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The ARCHITECT HSV-2 IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of specific IgG antibodies to herpes simplex virus type 2 (HSV-2) in human serum (collected in serum and serum separator tubes) and plasma (collected in dipotassium EDTA, lithium heparin plasma separator tubes) on the ARCHITECT i System.

The ARCHITECT HSV-2 IgG assay is to be used for testing sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-2 infection. The test results may not determine the state of active lessociated disease manifestations, particularly for primary infection. The predictive value of a reactive or nonreactive result depends on the prevalence of HSV-2 infection in the population and the pre-test likelihood of HSV-2 infection.

NOTE: The performance of the ARCHITECT HSV-2 IgG assay has not been established for use in the pediatric population, for neonatal screening, or for testing immunosompromised or immunosuppressed patients. The assay has not been FDA cleared or approved for screening blood or plasma donors.

The ARCHITECT HSV-2 IgG assay is an automated, two-step immunoassay for the qualitative detection of IgG antibodies to HSV-2 in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology.

The kit contains different components: Reagent (microparticles, conjugate and assay diluent), Calibrator, and external Controls (reactive and nonreactive).

The document describes the ARCHITECT HSV-2 IgG assay, a diagnostic device for detecting specific IgG antibodies to herpes simplex virus type 2 (HSV-2). The study aims to demonstrate that this new device is substantially equivalent to legally marketed predicate devices.

While the document does not explicitly state "acceptance criteria" in the format of a separate table setting thresholds beforehand, the performance summary sections detail the studies and the observed performance. The key performance metrics demonstrated are:

• Clinical Performance (Positive Percent Agreement - PPA and Negative Percent Agreement - NPA): This is the primary measure of the device's accuracy in correctly identifying positive and negative samples for HSV-2 IgG antibodies.
• Precision (Within-Laboratory and Reproducibility): These studies evaluate the consistency and reliability of the assay results across different runs, days, and sites.
• Analytical Specificity (Interference and Cross-reactivity): These studies assess the device's ability to accurately measure HSV-2 IgG without being affected by other substances or related conditions.
• Specimen Collection Types: This confirms the assay's performance across various accepted sample types.
• Carry-Over: Verifies that prior samples do not affect subsequent sample results.

Here's an interpretation of the implied acceptance criteria and reported performance based on the provided document:

Acceptance Criteria and Reported Device Performance

Study Details:

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

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

   • Clinical Agreement Study: 915 specimens total (prospectively collected). Data provenance: Collected prospectively within the United States.
     • Sexually Active Population: 618 specimens (228 positive, 3 equivocal, 387 negative by composite comparator)
     • Pregnant Population: 297 specimens (82 positive, 0 equivocal, 215 negative by composite comparator)
   • CDC Panel Agreement: 100 blind characterized serum samples (50 unique samples, 2 aliquots each). Data provenance: From the Centers for Disease Control and Prevention (CDC).
   • Cut-off Establishment: 505 serum samples (271 reactive, 228 nonreactive, 6 equivocal for HSV-2 IgG antibodies).
   • Specimen Collection Types: 61 sets of unique serum samples paired with other tube types.
   • Precision Studies: 240-244 samples per panel/control for 20-day study, 96 samples per panel for 12-day study, 90 samples per panel for reproducibility study (all tested multiple times).
   • Analytical Specificity (Interference/Cross-reactivity): Varies per substance/condition, typically around 8-13 samples each.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
   The document does not explicitly state the number or qualifications of experts for establishing ground truth for the clinical agreement study. Instead, for the clinical performance evaluation, a "composite comparator method of 3 commercially available anti-HSV-2 IgG assays where a 2 out of 3 approach was followed" was used as the ground truth. This indicates a consensus or analytical comparison approach rather than expert human interpretation of results.
   For the CDC panel, it states "100 blind characterized samples," implying the CDC characterized these samples, likely through a robust expert-derived or reference method.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
   For the main clinical agreement study, the ground truth was established by a "2 out of 3 approach" using three commercially available anti-HSV-2 IgG assays. This is a form of adjudicated ground truth.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
   Not applicable. This device is a fully automated chemiluminescent microparticle immunoassay (CMIA) for the qualitative detection of specific IgG antibodies to HSV-2. It does not involve human readers for interpretation in the same way an AI for medical imaging (e.g., radiology) would, nor does it describe a human-in-the-loop AI assistance scenario. The output is a quantitative measure (S/CO) interpreted against a fixed cutoff.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
   Yes, the entire study effectively describes the standalone performance of the ARCHITECT HSV-2 IgG assay. As an automated immunoassay, it inherently operates without human interpretation of the primary result output, beyond clerical tasks and result reporting based on predefined cutoffs.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
   For the primary clinical agreement study, the ground truth was established by a "composite comparator method" derived from the results of three commercially available anti-HSV-2 IgG assays, using a "2 out of 3 approach." This is a form of analytical ground truth based on established diagnostic methods.
   For the CDC panel, the ground truth was "characterized samples" provided by the CDC, implying a reference standard or validated characterization by that institution.

