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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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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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lmmunoassay for the in vitro qualitative determination of IgG class antibodies to HSV-2 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-2 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 or negative results depends on the population's prevalence and the pretest likelihood of HSV-2.

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, or immunocompromised patients or for use at point-of-care facilities.

The Elecsys HSV-2 IgG immunoassay makes use of a sandwich test principle using biotinylated recombinant HSV-2-specific antigens and HSV-2-specific recombinant antigens labeled with a ruthenium complex. The Elecsys HSV-2 IgG immunoassay is intended for the qualitative determination of lgG class antibodies to HSV-2 in human serum and in the presumptive diagnosis of HSV-2 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 Elecsys HSV-2 IgG (08948887160) device is an immunoassay for the qualitative determination of IgG class antibodies to HSV-2. The study involved a comparison against a predicate device (K121895).

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of acceptance criteria with specific performance metrics (e.g., sensitivity, specificity thresholds) that were required for clearance or the corresponding reported device performance values in a quantitative manner. Instead, it focuses on demonstrating substantial equivalence to a predicate device and improved technical characteristics.

The "Non-Clinical and/or Clinical Tests Summary & Conclusions 21 CFR 807.92(b)" section is where such data would typically be found, but it is not expanded upon in the provided text. The submission describes technological improvements to biotin tolerance and streptavidin interference, which are performance characteristics.

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

The provided text does not specify the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective). This information would typically be detailed within the non-clinical and/or clinical test summary.

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

The provided text does not specify the number of experts used to establish the ground truth for the test set or their qualifications. For an immunoassay, the ground truth would typically be established by a reference method or a panel of samples with confirmed HSV-2 status, rather than expert interpretation of images or clinical cases.

4. Adjudication Method

The provided text does not specify any adjudication method. For an immunoassay, adjudication might not be relevant in the same way as for subjective diagnostic tasks like image interpretation, as the result is typically a quantitative measurement converted to a qualitative outcome.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted, as this device is an immunoassay and does not involve human readers interpreting cases in the same way an imaging diagnostic device would. Therefore, there is no effect size reported for human readers improving with or without AI assistance.

6. Standalone Performance

The device itself is a standalone immunoassay. Its performance is measured directly through its ability to detect HSV-2 IgG antibodies. While the document mentions "cobas e immunoassay analyzers" for its use, the performance described would implicitly be the standalone performance of the assay on these automated platforms. The provided text does not provide quantitative standalone performance metrics such as sensitivity and specificity.

7. Type of Ground Truth Used

The type of ground truth used is not explicitly stated in the provided text. However, for an immunoassay for antibodies, the ground truth for test samples would typically be established by:

• Reference methods: Such as Western blot, more sensitive PCR, or another highly validated immunoassay.
• Clinical diagnosis and follow-up: Including a history of recurrent genital lesions confirmed by viral culture or PCR.
• Well-characterized seroconversion panels: For sensitivity studies.

Given that this is an immunoassay for IgG antibodies to HSV-2, the ground truth would likely involve confirmed HSV-2 infection status based on established laboratory methods and/or clinical presentation.

8. Sample Size for the Training Set

The provided text does not specify the sample size for the training set. Immunoassays are typically "trained" during their development and optimization phases using numerous characterized samples to establish appropriate cut-offs and ensure performance.

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

The provided text does not specify how the ground truth for the training set was established. Similar to the test set, it would have involved established laboratory reference methods and/or clinical confirmation of HSV-2 status. For an immunoassay, training involves optimizing reagent concentrations, reaction conditions, and setting cut-off values using panels of known positive and negative samples.

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The SeraQuest HSV Type 2 Specific IgG assay is an enzyme-linked immunosorbent assay (ELISA) intended for the qualitative detection of human IgG antibodies to type 2 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-2 infection. The predictive value of a positive or negative result depends on the prevalence of HSV-2 infection in 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.

The SeraQuest® HSV Type 2 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 IgG antibodies which are directed against HSV 2 type-specific antigens in human serum. The Calibrator in the SeraQuest® HSV Type 2 Specific IgG test set has been assigned Index values based on an in-house standard. Test results are reported as Index values.

This document describes the performance of the SeraQuest® HSV Type 2 Specific IgG assay when performed on the ChemWell® Automated Analyzer, comparing it to the previously cleared manual method.

