Search Results

The GenASIs HiPath IHC Family provides image capture, management, analysis, and viewing of specific immunohistochemically stained slides. 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:

1. The GenASIs HiPath IHC Family for HER2 (4B5) is for image capture and analysis applications. This particular system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2 protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to Ventana Medical Systems, Inc. PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody. The PATHWAY® anti-HER2/ neu (4B5) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.

NOTE: The GenASIs HiPath IHC Family for HER2 (4BS) image capture and analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and semi-quantitative measurement of images from microscope glass slides of breast cancer specimens stained for the presence of HER-2/neu receptor protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results on the quality of the immuchistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the PATHWAY® anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody assay used to assure the validity of the GenASIs HiPath IHC Family for HER2 (4B5) image capture and analysis scores. The actual correlation of PATHWAY® anti-HER-2/neu (4B5) to clinical outcome has not been established.

2. The GenASIs HiPath IHC Family for PR (1E2) is for image capture and analysis applications. This particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of progesterone receptor (PR) protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to Ventana Medical Systems, Inc. CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay. The CONFIRMTM 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 GenASIs HiPath IHC for PR (1E2) image capture and analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and qualitative 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 by reviewing the glass slide under the microscope. 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 GenASIs HiPath IHC Family for PR (1E2) image capture and analysis scores. The actual correlation of CONFIRMTM anti-PR antibody to clinical outcome has not been established.

3. The GenASIs HiPath IHC Family for ER (SP1) is for image capture and analysis applications. The particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of ER (SP1): protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody. The Ventana Medical Systems, Inc. CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of ER status in breast cancer patients (but is not the sole basis for treatment).

Note: The GenASIs HiPath IHC Family for ER (SP1) image capture and analysis applications are adjunctive computerassisted methodologies for the qualified pathologist in the acquisition and qualitative measurement of images from microscope glass slides of breast cancer specimens stained for the protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results depends on the immuohistochemical 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-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody to assure the validity of the GenASIs HiPath IHC Family for ER (SP1) image capture and analysis scores. The actual correlation of CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody to clinical outcome has not been established.

4. The GenASIs HiPath IHC Family for Ki67 (30-9) is for image capture and analysis applications. The particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of Ki67 (30-9): protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRMTM anti-Ki67 (30-9) assay is indicated for use in assessing the activity of breast cancer tissue. When used with this assay, the GenASIs HiPath IHC Family for Ki67 (30-9) is indicated for use as an aid in the assessment of Ki-67 status in breast cancer patients (but is not the sole basis for treatment).

Note: The GenASIs HiPath IHC Family for Ki67 (30-9) image capture and analysis applications are adjunctive computerassisted methodologies for the qualified pathologist in the acquisition and qualitative measurement of images from microscope glass slides of breast cancer stained for the presence of Ki67 protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. 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 as specified in the instructions for the CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay to assure the validity of the GenASIs HiPath IHC Family for Ki67 (30-9) image capture and analysis scores. The actual correlation of CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary antibody assay to clinical outcome has not been established.

The GenASIs HiPath IHC Family, including software is designed to assist the qualified pathologist in the consistent assessment in inmmohistochemnically stained histologic sections from formalin-fixed, paraffin-embedded breast cancer tissues. The device consists of a slide capture camera, Microscope, computer, monitor, keyboard, mouse, image analysis algorithms for specific immunohistochemical markers, and software with a Graphic User Interface (GUI).

The GenASIs HiPath IHC Family is an intranet-based, end-to-end, digital pathology software solution that allows pathology laboratories, to acquire, manage, view, analyze, share, and report test results of pathology specimens. Using the GenASIs HiPath IHC Family software the pathologist can view captured images, add annotations, make measurements, perform image analysis and generate reports.

Hardware: A camera based acquisition device designed to captures bright-field microscope digital images of formalin-fixed, paraffin-embedded tissues that are suitable for storage and viewing. The device includes a digital slide acquisition camera, X-Y Stage with holder adaptor for loading glass slides on a microscope and a workstation including a computer, keyboard, mouse and monitor.

Software: The GenASIs HiPath IHC Family 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 a breakdown of the acceptance criteria and the study details for the GenASIs HiPath IHC Family device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the "Overall Agreement," "Positive Agreement," and "Negative Agreement" percentages. These percentages represent the agreement between the device's analysis and manual pathological analysis.

