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Roche Digital Pathology Dx is an automated digital slide creation, viewing and management system. Roche Digital Pathology Dx is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of scanned pathology slides prepared from formalin-fixed paraffin-embedded (FFPE) tissue. Roche Digital Pathology Dx is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. Roche Digital Pathology Dx is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy.

Roche Digital Pathology Dx is composed of VENTANA DP 200 slide scanner, VENTANA DP 600 slide scanner, Roche uPath enterprise software, and ASUS PA248QV display. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using Roche Digital Pathology Dx.

Roche Digital Pathology Dx (hereinafter referred to as RDPD), is a whole slide imaging (WSI) system. It is an automated digital slide creation, viewing, and management system intended to aid pathologists in generating, reviewing, and interpreting digital images of surgical pathology slides that would otherwise be appropriate for manual visualization by conventional light microscopy. RDPD system is composed of the following components:

• · VENTANA DP 200 slide scanner,
• · VENTANA DP 600 slide scanner,
• · Roche uPath enterprise software, and
• · ASUS PA248QV display.
  VENTANA DP 600 slide scanner has a total capacity of 240 slides through 40 trays with 6 slides each. The VENTANA DP 600 slide scanner and VENTANA DP 200 slide scanner use the same Image Acquisition Unit.

Both VENTANA DP 200 and DP 600 slide scanners are bright-field digital pathology scanners that accommodate loading and scanning of 6 and 240 standard glass microscope slides, respectively. The scanners each have a high-numerical aperture Plan Apochromat 20x objective and are capable of scanning at both 20x and 40x magnifications. The scanners feature automatic detection of the tissue specimen on the glass slide, automated 1D and 2D barcode reading, and selectable volume scanning (3 to 15 focus layers). The International Color Consortium (ICC) color profile is embedded in each scanned slide image for color management. The scanned slide images are generated in a proprietary file format, Biolmagene Image File (BIF), that can be uploaded to the uPath Image Management System (IMS), provided with the Roche uPath enterprise software.

Roche uPath enterprise software (uPath), a component of Roche Digital Pathology Dx system, is a web-based image management and workflow software application. uPath enterprise software can be accessed on a Windows workstation using the Google Chrome or Microsoft Edge web browser. The user interface of uPath software enables laboratories to manage their workflow from the time the whole slide image is produced and acquired by VENTANA DP 200 and/or DP 600 slide scanners through the subsequent processes, such as review of the digital image on the monitor screen and reporting of results. The uPath software incorporates specific functions for pathologists, laboratory histology staff, workflow coordinators, and laboratory administrators.

The provided document is a 510(k) summary for the "Roche Digital Pathology Dx" system (K242783), which is a modification of a previously cleared device (K232879). This modification primarily involves adding a new slide scanner model, VENTANA DP 600, to the existing system. The document asserts that due to the identical Image Acquisition Unit (IAU) between the new DP 600 scanner and the previously cleared DP 200 scanner, the technical performance assessment from the predicate device is fully applicable. Therefore, the information provided below will primarily refer to the studies and acceptance criteria from the predicate device that are deemed applicable to the current submission due to substantial equivalence.

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

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

The document does not explicitly present a discrete "acceptance criteria" table with corresponding numerical performance metrics for the current submission (K242783). Instead, it states that the performance characteristics data collected on the VENTANA DP 200 slide scanner (the predicate device) are representative of the VENTANA DP 600 slide scanner performance because both scanners use the same Image Acquisition Unit (IAU). The table below lists the "Technical Performance Assessment (TPA) Sections" as presented in the document (Table 3), which serve as categories of performance criteria that were evaluated for the predicate device and are considered applicable to the current device. The reported performance for these sections is summarized as "Information was provided in K232879" for the DP 600, indicating that the past performance data is considered valid.

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

The document explicitly states that the technical performance assessment data was "collected on the VENTANA DP 200 slide scanner" (the predicate device). However, the specific sample sizes for these technical studies (e.g., number of slides used for focusing tests, stitching error analysis, etc.) are not detailed in this summary. The data provenance (country of origin, retrospective/prospective) for these underlying technical studies from K232879 is also not provided in this document.

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

This section is not applicable or not provided by the document. The studies mentioned are primarily technical performance assessments related to image quality, system components, and usability, rather than diagnostic accuracy studies requiring expert pathologist interpretation for ground truth. For the predicate device, it mentions "a qualified pathologist" is responsible for interpretation, but this refers to the end-user clinical use, not the establishment of ground truth for device validation.

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

This section is not applicable or not provided by the document. As noted above, the document details technical performance studies rather than diagnostic performance studies that would typically involve multiple readers and adjudication methods for diagnostic discrepancies.

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

No MRMC comparative effectiveness study is mentioned in the provided text. The device, "Roche Digital Pathology Dx," is described as a "digital slide creation, viewing and management system" intended "as an aid to the pathologist to review and interpret digital images." It is a Whole Slide Imaging (WSI) system, and the submission is focused on demonstrating the technical equivalence of a new scanner component, not on evaluating AI assistance or its impact on human reader performance.

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

No standalone algorithm performance study is mentioned. The device is a WSI system for "aid to the pathologist to review and interpret digital images," implying a human-in-the-loop system. The document does not describe any specific algorithms intended for automated diagnostic interpretation or analysis in a standalone capacity.

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

For the technical performance studies referenced from the predicate device (K232879), the "ground truth" would be established by physical measurements and engineering specifications for aspects like spatial resolution, color reproducibility, focusing quality, tissue coverage, and stitching errors, rather than clinical outcomes or diagnostic pathology. For instance, color reproducibility would be assessed against a known color standard, and spatial resolution against resolution targets. The document does not explicitly state the exact types of ground truth used for each technical assessment but refers to "test data to evaluate" these characteristics.

8. The sample size for the training set

Not applicable/not provided. The document describes a WSI system, not an AI/ML-based diagnostic algorithm that would typically require a training set. The specific "Image Acquisition Unit" components (hardware and software for pixel pipeline) are stated to be "functionally identical" to the predicate, implying established design rather than iterative machine learning.

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

Not applicable/not provided. As there is no mention of a training set for an AI/ML algorithm, the method for establishing its ground truth is not discussed.

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Roche Digital Pathology Dx (VENTANA DP 200) is an automated digital slide creation, viewing and management system. Roche Digital Pathology Dx (VENTANA DP 200) is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of scanned pathology slides prepared from formalin-fixed paraffin-embedded (FFPE) tissue. Roche Digital Pathology Dx (VENTANA DP 200) is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. Roche Digital Pathology Dx (VENTANA DP 200) is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy.