Here's the breakdown of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state numerical acceptance criteria in a dedicated section. However, the "Method Comparison Study" presents the core performance metrics (Positive Percent Agreement and Negative Percent Agreement) against the predicate device. For the purpose of this response, we infer that high agreement with the predicate device is the acceptance criterion.

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

• Sample Size for Test Set: 226 samples.
• Data Provenance: Samples were developed from "remnants of patient samples and samples from vendors." Additional samples were prepared by spiking negative samples with positive samples or dilution with diluent reagent to span the range of the assay's measuring interval. The country of origin is not specified, but it can be inferred as being related to the applicant's location (Palm City, Florida, USA). The study appears to be a retrospective evaluation using existing or manufactured samples.

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

The ground truth for the test set was established by comparison against a predicate device (manual method), not by independent expert interpretation. Therefore, experts were not explicitly used to establish the ground truth for this device in the context of this study. The "ground truth" here is the result obtained from the established manual method.

4. Adjudication Method for the Test Set

No adjudication method using multiple readers or experts is described, as the comparison is between two automated/semi-automated assay methods (the new device vs. the predicate). The "truth" for the comparison was the result generated by the manual method.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done. This study focuses on the equivalence of an automated assay to a manual assay, not on human reader performance.

6. Standalone (Algorithm Only) Performance

Yes, a standalone comparison was done. The study directly compares the performance of the "SeraQuest® HSV Type 2 Specific IgG assay performed by ChemWell® Automated Analyzer" (the new device) against the "SeraQuest® HSV Type 2 Specific IgG assay performed by Manual Method" (the predicate device). This evaluates the algorithm/device performance independently of human interpretation, focusing on concordance between the two methods.

7. Type of Ground Truth Used

The type of ground truth used was comparison to a predicate device (manual assay results). This means the "truth" for evaluating the automated analyzer was the result provided by the already cleared manual method.

8. Sample Size for the Training Set

The document does not explicitly mention a separate training set or its sample size. The study focuses on verifying the performance of the automated analyzer against the predicate manual method using the 226 samples for method comparison and additional samples for precision studies.

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

Since a separate training set is not explicitly described, the method for establishing its ground truth is also not detailed. The validation approach is based on demonstrating equivalence to an existing, cleared method.

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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 Sentosa® SA201 HSV-1/2 PCR Test is a real-time PCR-based qualitative in vitro diagnostic test for detection and differentiation of Herpes Simplex Virus (HSV-1 and HSV-2) DNA from male and female skin lesions from anogenital or oral sites. The test is intended for use as an aid in diagnosis of herpes infection in symptomatic patients.

Warning: The Sentosa® SA201 HSV-1/2 PCR Test is not FDA cleared for use with cerebrospinal fluid (CSF). The test is not intended to be used for prenatal screening.

The Sentosa® SA201 HSV-1/2 PCR Test is a (4x24) configuration contains reagents and enzymes for specific amplification of a 104 bp (base-pair) fragment of the UL30 gene common to both HSV1 and HSV2, and specific probes for the direct detection and differentiation of HSV1 and HSV2 amplicons, respectively. Pathogen detection by PCR is based on the amplification of specific regions of the pathogen genome. In real-time PCR, the amplified product is detected via fluorescent dyes, which are usually linked to oligonucleotide probes that bind specifically to the target sequences. Real-time monitoring of the fluorescence intensities during a PCR run allows the detection of the accumulating product. Amplification of the targets occurs in three channels: green, orange and red on the Sentosa® SA201. Output is recorded as the increase of fluorescence over time in comparison to background signal. Monitoring the fluorescence intensities during the PCR run allows the detection of the accumulating product without having to re-open the reaction tubes after the PCR run.

The Sentosa® SA201 HSV-1/2 PCR Test workflow starts with extraction of nucleic acids from samples (anogenital or oral swabs) using the Sentosa® SX Virus Total Nucleic Acid Kit on the Sentosa SX101 instrument. Following extraction, the instrument will automatically set up the PCR with the extracted nucleic acids in a 96-well PCR plate. Subsequently, the 96-well PCR plate is sealed and transferred to the Sentosa® SA201 for PCR amplification, followed by data analysis.