HER2/neu (4B5)

PR (1E2)

ER (SP1)

Ki67 (30-9)

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

The study was conducted across three clinical sites. The data provenance is not explicitly stated (e.g., country of origin), nor is it specified whether the data was retrospective or prospective. However, it involved "stained samples," implying real patient data.

• HER2/neu (4B5): 357 stained samples
• PR (1E2): 385 stained samples
• ER (SP1): 427 stained samples
• Ki67 (30-9): 373 stained samples

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

• Number of Experts: Three (3) pathologists.
• Qualifications: "Pathologist that followed the recommendations of the Ventana user insertions for the different panel antibodies." This implies they are qualified experts in immunohistochemical analysis. Specific experience levels (e.g., years of experience) are not provided.

4. Adjudication Method for the Test Set

The ground truth was established by manual evaluation through microscope eyepieces performed by three different pathologists. The document refers to "comparison to the measures of agreement test of conventional manual evaluation through the microscope eyepieces, performed by pathologist." It then presents "Pooled Results; Frequency distribution of agreement of Manual versus GenASIs HiPath IHC Family." This indicates that the manual reads by the three pathologists were likely combined to form a consensus or reference standard, against which the device's results were compared. An explicit adjudication method like "2+1" or "3+1" is not detailed, but the pooling of results suggests a form of consensus was used to derive the "Manual analysis" column in the tables.

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

The document describes a comparison study where "manual evaluation through the microscope eyepieces, performed by pathologist" was compared to the device's analysis. However, it does not present a MRMC comparative effectiveness study in the sense of evaluating how much human readers improve with AI vs without AI assistance. Instead, it evaluates the agreement between the standalone AI device and the human readers' manual interpretations. There is no mention of human readers using the AI as assistance and then assessing their improved performance.

6. Standalone Performance Study

Yes, a standalone performance study was conducted. The "Analytical Performance" section details the "agreement rates of the comparison between manual and GenASIs HiPath IHC Family system statistical test results." This directly presents the device's performance in categorizing samples (Negative/Positive) against the ground truth established by manual pathological analysis, without human-in-the-loop during the device's diagnostic output generation.

7. Type of Ground Truth Used

Expert Consensus: The ground truth for the test set was established through "conventional manual evaluation through the microscope eyepieces, performed by pathologist that followed the recommendations of the Ventana user insertions for the different panel antibodies." This indicates that the ground truth was based on the consensus or established interpretations of qualified pathologists.

8. Sample Size for the Training Set

The document does not explicitly state the sample size used for the training set. The "Analytical Performance" section focuses on the validation study (test set).

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

As the training set sample size is not specified, neither is the method for establishing its ground truth. However, given the context of a medical device submission, it would be expected that if a machine learning model was developed, the training data would also be expert-annotated.

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.

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. 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 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 CONFIRM™ 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.

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.

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

Acceptance Criteria and Device Performance

As stated in the document, "The overall agreement between the digital read and the manual read was 95.6%, the overall agreement between image analysis and the manual read was 96.5%, and the predetermined acceptance criterion for each measurement of 75% has been met."

Study Details

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

• Sample Size: Approximately 120 cases. For the Digital Read analysis, 113 cases were analyzed. For the Image Analysis, 114 cases were analyzed.
• Data Provenance: The document does not explicitly state the country of origin. It was a retrospective study as it compares different assessment methods of already prepared slides.

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

• Number of Experts: One pathologist.
• Qualifications of Experts: The document specifies "one pathologist" but does not explicitly state their experience level (e.g., "10 years of experience"). It implies they are a "qualified pathologist."

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

• Adjudication Method: Not explicitly stated as a formal adjudication process involving multiple pathologists. The ground truth ("manual score") was established by a single pathologist performing a routine microscopic read.

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: No, a multi-reader, multi-case (MRMC) comparative effectiveness study was not explicitly described. The study involved one pathologist evaluating cases in three different ways (manual, digital read, image analysis).
• Effect Size of Human Improvement with AI: This study does not provide data on the effect size of how much human readers improve with AI assistance. It focuses on the concordance between the digital methods (digital read and image analysis) and the manual read by a single pathologist.

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

• Standalone Performance: Yes, the "Image Analysis Read" data in the table represents the performance of the algorithm as an aid to the pathologist. While the pathologist selected the fields of view, the scores themselves are generated by the software. The document also states "The software makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process." This implies it's not a purely standalone, fully automated system without human oversight, but the "Image Analysis Read" itself is the algorithmic output.

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

• Type of Ground Truth: Expert individual pathologist's manual microscopic read ("manual score").