Roche Digital Pathology Dx (VENTANA DP 200), hereinafter referred to as Roche Digital Pathology Dx, is a whole slide imaging (WSI) system. It is an automated digital slide creation, viewing, and management system intended to aid pathologists in generating, reviewing, and interpreting digital images of surgical pathology slides that would otherwise be appropriate for manual visualization by conventional light microscopy. Roche Digital Pathology Dx system is composed of the following components:

• · VENTANA DP 200 slide scanner
• · Roche uPath enterprise software 1.1.1 (hereinafter, "uPath")
• · ASUS PA248QV display

VENTANA DP 200 slide scanner is a bright-field digital pathology scanner that accommodates loading and scanning of up to 6 standard slides. The scanner comprises a high-resolution 20x objective with the ability to scan at both 20x and 40x. With its uniquely designed optics and scanning methods, VENTANA DP 200 scanner enables users to capture sharp, high-resolution digital images of stained tissue specimens on glass slides. The scanner features automatic detection of the tissue specimen on the slide, automated 1D and 2D barcode reading, and selectable volume scanning (3 to 15 focus layers). It also integrates color profiling to ensure that images produced from scanned slides are generated with a color-managed International Color Consortium (ICC) profile. VENTANA DP 200 image files are generated in a proprietary format (BIF) and can be uploaded to an Image Management System (IMS), such as the one provided with Roche uPath enterprise software.

Roche uPath enterprise software (uPath), a component of Roche Digital Pathology system, is a web-based image management and workflow software application. uPath enterprise software can be accessed on a Windows workstation using Google Chrome or Microsoft Edge. The interface of uPath software enables laboratories to manage their workflow from the time the digital slide image is produced and acquired by a VENTANA slide scanner through the subsequent processes including, but not limited to, review of the digital image on the monitor screen, analysis, and reporting of results. The software incorporates specific functions for pathologists, laboratory histology staff, workflow coordinators, and laboratory administrators.

The provided text describes the acceptance criteria and the study that proves the Roche Digital Pathology Dx (VENTANA DP 200) device meets these criteria for FDA 510(k) clearance.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The core clinical acceptance criterion for the Roche Digital Pathology Dx system was non-inferiority of digital read (DR) accuracy compared to manual read (MR) accuracy.

Acceptance Criteria for Clinical Accuracy:

Acceptance Criteria for Analytical Performance (Precision):

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

• Clinical Accuracy Study (Test Set):

  • Sample Size: 2047 cases (total of 3259 slides) consisting of multiple organ and tissue types.
  • Data Provenance: Multi-center study conducted at four sites. The text doesn't explicitly state the country of origin, but it is an FDA submission based in Tucson, Arizona, implying data from the United States. The cases were retrospective, pre-screened from archived specimens from the clinical database of the study sites, with a minimum of one year between the date of sign-out diagnosis and the beginning of the study.

• Precision Study (Test Set):

  • Sample Size: 69 study cases (slides), each with 3 ROIs, totaling 207 "study" ROIs. An additional 12 "wild card" cases (36 wild card ROIs) were included to reduce recall bias but excluded from statistical analysis.
  • Data Provenance: Study conducted at 3 external pathology laboratories (study sites). The text doesn't explicitly state the country of origin. The cases contained H&E-stained archival slides of FFPE human tissue.

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

• Clinical Accuracy Study (Establishing Reference Diagnosis / Sign-Out Truth):

  • Initial Verification: Two Screening Pathologists at each study site pre-screened cases and determined inclusion/exclusion criteria. The first Screening Pathologist reviewed H&E and ancillary stained slides using manual microscopy to identify representative slides and confirmed the diagnosis against the sign-out report. A second Screening Pathologist then verified the sign-out diagnosis data.
  • Qualifications: "Qualified pathologist" is mentioned. The study design implies these are experienced professionals involved in routine diagnostic pathology.

• Precision Study (Establishing Reference Feature):

  • "Primary feature for that case" acted as the reference. The mechanism for establishing this ultimate ground truth for features in the ROIs is not explicitly detailed beyond being "protocol-specified." However, Screening Pathologists were involved in selecting ROIs for each slide. It's implied that the reference for the presence of the 23 specific histopathologic features was expert-derived based on consensus or previous established pathology.

4. Adjudication Method for the Test Set (Clinical Accuracy Study)

• Method: A (2+1) or (2+1+panel) adjudication method was used.
  • For each Reading Pathologist's diagnosis, two Adjudication Pathologists (blinded to site, Reading Pathologist, and reading modality) separately assessed agreement with the original sign-out diagnosis (reference diagnosis).
  • If the two adjudicators disagreed, a third Adjudication Pathologist reviewed the case to achieve a majority consensus.
  • In cases where all three adjudicators had different opinions, consensus was reached in an adjudication panel meeting consisting of the same three Adjudication Pathologists.

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

• Yes, a MRMC comparative effectiveness study was done. This was the Clinical Accuracy Study.
• Effect Size of Human Readers Improvement with AI vs. Without AI Assistance:
  • The study design was a non-inferiority study to show that viewing digital images (AI-assisted, as the WSI system is the "aid") is not worse than manual microscopy. It did not directly quantify improvement of human readers with AI vs. without AI.
  • Instead, it compared the diagnostic accuracy of pathologists using the digital system (DR) versus traditional microscopy (MR) directly against the reference sign-out diagnosis.
  • The observed overall agreement rate was 92.00% for DR and 92.61% for MR. The difference (DR - MR) was -0.61%. This suggests a slight decrease in agreement rate when using DR compared to MR, but it was statistically non-inferior (i.e., not significantly worse than MR, within the defined margin). The study states, "These model results failed to show any statistically significant difference between the 2 reading modalities."
  • Therefore, the effect size is that there was no statistically significant difference in diagnostic agreement rates between digital review and manual review, demonstrating non-inferiority rather than an improvement.

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

• No, a standalone (algorithm-only) performance study was not done for diagnostic accuracy.
• The device is a "Whole slide imaging system" intended "as an aid to the pathologist to review and interpret digital images." Its performance evaluation (clinical accuracy) was explicitly designed as a human-in-the-loop study (pathologists using the system for diagnosis).
• However, technical studies (e.g., color reproducibility, spatial resolution, focusing, whole slide tissue coverage, stitching error) assessed specific algorithm/system components in a standalone or technical performance manner. For instance, the "Image Processing Software" section describes various algorithms (exposure control, white balance, color correction, etc.), and "Image Composition" discusses scanning methods. These are technical assessments of the system's output quality rather than diagnostic accuracy.