8. The sample size for the training set:
   The document does not explicitly describe a separate "training set" in the context of an AI/machine learning model development. This is a traditional IVD device (immunoassay). The "Cut-off" section mentions a study using 505 serum samples to establish the assay's cutoff, which is a key parameter for defining reactive/nonreactive results. This could be considered analogous to a "training" or "calibration" set for the assay's performance characteristics.

9. How the ground truth for the training set was established:
   As mentioned in point 8, the assay's cutoff was established using a Receiver-Operating Characteristic (ROC) curve analysis on 505 serum samples. The ground truth for these 505 samples (whether they were truly reactive or nonreactive for HSV-2 IgG antibodies) is not explicitly stated but would have been determined by a reference method or clinical diagnosis prior to cutoff establishment. The document states these samples were "271 reactive, 228 nonreactive, and 6 equivocal for HSV-2 IgG antibodies," implying this pre-classification was the ground truth for selecting the optimal cutoff.

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The ARCHITECT HSV-1 IgG assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of specific IgG antibodies to herpes simplex virus type 1 (HSV-1) in human serum (collected in serum and serum separator tubes) and plasma (collected in dipotassium EDTA, lithium heparin plasma separator tubes) on the ARCHITECT i System.

The ARCHITECT HSV-1 IgG assay is to be used for testing sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-1 infection. The test results may not determine the state of active lessociated disease manifestations, particularly for primary infection. The predictive value of a reactive or nonreactive result depends on the prevalence of HSV-1 infection in the population and the pre-test likelihood of HSV-1 infection.

NOTE: The performance of the ARCHITECT HSV-1 IgG assay has not been established for use in the pediatric population, for neonatal screening, or for testing immunosompromised or immunosuppressed patients. The assay has not been FDA cleared or approved for screening blood or plasma donors.

This assay is an automated, two-step immunoassay for the qualitative detection of specific IgG antibodies to HSV-1 in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology. Sample, HSV-1 specific recombinant gG1 antigen coated paramagnetic microparticles, and assay diluent are combined and incubated. The IgG antibodies to HSV-1 (HSV-1 IgG) present in the sample bind to the HSV-1 specific recombinant gG1 antigen coated microparticles. The mixture is washed. Anti-human IgG acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added. The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a relationship between the amount of HSV-1 IgG in the sample and the RLU detected by the system optics. The presence or absence of HSV-1 IgG in the sample is determined by comparing the chemiluminescent RLU in the reaction to the cutoff RLU determined from an active calibration.

Here's a breakdown of the acceptance criteria and the studies performed for the ARCHITECT HSV-1 IgG assay, based on the provided document:

Acceptance Criteria and Device Performance

Study Details

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

• Tube Type Matrix Comparison: 62 sets of unique human serum samples, with each set including samples collected in serum, serum separator, dipotassium EDTA plasma, lithium heparin plasma, and lithium heparin plasma separator tubes.
  • Data Provenance: Not explicitly stated, but the company is based in Barcelona, Spain and the clinical study was conducted in the US. The type of samples suggests they would be clinical specimens. (Retrospective/Prospective not specified for this specific study, but the clinical agreement study was prospective).
• Precision (20-Day): 80 replicates per sample type (Negative Control, Positive Control, 3 Serum Panels, 3 Plasma Panels). Total of 8 samples * 80 replicates = 640 tests per reagent/calibrator lot combination (3 combinations used).
  • Data Provenance: Human serum and plasma panel samples. (Country/Retrospective/Prospective not specified for this specific study).
• Precision (12-Day): 96 replicates per sample type (2 Serum Panels, 2 Plasma Panels). Total of 4 samples * 96 replicates = 384 tests per lot combination (2 reagent lots).
  • Data Provenance: Human serum and plasma panel samples. (Country/Retrospective/Prospective not specified for this specific study).
• Reproducibility: 90 replicates per sample type (Negative Control, Positive Control, 3 Serum Panels, 3 Plasma Panels) across 3 sites.
  • Data Provenance: Human serum and plasma panel samples. (Country/Retrospective/Prospective not specified for this specific study).
• Interference (Endogenous & Drugs): Not a direct sample count, but 12 replicates for each negative and low reactive HSV-1 IgG sample for each substance tested.
  • Data Provenance: HSV-1 IgG negative and low reactive samples. (Country/Retrospective/Prospective not specified for this specific study).
• Cross-Reactivity: Total of 244 specimens (sum of 'n' column in the table).
  • Data Provenance: Specimens from individuals with antibodies to other microorganisms or medical conditions unrelated to HSV-1. Confirmed negative for HSV-1 IgG by a comparator immunoblot method. (Country/Retrospective/Prospective not specified for this specific study).
• CDC Panel Agreement: 100 aliquots (2 aliquots each of 50 serum samples).
  • Data Provenance: Obtained from the Centers for Disease Control and Prevention (CDC). Serum samples with unknown HSV-1 status, implying they are real-world clinical samples. (Country would be USA, retrospective).
• Clinical Agreement Study: 915 specimens.
  • Data Provenance: Collected prospectively within the US. Included sexually active individuals and pregnant females. Tested at 3 independent external laboratories.

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

• Clinical Agreement Study: A "composite comparator method" was used, consisting of:
  • A commercially available anti-HSV-1 IgG immunoblot method.
  • A Western Blot reference confirmatory test (University of Washington, Seattle).
• The document does not specify the number of experts or their qualifications for establishing the ground truth using these comparator methods. It refers to the methods themselves as the ground truth.

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

• Clinical Agreement Study: The "composite comparator method" suggests an adjudication process, where the immunoblot results were presumably confirmed or clarified by the Western Blot. However, the exact adjudication method (e.g., 2+1, 3+1) is not explicitly detailed. The document only states the combination of methods used to establish the comparator.

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 device is an automated, two-step chemiluminescent microparticle immunoassay (CMIA), not an AI-based imaging or diagnostic tool that involves human readers interpreting results. Therefore, an MRMC comparative effectiveness study comparing human readers with and without AI assistance is not applicable and was not performed.

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

• Yes, the performance studies described (Precision, Interference, Cross-Reactivity, CDC Panel Agreement, and Clinical Agreement) all represent standalone performance of the ARCHITECT HSV-1 IgG assay. The device is fully automated and provides a qualitative result (reactive/nonreactive) based on the measured Relative Light Unit (RLU) compared to a cutoff. There is no human interpretation of the assay's output involved in its primary function.

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

• Tube Type Matrix Comparison, Precision, Interference: These studies used internal controls, spiked samples, or reference materials. The "ground truth" for these is defined by the expected values of these controls/samples.
• Cross-Reactivity: Comparator method (immunoblot) confirmed negative for HSV-1 IgG.
• CDC Panel Agreement: The "unknown HSV-1 status" samples from the CDC would have their 'true' status determined by the CDC's reference methods, which serve as the ground truth.
• Clinical Agreement Study: A composite comparator method comprising a commercially available anti-HSV-1 IgG immunoblot method and a Western Blot reference confirmatory test (University of Washington, Seattle). This acts as the "expert consensus" or "reference method" ground truth for the clinical samples.

8. The sample size for the training set

• The document does not specify a training set size because this device is an immunoassay, not a machine learning or AI algorithm that typically requires a separate training set. Immunoassays are developed through analytical optimization and validation, rather than model training.

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

• As this is an immunoassay and not an AI/ML algorithm, there isn't a "training set" in the conventional sense used for machine learning. The development process would involve optimizing reagents and assay parameters against known positive and negative controls and clinical samples, but these are part of the assay development and validation, not a distinct "training set" for an algorithm.

