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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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Immunoassay for the in vitro qualitative determination of IgG class antibodies to HSV-1 in human serum and lithium-heparin plasma, K2-EDTA plasma, and K3-EDTA plasma. The test is intended for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-1 infection. The test results may not determine the state of active lesions or associated disease manifestations, particularly for primary infection. The predictive value of positive and negative results depends on the population's prevalence and the pretest likelihood of HSV-1.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

This test is not FDA-cleared for screening blood or plasma donors.

The performance of this assay has not been established for use in a pediatric population, neonates, immunocompromised patients, or for use at point-of-care facilities.

The Elecsys HSV-1 IgG immunoassay makes use of a sandwich test principle using biotinylated recombinant HSV-1-specific antigens and HSV-1-specific recombinant antigens labeled with a ruthenium complex. The Elecsys HSV-1 IgG immunoassay is intended for the qualitative determination of IgG class antibodies to HSV-1 in human serum and in the presumptive diagnosis of HSV-1 infection. It is intended for use on the cobas e immunoassay analyzers. Results are determined automatically by the software by comparing the electrochemiluminescence signal obtained from the reaction product of the sample with the signal of the cutoff value previously obtained by calibration.

The provided text describes the Elecsys HSV-1 IgG immunoassay (08948844160) and its substantial equivalence to a legally marketed predicate device (Elecsys HSV-1 IgG, K120625). However, the document does not contain specific acceptance criteria, reported device performance figures, or detailed study information such as sample sizes, data provenance, ground truth establishment methods, or the results of comparative effectiveness studies.

The document primarily focuses on the regulatory aspects of the device, its intended use, and the technological updates made to improve biotin and streptavidin tolerance.

Therefore, many of the requested fields cannot be filled from the provided text.

Here's a breakdown of what can be extracted and what cannot:

1. Table of Acceptance Criteria and Reported Device Performance:

• Acceptance Criteria: Not explicitly stated in the document.
• Reported Device Performance: Not provided in the document.

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

• Sample Size (Test Set): Not provided.
• Data Provenance: Not provided.

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

• Not provided.

4. Adjudication method for the test set:

• Not provided.

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 is an immunoassay, not an AI-assisted diagnostic imaging or interpretation device. Therefore, an MRMC study as typically understood for AI in medical imaging would not be applicable, and no such study is mentioned.

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

• This is a standalone immunoassay device. The document mentions: "Results are determined automatically by the software by comparing the electrochemiluminescence signal obtained from the reaction product of the sample with the signal of the cutoff value previously obtained by calibration." This suggests standalone performance, but no specific study or performance metrics are detailed in this document.

7. The type of ground truth used:

• Not explicitly stated for performance evaluation. For HSV-1 serological assays, ground truth is typically established through a combination of confirmatory methods (e.g., Western blot, PCR, or clinical diagnosis based on symptoms and other tests), but the document does not specify this for its validation.

8. The sample size for the training set:

• Not provided.

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

• Not provided.

Summary of Available Information (with placeholders for missing data):

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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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For In Vitro Diagnostic Use Only. The SeraQuest HSV Type 1 Specific IgG assay is an enzyme-linked immunosorbent assay (ELISA) intended for the qualitative detection of human IgG antibodies to type 1 herpes simplex virus (HSV) in human serum. The test is indicated for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-1 infection. The predictive value of a positive 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, pediatric patients or matrices other than human serum.

The SeraQuest® HSV Type 1 Specific IgG test is a solid-phase enzyme-linked immunoassay (ELISA), which is performed in microwells, at room temperature, and in three thirty minute incubations. The test detects IqG antibodies which are directed against HSV 1 type-specific antigens in human serum. The Calibrator in the SeraQuest® HSV Type 1 Specific IgG test set has been assigned Index values based on an in-house standard. Test results are reported as Index values.

The SeraQuest HSV Type 1 Specific IgG assay is an enzyme-linked immunosorbent assay (ELISA) intended for the qualitative detection of human IgG antibodies to type 1 herpes simplex virus (HSV) in human serum.

Here's an analysis of the acceptance criteria and the studies performed:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document does not explicitly state pre-defined acceptance criteria (e.g., "Sensitivity must be >= X%"). Instead, it presents the results of a comparison study against a predicate device and a CDC panel, inferring that the performance achieved is deemed acceptable for substantial equivalence.