7. The Type of Ground Truth Used

• Clinical Accuracy Study: The ground truth for diagnostic accuracy was the original sign-out pathologic diagnosis rendered at the study sites using an optical (light) microscope, verified by two screening pathologists. This represents expert consensus/established clinical diagnosis.
• Precision Study: The ground truth for feature detection was the "reference primary feature for that case." This was established by "Screening Pathologists" who selected the ROIs containing these features, implying expert-identified features.

8. The Sample Size for the Training Set

The provided document describes studies for device validation and clearance, not for the development and training of a machine learning model. Therefore, no information on the sample size for a training set is provided. The Roche Digital Pathology Dx system is described as a "whole slide imaging (WSI) system" and its components (scanner, software, display), without mention of AI/ML components for automated diagnosis or feature detection that would require a separate training set. The "AI" mentioned in question 5 refers to the digital WSI system as an "aid" to the human reader, not necessarily an AI algorithm performing diagnosis independently.

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

As no training set is described (since this is primarily a WSI system for human review, not an autonomous AI diagnostic algorithm), this information is not applicable.

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CINtec® Histology is a qualitative immunohistochemistry (IHC) test using mouse monoclonal anti-p16 antibody clone E6H4, and is intended for use in the light microscopic assessment of the p16INK4a protein in formalin-fixed, paraffinembedded (FFPE) cervical punch biopsy tissues using OptiView DAB IHC Detection Kit on a VENTANA BenchMark ULTRA instrument. The test is indicated as an adjunct to examination of hematoxylin and eosin (H&E) stained slide(s), to improve consistency in the diagnosis of cervical intraepithelial neoplasia (CIN). Diagnosis of CIN presence or level should be based on H&E stained slide(s) and other clinical and laboratory test information.

Intended for in vitro diagnostic (IVD) use. Prescription Use Only.

CINtec® Histology is a single dispenser immunohistochemical (IHC) assay system comprised of an anti-p16 primary antibody optimized for use with the BenchMark ULTRA automated slide staining instrument and the OptiView DAB IHC Detection Kit. The antibody is diluted in a Tris-HCl buffer containing carrier protein and 0.1% ProClin 300 as a preservative and provided as a ready-to-use liquid in a FloLock dispenser. CINtec Histology is available in a 50-test size and a 250-test size.

The OptiView DAB IHC Detection Kit (OptiView) is an indirect, biotin-free system for detecting mouse IgG, mouse IgM, and rabbit IgG primary antibodies and is comprised of 6 dispensers packaged together in one box.

Ancillary reagents required to perform the CINtec Histology assay include EZ Prep, Reaction Buffer, ULTRA High Temperature Liquid Coverslip (LCS), ULTRA Cell Conditioning 1 Solution (CC1), Hematoxylin II Counterstain, and Bluing Reagent.

Positive and negative tissue controls that are fixed and processed in the same manner as the test specimens should be used when performing this test. A negative reagent control mouse monoclonal antibody shall be used to evaluate nonspecific staining.

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text.

Device Name: CINtec® Histology
Description: A qualitative immunohistochemistry (IHC) test using mouse monoclonal anti-p16 antibody clone E6H4, intended for use in the light microscopic assessment of the p16INK4a protein in formalin-fixed, paraffin-embedded (FFPE) cervical punch biopsy tissues. It's an adjunct to H&E stained slides for improving consistency in diagnosing cervical intraepithelial neoplasia (CIN).

1. Table of Acceptance Criteria and Reported Device Performance

The provided text focuses on the non-clinical performance evaluation of a recombinant CINtec Histology device compared to a hybridoma predicate device, primarily to show their equivalency. The tests are designed to demonstrate the recombinant device's performance against established criteria.

2. Sample sizes for the test set and data provenance

The document describes non-clinical performance evaluation, not a typical "test set" in the machine learning sense with a distinct training/test split for generalizability. The sample sizes are specific to each validation test:

• Peptide Inhibition: Multi-tissue block (MTB) containing various cervical diagnoses.
• Between Lots precision: 26 cervical cases with various diagnoses.
• Immunoreactivity: Tour of Body (TOB), Tour of Tumor (TOT), and 20 additional cases.
• Equivalency/Method Comparison: 249 cervical cases with various diagnoses.
• Stability: Normal cervix, cervical squamous cell carcinoma (SCC), tonsil.

The data provenance (country of origin, retrospective/prospective) is not specified in the provided text. Given it's a device submission, it's likely retrospective use of archived FFPE tissue blocks.

3. Number of experts and qualifications for ground truth

The document does not specify the number of experts or their qualifications used to establish ground truth for the non-clinical performance evaluation. It mentions "qualified reader" for morphology assessment in Immunoreactivity and Equivalency/Method Comparison studies, implying expert assessment, but no details are provided. For the Indications for Use, it states "Diagnosis of CIN presence or level should be based on H&E stained slide(s) and other clinical and laboratory test information," implying that the final diagnosis relies on established pathology expertise in a clinical setting.

4. Adjudication method

The document does not specify any formal adjudication method (e.g., 2+1, 3+1) for the non-clinical performance studies. The "within 0.5 point" criteria for duplicate samples in the Peptide Inhibition test suggests internal consistency checks rather than multi-reader adjudication of a ground truth.

5. Multi-Reader Multi-Case (MRMC) comparative effectiveness study

The document explicitly states: "The substantial equivalence is not based on an assessment of clinical performance data." This indicates that an MRMC comparative effectiveness study, which would typically assess human reader improvement with AI assistance, was not performed or submitted as part of this specific 510(k) (which focuses on equivalency of recombinant vs. hybridoma antibody).

6. Standalone (algorithm only without human-in-the-loop) performance

The device described is an immunohistochemistry (IHC) test (a laboratory assay), not an AI algorithm. Therefore, "standalone (algorithm only without human-in-the-loop) performance" is not applicable in the typical sense of AI device evaluation. The performance metrics focus on the assay's biochemical and staining characteristics, and its interpretation is intended to be by a human pathologist as an "adjunct to examination of hematoxylin and eosin (H&E) stained slide(s)."