The Sentosa® Link facilitates data transfer between the Sentosa® SX101, the Sentosa® SA201 Reporter and existing LIS/LIMS (laboratory information systems) in the clinical lab. The Sentosa SX101 instrument communicates with Sentosa® SA201 thermocycler. This creates a user environment that links the SX101 and the Sentosa® SA201 to facilitate automated workflow to export results in a LIS/LIMS-compatible format.

The provided document describes the analytical and clinical performance of the Sentosa SA201 HSV-1/2 PCR Test, a qualitative in vitro diagnostic test for the detection and differentiation of Herpes Simplex Virus (HSV-1 and HSV-2) DNA. It is not an AI/ML-based device. Therefore, the questions related to AI/ML specific aspects (e.g., number of experts, adjudication, MRMC study, training set, ground truth for training set) are not applicable. The information focuses on the device's ability to accurately detect and differentiate HSV-1 and HSV-2 DNA in patient samples.

Here's an analysis of the provided information, focusing on the device's acceptance criteria and the studies proving it meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a single table, but the performance studies demonstrate implied criteria. For diagnostic devices like this, the key performance metrics are sensitivity, specificity, limit of detection (LoD), precision, and freedom from interference.

2. Sample Sizes and Data Provenance

• Test Set (Clinical Study):

  • Total Samples Enrolled: 2684
  • Samples in Final Analysis: 2295 (389 excluded due to unspecified reasons)
  • Oral Lesions: 317
  • Anogenital Lesions: 1978
  • Data Provenance: Residual anogenital lesion or oral lesion samples from male and female patients with signs and symptoms of HSV infections. Collected from 8 sites in the USA. Samples were tested either at the same facility they were obtained or shipped to a different testing site.
  • Retrospective/Prospective: The text does not explicitly state retrospective or prospective. However, "residual samples" suggest a retrospective collection. "Samples were either tested at the same facility at which they were obtained, or were shipped to a different testing site" could imply some forward-looking testing strategy, but it's not clearly defined as a prospective study. Given the clinical study results are compared against a "reference test," it most likely involves previously collected and banked samples.

• Test Set (Analytical Studies):

  • Limit of Detection: Determined by Probit analysis; specific sample numbers not explicitly given beyond "multiple replicates" across concentrations.
  • Precision: 60 replicates per sample type (NC, PC, 3xLoD HSV-1, 1.5xLoD HSV-1, 3xLoD HSV-2, 1.5xLoD HSV-2).
  • Reproducibility: 90 replicates per sample type (same as precision).
  • Analytical Reactivity / Cross-reactivity: 55 organisms tested, plus high and low concentration HSV-1/2 samples with competing organisms. Specific replicate numbers not given for all reactivity tests.
  • Interfering Substances: Each of 31 substances assayed in triplicate. Competitive interference study used 20 replicates for each combination.
  • Carry-over and Cross-contamination: 12 runs; 96 positive samples, 183 negative samples.

• Training Set: Not applicable for this type of PCR diagnostic device. This device is based on a well-defined molecular biology assay (real-time PCR) and does not involve AI/ML models that require dedicated training data sets in the typical sense. Performance is assessed through analytical validation (LoD, precision, specificity) and clinical concordance with a reference method.

3. Number of Experts and Qualifications to Establish Ground Truth

Not applicable. This is a molecular diagnostic test, not an image-based AI/ML device relying on expert human interpretation for ground truth.

4. Adjudication Method for the Test Set

Not applicable. Ground truth for the clinical study was established by a "reference test" (ELVIS® HSV ID and D3 Typing Test System) and supplemented by "bi-directional sequencing analysis" for discordant samples. This is a confirmatory molecular method, not human adjudication.

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

Not applicable. This is a diagnostic test; it is not described as providing AI assistance to human readers.

6. Standalone (Algorithm Only) Performance

The entire performance evaluation of the Sentosa SA201 HSV-1/2 PCR Test represents its "standalone" performance, as it is a fully automated system from nucleic acid extraction to result reporting. There is no human interpretative step described for the final result.