2. Sample Size and Data Provenance

   • Test Set (Comparative Study with Predicate Device):
     • Sexually Active Adults: 164 serum samples.
     • Expectant Mothers: 242 serum samples (198 during the first trimester, 19 during the second, 25 during the third).
     • Data Provenance: Prospectively collected, masked, and archived serum samples submitted for HSV serology to clinical laboratories in the Southeastern United States (for sexually active adults) and Northeastern and Southeastern United States (for expectant mothers). This indicates prospective data collection from the United States.
   • Test Set (CDC Panel): 100 serum samples (46 HSV-1 IgG positive, 54 HSV-1 IgG negative).
     • Data Provenance: This is a characterized serum panel provided by the Centers for Disease Control and Prevention (CDC). The specific country of origin for individual samples within the CDC panel is not specified, but the panel itself is a US-based reference.

3. Number of Experts and Qualifications for Ground Truth

   • The document does not mention the use of experts to establish ground truth for the comparative studies.
   • For the comparative study, the predicate device (Focus HerpeSelect® 1 and 2 Immunoblot IgG) served as the reference standard. The ground truth was based on the results of this legally marketed predicate device.
   • For the CDC panel, the CDC HSV 1 Result was used as the ground truth. This panel is composed of "well characterized serum panel" but the methods or experts used by CDC to characterize it are not detailed in this document.

4. Adjudication Method for the Test Set

   • No adjudication method (e.g., 2+1, 3+1) is mentioned for the test set. The results are directly compared to the predicate device's findings or the CDC's characterization of the panel.

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

   • No MRMC comparative effectiveness study was done. The device is an in-vitro diagnostic (IVD) assay, not an imaging device typically evaluated with human readers. Therefore, there is no discussion of human reader improvement with or without AI assistance.

6. Standalone Performance

   • Yes, standalone performance was done. The entire submission details the performance of the SeraQuest HSV Type 1 Specific IgG assay as a standalone device, directly comparing its results to a legally marketed predicate device (immunoblot) and a characterized CDC panel. The performance metrics (sensitivity, specificity, precision) are derived from the device's independent operation.

7. Type of Ground Truth Used

   • Comparative Studies: The ground truth was established by another legally marketed device (predicate device): the Focus HerpeSelect® 1 and 2 Immunoblot IgG.
   • CDC Panel: The ground truth was based on the characterization of the CDC serum panel, which is described as "well characterized."

8. Sample Size for the Training Set

   • The document does not explicitly state a "training set" size. For IVD devices, the development and optimization of the assay might involve internal studies and smaller panels, but these are typically not referred to as a separate "training set" in the same way machine learning models are. The performance studies presented are generally considered validation studies on independent test sets.

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

   • As no explicit "training set" is mentioned in the context of this IVD device, the method for establishing its ground truth is not provided. The document focuses on the validation of the device against established external references.

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The Theranos™ HSV-1 IgG Assay is a chemiluminescent immunoassay intended for the qualitative detection of IgG antibodies to herpes simplex virus type 1 (HSV-1) in human serum, in K2-EDTA anticoagulated human plasma from venous blood, and in human fingerstick K2-EDTA anticoagulated whole blood obtained with the Theranos Capillary Tubes and Nanotainer Tubes. The test is indicated for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-1 infection. The predictive value of positive and negative results depends on the population's prevalence and the pretest likelihood of HSV-1.

The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates and immunocompromised patients.

The Theranos HSV-1 IgG Assay is for use with the Theranos System which performs automated sample processing steps and result analysis.

The Theranos HSV-1 IgG Assay is for use with the Theranos System. The Theranos System performs automated sample processing steps and analysis to produce the test results.

The Theranos HSV-1 IgG Assay is a three-step sandwich immunoassav with an HSV-1 glycoprotein G (gG) recombinant antigen coated surface, an anti-human IgG detection reagent conjugated to alkaline phosphatase (AP) and chemiluminescent substrate. During the first incubation step, the HSV-1 IgG antibodies present in the positive control and sample bind to the gG recombinant antigen on the coated surface. Following the first incubation step, unbound materials are removed with a wash cycle. Then the detection reagent-AP conjugate is added and during the second incubation step, the detection reagent-AP conjugate reacts with the HSV-1 IgG antibodies already bound to the capture surface. Following the second incubation, unbound materials are removed with a wash cycle. The chemiluminescent substrate is added to the capture-analyte-detection complex during the third incubation step to initiate the chemiluminescence reaction. Light generated by this reaction is detected and analyzed by the Theranos System using a calibration function to determine the cut-off index (COI) values for the sample and controls. The results for the Positive and Negative controls must be within specified limits for a run to be considered valid.