7. Type of ground truth used

For the peptide inhibition, immunoreactivity, and equivalency/method comparison studies, the ground truth implied is the known characteristics of the tissue samples (e.g., tissues with varying levels of p16 expression, normal vs. carcinoma, various diagnoses). The "qualified reader" assessment of morphology and staining intensity serves as a measure against accepted pathology interpretations for those samples.

8. Sample size for the training set

This document pertains to the submission of an IHC assay, not a machine learning or AI device. Therefore, the concept of a "training set" for an algorithm is not applicable here. The focus is on the analytical and technical performance of the assay itself.

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

As this is not an AI/ML device, there is no "training set" or corresponding ground truth establishment process for algorithm training. The ground truth for the various performance evaluation studies (e.g., confirming p16 expression in Western Blots, identifying known tissue types) would be established through standard laboratory and pathological methods.

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The VENTANA CD30 (Ber-H2) Assay is intended for laboratory use in the qualitative detection of the CD30 protein in formalin-fixed, paraffin-embedded tissue stained with a VENTANA BenchMark ULTRA instrument and OptiView DAB IHC Detection Kit. CD30 positive staining may aid in the identification of classical Hodgkin lymphoma (cHL), anaplastic large cell lymphoma (ALCL) and cutaneous T-cell lymphoma (CTCL). This product should be interpreted by a qualified pathologist in conjunction with histological examination, relevant clinical information and proper controls. This antibody is intended for in vitro diagnostic (IVD) use.

The VENTANA CD30 (Ber-H2) Assay consists of the primary CD30 (Ber-H2) antibody, detection reagents and an instrument (BenchMark ULTRA automated staining instrument). The VENTANA CD30 (Ber-H2) Assay is a mouse monoclonal antibody (IgG1, kappa) directed against CD30. CD30 antigen is expressed in mononuclear Hodgkin's cells and multinucleated Reed Sternberg cells of Hodgkin Lymphoma as well as on anaplastic large cell lymphomas. This antibody variably produces membranous, cytoplasmic, and Golgi staining of both lymphoma cells and of scattered large activated B and T cells in lymph nodes, spleen, tonsil, and thymus. The OptiView DAB IHC Detection Kit is an indirect, biotin-free system for detecting mouse IgG, mouse IgM, and rabbit primary antibodies. This kit is intended to detect antigens by IHC in sections of formalin-fixed, paraffin-embedded (FFPE) and frozen tissues that are stained on the BenchMark ULTRA instrument (note: the VENTANA CD30 (Ber-H2) Assay will not be recommended for use in frozen tissue). The OptiView DAB IHC Detection Kit produces a visible dark brown precipitate (3, 3'-Diaminobenzidine) via a horseradish peroxidase (HRP) enzymatic reaction at the antigen site. The Pathologist evaluates the brown precipitate using Bright-field microscopy.

The provided text describes the 510(k) summary for the VENTANA CD30 (Ber-H2) Assay, an immunohistochemistry (IHC) assay. It details the device's intended use and compares it to a predicate device to demonstrate substantial equivalence.

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

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

The document implicitly defines acceptance criteria through the comparison to the predicate device. The primary stated performance metric is "overall percent agreement rate".

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

• Test Set Sample Size: The text mentions two sample sizes based on the number of readers:
  • 568 cases for the study involving three readers (resulting in 517 agreed cases).
  • 796 cases for the study involving four readers (resulting in 739 agreed cases).
• Data Provenance: The document does not explicitly state the country of origin. It indicates the study was a "premethod comparison study" conducted to demonstrate substantial equivalence. It's implied to be retrospective, as it compares the new device's staining results to those obtained with cases using the predicate device. The samples are described as "formalin-fixed, paraffin-embedded human tissue."

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

• Number of Experts: The study used three readers for one analysis and four readers for another.
• Qualifications of Experts: The document states that the product "should be interpreted by a qualified pathologist." While it doesn't provide specific experience levels (e.g., "10 years of experience"), it implies that the readers involved in the comparison study were qualified pathologists.

4. Adjudication method for the test set:

The document mentions "overall percent agreement rate between three readers" and "overall agreement rate between four readers." This strongly suggests a consensus-based adjudication method, where the aggregate agreement among the multiple readers determines the final result used for comparison. It doesn't specify if a particular threshold for agreement was used (e.g., 2 out of 3, or majority rule), but the "agreement rate" implies a comparison of individual reader interpretations against each other or potentially against a predefined "truth" established by the collective. It's not a 2+1 or 3+1 method explicitly stated, but rather a direct comparison of agreement.

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

• MRMC Study: Yes, a multi-reader multi-case comparison study was implicitly done, as the performance metrics are based on agreement rates between multiple readers on a set of cases using both the new and predicate devices.
• Effect Size (AI Assistance): This study is not an AI-assisted study. It compares a new IHC assay (VENTANA CD30 (Ber-H2) Assay) against a predicate IHC assay (DAKO K965022). Therefore, there is no AI component and no mention of human readers improving with AI assistance.

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

This is an IHC assay, not an AI algorithm. The performance is inherently tied to the visual interpretation of stained tissue by a pathologist. Therefore, a standalone (algorithm only) performance is not applicable or discussed. The device is a reagent and an automated staining instrument for pathologist interpretation.

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

The ground truth for this study appears to be expert consensus among the pathologists interpreting the slides stained with both the predicate and proposed devices. The "overall percent agreement rate" signifies how well the new device's results align with the interpretations obtained from the predicate device, or how consistently different pathologists interpreted the slides stained by the new device. The predicate device's performance, previously cleared by the FDA, serves as the reference for substantial equivalence.

8. The sample size for the training set:

The document does not explicitly mention a training set sample size. This is an analytical validation and method comparison study for a diagnostic assay, not a machine learning model. Therefore, the concept of a "training set" in the context of AI is not relevant here. The samples used are for the comparison study itself.

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

As this is not an AI/machine learning study, the concept of a "training set" and establishing its ground truth in that context is not applicable. The study focuses on demonstrating substantial equivalence of the new IHC assay to an existing, cleared predicate device through a comparison study. The "ground truth" in this context is the established performance and interpretation patterns of the predicate device, against which the new device's performance is measured by experienced pathologists.

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CINtec Histology is a qualitative immunohistochemistry (IHC) test using mouse monoclonal anti-p16 antibody clone E6H4. and is intended for use in the light microscopic assessment of the p16thK4a protein in formalin-fixed, paraffin-embedded (FFPE) cervical punch biopsy tissues using OptiView DAB IHC Detection Kit on a VENTANA BenchMark ULTRA instrument. The test is indicated as an adjunct to examination of hematoxylin and eosin (H&E) stained slide(s), to improve consistency in the diagnosis of cervical intraepithelial neoplasia (CIN). Diagnosis of CIN presence or level should be based on H&E stained slide(s) and other clinical and laboratory test information.