8. The sample size for the training set

• Training Set Sample Size: The document does not provide information about the sample size used for the training set of the Virtuoso software. The study described is a clinical validation study, not a development or training study.

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

• Ground Truth for Training Set: The document does not explain how the ground truth for the training set was established, as it does not detail the training phase of the algorithm.

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 p53 (DO-7) 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 p53 (DO-7) protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRM™ anti-p53 (DO-7) Mouse Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRM™ anti-p53 assay is indicated for the assessment of p53 protein where mutations have been linked to tumor proliferation. When used with this assay, the Virtuoso™ System for p53 (DO-7) is indicated for use as an aid in the assessment of p53 status in breast cancer patients (but is not the sole basis for treatment).

Note: The IHC p53 (D0-7) 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 p53 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-p53 (DO-7) Mouse Monoclonal Primary Antibody assay used to assure the validity of the Virtuoso System for IHC p53 Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-p53 (DO-7) Mouse Monoclonal Primary 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 for the Virtuoso™ System for IHC p53 (DO-7), based on the provided document:

Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria with specific thresholds for agreement percentages. Instead, it presents the results of several agreement and reproducibility studies. For the purpose of this summary, the reported performance values themselves are considered against an implicit expectation of high agreement.

Study Details

The evaluation involved two studies: a primary study for overall system performance and a secondary study for scanner precision.

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

   • Agreement Studies (Virtuoso vs Manual): The sample sizes for the primary agreement study were 119 cases for Site 1, 119 cases for Site 2, 117 cases for Site 3, and 114 cases for Site 4 for the Digital Read analysis. For Image Analysis, Site 4 had 105 cases.
   • Reproducibility Studies: The sample sizes for reproducibility studies are not explicitly stated as total number of cases. However, the confusion matrices for intra-pathologist reproducibility (pages 5 & 6) suggest working with sample sizes in the range of 30-40 cases across sessions (e.g., for Digital Read: 27 Neg, 13 Pos in Session 1, implying around 40 cases). For inter-pathologist reproducibility (pages 6 & 7), the sample sizes range from 119 to ~120 (e.g., Site 1 vs Site 2 had counts summing to 119).
   • Scanner Precision Study: A subset of 40 clinical cases from the primary study was used.
   • Data Provenance: Not explicitly stated, but the mention of "four sites" suggests data was collected from multiple clinical institutions. It is a clinical validation study and, given the nature of regulatory submissions, is almost certainly retrospective analysis of previously collected and stained slides. No country of origin is specified, but the submission is to the US FDA, implying US (and potentially international) clinical data.

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

   • Number of Experts: For the primary study, at least three pathologists were involved for inter-pathologist reproducibility, and each of them performed manual readings for comparison. For the agreement with the manual method, "Each pathologist's Virtuoso digital read results were compared to their manual results." This implies that the manual reading by the same pathologist served as a direct comparison for their digital (DR or IA) reading.
   • Qualifications of Experts: The document states the device is "designed to assist the qualified pathologist" and requires "competent human intervention." While specific years of experience are not mentioned, it is implicit that these were qualified pathologists using traditional diagnostic methods.

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

   • The primary study compared the Virtuoso system's readings (Digital Read and Image Analysis) against the manual method findings of the same pathologist. This means the pathologist's own manual interpretation served as the reference for their digital assessment, rather than an independent adjudicated ground truth from multiple experts.
   • The inter-pathologist agreement section compares readings among three pathologists but does not describe an explicit adjudication process (like 2+1 majority vote) to establish a single "ground truth" across them for the reproducibility analysis itself. Instead, it measures the agreement between them.

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

   • This document does not describe a MRMC comparative effectiveness study that measures the improvement of human readers with AI assistance vs. without AI assistance.
   • Instead, it evaluates the agreement of the AI system's outputs (Digital Read and Image Analysis) with human manual readings, and the reproducibility of human readings, both with and without the digital system (manual vs. digital read, IA vs. manual). It's more of a validation of the digital system as an equivalent tool, rather than an AI-assisted improvement study.

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

   • The "Image Analysis" portion of the Virtuoso system represents the algorithm's standalone performance, albeit within a workflow where a pathologist selects the fields of view. The software "produces a quantitative score for the FOV and an aggregate score over all the FOVs for the whole slide," and "the pathologist has the choice of accepting the result or overriding with his/her own score."
   • The agreement of "Virtuoso Image Analysis vs Manual Method" (page 5) effectively serves as an evaluation of the algorithm's standalone performance (after FOV selection), compared to a human's manual assessment.