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Automated latex enhanced immunoassay for the quantitative in vitro determination of total immunoglobulin E (1gE) in human serum or plasma (EDTA, heparin, citrate) using the ARCHITECT c Systems. The measurement of total IgE is useful in the clinical diagnosis of IgE-mediated allergies, if used in conjunction with other clinical studies.

The Quantia IgE reagent is a suspension of polystyrene latex particles of uniform size coated with mouse anti-human IgE. When a sample containing IgE is mixed with the latex reagent and the reaction buffer included in the kit, agglutination occurs. The degree of agglutination is directly proportional to the concentration of IgE in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates. Methodology: Turbidimetric/Immunoturbidimetric.

The provided document outlines the acceptance criteria and study results for the Quantia IgE assay, a device for quantitatively determining total IgE in human serum or plasma. It's important to note that this document is a 510(k) summary, focusing on demonstrating substantial equivalence to a predicate device after a modification, rather than a comprehensive de novo approval study. Therefore, some information typically found in a de novo clinical trial report (e.g., specific details on training set size, number of experts for training ground truth) might not be explicitly detailed.

Here's an analysis of the provided information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the performance characteristics presented and their comparison to the predicate device or established clinical standards (e.g., CLSI guidelines). The document focuses on demonstrating that the modified device performs as well as the predicate and meets relevant analytical performance metrics.

The table clearly shows that the modified device's performance metrics are either improved (e.g., lower LoD, LoQ, extended stability) or remain comparable to the predicate device, demonstrating that the device meets or exceeds the previous performance. The linearity range was expanded downwards from 25.0 to 20.0 IU/mL. The precision values reported for the subject device are well within the specified acceptance criteria for the predicate.

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

The document provides sample sizes for various analytical validation studies:

• Sample Matrix Comparison:
  • Predicate device: Five sets of 52 paired samples were run (total 260 samples).
  • Subject device: Forty paired samples were run (serum vs. various plasma types).
• Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ):
  • LoB: n ≥ 60 replicates of zero-analyte samples.
  • LoD: n ≥ 60 replicates of low-analyte level samples.
  • LoQ: n ≥ 60 replicates of low-analyte level samples.
• Precision:
  • Control (Level I, Mixture I&II, Level II): 50 replicates each (for predicate data summary).
  • Subject device: 80 replicates for "Panel 50 IU/mL", "Control I", "1:1 Mix Control I and II", "Control II", "Panel 800 IU/mL" (tested in a minimum of 2 replicates, twice per day on 20 days).
  • Additionally, 3 native serum pools (Panel A, B, C) were tested with 48 replicates each (in a minimum of 2 replicates, twice per day on 12 days).

Data Provenance: The document does not explicitly state the country of origin for the data or whether the studies were retrospective or prospective. However, based on the nature of analytical validation studies for an in-vitro diagnostic device, these are typically prospective laboratory studies conducted at the manufacturer's R&D facilities or contracted labs.

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

For an in-vitro diagnostic (IVD) device like Quantia IgE, the ground truth for performance evaluation (e.g., linearity, LoD, LoQ, precision, matrix effects) is established through analytical reference methods and calibrated standards, not human expert review. These studies rely on precise laboratory measurements and established protocols (e.g., CLSI guidelines). Therefore, there are no "experts" in the sense of radiologists reviewing images to establish ground truth.

4. Adjudication Method for the Test Set

Not applicable for analytical performance studies of an IVD. Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies, particularly for diagnostic imaging or subjective assessments, where human agreement on a diagnosis or finding is crucial. Here, the values are quantitative measurements compared to reference values or statistical criteria.

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

Not applicable. This device is an in-vitro diagnostic assay for measuring total IgE levels, not an imaging device or AI-assisted diagnostic tool that would involve human readers interpreting results. Therefore, an MRMC study is irrelevant to its validation.

6. Standalone (Algorithm Only) Performance

This entire submission describes the standalone performance of the Quantia IgE assay, a laboratory test. It is not an "algorithm" in the typical sense of AI, but rather a biochemical assay system. All performance metrics described (linearity, LoD, LoQ, precision, etc.) are characteristics of the assay system itself, without human interpretation beyond standard laboratory procedures and result reporting.