The CINtec Histology test is a single dispenser IHC assay system comprised of an anti-p16 primary antibody optimized for use with the BenchMark ULTRA automated slide staining instrument and the OptiView DAB IHC Detection Kit. The antibody is diluted in a Tris-HCl buffer containing carrier protein and 0.1% ProClin 300 as a preservative, and provided as a ready-to-use liquid in a FloLock dispenser. CINtec Histology is available in a 50 test size and a 250 test size.

The OptiView DAB IHC Detection Kit (OptiView) is an indirect, biotin-free system for detecting mouse IgG, mouse IgM, and rabbit primary antibodies and is comprised of 6 dispensers packaged together in one box.

Here's a breakdown of the acceptance criteria and study details for the CINtec Histology device:

1. Acceptance Criteria and Reported Device Performance

The general acceptance criteria for this device type are outlined in 21 CFR 864.1865, specifically under "Special Controls." The clinical study data demonstrated a statistically significant improvement in the consistency of diagnoses by Community Pathologists (CPs) when using CINtec Histology staining. The reported performance relates to the improvement in agreement rates.

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

The primary clinical study evaluating diagnostic consistency used 1,100 retrospectively collected FFPE cervical punch biopsy specimens.

The data provenance is described as: "retrospectively collected FFPE cervical punch biopsy specimens, which represent a colposcopy referral population." The study involved Board Certified CPs from across the United States.

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

• Number of Experts: Three (3) Expert Pathologists (XPs).
• Qualifications of Experts: Not explicitly stated beyond "Expert pathologists" and "Board Certified CPs" (for community pathologists). However, the role and processes imply their expertise in cervical pathology.

4. Adjudication Method for the Test Set

The ground truth (Expert-derived Reference Diagnosis) for the test set was established using a 3+1 adjudication method:

• Two XPs initially established independent diagnoses based on H&E-stained slides.
• Discordant cases were evaluated by a third XP.
• Cases for which a "2 out of 3 majority diagnosis" was not achieved were reviewed during an adjudication review meeting that included all three XPs.
• "Majority (or consensus) results established the Expert-derived Reference Diagnosis for each case."

This process was repeated for establishing the reference diagnosis based on H&E and CINtec Histology stained slides.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance

Yes, an MRMC comparative effectiveness study was done. This study compared the diagnostic consistency of community pathologists (CPs) with and without the aid of CINtec Histology staining.

The "effect size" can be quantified by the observed differences in Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) between the "H&E Only" and "H&E and CINtec Histology" conditions. The study demonstrated a statistically significant improvement in consistency.

• PPA Improvement for ≥HSIL-histology (LAST Cases): 29.5% (from 66.4% to 95.9%)
• NPA Improvement for ≤LSIL-histology (LAST Cases): 7.1% (from 42.5% to 49.6%)
• PPA Improvement for ≥HSIL-histology (ALL Cases): 22.8% (from 71.3% to 94.1%)
• NPA Improvement for ≤LSIL-histology (ALL Cases): 7.9% (from 56.5% to 64.4%)

These values represent the improvement in agreement rates of CPs with the expert reference diagnosis when using CINtec Histology as an adjunct to H&E.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

No, a standalone (algorithm only) performance study was not done or described. The CINtec Histology device is a qualitative immunohistochemistry test where results are "interpreted using a light microscope by a pathologist." Its indication for use is "as an adjunct to examination of hematoxylin and eosin (H&E) stained slide(s), to improve consistency in the diagnosis of cervical intraepithelial neoplasia (CIN)."

7. The Type of Ground Truth Used

The primary ground truth used for the clinical study was an Expert Consensus Diagnosis (referred to as "Expert-derived Reference Diagnosis"). This was established by a panel of three expert pathologists through initial independent readings and subsequent adjudication (2 out of 3 majority, followed by a review meeting for persistent discordance). This consensus was established twice: once based on H&E alone, and once based on H&E + CINtec Histology.

8. The Sample Size for the Training Set

The document does not explicitly state a separate "training set" for the CINtec Histology product itself. As an immunohistochemistry (IHC) assay for detecting a protein marker, it is a laboratory test with defined reagents and protocols, rather than a machine learning algorithm that requires a dedicated training set. The various analytical and precision studies describe the evaluation of the assay's performance characteristics.

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

As noted above, there is no explicit mention of a "training set" for the device in the context of an algorithm. The development and optimization of the IHC assay would have involved standard laboratory practices, including using known positive and negative control tissues. For instance, the analytical performance section mentions using "cervical carcinoma or CIN2/3 cervical tissue positive for CINtec Histology staining" as a positive control and "normal cervical tissue with negative staining" as a negative control. These are used to confirm assay performance rather than to "train" an algorithm.

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The Virtuoso TM system provides automated digital slide creation, management, analysis, and viewing. It is intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest based on particular morphology, color, intensity, size, pattern and shape.

The Virtuoso™ System for IHC PR (1E2) using the VENTANA iScan HT is for the digital read application. This particular Virtuoso system is intended for use as an aid to the pathologist in the qualitative detection of progesterone receptor (PR) protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to Ventana Medical Systems, Inc. CONFIRM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay. The CONFIRM™ anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay is indicated for use as an aid in the assessment of breast cancer patients for whom endocrine treatment is being considered (but is not the sole basis for treatment).

Note: The IHC PR (1E2) Digital Read application is an adjunctive computer-assisted methodology for the qualified pathologist in the acquisition and interpretation of images from microscope glass slides of breast cancer specimens stained for the presence of PR protein. The accuracy of the test results depends on the quality of the immunohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRM™ anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody used to assure the validity of the Virtuoso System for IHC PR Digital Read scores. The actual correlation of CONFIRM™ anti-PR antibody to clinical outcome has not been established. This device is intended for IHC slides stained on the BenchMark ULTRA stainers. For prescription use only.

The Virtuoso™ System is an instrument-plus-software system designed to assist the qualified pathologist in the consistent assessment of protein expression in immunohistochemically stained histologic sections from formalin-fixed, paraffinembedded normal and neoplastic tissues. The system consists of a slide scanner, computer, monitor, keyboard, and mouse for specific immunohistochemical markers, and software with a Windows web browser-based user interface. Virtuoso is a web-based, end-to-end, digital pathology software solution that allows pathology laboratories to acquire, manage, view, analyze, share, and report digital images of pathology specimens. Using the Virtuoso software, the pathologist can view digital images, add annotations and generate reports.