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

   • The ground truth for comparison was established by the manual interpretation of qualified pathologists using traditional microscopy. This is termed the "reference manual method."
   • The p53 classifications were "less than or equal to 10% to describe negative, and greater than 10% to describe positive." This threshold-based binary classification was applied by the pathologists.

7. The sample size for the training set:

   • The document does not provide any information about the sample size used for the training set of the Virtuoso system's image analysis algorithms.

8. How the 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.

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. 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 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 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) (IE2) 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 algorithm for specific immunohistochemical marker, 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, 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 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 for the VENTANA® Virtuoso™ System for IHC PR (1E2) based on the provided 510(k) summary (K111869):

1. Table of Acceptance Criteria and Reported Device Performance

The 510(k) summary does not explicitly list pre-defined "acceptance criteria" with specific thresholds for overall agreement, reproducibility, and precision. Instead, it reports the "overall agreements," "negative % agreement," and "positive % agreement" along with 95% confidence intervals (CIs) as the key performance metrics of the device compared to manual methods. For reproducibility and precision, it reports percent agreements and %CV.

Below is a table summarizing the reported device performance. Since explicit acceptance criteria weren't stated quantitatively in the document, I will indicate the reported performance.

• Site 1 vs 2: 96.6% (91.5%-98.7%), n=117 FOVs
• Site 1 vs 3: 97.4% (92.7%-99.1%), n=117 FOVs
• Site 2 vs 3: 94.0% (88.2%-97.1%), n=117 FOVs |
  | | Inter-Scanner %CV Analyses | Site (Scanner) %CV: 0.00% (mean % positivity 25.93%, n=351 FOVs) |
  | | Intra-Scanner/Inter-Day Agreement Rates | Overall percent agreements for three categories (10%) ranged from 97.3% to 98.2% for all FOVs combined.
• Session 1 vs 2: 97.4% (92.7%-99.1%), n=117 FOVs
• Session 1 vs 3: 98.2% (93.7%-99.5%), n=111 FOVs
• Session 2 vs 3: 97.3% (92.4%-99.1%), n=111 FOVs |
  | | Intra-Scanner/Inter-Day %CV Analyses | Day %CV: 0.00% (mean % positivity 26.014%, n=345 FOVs) |

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

• Test Set Sample Size:

  • Agreement/Concordance & Reproducibility Studies: For primary comparisons against manual methods, "n" values are primarily shown as the number of cases per site: Site 1 (n=112), Site 2 (n=114 or 115), Site 3 (n=114 or 116). These numbers refer to the number of patient cases evaluated.
  • Scanner Precision Study: 40 clinical cases were used. For the agreement rates, the tables denote n=117 and n=111 which likely represent the total number of Fields of View (FOVs) analyzed (40 cases * 3 FOVs per case, with slight variations potentially due to unevaluable FOVs). For %CV analyses, n=351 (inter-scanner) and n=345 (intra-scanner) represent the number of evaluable FOVs.

• Data Provenance: The document does not explicitly state the country of origin for the data. However, given the submitting company (Ventana Digital Pathology, Sunnyvale, CA) and FDA submission for the US market, it is highly probable the data was primarily collected in the US. The study is described as "clinical validation" implying it's derived from patient samples. It is not explicitly stated whether the study was retrospective or prospective, but clinical validation studies often use retrospectively collected samples, and the language "evaluated overall system performance" suggests a designed study rather than real-time prospective use.

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

• Number of Experts: For the agreement/concordance and inter-pathologist reproducibility studies, three pathologists were involved in establishing the ground truth (manual read).
• Qualifications of Experts: The document states the device is "designed to assist the qualified pathologist" and requires "competent human intervention." However, it does not explicitly state the specific qualifications or years of experience for the pathologists who participated in the studies.

4. Adjudication Method for the Test Set

• The document states that the "reference manual method (with a traditional microscope)" served as the ground truth. Each pathologist's Virtuoso digital read results were compared to their own manual results, and the image analysis results were also compared to the pathologist's manual results.
• For inter-pathologist comparisons, the three manual readings across the three pathologists were compared to each other.
• The document does not describe a formal adjudication method (e.g., 2+1, 3+1 consensus) to create a single 'expert ground truth' label. Instead, it treats each pathologist's manual read as the "true score" for purposes of comparison with the digital read and image analysis, and then separately assesses inter-pathologist agreement.

