratories as an aid in the diagnosis of celiac disease in conjunction with other laboratory and clinical findings, and requires the SQiDworks™ Diagnostics Platform.

The IgX PLEX™ Celiac Qualitative Assay is a consumable reagent kit. It is designed to run on the SQiDworks™ Diagnostics Platform. The kit includes a Microarray Plate, Reporter mix, standards, controls, sample diluents, wash buffer concentrates and a CD-ROM.

The Assay Kit detects the presences of the IgG classes of anti-tissue transglutaminase antibody. This is performed in an integrated fashion on the SQiDworks™ Diagnostics Platform (platform) that reports both analytes simultaneously to aid in the diagnosis of Celiac Disease.

The platform automates the entire immunoassay procedure from end-to-end, including calibrator/standards and sample pipetting, sample dilution, incubation, washing, and drying. Once the assay's biochemical reactions have completed, the instrument automatically performs a multi-color fluorescent scan of each well in the microarray, analyzes the data, and generates a report containing qualitative results for both assay markers. Results for each patient sample from the IgX PLEX™ Celiac Qualitative assay are obtained simultaneously for each of the two markers using the results from one well containing one aliquot of the patient's serum. Results are reported independently.

Here's a breakdown of the acceptance criteria and study information for the IgX PLEX™ Celiac Qualitative Assay, based on the provided text:

Acceptance Criteria and Reported Device Performance

Study Information

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

   • The document does not specify the sample size used for the test set.
   • The document does not specify the data provenance (e.g., country of origin, retrospective or prospective).

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

   • This information is not provided in the document. The study focuses on "clinical sensitivity" and "specificity" and "overall agreement with established predicate test systems," which suggests comparison to existing diagnostic methods rather than a panel of human experts for ground truth in the traditional sense for image-based AI.

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

   • This information is not provided in the document.

4. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

   • No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is an in vitro diagnostic (IVD) assay that automates the immunoassay procedure and provides qualitative results, intended to aid in diagnosis in conjunction with other clinical findings, rather than an AI system assisting human readers of images.

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

   • Yes, the performance metrics reported (reproducibility, clinical sensitivity, specificity, agreement) directly reflect the standalone performance of the IgX PLEX™ Celiac Qualitative Assay. The device is an automated system described as running "from end-to-end" and generating reports with "qualitative results." Human "in-the-loop" performance in the sense of an algorithm assisting a human reader is not applicable here as it autonomously provides the diagnostic result.

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

   • The document implies that the ground truth for "clinical sensitivity" and "specificity" and "overall agreement" was established by comparison to established predicate test systems and presumably clinical diagnoses of celiac disease. It does not explicitly state the ultimate "ground truth" method (e.g., small intestinal biopsy for celiac disease diagnosis, which is the gold standard). The phrase "aid in the diagnosis of celiac disease in conjunction with other laboratory and clinical findings" suggests that the "true" diagnosis of celiac disease, against which the assay's performance is measured, would involve a combination of clinical information, and potentially the gold standard of biopsy.

7. The sample size for the training set:

   • This information is not provided. The description mentions "standards, controls, sample diluents" as part of the kit, which are generally used for calibration and quality control rather than a "training set" in the machine learning sense.

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

   • This information is not provided. As this is an IVD assay rather than a machine learning model, the concept of a "training set" and establishing its ground truth in the typical AI/ML context doesn't directly apply in the same way.

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The QUANTA Flash h-tTG IgG is a chemiluminescent immunoassay (CIA) for the semi-quantitative detection of IgG anti-human tissue transglutaminase (h-ITG) antibodies in human serum. The presence of IgG anti-h-tTG antibodies, in conjunction with clinical findings and other laboratory tests, can aid in the diagnosis of the gluten sensitive enteropathy celiac disease, particularly in patients with selective IgA deficiency.

The QUANTA Flash™ h-tTG IgG Calibrators are intended for use with the QUANTA Flash™ h-tTG IgG chemiluminescent immunoassay (CIA) on the BIO-FLASH® instrument. Each calibrator establishes a point of reference for the working curve that is used to determine values in the measurement of IgG anti-h-tTG antibodies in serum.

The QUANTA Flash™ h-tTG IgG Controls are intended for quality control purposes of the QUANTA Flash™ h-tTG IgG chemiluminescent immunoassay (CIA) kit run on a BIO-FLASH® instrument.

Not Found

This document describes the FDA's decision to clear the QUANTA Flash™ h-tTG IgG device, along with its calibrators and controls, as substantially equivalent to legally marketed predicate devices. The document does not contain the acceptance criteria for a study proving the device meets those criteria, nor any of the detailed study information requested in your prompt (e.g., sample sizes, expert qualifications, adjudication methods, MRMC studies, standalone performance, ground truth types, or training set details).