Hardware: The iScan HT scanning device captures digital images of formalinfixed, paraffin-embedded tissues that are suitable for storage and viewing. The device includes a digital slide scanner, a carousel for loading glass slides, computer, scanner software, keyboard, mouse and monitor.

Software: The Virtuoso software is designed to complement the routine workflow of a qualified pathologist in the review of immunohistochemically stained histologic slides. The software makes no independent interpretations of the data and requires competent human intervention for all steps in the process.

Acceptance Criteria and Device Performance for Virtuoso™ System for IHC PR (1E2) using the VENTANA iScan HT

This response summarizes the acceptance criteria and study findings for the Virtuoso™ System for IHC PR (1E2) using the VENTANA iScan HT, based on the provided FDA 510(k) summary (K142965).

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly derived from the reported agreement rates. For the purpose of this table, we will highlight the reported agreement rates as the measure of meeting the acceptance of substantial equivalence.

Note: The document states that the test system was shown to be "as safe and effective (therefore substantially equivalent) as the predicate devices". The provided agreement rates are the key metrics demonstrating this substantial equivalence. Specific predefined numerical acceptance criteria are not explicitly stated as distinct thresholds in the provided text but are implicitly met by achieving high concordance with manual methods and good reproducibility, consistent with existing legally marketed devices.

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

• Sample Size for Method Comparison Test Set:
  • Site 1: 159 cases
  • Site 2: 162 cases
  • Site 3: 156 cases
  • Overall: 477 cases (sum of evaluable cases from the three sites)
• Sample Size for Reproducibility Test Set: 39 cases (for intra-pathologist reproducibility)
• Sample Size for Scanner Precision Test Set: 40 cases
• Data Provenance: The document does not explicitly state the country of origin. However, the study involved three different "sites", implying a multi-center study possibly within the US, but this is not explicitly confirmed. The study appears to be retrospective in nature, using existing formalin-fixed, paraffin-embedded tissue blocks that were then stained and digitally scanned.

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

• Number of Experts: 3 pathologists (referred to as "Readers" or "Investigators"). The method comparison study involved each of these 3 pathologists providing both manual and digital reads. The reproducibility studies also involved these 3 pathologists.
• Qualifications of Experts: The document refers to them as "qualified pathologists" or "investigators." Specific details regarding their years of experience or sub-specialty (e.g., radiologist, breast pathologist) are not provided.

4. Adjudication Method for the Test Set

• Method Comparison: The ground truth for the device's performance was established using the manual read (MR) by the same pathologist as the reference for the digital read (DR) evaluation. Each pathologist's DR results were compared to their own MR results. There is no explicit mention of an independent adjudication committee or consensus among multiple experts for the ground truth itself.
• Reproducibility: For intra-pathologist reproducibility, the comparison was between the same pathologist across three different reading sessions. For inter-pathologist reproducibility, the comparison was between pairs of pathologists.
• Scanner Precision: The comparison was between clinical scoring categories agreed upon at different sites/days for the same FOVs.
• It appears no formal "N+1" or similar adjudication method was employed to establish a single, definitive ground truth independent of the readers whose digital reads were being assessed. Instead, the agreement between the digital read and a human's manual read served as the primary performance indicator, and reproducibility between humans (both manual and digital) was also evaluated.

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

• Yes, a form of MRMC study was implicitly done. The method comparison study involved 3 pathologists (multi-reader) evaluating multiple cases (multi-case), where their digital reads were compared to their manual reads. The reproducibility studies also involved multiple readers and multiple cases.
• Effect Size (Human Reader Improvement with AI vs. without AI): The document does not report an effect size for human readers improving with AI assistance. The study design is primarily focused on demonstrating the substantial equivalence of the digital read system to the manual read, rather than measuring the improvement in human performance when assisted by the AI. The Virtuoso™ System is described as an "aid to the pathologist" and an "adjunctive computer-assisted methodology," but the study evaluates its standalone performance against manual reading, and its reproducibility, not its comparative effectiveness in improving reader accuracy or efficiency.

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

• No, a standalone (algorithm only) performance study was not done or reported. The device is described as an "aid to the pathologist" and the software explicitly "makes no independent interpretations of the data and requires competent human intervention for all steps in the process."
• The Digital Read (DR) method involves the pathologist reviewing the digital images. The performance metrics (OPA, PPA, NPA) are based on the pathologist's interpretation using the digital system, not an automated algorithm's output directly.

7. The Type of Ground Truth Used

• The primary ground truth used for the method comparison study was the expert's own manual microscopic assessment of the formalin-fixed, paraffin-embedded tissue slides, using a traditional microscope. This acts as the "reference manual method."
• For the reproducibility and precision studies, the ground truth for comparison was the clinical score assigned by pathologists (either their own previous scores for intra-reader, or other pathologists' scores for inter-reader/inter-scanner).
• The ground truth categories were defined as:
  • Negative: PR score of 0 to 0.99% positive staining
  • Positive: PR score of ≥1% positive staining
  • For scanner precision: 0 – 0.99%, 1–10%, and ≥ 10% positive staining.
• There is no mention of pathology or outcomes data being used as an independent, external ground truth beyond expert consensus.

8. The Sample Size for the Training Set

• The document does not provide information on the sample size used for the training set for the Virtuoso™ System's software. The study focuses on the clinical validation of the device, implying that the algorithm development (training) phase was completed prior to these validation studies.

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

• The document does not provide information on how the ground truth for the training set was established. This information is typically part of the device development process and is not always included in the 510(k) summary for validation studies.

Ask a specific question about this device

The Virtuoso system provides automated digital slide creation, management, analysis, and viewing. It is intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest based on particular morphology, color, intensity, size, pattern and shape.

The Virtuoso™ System for IHC ER (SPI) is for digital read and image analysis applications. This particular Virtuoso system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of estrogen receptor (ER) protein in formalin-fixed, paraffin-embedded neoplastic tissue. This device is an accessory to Ventana Medical Systems, Inc. CONFIRM™ anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody assay. The CONFIRM™ anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody assay is indicated for use as an aid in the assessment of breast cancer patients for whom endocrine treatment is being considered (but is not the sole basis for treatment). For prescription use only.