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

• Yes, a form of multi-reader, multi-case study was performed, although it focuses on agreement/reproducibility rather than a direct "with AI vs without AI assistance" comparative effectiveness study in the sense of improved performance metrics with assistance.
• The study involved multiple pathologists (three) and multiple cases (over 100 for agreement studies, 40 for scanner precision).
• Effect Size of Human Reader Improvement with AI vs. Without AI Assistance: The document does not directly report an "effect size" of how much human readers improve with AI assistance. Instead, it establishes the agreement between the automated system's outputs (digital read and image analysis) and the a pathologist's manual interpretations. It also assesses inter- and intra-pathologist reproducibility both for manual and digital reads. The system is described as an "aid to the pathologist," and the pathologist has the "choice of accepting the result or overriding with his/her own score." The clinical study validates the agreement of the AI outputs with human pathologists, supporting its role as an aid. It does not quantify a delta improvement in diagnostic accuracy or efficiency for pathologists using the AI versus not using it.

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

• Yes, the "Virtuoso Image Analysis" component of the system demonstrates standalone algorithm performance. The agreement of Virtuoso Image Analysis vs. Manual Method was assessed (reported as 92-97% overall agreement across sites).
• Additionally, the "Scanner Precision" study specifically focused on the image analysis application, stating, "Limiting the study to image analysis only ensured that only scanner precision was under evaluation, as all other factors were kept constant." This further supports that standalone algorithm performance was evaluated for the image analysis module.

7. The Type of Ground Truth Used

• The primary ground truth used for agreement and reproducibility studies was expert consensus (manual read by qualified pathologists). Specifically, each pathologist's manual interpretation of the IHC PR slides using a traditional microscope served as the reference for comparison with their own digital read and the system's image analysis.

8. The Sample Size for the Training Set

• The document does not report the sample size for the training set used to develop the Virtuoso Image Analysis software. The 510(k) summary focuses on the clinical validation (test set) of the final device.

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 detail is typically omitted in 510(k) summaries, which focus on the post-development validation rather than the development process itself.

Ask a specific question about this device

The PATHIAM System is intended as an aid to the pathologist to detect, count, and classify cells of clinical interest based on recognition of cellular objects of particular color, size, and shape, using appropriate controls to assure the validity of the scores.

The p53 results provided by the PATHIAM System are indicated for use for the identification of p53 accumulation in human neoplasias when used with IVD reagents marketed for this indication. Interpretation should be made within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist. The pathologist must verify agreement with the PATHIAM score.

Ki-67 results provided by the PATHIAM System are indicated for use to assess proliferative activity when used with in vitro diagnostic reagents marketed for this indication. Interpretation should be made within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist. The pathologist must verify agreement with the PATHIAM score.

The PATHIAM™ System is an instrument and software system designed to assist the qualified pathologist in the consistent quantitative 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. PATHIAM is a web-based, end-to-end digital pathology software solution that allows pathology labs to acquire, manage, view, analyze, share, and report on digital images of pathology specimens. Using the PATHIAM 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, 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 PATHIAM 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 at all steps in the analysis process.

Here's a breakdown of the acceptance criteria and study details for the PATHIAM™ System with iScan for p53 and Ki-67, extracting information from the provided document:

Acceptance Criteria and Device Performance

1%: 82% - 90%
5%: 77% - 85%
10%: 83% - 89% |
| PATHIAM-assisted vs. PATHIAM-assisted Reproducibility (Inter-Pathologist) | ≥ 75% concordance | Exceeded 75% concordance at all three clinical cut-offs, and was higher than manual microscopy reproducibility.
1%: 88% - 93%
5%: 90% - 93%
10%: 93% - 97% |
| PATHIAM-assisted vs. PATHIAM-assisted Reproducibility (Intra-Pathologist) | ≥ 75% concordance (for 3 scoring events) | Exceeded 75% concordance at all three clinical cut-offs.
1%: 85%
5%: 80%
10%: 80% |
| Ki-67 Scoring | | |
| Manual vs. PATHIAM-assisted Substantial Equivalence Concordance | ≥ 75% concordance | Met by all three pathologists for all three clinical cut-offs (>1%, >5%, >10%).
1%: 88% - 93%
5%: 87% - 93%
10%: 81% - 89% |
| PATHIAM-assisted vs. PATHIAM-assisted Reproducibility (Inter-Pathologist) | ≥ 75% concordance | Exceeded 75% concordance at all three clinical cut-offs, and was higher than manual microscopy reproducibility.
1%: 92% - 94%
5%: 90% - 93%
10%: 88% - 95% |
| PATHIAM-assisted vs. PATHIAM-assisted Reproducibility (Intra-Pathologist) | ≥ 75% concordance (for 3 scoring events) | Exceeded 75% concordance at all three clinical cut-offs.
1%: 80%
5%: 85%
10%: 85% |
| System Precision/Reproducibility | Precision and reproducibility similar to predicate devices | The tables for intra- and inter-system studies "confirm the precision and reproducibility of Ki-67 and p53 scoring within the same system and between different systems." and "showed that PATHIAM System precision and reproducibility is similar to that of the predicate devices" (e.g., %CV values provided in tables 5-12). |