7. Type of Ground Truth Used

• Clinical Study: The primary ground truth for the clinical study was the ELVIS® HSV ID and D3 Typing Test System. For samples with discordant results between the Sentosa test and the ELVIS system, bi-directional sequencing analysis was used as a confirmatory method to resolve the discrepancy. This is a molecular gold standard.
• Analytical Studies: Ground truth for analytical studies was established by known concentrations of well-characterized viral strains (TCID50/mL) for LoD, precision, and reproducibility. For analytical specificity and interference studies, known panels of organisms and substances were used.

8. Sample Size for the Training Set

Not applicable, as this is not an AI/ML device requiring a training set in that context.

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

Not applicable.

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The Aptima Herpes Simplex Viruses 1 & 2 assay (Aptima HSV 1 & 2 assay) is an in vitro diagnostic nucleic acid amplification test (NAAT), using real time transcription-mediated amplification (TMA), for the qualitative detection and differentiation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) messenger RNA (mRNA) in clinician-collected swab specimens from anogenital skin lesions. The assay is intended for use with swab specimens placed in Aptima specimen transport medium (STM) or in viral transport media (VTM) that is immediately diluted into STM.

The Aptima HSV 1 & 2 assay is intended for use as an aid in the diagnosis of HSV-1 and/or HSV-2 infections in symptomatic male and female patients. The Aptima HSV 1 & 2 assay is indicated for use on the Panther® system.

The Aptima Herpes Simplex Virus 1 & 2 assay (Aptima HSV assay) is a nucleic acid amplification test (NAAT) developed for use on the fully automated Panther system that utilizes target capture, transcription mediated amplification (TMA), and real-time detection of HSV-1, HSV-2, and an internal control (IC). The Aptima HSV assay amplifies and detects mRNAs for HSV-1 and HSV-2. These RNAs are expressed from the viral genome during the infection cycle, and are packaged inside HSV-1 and HSV-2 viral particles prior to virus release from infected cells. The Aptima HSV assay therefore detects virus-infected cells and the mature virus particles themselves.

The Aptima HSV assay involves three main steps, which all take place in a single tube on the Panther® system: target capture, target amplification by TMA, and detection of the amplification products (amplicon) by the fluorescent labeled probes (torches). The assay incorporates an IC in every test to monitor targeted nucleic acid capture, amplification and detection.

When the Aptima HSV assay is performed, the targeted viral mRNA and IC are isolated using magnetic microparticles and target-specific capture oligomers, in a process called target capture. The capture oligomers contain sequences complementary to specific regions of the targeted RNA (HSV mRNA or IC) as well as a string of deoxyadenosine residues. During the hybridization step, the sequence-specific regions of the capture oligomers bind to specific regions of the RNA target molecules. The microparticles, including the captured RNA target molecules bound to them, are pulled to the side of the reaction tube using magnets and the supernatant is aspirated. The particles are washed to remove residual specimen matrix that may contain amplification inhibitors. After target capture steps are completed, the specimens are ready for amplification.

Target amplification occurs via TMA, which is a transcription-based nucleic acid amplification method that utilizes two enzymes, MMLV (Moloney murine leukemia virus) reverse transcriptase and T7 RNA polymerase. The reverse transcriptase is used to generate a DNA copy (containing a promoter sequence for T7 RNA polymerase) of the target sequence. T7 RNA polymerase produces multiple copies of RNA amplicon from the DNA copy template. Detection is achieved using single-stranded nucleic acid torches that are present during the amplification of the target and hybridize specifically to the amplicon in real time. Each torch has a fluorophore and a quencher. The quencher suppresses the fluorescence of the fluorophore as it is designed to be in close proximity when not hybridized to the amplicon. When the torch binds to the amplicon, the quencher is moved farther away from the fluorophore and it will emit a signal at a specific wavelength when excited by a light source. More torch hybridizes when more amplicon is present. The increase in fluorescent signal from progressive amplification is detected by fluorometers within the Panther system. The Panther system can detect and discriminate between the three fluorescent signals corresponding to HSV-1, HSV-2 and IC amplification products. The fluorescence (measured in relative fluorescence units [RFU]) is monitored over time to produce a real-time fluorescence emergence curve for each reporter dye. The Panther system software compares the fluorescence emergence curves to fixed cut off times to report results (TTime) for HSV-1, HSV-2 and IC.