7. Type of Ground Truth Used

The ground truth used for these analytical performance studies is based on:

• Reference Standards/Calibrators: For linearity, LoD, LoQ, and IgE International Standard Recovery, the ground truth is established by using highly characterized, traceable calibrators and reference materials with known concentrations.
• Statistical Definitions/Methodologies: The definitions for LoB, LoD, and LoQ explicitly state how they are determined using a certain number of replicates of zero-analyte or low-analyte samples, and statistical calculations (e.g., 95th percentile, mean + 2 SD).
• Established CLSI Protocols: The studies explicitly state that they were performed based on guidance from CLSI (Clinical and Laboratory Standards Institute) protocols, such as NCCLS EP6-A (now EP06), EP17-A2, EP07-A2, EP37, and EP05-A3. These protocols outline the scientifically accepted methods for establishing analytical performance characteristics.

8. Sample Size for the Training Set

This document describes a "Special 510(k)" for a modification to an existing device (Quantia IgE) to demonstrate substantial equivalence. For IVD analytical performance studies, there isn't a "training set" in the machine learning sense alongside a "test set." The studies performed are the analytical validation studies on actual samples or controls covering the relevant range. The sample sizes for these studies are provided above (e.g., 40 paired samples for matrix comparison, ≥60 replicates for LoD/LoQ, 80 replicates for precision controls, 48 for native serum panels).

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

As explained under points 3 and 7, the concept of a "training set" and "ground truth established by experts" for this type of device and study is not directly applicable. The "training" for such an IVD device happens during its development and optimization phases, where various reagent formulations and assay parameters are tested against known concentration panels to achieve optimal performance. The "ground truth" during this development is based on the known concentrations of calibrators and reference materials, and the adherence to established analytical performance standards. The studies detailed in this 510(k) summary are the formal validation (test set) of the modified device's performance.

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The ADVIA Centaur® Herpes-1 IgG (HSV1) assay is for in vitro diagnostic use in the qualitative determination of IgG antibodies to herpes simplex virus type 1 (HSV-1) in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur systems. The test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of HSV infection. The predictive or negative result depends on the prevalence of HSV-1 infection in the population and the pre-test likelihood of HSV-1 infection.

The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for immunocompromised patients, pediatic patients or matrices other than human serum and plasma (EDTA and lithium heparin).

Not Found

The provided text describes the performance study for the ADVIA Centaur Herpes-1 IgG (HSV1) assay, an in vitro diagnostic device. This device is intended for the qualitative determination of IgG antibodies to HSV-1 in human serum and plasma, aiding in the presumptive diagnosis of HSV infection and serological status determination.

The study aims to demonstrate that the device meets its performance requirements, which can be interpreted as acceptance criteria for precision, matrix equivalency, panel agreement, interference, cross-reactivity, and clinical accuracy (sensitivity and specificity).

Here is a breakdown of the requested information:

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

The document implicitly defines acceptance criteria through its "Design Requirement" for precision and agreement percentages for panels, interference, cross-reactivity, and clinical studies.

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

• Precision Study: 80 replicates per level (for 2 controls and 6 samples). The data provenance is not explicitly stated beyond "performed according to CLSI EP05-A3," suggesting controlled laboratory conditions.
• Sample Matrix Study: 68 sets of matched samples (serum, SST, EDTA plasma, lithium heparin plasma) from "commercial sources." Provenance not explicitly country-specific, but generally implies a controlled study.
• Panels Study:
  • Seracare Diagnostics panel: 25 characterized HSV samples.
  • ToRCH-mixed Zeptometrix panel: 24 characterized HSV samples.
  • CDC panel: 100 blind characterized HSV samples.
  • Provenance: Commercial sources and CDC (likely US-based).
• Interferences Study: Not specified, but involved testing at three levels of samples for each interfering substance.
• Cross-reactivity Study: 431 specimens across various clinical categories. Provenance not specified.
• Clinical Study:
  • Sample Size: 864 specimens (total enrollment)
  • Provenance: "Collected within the United States" and tested at "3 independent external laboratories." This indicates a prospective collection for the clinical study.

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

The document does not specify the number of experts or their qualifications for establishing ground truth.