The Theranos Herpes Simplex Virus-1 (HSV-1) IgG Assay is a chemiluminescent immunoassay for the qualitative detection of IgG antibodies to HSV-1 in human serum, K2-EDTA anticoagulated human plasma from venous blood, and human fingerstick K2-EDTA anticoagulated whole blood. It is intended to aid in the presumptive diagnosis of HSV-1 infection in sexually active individuals and expectant mothers.

Here's an analysis of the acceptance criteria and supporting study details:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state a consolidated table of acceptance criteria for all performance aspects. However, based on the studies described, we can infer some key criteria and the reported performance. The most critical performance metrics for a diagnostic assay like this are Sensitivity and Specificity in the intended use populations.

2. Sample Sizes and Data Provenance:

• Clinical Performance Study (Sexually Active Adults): 260 retrospectively collected, archived venous serum samples. Samples obtained from multiple specimen sources covering 10 US states and Mexico.
• Clinical Performance Study (Pregnant Women): 298 retrospectively collected, archived venous serum samples. Samples obtained from multiple specimen sources covering 10 US states and Mexico.
• Low Prevalence Population Study: 82 samples. Samples obtained from multiple specimen sources covering 10 US states and Mexico.
• CDC Panel Testing: 100 well-characterized serum samples. Origin: U.S. Centers for Disease Control and Prevention (CDC).
• Precision (Venous Serum): 6 serum samples, with varying replicates (72-94 total replicates per panel member). One site (CLIA Laboratory model).
• Precision (Fingerstick Whole Blood): 3 fingerstick plasma samples, with 170-171 total replicates per panel member. One site (CLIA Laboratory model).
• Reproducibility (Fingerstick Whole Blood): 30 subjects (10 subjects at each of 3 collection sites). From each subject, 9 Capillary Tubes and Nanotainer Tubes and 2 serum separator tubes (SSTs) were collected.
• Analyte Stability: Not explicitly stated but implied sufficient samples to represent different baseline COI values and matrices.
• Interfering Substances: 3 serum samples (negative, high negative, low positive) contrived from a high positive sample and pooled negative serum. Each pool tested in duplicate.
• Cross-reactivity: 21 different infectious agents/conditions, with at least 3 samples per agent (total of 139 samples). Samples acquired from commercial vendors.
• Assay Cut-off Establishment/Validation: 192 serum samples to establish, then 120 independent serum samples to validate.

3. Number of Experts and Qualifications for Ground Truth:

The document primarily relies on reference methods for ground truth, rather than independent experts for adjudication of individual cases.

• Clinical Performance (Sexually Active Adults & Pregnant Women): The FOCUS HerpeSelect Immunoblot was used as the reference method. When initial results were equivocal on the Focus HerpeSelect Immunoblot, a validated western blot reference test (University of Washington, Seattle) was used for resolution.
• CDC Panel Testing: The CDC itself provided a panel of "well characterized serum samples" (implies expert characterization and consensus by the CDC).
• Cross-reactivity: Banked serum samples "confirmed positive for IgG against the infectious agents of interest" and "negative for HSV-1 IgG on the reference method" were acquired from commercial vendors. The implicit experts are those who characterized these commercial samples and the reference method used.

No specific number or qualifications of experts are given beyond the implicit expertise associated with the CDC and the University of Washington laboratory performing the western blot.

4. Adjudication Method:

• Clinical Performance Studies: For equivocal results on the primary reference method (Focus HerpeSelect Immunoblot), a secondary reference method (University of Washington western blot) was used. This acts as a 2+1 adjudication method, where the primary reference method's equivocal cases are resolved by a more definitive test. Specifically, for sexually active adults, 10 samples were initially equivocal, and a western blot resolved 9 (2 negative, 7 positive), with 1 unresolved. For pregnant women, 8 samples were initially equivocal, with 4 resolved by western blot (1 negative, 3 positive) and 4 unresolved due to insufficient volume.

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

• No MRMC study was done. This device is an automated, standalone diagnostic assay (algorithm only) that provides a qualitative result (positive, negative, equivocal). It does not involve human readers interpreting results in the loop, or any comparison of human readers with vs. without AI assistance.

6. Standalone Performance:

• Yes, a standalone (algorithm only) performance study was done. The entire submission describes the performance of the Theranos HSV-1 IgG Assay and the Theranos System (which performs automated sample processing and result analysis) as a standalone device. The device itself generates the final qualitative result (positive, negative, equivocal) without human interpretation of the assay signal.