Note: The IHC ER (SP1) Digital Read and Image Analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and measurement of images from microscope glass slides of breast cancer specimens stained for the presence of ER protein. The pathologist should verify agreement with the Image Analysis software application score. The accuracy of the test results depends on the quality of the immunohistochemical staining. If is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRM™ anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody used to assure the validity of the Virtuoso System for IHC ER Digital Read and Image Analysis scores.

The Virtuoso™ System is an instrument-plus-software system designed to assist the qualified pathologist in the consistent assessment of protein expression in immunohistochemically stained histologic sections from formalin-fixed, paraffin-embedded normal and neoplastic tissues. The system consists of a slide scanner (iScan), computer, monitor, keyboard, mouse, image analysis algorithms for specific immunohistochemical markers, and software with a Windows web browser-based user interface. Virtuoso is a web-based, end-to-end, digital pathology software solution that allows pathology laboratories to acquire, manage, view, analyze, share, and report digital images of pathology specimens. Using the Virtuoso software, the pathologist can view digital images, add annotations, make measurements, perform image analysis, and generate reports.

The iScan slide scanning device captures digital images of formalin-fixed, Hardware: paraffin-embedded tissues that are suitable for storage and viewing. The device includes a digital slide scanner, racks for loading glass slides, computer, scanner software, keyboard, mouse and monitor.

The Virtuoso software is designed to complement the routine workflow of a Software: qualified pathologist in the review of immunohistochemically stained histologic slides. It allows the user to select fields of view (FOVs) in the digital image for analysis and provides quantitative data on these FOVs to assist with interpretation. The software makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process.

Here's a breakdown of the acceptance criteria and the study details for the Virtuoso™ System for IHC ER (SP1), based on the provided document:

Acceptance Criteria and Device Performance

Study Details

2. Sample Size and Data Provenance

• Test Set Sample Size: 111 evaluable cases.
• Data Provenance: Not explicitly stated, but the study was conducted at "one site," which implies a single-center study. The text doesn't specify the country of origin, nor whether it was retrospective or prospective, though the nature of "available from the original study" and "blinding" suggests a retrospective analysis of previously collected samples.

3. Number of Experts and Qualifications for Ground Truth

• Number of Experts: One pathologist.
• Qualifications: "one pathologist," no further specific qualifications (e.g., years of experience, subspecialty) are provided in the document.

4. Adjudication Method for the Test Set

• Adjudication Method: Not applicable. The study used a single pathologist to establish the manual microscopic read as the reference (ground truth). Discrepancies between the digital read/image analysis and the manual read were directly evaluated against this single reference, rather than being arbitrated by multiple experts.

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

• MRMC Study Done?: No. The study evaluated agreement of the system with one pathologist's manual reads and did not assess improvement of human readers with AI assistance. The study design involved the same pathologist scoring cases in three different ways (manual, digital, image analysis) in a blinded fashion.

6. Standalone Performance (Algorithm Only)

• Standalone Performance Done?: Yes, to an extent. The "Image Analysis Read" directly reflects the algorithm's performance, which was then compared to the manual read. The "digital read" also represents a form of standalone performance where the pathologist reviews the digital image without the algorithm's quantitative output. Both were compared to the manual microscopic read.

7. Type of Ground Truth Used

• Type of Ground Truth: Expert consensus (from a single pathologist) on manual microscopic examination. The document explicitly states, "The manual score (reference result) was compared to both the digital read result and the image analysis result."

8. Sample Size for the Training Set

• Training Set Sample Size: Not specified in this document. The document describes the validation study for the device. Information about the training set size would typically be found in the device's development or internal validation reports, not usually detailed in a 510(k) summary focused on demonstrating substantial equivalence.

9. How Ground Truth for the Training Set Was Established

• Ground Truth Establishment for Training Set: Not specified in this document. Similar to the training set size, the method for establishing ground truth for training data is usually part of the algorithm's development process and not typically detailed in this type of regulatory submission.

Ask a specific question about this device

The Virtuoso system provides automated digital slide creation, management, analysis, and viewing. It is intended for in vitro disgnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest based on particular morphology, color, intensity, size, pattern and shape.

The Virtuoso™ System for IHC ER (SPI) is for digital read and image analysis spplications. This particular Virtures system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of estrogen receptor (ER) protein in formalin-fixed, paraffin-embedded neoplastic tissue. This device is sn accessory to Ventana Medical Systems, Inc. CONFIRM™ anti-Estrogan Receptor (ER) (SPI) Rabbit Monoclonal Primary Antibody assay. The CONFIRM™ anti- ER (SPI) Rabbit Monoclonal Primary Antibody assay is indicated for use as an aid in the assessment of breast cancer patients for whom endocrine treatment is being considered (but is not the sole basis for treatment).

Note: The IHC ER (SPI) Digital Read and Image Analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and measurement of images from microscope glass slides of breast cancer specified for the presence of ER protein. The pathologist should verify agreement with the Image Analysis software application score. The accuracy of the test results depends on the immunobistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the CONFIRM™ ani-Estrogen Receptor (RR) (SPI) Rabit Monoclonal Primary Antibody used to assure the validity of the Virtusso System for IBC ER Digital Read and Invage Analysis scores. The actual correlation of CONFIRM anti-Estrogen Receptor (ER)(SPI) Rabbit Monocload Antibody to clinical outcome has not been established.

Not Found

This detailed response is based on the provided text, but it's important to note that the document is a 510(k) clearance letter and not the 510(k) summary itself. Therefore, specific details about the study design, sample sizes for training, and ground truth establishment in the scientific study are not explicitly present in this document. The information provided heavily relies on the content within the "Indications for Use" section.

Here's the breakdown based on the input document:

Acceptance Criteria and Device Performance Study for Virtuoso System for IHC ER(SP1)

The Virtuoso System for IHC ER (SP1) is intended as an aid to the pathologist for digital read and image analysis applications in the detection and semi-quantitative measurement of estrogen receptor (ER) protein in formalin-fixed, paraffin-embedded neoplastic tissue, specifically in breast cancer.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state quantitative acceptance criteria (e.g., minimum sensitivity, specificity, or agreement rates) or detailed reported device performance metrics from a specific study. Instead, the "Indications for Use" section describes the intended functionality and adjunctive nature of the device.

The qualitative "acceptance criteria" can be inferred from the device's stated purpose: "an aid to the pathologist in the detection and semi-quantitative measurement of estrogen receptor (ER) protein in formalin-fixed, paraffin-embedded neoplastic tissue." The "reported device performance" is that the system fulfills this role as an adjunctive, computer-assisted methodology, requiring pathologist verification.