Study Details

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

   • Test Set (for comparative and pathologist reproducibility studies):
     • p53 study: 120 de-identified archived breast carcinoma sections in Tissue Micro Array (TMA) form.
     • Ki-67 study: 120 de-identified archived breast carcinoma sections in TMA form.
     • Data Provenance: The samples were sourced from a single research center, Ohio State University Medical Center (OSU). The data is retrospective, using archived pathological specimens. The country of origin is the United States (Ohio).
   • Test Set (for system precision/reproducibility studies):
     • 8 pre-selected fields of view (EOVs) from TMA cores for both p53 and Ki-67.
     • These 8 samples were among the 120 cases from the clinical studies.

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

   • Number of Experts: Three investigators.
   • Qualifications: "Qualified pathologists". Specific experience levels (e.g., "10 years of experience") are not provided, but they are from different clinical labs.
   • The ground truth used for comparative studies was manual microscopy scores by these pathologists. The system also performs automated scoring as part of its operation, which is then compared to the human pathologist's assessment.

3. Adjudication method for the test set:

   • The study design does not explicitly mention a formal adjudication method (e.g., 2+1, 3+1) for resolving disagreements between pathologists' scores in the inter-pathologist studies.
   • Concordance was calculated based on the agreement between individual pathologists' scores, or between a pathologist's score and the PATHIAM-assisted score, or between two pathologists' manual scores. The study focused on assessing agreement rather than establishing a single adjudicated ground truth from multiple readers.

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

   • Yes, an MRMC-like comparative effectiveness study was conducted ("PATHIAM System Comparison Studies (Inter and Intra Pathologist Studies)").
   • Effect Size (Improvement with AI assistance):
     • The study reports that Inter-Pathologist reproducibility using the PATHIAM system was higher than Inter-Pathologist reproducibility using manual microscopy at all three clinical cut-offs. This indicates an improvement in consistency among human readers when assisted by the AI.
     • For p53:
       • PATHIAM-assisted vs. PATHIAM-assisted Reproducibility: 88-97%
       • Manual vs. Manual Reproducibility: 78-95%
       • (Improvement is visible, but an exact "effect size" (e.g., AUC difference, specific statistical metric) is not quantified beyond showing higher concordance ranges.)
     • For Ki-67:
       • PATHIAM-assisted vs. PATHIAM-assisted Reproducibility: 88-95%
       • Manual vs. Manual Reproducibility: 80-91%
       • (Similar indication of improvement in consistency.)

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

   • Yes, standalone performance was assessed in the "PATHIAM System Reproducibility and Precision Study (Inter and Intra System Studies)".
   • This study specifically aimed to "assess the consistency and reproducibility of the PATHIAM system (no pathologist)" for p53 and Ki-67 scoring on different systems.
   • The PATHIAM system's raw scores were used directly for comparison in these precision studies.

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

   • For comparative effectiveness studies: The ground truth for comparative performance (manual vs. PATHIAM-assisted) was derived from individual manual microscopy scores by qualified pathologists.
   • For pathologist reproducibility studies: The ground truth for inter-pathologist reproducibility was agreement between the PATHIAM-assisted scores of different pathologists. For intra-pathologist reproducibility, it was agreement of a single pathologist's PATHIAM-assisted scores across multiple reads.
   • For system precision/reproducibility studies: The "ground truth" was the PATHIAM system's own raw score for a given field of view, and the studies assessed the consistency of these scores across repeated measurements and different systems. There was no independent external ground truth (like a molecular test or pathology review report) in these specific precision studies; they validated the system's internal consistency.

7. The sample size for the training set:

   • The document does not explicitly state the sample size used for training the PATHIAM algorithms. The description focuses on the validation studies.

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

   • Since the training set size is not provided, the method for establishing its ground truth is also not detailed in this document.

Ask a specific question about this device

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

The IHC ER Image Analysis application is intended for use as an aid to the pathologist in the detection and quantitative measurement of ER (Estrogen Receptor) in formalin-fixed paraffinembedded normal and neoplastic tissue.