7. Type of Ground Truth Used:

• The ground truth for the clinical performance studies (Sexually Active Adults, Pregnant Women, Low Prevalence Population) was established by a reference method, specifically the FOCUS HerpeSelect Immunoblot, with equivocal results resolved by a validated western blot reference test (from the University of Washington, Seattle).
• For the CDC panel testing, the ground truth was based on the CDC's characterization of the serum samples.
• For cross-reactivity, ground truth was based on third-party validated positive samples for other infectious agents and negative for HSV-1.

8. Sample Size for the Training Set:

The document does not explicitly state the sample size for a "training set." This type of regulatory submission (510(k)) focuses on validation rather than the development and training phases of an algorithm. Therefore, details about the internal development (training and internal validation) of the device's algorithm are typically not included or required in this format. The performance studies discussed are considered validation studies.

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

As no "training set" details are provided in this document, the method for establishing its ground truth is also not described. The document focuses on the validation of the device's performance against established reference methods.

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The Gold Standard Diagnostics Herpes Simplex Virus Type 1 IgG ELISA Test Kit is intended for the qualitative detection of IgG antibodies to Herpes Simplex Virus Type 1 (HSV-1) in human serum. The test is indicated for sexually active individuals and expectant mothers as an aid for the presumptive diagnosis of HSV-1 infection.

The predictive value of positive or negative results depends on the population's prevalence and the pretest likelihood of HSV-1. The test is not intended for screening of blood and plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates, or immunocompromised patients.

The Gold Standard Diagnostics Herpes Simplex Virus (HSV) Type I IgG ELISA Test is an enzyme linked immunosorbent assay for the qualitative detection of IgG antibodies to HSV-1 in human serum. The assay requires a total of 90 minutes incubation time. The test uses microtiter wells coated with a recombinant gG1 protein of HSV-1. Serum is added to each well and incubated for 30 minutes at 37℃. If antibodies are present they will bind to the antigen in the well. Unbound antibodies are removed by washing the wells three times. A Horse Radish Peroxidase (HRP) conjugated goat anti-human IgG (conjugate) is then added to each well and incubated for 30 minutes at 37°C. If antibodies are present in the patient's serum, the conjugate will bind to the antibody attached to the antigen on the wells are again washed to remove any unbound conjugate. In order to detect the bound conjugate a substrate containing tetramethylbenzidine (TMB) is added to each well and incubated for 30 minutes at 37°C. If conjugate is present, the HRP will react with the substrate to generate a colored product. After the incubation period, the reaction is stopped with a . Stop Solution and the color intensity is measured spectrophotometrically. The kit also includes a Wash Buffer, Diluent, a Negative Control, and a Cutoff Control. The cut-off control is used to determine the validity of the assay and subsequently to determine the result of the sample. Positive and Negative controls are provided to determine if the assay is functioning properly. The kit contains 12 x 8well antigen coated microtiter strips in a frame. The reagents are sufficient for 96 determinations.

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

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are implicitly defined by its comparison to a legally marketed predicate device (Focus Diagnostics HerpeSelect® 1 and 2 Immunoblot IgG) and by demonstrating acceptable precision, reproducibility, cross-reactivity, and interference performance. The document doesn't explicitly state numerical acceptance criteria for sensitivity and specificity a priori but lists the achieved performance values.

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

• Clinical Performance Test Set:
  • Total Samples: 703 samples.
  • Pregnant Women: 185 samples.
  • Sexually Active Adults: 518 samples.
  • Low Prevalence Population: 96 samples (sera ages 16-19 years old).
  • CDC Seroconversion Panel: 100 samples (46 positive, 54 negative - implied from counts).
• Data Provenance:
  • Pregnant Women and Sexually Active Adults: Prospectively collected.
  • Low Prevalence Population: Prospectively collected in a non-STD setting. Tested in-house.
  • CDC Seroconversion Panel: Obtained from the CDC. Tested in-house.
  • Cross-reactivity samples: Obtained from serum brokers.

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

The ground truth for the clinical performance study (the primary test set) was established by comparison to a commercially available predicate device: Focus Diagnostics HerpeSelect® 1 and 2 Immunoblot IgG test (K000238). The document does not mention the use of human experts to establish ground truth for this comparison study, as the predicate device itself serves as the reference.

For the cross-reactivity study, ground truth for the "positive for" status of the samples was confirmed by "serum brokers who confirmed positivity for each respective disease and conditions using FDA cleared tests." The number and specific qualifications of these "serum brokers" or the experts validating the FDA cleared tests are not specified.

4. Adjudication Method for the Test Set

For the clinical performance studies comparing the Gold Standard Diagnostics ELISA to the Focus Diagnostics Line Blot, the adjudication method for discordant results (equivocal results) was explicitly stated: "Equivocal results were treated as the worst case results (disagreement)". This implies that equivocal results were counted as disagreements with the predicate device's result when calculating sensitivity and specificity.