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

The provided 510(k) clearance letter and "Indications for Use" statement do not contain information regarding the specific sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective nature). These details would typically be found in the 510(k) summary document or the underlying study report.

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

The provided document does not specify the number of experts used to establish the ground truth for the test set or their qualifications. However, it does emphasize that the device is an "aid to the pathologist" and that "It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified...to assure the validity of the Virtusso System for IBC ER Digital Read and Invage Analysis scores." This implies that qualified pathologists are central to the interpretation and validation process.

4. Adjudication Method for the Test Set

The document does not specify the adjudication method used for the test set.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size.

The provided document does not indicate whether a MRMC comparative effectiveness study was done, nor does it provide any effect size of how much human readers improve with AI vs. without AI assistance. The language ("adjunctive computer-assisted methodologies") suggests the device is intended to assist, but no performance metrics for this assistance are given in this document.

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

The provided document does not explicitly state if a standalone performance study was conducted. However, the consistent phrasing "aid to the pathologist" and "pathologist should verify agreement with the Image Analysis software application score" strongly implies that the device is not intended for standalone interpretation and its performance is always considered in conjunction with a human expert.

7. The Type of Ground Truth Used

The document implies that the ground truth for evaluation would be established by expert consensus/pathologist assessment, particularly given the statement: "The pathologist should verify agreement with the Image Analysis software application score. The accuracy of the test results depends on the immunohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls..." This suggests that expert pathological review, potentially supported by appropriate controls and validated IHC staining, forms the basis of ground truth. There is no mention of pathology reports as the sole ground truth, or outcomes data.

8. The Sample Size for the Training Set

The provided document does not contain information regarding the sample size used for the training set.

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

The provided document does not contain information on how the ground truth for the training set was established. Given the nature of the device, it is highly probable that expert pathologists would have been involved in establishing the ground truth for training data, similar to the inference for the test set ground truth.

Ask a specific question about this device

The Virtuoso system provides automated digital slide creation, management, analysis, and viewing. It is intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest based on particular morphology, color, intensity, size, pattern and shape.

The Virtuoso™ System for IHC PR (1E2) is for digital read and image analysis applications. This particular Virtuoso system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of progesterone receptor (PR) protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to Ventana Medical Systems, Inc. CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay. The CONFIRM™ anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay is indicated for use as an aid in the assessment of breast cancer patients for whom endocrine treatment is being considered (but is not the sole basis for treatment).

Note: The IHC PR (1E2) Digital Read and Image Analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and measurement of images from microscope glass slides of breast cancer specimens stained for the presence of PR protein. The pathologist should verify agreement with the Image Analysis software application score. The accuracy of the test results depends on the quality of the immunohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody used to assure the validity of the Virtuoso System for IHC PR Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-PR antibody to clinical outcome has not been established.

The Virtuoso™ System is an instrument-plus-software system designed to assist the qualified pathologist in the consistent assessment of protein expression in immunohistochemically stained histologic sections from formalin-fixed, paraffinembedded normal and neoplastic tissues. The system consists of a slide scanner (iScan), computer, monitor, keyboard, mouse, image analysis algorithms for specific immunohistochemical markers, and software with a Windows web browser-based user interface. Virtuoso is a web-based, end-to-end, digital pathology software solution that allows pathology laboratories to acquire, manage, view, analyze, share, and report digital images of pathology specimens. Using the Virtuoso software, the pathologist can view digital images, add annotations, make measurements, perform image analysis, and generate reports.

Hardware: The iScan slide scanning device captures digital images of formalin-fixed, paraffin-embedded tissues that are suitable for storage and viewing. The device includes a digital slide scanner, racks for loading glass slides, computer, scanner software, keyboard, mouse and monitor.

Software: The Virtuoso software is designed to complement the routine workflow of a qualified pathologist in the review of immunohistochemically stained histologic slides. It allows the user to select fields of view (FOVs) in the digital image for analysis and provides quantitative data on these FOVs to assist with interpretation. The software makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process.

Here's an analysis of the acceptance criteria and study details based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

Note: While PPA and NPA thresholds are not explicitly stated, the context of the 75% OPA suggests that these individual agreement metrics would also be expected to be above this threshold for the overall agreement to be met. The reported performance far exceeds this implied threshold.

2. Sample Size and Data Provenance

• Test Set Sample Size: Approximately 120 cases. The specific numbers reported in the tables are 113 for Digital Read and 114 for Image Analysis, likely due to a slight difference in cases included in the analysis after exclusions or variations in how certain cases were processed.
• Data Provenance: The document does not explicitly state the country of origin. It indicates the study was conducted "at one site." It was a retrospective study since the cases were "evaluated three ways" after staining.

3. Number of Experts and Qualifications for Ground Truth

• Number of Experts: One pathologist.
• Qualifications: "one pathologist" – no further specific qualifications (e.g., years of experience, sub-specialty) are provided in this document.

4. Adjudication Method for the Test Set

• Adjudication Method: "The manual score (reference result) was compared to both the digital read result and the image analysis result." This indicates a single-reader manual interpretation served as the ground truth against which both digital read and image analysis were compared. There was no explicit multi-reader adjudication process mentioned for establishing the "manual score" ground truth itself.

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

• Was an MRMC study done? No, an MRMC comparative effectiveness study, which typically compares human readers with and without AI assistance across multiple readers and cases to quantify improvement, was not explicitly described.
• Effect Size of Human Readers' Improvement with AI: Not applicable, as an MRMC study was not described. The study compared the device (digital read and image analysis) directly to the pathologist's manual read.

6. Standalone (Algorithm Only) Performance

• Was a standalone performance study done? Yes, the "Image Analysis" arm of the study specifically assessed the performance of the algorithm without direct human input beyond selecting fields of view. The results demonstrated a 96.5% Overall Percent Agreement with the manual read. The "Digital Read" arm assesses the pathologist's interpretation using the digital image, which is also a form of standalone performance of the digital viewing system, but with human-in-the-loop.

7. Type of Ground Truth Used

• Type of Ground Truth: Expert consensus, specifically a "manual score (reference result)" established by "one pathologist." This manual score was determined using a routine microscope.

8. Sample Size for the Training Set

• The document does not provide any information regarding the sample size of the training set. The clinical validation section focuses solely on the performance evaluation of the final device.

9. How Ground Truth for the Training Set was Established

• The document does not provide any information on how the ground truth for the training set was established.

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