• For the panel studies, "characterized HSV samples" from commercial sources and "blind characterized HSV samples" from the CDC were used. This implies that the ground truth for these samples was established by the respective commercial supplier or the CDC, likely through a validated reference method, but the specific expertise of those who characterized them is not detailed.
• For the cross-reactivity study, the HSV-1 IgG status of specimens was verified using a "Comparative Assay" (a commercially available anti-HSV-1 IgG immunoblot method) and, for equivocal cases, a "validated Western Blot reference confirmatory test (University of Washington, Seattle)." This points to a recognized reference laboratory (University of Washington) for confirmatory testing, but the specific experts (e.g., medical technologists, scientists, physicians) and their qualifications involved in interpreting these reference methods are not stated.
• For the clinical study, the ground truth was established by comparing the device's performance to a "commercially available anti-HSV-1 IgG immunoblot method (Comparative Assay)" and a "validated Western Blot reference confirmatory test (University of Washington, Seattle)" for equivocal results. Again, the specific experts involved in the interpretation of these reference methods are not detailed.

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

The document states that for the clinical study, 22 "equivocal" results from the Comparative Assay were "further tested by the Western Blot test." This serves as a form of adjudication, where a higher-level, confirmed reference method (Western Blot) resolves uncertain or equivocal results from the primary comparative method. It's not a multi-reader, consensus-based adjudication, but rather a hierarchical resolution using a more definitive test.

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, this is not a multi-reader multi-case (MRMC) comparative effectiveness study. The device reviewed is an in vitro diagnostic assay (HSV-1 IgG antibody test), not an AI-based imaging or interpretive software that would be used by human readers. Therefore, the concept of human readers improving with AI assistance is not applicable to this device.

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

Yes, the studies presented (precision, matrix, panels, interference, cross-reactivity, and clinical sensitivity/specificity) reflect the standalone performance of the ADVIA Centaur HSV1 assay as an automated in vitro diagnostic device. Its output (qualitative determination of IgG antibodies) is directly provided by the instrument based on its chemical reactions and detector, without a human-in-the-loop directly influencing the test result. Human intervention would be for specimen handling, loading, and result review, but not for the determination of the assay's output itself.

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

The ground truth for this in vitro diagnostic device was established primarily through:

• Reference Assays/Methods:
  • A "reference assay 1" for commercial panels.
  • "Results provided by the CDC" for the CDC panel.
  • A "commercially available anti-HSV-1 IgG immunoblot method (Comparative Assay)" and a "validated Western Blot reference confirmatory test (University of Washington, Seattle)" for the clinical and cross-reactivity studies.
  • This falls under the category of reference standard comparison using established laboratory methods believed to be highly accurate.

8. The sample size for the training set

The document describes performance studies for regulatory submission (510(k)). It does not provide information about a "training set" in the context of machine learning, as this is an immunoassay, not an AI/ML-based device. If "training set" refers to samples used during the assay's development or optimization prior to these validation studies, that information is not provided in this regulatory summary. The presented data represents the validation/test set.

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

As there is no mention of a "training set" in the context of an AI/ML device, this question is not applicable. The assay's performance relies on its biochemical design and manufacturing controls, not on a machine learning model that requires a ground-truth-labeled training set.

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The ADVIA Centaur® Herpes-2 IgG (HSV2) assay is for in vitro diagnostic use in the qualitative determination of IgG antibodies to herpes simplex virus type 2 (HSV-2) in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur systems. The test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of HSV infection. The predictive value of a positive or negative result depends on the prevalence of HSV-2 infection in the population and the pre-test likelihood of HSV-2 infection.

The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for immunocompromised patients, pediatric patients or matrices other than human serum and plasma (EDTA and lithium heparin).

The ADVIA Centaur Herpes-2 IgG (HSV2) assay is a fully automated two-step sandwich immunoassay using indirect chemiluminometric technology. The specimen is incubated with the Solid Phase, which contains HSV-2-specific recombinant-gG2 antigen. Antigen-antibody complexes will form if anti-HSV-2 antibody is present in the specimen. The Lite Reagent contains monoclonal anti-human IgG labeled with acridinium ester, and is used to detect HSV-2 IgG in the specimen.

The provided document describes the performance of the ADVIA Centaur Herpes-2 IgG (HSV2) assay, which is an in vitro diagnostic device. The study aims to demonstrate that the device meets acceptance criteria for substantial equivalence to a predicate device.