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

No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) ELISA test, which does not involve human readers interpreting images or data to the extent that an MRMC study for AI would typically describe. The "reading" is done by a spectrophotometer, and the comparison is between two IVD assay technologies.

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

Yes, the device's performance as an algorithm-only system (an ELISA test measured by a spectrophotometer) was evaluated. The results presented for sensitivity, specificity, precision, reproducibility, cross-reactivity, and interfering substances all represent the standalone performance of the Gold Standard Diagnostics Herpes Simplex Virus Type 1 IgG ELISA Test Kit. There is no human-in-the-loop component described for the operation or interpretation of this particular assay's results.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The primary type of ground truth used was comparison to a legally marketed predicate device (Focus Diagnostics HerpeSelect® 1 and 2 Immunoblot IgG test).

Additionally:

• For the cross-reactivity panel, the ground truth for specific infections was established by "FDA cleared tests" as reported by serum brokers.
• For the CDC seroconversion panel, the ground truth was based on "well-characterized HSV I serum samples" obtained from the CDC, indicating a highly validated and accepted reference standard.

8. The Sample Size for the Training Set

The document does not mention a training set in the context of an algorithm or machine learning. This is an ELISA kit, which is a biochemical assay, not an AI/ML algorithm that requires training data in the traditional sense. The development and optimization of the ELISA kit would involve internal validation and batch testing, but this is distinct from an AI training set.

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

As explained above, there is no "training set" for this type of device in the AI/ML context. The assay's performance characteristics are established through analytical and clinical studies comparing it to known standards (predicate device, CDC panel) and characterized samples.

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The Roche Elecsys HSV-1 IgG immunoassay is a test for the in vitro qualitative determination of IgG class antibodies to HSV-1 in human serum and lithium-heparin plasma, K2—EDTA plasma, and K3—EDTA plasma. The test is intended for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-1 infection. The predictive value of positive and negative results depends on the population's prevalence and the pretest likelihood of HSV-1. The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers. The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates, immunocompromised patients, or for use at point of care facilities.

PreciControl HSV is used for quality control of the Elecsys HSV-1 IgG immunoassay on the Elecsys and cobas e immunoassay analyzers.

(1) The Elecsys HSV-1 IgG immunoassay is a two-step sandwich immunoassay with streptavidin microparticles, biotinylated recombinant HSV-1-specific antigen labeled with a ruthenium complex and electrochemiluminescence detection. This assay is a qualitative test based on a cut-off formula dependent on the negative and positive calibrators. Cut-off index (COI) is based on the ratio of assay signal to cut-off signal (also abbreviated s/co). COI values greater than or equal to 1.0 are considered positive for the presence of anti-HSV-1 IgG antibody. Results are determined using a two-point calibration. The test system contains the human serum-based calibrators intended for use with the system. (2) PreciControl HSV contains lyophilized control serum based on human serum. The controls are used for monitoring the accuracy of the Elecsys HSV-1 IgG immunoassay.

Here's an analysis of the acceptance criteria and study details for the Elecsys HSV-1 IgG Immunoassay, extracted from the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Elecsys HSV-1 IgG Immunoassay are demonstrated through its agreement with a Western Blot (WB) assay within different cohorts. The performance is reported as Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA).

Note: The document implicitly establishes the reported performance as meeting acceptance criteria by presenting it in the context of substantial equivalence.

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

• Expectant Mother Cohort: n=125
• Sexually Active Cohort: n=600
• Low Prevalence Cohort: n=200
• CDC Panel: Not explicitly stated, but 100% agreement indicates a comparison against a reference standard panel.

Data Provenance: The document does not explicitly state the country of origin for the data or whether it was retrospective or prospective.

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

The ground truth for the device's performance comparison was established using a Western Blot (WB) assay as the comparator (predicate device: Focus HerpeSelect 1 and 2 Immunoblot IgG (K000238)). This is a laboratory test, not an interpretation by human experts.

For the "Agreement with CDC Panel," the CDC panel itself represents a reference standard, implying established truth without direct mention of human experts in this section.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method involving multiple human readers for the test set. The direct comparison is between the candidate device (Elecsys HSV-1 IgG Immunoassay) and a predicate Western Blot assay.

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. The study compares the performance of the device against a predicate laboratory assay (Western Blot), not against human readers.