The IHC PR Image Analysis application is intended for use as an aid to the pathologist in the detection and quantitation measurement of PR (Progesterone Receptor) in formalin-fixed. paraffin-embedded normal and neoplastic tissue.

It is indicated for use as an aid in the management, prognosis, and prediction of therapy outcomes of breast cancer.

Note: The IHC ER and PR Image Analysis applications are an adjunctive computer-assisted methodology to assist the reproducibility of a qualified pathologist in the acquisition and measurement of images from microscope slides of breast cancer specimens stained for the presence of estrogen and progesterone receptor proteins. The accuracy of the test result depends upon 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 ER and PR reagent/kit used to assure the validity of the IHC ER and PR Image Analysis application assisted scores.

The system comprises a ScanScope® XT digital slide scanner instrument and a computer system executing Spectrum " software. The system capabilities include digitizing microscope slides at diagnostic resolution, storing and managing the resulting digital slide images, retrieving and displaying digital slides, including support for remote access over wide-area networks, providing facilities for annotating digital slides and entering and editing metadata associated with digital slides, and facilities for image analysis of digital slides, including the ability to quantify characteristics useful to Pathologists, such as measuring and scoring immunohistochemical stains applied to histology specimens, such as Dako ER/PR, which reveal the presence of ER (Estrogen Receptor) protein and PR (Progesterone Receptor) protein expression, which may be used to determine patient treatment for breast cancer.

Hardware Operation: The ScanScope XT digital slide scanner creates seamless true color digital slide images of entire glass slides in a matter of minutes. A high numeric aperture 20x, as found on conventional microscopes, is used to produce high-quality images. (When the 2X magnification changer is inserted, the effective magnification of the images is 40X.) The ScanScope XT employs a linear-array scanning technique that generates images free from optical aberrations along the scanning axis. The result is digital slide images that have no tiling artifacts and are seamless.

Software Operation: The Spectrum software is a full-featured digital pathology management system. The software runs on a server computer called a Digital Slide Repository (DSR), which stores digital slide images on disk storage such as a RAID array, and which hosts an SQL database that contains digital slide metadata. Spectrum includes a web application and services which encapsulate database and digital slide image access for other computers. The Spectrum server supports the capability of running a variety of image analysis algorithms on digital slides, and storing the results of analysis into the database. Spectrum also includes support for locally or remotely connected image workstation computers, which run digital slide viewing and analysis software provided as part of Spectrum.

Overview of System Operation: The laboratory technician or operator loads glass microscope slides into a specially designed slide carrier with a capacity of up to 120 slides. The scanning process begins when the operator starts the ScanScope scanner and finishes when the scanner has completed scanning of all loaded slides. As each glass slide is processed, the system automatically stores individual "striped" images of the tissue contained on the glass slide and integrates the striped images into a single digital slide image, which represents a histological reconstruction of the entire tissue section. After scanning is completed, the operator is able to view and perform certain analytical tests on the digital slides.

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

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied through the results presented, which aim to demonstrate substantial equivalence to manual microscopy. The study primarily focuses on inter-pathologist agreement for both manual microscopy and the device's image analysis, as well as agreement between manual microscopy and the device's image analysis. Precision studies also demonstrate the device's consistency.

Given the document structure, the "acceptance criteria" appear to be defined not as specific numerical thresholds prior to the study, but rather by demonstrating that the device performs comparably to manual microscopy and shows acceptable levels of precision. The reported performance shows the ranges of agreement found.

2. Sample Size for the Test Set and Data Provenance

• ER Study Test Set: 80 formalin-fixed, paraffin-embedded breast tissue specimens.
  • Data Provenance: Retrospective, from a single CLIA-qualified clinical site in the US (implied by CLIA qualification, as it's a US regulatory standard). Specimens were "selected based on their clinical scores on file."
• PR Study Test Set: 180 formalin-fixed, paraffin-embedded breast tissue specimens.
  • Data Provenance: Retrospective, from two CLIA-qualified clinical sites in the US. 80 slides from the first site (selected based on clinical scores) and 100 slides from the second site (routine clinical specimens, representing the target population).

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

• Number of Experts: Three board-certified pathologists at each clinical site.
• Qualifications: "Board-certified staff pathologists" at CLIA-qualified clinical sites. (No specific years of experience are mentioned).

4. Adjudication Method for the Test Set

The document describes a form of expert consensus and comparison rather than a strict adjudication to arrive at a single "ground truth" value for the test set.