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

Acceptance Criteria and Device Performance for Aptima Herpes Simplex Viruses 1 & 2 Assay

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the clinical performance targets presented in the study. While explicit pre-defined acceptance thresholds (e.g., "Sensitivity must be >90%") are not directly stated as pass/fail criteria, the reported performance metrics demonstrate the device's capability. For this analysis, I will use the clinical performance study results as the reported device performance against generally expected high standards for diagnostic accuracy.

Note: The document does not explicitly state the pre-defined "acceptance criteria" numerical targets. The reported performance below represents the observed results of the clinical study, which presumably met the internal performance requirements for the manufacturer and FDA review.

Table 1: Acceptance Criteria (Implied) and Reported Device Performance

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

• Clinical Test Set Sample Size:
  • Total Subjects: 544 evaluable subjects (195 males and 349 females).
  • Evaluated for HSV-1: 528 VTM specimens and 531 STM specimens.
  • Evaluated for HSV-2: 533 VTM specimens and 535 STM specimens.
• Data Provenance:
  • Country of Origin: United States. The study was conducted at 17 US clinical sites.
  • Retrospective or Prospective: Prospective. The study is described as a "prospective, multicenter 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 used to establish the ground truth or their specific qualifications (e.g., "radiologist with 10 years of experience").

However, it describes the methods used for the composite reference method:

• ELVIS HSV ID and D3 Typing Test system viral culture
• A validated bidirectional PCR/sequencing procedure
• A third FDA-cleared assay for HSV-1 and HSV-2 was used for final composite reference interpretation when the initial methods disagreed or when PCR/sequencing detected both types.

This suggests that the ground truth was established through a combination of highly reliable laboratory tests, implying a rigorous approach to defining true positive/negative cases, rather than relying solely on individual expert interpretation without further clarification.

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

The document describes an adjudication method for the ground truth:

• "A third FDA-cleared assay for HSV-1 and HSV-2, was used to determine the final composite reference interpretation when the ELVIS D3 culture and PCR/sequencing results did not agree on the type of HSV detected or when PCR/sequencing detected both HSV-1 and HSV-2."

This indicates a hierarchical or tie-breaking system rather than a simple 2+1 or 3+1 consensus among human readers. It relies on a "composite reference method" combining results from multiple validated laboratory tests.

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 a diagnostic assay for detecting viral RNA, not an imaging device that involves human readers interpreting images with or without AI assistance. Therefore, no MRMC comparative effectiveness study involving human readers with AI assistance was performed or reported in this submission. The device (Aptima HSV 1 & 2 Assay) is designed to provide a direct qualitative result (positive/negative for HSV-1 and/or HSV-2) from a processed specimen.

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

Yes, a standalone performance study was done in the sense that the Aptima HSV 1 & 2 Assay (the "algorithm" in this context) directly processes specimens and generates results without requiring human interpretation for its output. The clinical performance study directly evaluated the accuracy of the assay's results against a composite reference standard. The "human-in-the-loop" would be the clinician collecting the sample and laboratory technicians running the test and reporting the results, but the analytical output itself is determined by the assay system.

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

The ground truth used was a composite reference method combining:

• ELVIS HSV ID and D3 Typing Test system viral culture
• A validated bidirectional PCR/sequencing procedure
• A third FDA-cleared assay for HSV-1 and HSV-2 (used for tie-breaking/discrepancy resolution)

This is a robust form of ground truth based on multiple established laboratory diagnostic methods.

8. The sample size for the training set

The document does not report a sample size for a training set. This is expected for a diagnostic assay of this type, as it's not a machine learning or AI algorithm that requires a separate "training set" in the conventional sense. The assay's design and optimization (e.g., probe sequences, amplification conditions) would have been developed iteratively, but a distinct "training set" for performance evaluation is not applicable here. The analytical studies (LoD, cross-reactivity, etc.) and the clinical performance study represent the validation of the finalized assay.

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

As there is no explicit "training set" in the context of machine learning, this question is not directly applicable. The assay's components and parameters would have been optimized using internal development processes and validated through analytical studies. For these analytical studies (e.g., LoD, cross-reactivity), the "ground truth" (i.e., known-positive or known-negative samples, specific viral strains/concentrations) would have been established through well-characterized laboratory standards, spiked samples, and reference materials.

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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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