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

Yes, the performance study performed appears to be a standalone assessment of the Elecsys HSV-1 IgG Immunoassay. The assay produces a quantitative result (Cut-off Index, COI) that is interpreted as reactive (≥ 1.0 COI) or non-reactive (< 1.0 COI). This is an automated algorithmic output, and its performance is compared directly to the Western Blot without human interpretation loops being described as part of the core performance evaluation study.

7. The Type of Ground Truth Used

The primary ground truth used for establishing the performance metrics (Positive Percent Agreement and Negative Percent Agreement) was the Focus HerpeSelect 1 and 2 Immunoblot IgG (K000238) Western Blot assay. This is a laboratory-based serological test, which serves as a reference standard for HSV-1 IgG antibody detection. Additionally, agreement with a CDC Panel was used as a ground truth comparison.

8. The Sample Size for the Training Set

The document does not provide information regarding the sample size of a training set for the Elecsys HSV-1 IgG Immunoassay. As this is a laboratory immunoassay and not an AI/machine learning algorithm in the typical sense of needing a distinct training set for model development, such information is generally not applicable or explicitly provided in this type of submission. The device's cut-off is based on a formula dependent on calibrators.

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

Since no training set for an AI/machine learning model is described, the method for establishing its ground truth is not applicable or provided in the document. The assay's operational parameters, including cut-offs, are established through internal assay development and calibration procedures.

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The BioPlex® 2200 HSV-1 & HSV-2 IgG kit is a multiplex flow immunoassay intended for the qualitative detection and differentiation of IgG antibodies to herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) in human serum and EDTA or heparinized plasma. The test is indicated for sexually active individuals and expectant mothers as an aid for the presumptive diagnosis of HSV-1 or HSV-2 infection. The predictive value of positive or negative results depends on the population's prevalence and the pretest likelihood of HSV-1 and HSV-2. The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates and immunocompromised patients or for use at point of care facilities.

The BioPlex® 2200 HSV-1 & HSV-2 IgG kit is intended for use with the Bio-Rad BioPlex® 2200 System.

The BioPlex® 2200 HSV-1 & HSV-2 IgG Calibrator Set is intended for the calibration of the BioPlex® 2200 HSV-1 & HSV-2 IgG Reagent Pack.

The BioPlex® 2200 HSV-1 & HSV-2 IgG Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex® 2200 Instrument and BioPlex® HSV-1 & HSV-2 IgG Reagent Pack in the clinical laboratory. The performance of the BioPlex® 2200 HSV-1 & HSV-2 IgG Control Set has not been established with any other HSV-1 and HSV-2 antibody assays.

The BioPlex® 2200 HSV-1 & HSV-2 IgG kit uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. Two (2) different populations of dyed beads are each coated with antigens associated with herpes simplex virus, types 1 and 2.

The BioPlex® 2200 System combines an aliquot of patient sample, sample diluent, and bead reagent into a reaction vessel; the mixture is incubated at 37°C. After a wash cycle, antihuman IgG antibody, conjugated to phycoerythrin (PE), is added to the dyed beads, and this mixture is incubated at 37℃. The excess conjugate is removed in another wash cycle, and the beads are re-suspended in wash buffer. The bead mixture then passes through the detector. The identity of the dyed beads is determined by the fluorescence of the dyes, and the amount of antibody captured by the antigen is determined by the fluorescence of the attached PE. Raw data are calculated in relative fluorescence intensity (RFI).

Three additional dyed beads, an Internal Standard Bead (ISB), a Serum Verification Bead (SVB) and a Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum or plasma to the reaction vessel and the absence of significant non-specific binding in serum or plasma. Refer to the BioPlex® 2200 System Operation Manual for more information.

The instrument is calibrated using a set of four (4) distinct calibrator vials, supplied separately by Bio-Rad Laboratories. The four (4) vials representing four (4) different antibody concentrations are used for calibration. The result for each of these antibodies is expressed as an antibody index (AI).

The BioPlex® 2200 HSV-1 & HSV-2 IgG Control Set includes a negative control as well as multi-analyte positive control. The Positive Control is manufactured to give positive results, with values above the cut-off for each specific analyte. The Negative Control is manufactured to give negative results, with values below the cut-off for each specific analyte.

This document describes the BioPlex® 2200 HSV-1 & HSV-2 IgG kit for qualitative detection and differentiation of IgG antibodies to HSV-1 and HSV-2. The primary acceptance criteria provided relate to comparative testing against a predicate device and a CDC panel, as well as precision studies and interference testing.