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

1. Table of Acceptance Criteria and Reported Device Performance

The document presents performance characteristics and compares them against design requirements or expected outcomes.

2. Sample Size and Data Provenance

• Precision Study: 6 samples and Negative/Positive Controls. Each material tested in duplicate, twice a day for 20 days.
  • N = 80 replicates per level for within-lab precision.
• Sample Matrix Study: 68 sets of matched samples (serum, serum separator tube, EDTA plasma, lithium heparin plasma).
• Panel Testing:
  • ToRCH-mixed Zeptometrix panel: 24 characterized HSV samples.
  • CDC panel: 100 blind characterized HSV samples.
• Cross-Reactivity Study: 522 specimens across various clinical categories.
• Multi-site Reproducibility: 6 samples and Negative/Positive Controls.
  • N = 90 replicates per level (from 3 external sites, 5 days, 2 runs/day, 3 replicates/run).
• Clinical Study:
  • Total: 864 specimens (≥ 18 years of age), including 274 pregnant women.
  • Data Provenance: Specimens collected within the United States. The study was conducted at 3 independent external laboratories. The nature of the specimen collection implies it was prospective for the purpose of this study, although the individual samples may have been sourced retrospectively from biobanks or collected prospectively for the study itself. The document does not explicitly state "retrospective" or "prospective" for the clinical sample collection, but "collected within the United States" and tested at external labs suggests purpose-collected samples for the study.

3. Number of Experts and Qualifications for Ground Truth

• The document implies the use of "reference assay 1" for the ToRCH-mixed Zeptometrix panel and "results provided by the CDC" for the CDC panel, as well as a "Comparative Assay" and "validated Western Blot reference confirmatory test (University of Washington, Seattle)" for the clinical study and cross-reactivity assessment.
• Number of Experts: Not explicitly stated how many individual experts established the ground truth for these reference methods. The description refers to "characterized HSV samples" for panels and "validated Western Blot" from a university, which implies expert consensus or highly standardized laboratory procedures.
• Qualifications of Experts: Not explicitly stated (e.g., "radiologist with 10 years of experience" is not applicable here as it's an in vitro diagnostic test for antibodies). However, the use of "validated Western Blot" from a reputable institution (University of Washington, Seattle) and "CDC" as sources for ground truth implies the highest level of expertise and validated methodologies in serological testing.

4. Adjudication Method for the Test Set

• For the clinical study: Of the 864 specimens, 22 were equivocal with the Comparative Assay. These 22 samples were resolved by Western Blot testing. 20 were resolved to be negative, and 2 remained equivocal. This describes a form of adjudication where an equivocal result from one reference method is adjudicated by a more definitive reference method (Western Blot).
• No multi-reader consensus (e.g., 2+1, 3+1) is mentioned, as this is an in vitro diagnostic assay, not an image-reading task.

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

• No MRMC comparative effectiveness study was done. This type of study is typically performed for AI/CAD systems that assist human readers in interpreting medical images, not for in vitro diagnostic assays like this one which provides a quantitative or qualitative result directly.

6. Standalone (Algorithm Only) Performance

• This device is an automated immunoassay (ADVIA Centaur HSV2 assay). Its performance is inherently "standalone" in the sense that it directly measures antibodies without human interpretation in the loop to generate the initial result. The reported sensitivity and specificity values are for the device (algorithm) itself against the established ground truth.

7. Type of Ground Truth Used

• Expert Consensus / Highly-validated Reference Methods:
  • For panels: "characterized HSV samples," "reference assay 1," and "results provided by the CDC."
  • For clinical and cross-reactivity studies: A Comparative Assay (likely another FDA-cleared or well-established commercial immunoassay) and a validated Western Blot reference confirmatory test (University of Washington, Seattle). Western Blot is generally considered a highly specific and confirmatory test for antibody presence in serology. The use of a confirmatory test like Western Blot for equivocal results strengthens the ground truth.

8. Sample Size for the Training Set

• The document describes a 510(k) submission for an in vitro diagnostic device (immunoassay). Immunoassays are based on biochemical reactions and established calibration curves, not typically on machine learning models requiring large "training sets" in the same sense as AI/ML software. Therefore, a "training set" for an algorithm, as understood in AI/ML, isn't applicable or mentioned for this device. The development process would involve characterization, optimization, and validation using various samples, but not "training data" for a learnable algorithm.