The FDA letter confirms that the device can be marketed based on its substantial equivalence to existing devices, implying that the provided information (not included in this excerpt) was sufficient to demonstrate this. However, it does not disclose the specific performance metrics or detailed study design used to support this claim in the way you've outlined for a typical AI/medical device acceptance criteria and study report.

Therefore, I cannot provide the requested table and study details.

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The Eu-tTG® IgA is an in vitro diagnostic enzyme immunoassay for the semi-quantitative detection of IgA specific antibodies directed against tissue transglutaminase (tTG) in human serum. It is an aid in the diagnosis of celiac disease and should be used in conjunction with other serological tests and clinical findings.

The Eu-tTG® IgG is an in vitro diagnostic enzyme immunoassay for the semi-quantitative detection of IgG specific antibodies directed against tissue transglutaminase (tTG) in human serum. It is an aid in the diagnosis of celiac disease and should be used in conjunction with other serological tests and clinical findings.

Each test kit for Eu-tTG® IgA & Eu-tTG® IgG consists of one (1) microtiter plate (12 strips with 8 microwells coated with the human recombinant tTG antigen), assay controls (positive and negative), a ready-to-use set of five (5) calibrators, Horseradish Peroxidase (HRP) goat anti-human IgA or IgG conjugate, serum diluent, Tetramethylbenzidine (TMB) enzyme substrate, stop solution, and washing solution required for the assay.

The provided text describes two diagnostic devices, Eu-tTG® IgA and Eu-tTG® IgG, both intended as aids in the diagnosis of celiac disease. The study described focuses on their analytical and clinical performance.

Here's the breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria (e.g., "The device must achieve a sensitivity of at least X%"). Instead, it presents the results of method comparison and clinical studies, implying that the achieved performance was deemed sufficient for substantial equivalence to predicate devices. The comparator devices' performance would implicitly serve as a benchmark for acceptability.

However, based on the provided data, we can infer performance metrics. For this response, I will list the observed performance from the clinical studies as the "Reported Device Performance." Since no explicit "acceptance criteria" are given for these values, they serve as the performance characteristics that were reviewed for market clearance.

Eu-tTG® IgA

Eu-tTG® IgG

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

• Eu-tTG® IgA Clinical Study Test Set: 363 clinical samples (121 positive celiac patients, 242 negative samples).
• Eu-tTG® IgG Clinical Study Test Set: 407 clinical samples (165 positive celiac patients, 242 negative samples).
• Data Provenance: The document does not explicitly state the country of origin. It indicates that samples were from "clinically diagnosed celiac positive" and "negative samples... from healthy blood donors, IBD patients, patients affected by food intolerances and patients with autoimmune or infectious diseases." This suggests the samples are retrospective, sourced from clinical settings or blood banks, and are clinical samples, not necessarily from a controlled prospective study for this submission.

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

The document states that "The positive celiac patient samples were diagnosed with clinical findings and/or confirmed with biopsy." It does not specify the number of experts or their qualifications involved in establishing this ground truth (e.g., gastroenterologists, pathologists, etc.).

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for establishing the ground truth. It relies on existing clinical diagnoses and biopsy confirmations.

In the method comparison studies, the "comparator test" results served as the reference for agreement calculations, but this is not an adjudication of ground truth for the clinical diagnosis itself.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study focuses on the performance of a diagnostic immunoassay, not on human readers' interpretation of images or other data, with or without AI assistance.

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

Yes, the studies presented are for the standalone performance of the Eu-tTG® IgA and Eu-tTG® IgG immunoassay kits. These are in vitro diagnostic devices that directly analyze human serum samples; they do not involve a human-in-the-loop for interpreting the assay's output to render a diagnosis. The results (AU/mL values) are generated solely by the device.

7. The Type of Ground Truth Used

The ground truth for the clinical studies was established by:

• Clinical findings: This implies a physician's assessment of symptoms, medical history, and other diagnostic indicators.
• Biopsy confirmation: This refers to histological examination of intestinal tissue, which is the gold standard for diagnosing celiac disease.
• For negative samples, the ground truth was based on being "healthy subjects and patients with autoimmune disorders, infectious disease and IBD" without celiac disease.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" in the context of machine learning or AI development. These are immunoassay kits, which are typically developed and optimized through laboratory procedures, rather than being "trained" on data in the AI sense.

However, the "Assay Cut-off" section refers to testing "153 samples" (103 healthy subjects and 50 non-celiac controls) to establish the normal range and cut-off values. While not a "training set" in the AI sense, these samples were used to define parameters of the assay.

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

As explained above, there isn't a "training set" in the typical AI sense. However, for the 153 samples used to establish cut-off values:

• Healthy subjects: Presumed to be healthy without celiac disease.
• Non-celiac controls (IBD patients): Diagnosed with IBD but implicitly confirmed not to have celiac disease.

The exact methods for establishing the "ground truth" (e.g., confirmation of health status, specific IBD diagnosis without co-occurring celiac disease) for these 153 samples are not detailed in the provided text.

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