Here's the breakdown of the information requested:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state numerical "acceptance criteria" independently, but rather presents the performance of the modified device in comparison to a predicate device and a CDC panel. The comparisons effectively serve as the standard for acceptance, implying that the modified device should perform comparably or better.

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

• Comparative Testing (Predicate Device):
  • Test Set Size: 399 samples for HSV-1, 399 samples for HSV-2.
  • Data Provenance: Samples from sexually active individuals where an HSV-1 or HSV-2 test was ordered. The country of origin is not explicitly stated but is implied to be within the jurisdiction of the Bio-Rad Laboratories, Inc. (Benicia, CA). The data is retrospective, as it involves comparison to an already marketed predicate device and characterization of existing samples.
• Comparative Testing (CDC HSV Panel):
  • Test Set Size: 80 samples.
  • Data Provenance: A "well characterized HSV serum panel from the CDC." This suggests existing, well-defined samples. The country of origin is the United States (CDC). This data is retrospective.
• Precision Studies:
  • Test Set Size: 8 panel members for each analyte (HSV-1 and HSV-2), each tested 20 times (2 replicates x 2 runs x 5 days).
  • Data Provenance: Prepared by Bio-Rad Laboratories, tested at Bio-Rad Laboratories. Retrospective/internal data.
• Interference Testing:
  • Test Set Size: Samples prepared by blending negative human serum with positive samples. Evaluated in replicates of ten. Specific number of donor samples not provided, but the interference substances are well-defined.
  • Data Provenance: Internal studies by Bio-Rad Laboratories. Retrospective.
• Matrix Comparison:
  • Test Set Size: >40 matched serum and plasma (EDTA and heparin sodium) samples for each assay (47 for HSV-1, 44 for HSV-2).
  • Data Provenance: Matched serum and plasma drawn from the same donor, acquired from commercial sources. Retrospective.

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

The ground truth for the test sets (comparative testing with predicate and CDC panel) was established through existing reference methods.

• Predicate Device Comparison: The "predicate method" served as the reference standard. The document does not specify the number or qualifications of experts involved in the initial determination by the predicate method.
• CDC HSV Panel: The panel is described as "well characterized," implying its status as a reference standard. The document does not specify the number or qualifications of experts involved in characterizing the CDC panel.

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

The document does not describe an adjudication method for disagreements. The comparisons rely on agreement with the predicate device results or the CDC panel's established status.

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

A multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) kit that directly measures antibody levels, not an AI-assisted diagnostic tool that interprets images or other complex data requiring human reader interaction. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.

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

Yes, the performance studies presented are for the standalone device (BioPlex® 2200 HSV-1 & HSV-2 IgG kit on the BioPlex® 2200 Multi-Analyte Detection System) without human interpretation as part of the primary diagnostic output. The results (antibody index) are objectively measured by the automated system.

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

The ground truth used was based on:

• Reference Method/Predicate Device: For the comparative testing against the predicate device, the results obtained from the legally marketed predicate device served as the reference standard.
• Reference Panel: For the CDC HSV Panel, the "well-characterized" status of the panel served as the established ground truth. This type of panel typically undergoes extensive testing and validation, often using a combination of methods and expert consensus to establish the definitive status of each sample.

8. The sample size for the training set

The document does not explicitly mention a "training set" in the context of machine learning or AI. This is an IVD kit, and studies focus on analytical and clinical performance. The studies performed are validation studies, not training studies for an algorithm.

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

As there is no "training set" in the context of an AI/ML algorithm for this IVD device, this question is not applicable. The development and validation of the device are based on laboratory testing and comparisons to established reference methods and panels.

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The BioPlex™ 2200 HSV-1 & HSV-2 IgG kit is a multiplex flow immunoassay intended for the qualitative detection and differentiation of IgG antibodies to herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) in human serum and EDTA or heparinized plasma. The test is indicated for sexually active individuals and expectant mothers as an aid for the presumptive diagnosis of HSV-1 or HSV-2 infection. The predictive value of positive or negative results depends on the population's prevalence and the pretest likelihood of HSV-1 and HSV-2.

The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates and immunocompromised patients or for use at point of care facilities.

The BioPlex 2200 HSV-1 & HSV-2 IgG kit is intended for use with the Bio-Rad BioPlex 2200 System.

The BioPlex 2200 HSV-1 & HSV-2 IgG kit uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube.