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

• As explained in point 8, the concept of a "training set" with ground truth establishment in the AI/ML sense does not apply to this immunoassay. The device's performance is driven by its reagent chemistry and instrumentation, not by a trained algorithm.

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The ARCHITECT SHBG assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of sex hormone binding globulin (SHBG) in human serum and plasma on the ARCHITECT i System. The ARCHITECT SHBG assay is used as an aid in the diagnosis of androgen disorders.

The ARCHITECT SHBG assay is a two-step immunoassay to determine the presence of SHBG in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology with flexible assay protocols, referred to as Chemiflex. In the first step, sample, assay diluent, and anti-SHBG coated paramagnetic microparticles are combined. SHBG present in the sample binds to anti-SHBG coated microparticles. After washing, the SHBG binds to the anti-SHBG acridinium-labeled conjugate that is added in the second step. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). A direct relationship exists between the amount of SHBG in the sample and the RLUs detected by the ARCHITECT i System optics. The concentration of SHBG in the sample is determined by comparing the chemiluminescent signal in the reaction to the ARCHITECT SHBG calibration.

This document is primarily a 510(k) summary for a labeling change to the ARCHITECT SHBG assay. It is not about a new device or an AI/ML device, but rather an update to the "Free Testosterone Index (FTI) / Free Androgen Index (FAI)" expected values section of the existing device's labeling. Therefore, many of the requested categories for acceptance criteria and study details for AI/ML devices are not applicable.

Here's an interpretation based on the provided text, focusing on the available information:

1. Table of Acceptance Criteria and Reported Device Performance

The device itself (ARCHITECT SHBG assay) was previously cleared. The current submission is for a labeling change to update expected values for the Free Testosterone Index (FTI) or Free Androgen Index (FAI). Therefore, there are no new performance acceptance criteria for the device itself as part of this submission. The performance of the underlying assay remains as established in K060818.

However, the "study" described in the document is the generation of new FTI/FAI expected values. The implicit acceptance criterion for this study is that the calculated FTI/FAI values are representative of the studied populations and are suitable for inclusion in the device labeling. The "reported device performance" in this context refers to the generated expected value ranges.

SHBG Expected Values (nmol/L)

Testosterone Expected Values

% FTI or % FAI Expected Values

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

• Sample sizes:
  • Males (21-49 years of age): 163 samples
  • Males (≥ 50 years of age): 144 samples
  • Females (Premenopausal, 21-49 years of age): 174 samples
  • Females (Postmenopausal, ≥ 50 years of age): 175 samples
  • Total samples: 163 + 144 + 174 + 175 = 656 samples
• Data Provenance: The document states "A new study was conducted in 2014 to calculate FTI or FAI..." It specifies "individuals in the following categories: normal males... normal females..." without explicitly stating the country of origin. The study appears to be prospective in nature, as it was specifically conducted to establish these new expected values.

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

• This is not applicable as the study involves quantitative measurements using an immunoassay device, not subjective expert assessment of images or clinical findings that would require ground truth established by experts.

4. Adjudication Method for the Test Set

• Not applicable for a quantitative in vitro diagnostic assay. The results are raw numerical measurements from the ARCHITECT i System.

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

• Not applicable. This is an immunoassay, not an imaging device or an AI/ML algorithm requiring human reader performance evaluation.

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

• Not applicable as this is not an AI/ML algorithm. The "standalone" performance here refers to the ARCHITECT SHBG and ARCHITECT 2nd Generation Testosterone assays themselves, which provide quantitative results directly from the instrument.

7. The Type of Ground Truth Used

• The "ground truth" in this context is the quantitative determination of SHBG and Testosterone concentrations in human serum/plasma samples using the respective ARCHITECT assays. These are measured values, not a 'ground truth' in the sense of a consensus diagnosis or pathology result. For FTI/FAI, the ground truth is derived calculation based on these assay results.

8. The Sample Size for the Training Set

• Not applicable as this is not an AI/ML device that undergoes a training phase. The study involved collecting new data to establish expected values for FTI/FAI, effectively acting as a validation/reference range study, not a training set for an algorithm.

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

• Not applicable.

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