• For Manual Microscopy: Three different board-certified pathologists at each clinical site performed a blinded manual review of each glass slide. They reported the percentage of positive nuclei and average intensity score. The study then uses the "manual microscopy average percentages of positive nuclei from the three pathologists" and "manual microscopy average intensity scores from the three pathologists" for comparisons. This suggests an averaging approach rather than a specific adjudication rule (e.g., 2-out-of-3 majority; a 3+1 method where a fourth expert adjudicates disagreements is not explicitly stated).
• For Image Analysis: Each of the three pathologists outlined tumor regions on digital slides (blinded from each other and from image analysis results). Image analysis was then performed on each set of outlined regions, resulting in a separate image analysis score for each of the three pathologists. No formal adjudication is described to combine these three algorithm scores into a single "ground truth" for the algorithm; rather, the agreement between the pathologists' manual scores and their respective image analysis scores is evaluated, as well as inter-pathologist agreement for both methods.

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

• This was a type of MRMC study, as multiple readers (pathologists) evaluated multiple cases (slides) both manually and with the assistance of the device (though the AI component was run after and blinded from the pathologists' region selection).
• Effect Size: The document does not report an effect size for how much human readers improve with AI vs. without AI assistance. Instead, it reports agreement percentages between pathologists' manual scores, between pathologists' AI-assisted scores, and between a pathologist's manual score and their corresponding AI-assisted score. The study's focus was on demonstrating substantial equivalence and agreement, not on measuring reader improvement with assistance.

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

• Yes, in part. The image analysis algorithm reported the percentage of positive nuclei and average intensity score for each digital slide. However, the input to the algorithm (the tumor regions) was still defined by human pathologists. The critical step of selecting the region of interest was human-in-the-loop, even if the quantitative analysis within that region was standalone.
• The document states: "Image analysis was run in batch processing mode completely separated from the pathologists outlining the tumor regions to avoid influencing the pathologists in their choice of tumor regions." This clarifies that the numerical output of the algorithm was standalone for a given region, but the selection of that region itself was pathologist-driven.

7. The Type of Ground Truth Used

• Expert Consensus (Averaged): For comparing the device performance, the "ground truth" for manual microscopy was established by taking the average percentage of positive nuclei and average intensity scores from three board-certified pathologists. This serves as the reference against which the digital system's performance (also tied to pathologist-defined regions) is compared.
• Not Pathology, but based on Pathology Scores: While pathology slides were used, the ground truth was not solely an independent pathology report in the traditional sense, but rather the statistically combined scores of the evaluating pathologists who were part of the study.
• Not Outcomes Data: The study did not use patient outcomes data.

8. The Sample Size for the Training Set

• The document does not specify the sample size used for the training set for the image analysis algorithm. The provided information focuses entirely on the clinical validation study (test set).

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, as the training set details are not described.

Ask a specific question about this device

The Ventana Image Analysis System (VIAS™) is an adjunctive computer-assisted image analysis system functionally connected to an interactive microscope. It is intended for use as an aid to the pathologist in the detection, classification and counting of cells of interest based on marker intensity, size and shape using appropriate controls to assure the validity of the VIAS scores.

In this application, the VIAS is intended to aid a qualified pathologist for the semi-quantitative detection of c-erbB-2 (HER2) antigen in formalin-fixed, paraffin-embedded normal and neoplastic tissue specimens immunohistochemically stained for the presence of HER2 proteins using Ventana® Medical Systems, Inc.'s (Ventana) PATHWAY® anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody as well as Ventana's DAB copper chromogen and nuclear hematoxylin.

Ventana's PATHWAY® anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody (PATHWAY HER2 (4B5)) is indicated as an aid in the assessment of breast cancer patients for whom Herceptin® treatment is considered.

The VIAS is an adjunctive computer-assisted methodology to assist the reproducibility of a qualified pathologist in the acquisition and measurement of images from microscope slides of breast cancer specimens stained for the presence of HER2 receptor protein. The accuracy of the test result depends upon 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 Ventana PATHWAY HER2 (4B5) to assure the validity of the VIAS-assisted HER2.

The Ventana Image Analysis System (VIAS™) is an adjunctive computer-assisted image analysis system functionally connected to an interactive microscope.

The provided text describes the 510(k) premarket notification for the Ventana Image Analysis System - PATHWAY® HER2 (4B5). While it outlines the device's indications for use and regulatory information, it does not contain specific details about the acceptance criteria, the study proving the device meets those criteria, or the methodology of such a study.

Therefore, I cannot provide the requested information. The document focuses on regulatory approval based on substantial equivalence to a predicate device rather than presenting detailed performance study results against predefined acceptance criteria.

Ask a specific question about this device