Two different populations of dyed beads are each coated with antigens associated with herpes simplex virus, types 1 and 2. The BioPlex 2200 System combines an aliquot of patient sample, sample diluent, and bead set reagent into a reaction vessel. The mixture is incubated at 37°C. After a wash cycle, anti-human IgG antibody, conjugated to phycoerythrin (PE), is added to the dyed beads and this mixture is incubated at 37°C. The excess conjugate is removed in another wash cycle, and the beads are re-suspended in wash buffer. The bead mixture then passes through the detector. The identity of the dyed beads is determined by the fluorescence of the dyes, and the amount of antibody captured by the antigen is determined by the fluorescence of the attached PE. Raw data is calculated in relative fluorescence intensity (RFI).

Three additional dyed beads, an Internal Standard Bead (ISB), a Serum Verification Bead (SVB) and a Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum to the reaction vessel and the absence of significant non-specific binding in serum. Refer to the BioPlex 2200 System Operation Manual for more information.

The instrument is calibrated using a set of 4 distinct calibrator vials, supplied separately by Bio-Rad Laboratories.

Here's a breakdown of the acceptance criteria and the study details for the BioPlex 2200 HSV-1 and HSV-2 IgG kit, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as a pass/fail threshold, but rather presents performance metrics. Thus, I've interpreted the "acceptance criteria" as the performance levels demonstrated by the predicate device (implicitly accepted by the FDA) and the "reported device performance" as the BioPlex 2200's performance as measured against a commercially available immunoblot.

Assumed "Acceptance Criteria" (based on predicate performance and FDA clearance of similar devices): High sensitivity and specificity, typically above 90% in relevant populations, to reliably detect and differentiate HSV-1 and HSV-2 IgG antibodies. Precision and reproducibility should also be high (low CV).

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

• Sexually Active Individuals with HSV-1 test ordered: N = 289
• Sexually Active Individuals with HSV-2 test ordered: N = 286
• Expectant Mothers: N = 399
• CDC Panel: N = 100
• Low Prevalence Population (16-19 years, non-STD setting): N = 200

Data Provenance:

• Country of Origin: The comparative studies were "conducted at a total of 3 U.S. clinical sites." The low-prevalence study was conducted at "2 U.S. clinical testing sites." The CDC panel is from the U.S. Centers for Disease Control.
• Retrospective or Prospective: The comparative study in intended use populations (sexually active individuals and expectant mothers) was described as a "prospective study." The low-prevalence study used "remnant serum samples," which suggests a retrospective collection, but the study itself was presumably designed prospectively for analysis. The CDC panel samples are well-characterized.

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 qualifications. The ground truth for comparative testing was established by a "commercially available immunoblot test" and a "masked, well characterized HSV serum panel from the CDC." This implies that the ground truth was based on the consensus or established characterization of these reference methods, rather than real-time expert adjudication of individual cases.

4. Adjudication Method for the Test Set

The document describes how equivocal results were handled for the comparative effectiveness study:

• "For purposes of sensitivity calculations, the BioPlex 2200 equivocal results were assigned to the opposite clinical interpretation than that of the corresponding immunoblot result."
• "Likewise, immunoblot equivocal results were assigned to the opposite clinical interpretation than that of the BioPlex 2200 result."

This method effectively forces equivocal results into either positive or negative, but it's important to note that this is a specific approach for calculating sensitivity and specificity and not a general adjudication method for reporting results. It doesn't describe an expert panel adjudication.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This device is an in-vitro diagnostic (IVD) assay that directly measures antibodies; it does not involve human readers interpreting images, and therefore, does not involve AI assistance for human readers.

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

Yes, the studies presented are standalone (algorithm only) performance analyses. The BioPlex 2200 HSV-1 and HSV-2 IgG kit is an automated system that processes samples and provides quantitative (Relative Fluorescence Intensity, RFI) or qualitative (Positive, Equivocal, Negative) results without direct human interpretive input beyond running the instrument and reviewing the automated output. Its performance is compared directly against the immunological ground truth.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth used for the comparative studies was:

• A commercially available immunoblot test (e.g., Focus HerpesSelect 1 and 2 Immunoblot IgG).
• A masked, well-characterized HSV serum panel from the CDC. These panels are typically established through extensive testing using multiple reference methods and expert consensus on their true status.

8. The Sample Size for the Training Set

The document describes studies for performance validation of the device. It does not provide information on a "training set" for the development of the BioPlex 2200 assay itself. IVD devices like this are typically developed internally by the manufacturer using their own validation processes, and the 510(k) submission focuses on clinical validation results rather than details of internal algorithm training. Therefore, the sample size for a training set (if applicable to the assay's internal development) is not disclosed in this summary.

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

Since information on a specific "training set" and its size is not provided (as it's beyond the scope of a 510(k) performance summary for an IVD), details on how its ground truth was established are also not available in this document.

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