Search Results

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

PATHIAM-Assisted Scoring: Intended for clinical laboratory use as an accessory to the DAKO HercepTest to aid in the detection and semi-quantitative measurement of Her2/neu in formalin fixed, paraffin-embedded normal and neoplastic tissue. When used with the DAKO HercepTest, Pathiam Assisted Scoring is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN (Trastuzumab) treatment is being considered. The pathologist should verify agreement with the PATHIAM System score.

HER2/neu results are indicated for use as an aid in the management, prognosis and predication of therapy outcomes of breast cancer. Note: The actual correlation of the DAKO HercepTest to Herceptin® clinical outcome has not been established.

The PATHIAMIM System is an instrument (iScan) and image analysis software system designed to assist the qualified pathologist in the consistent quantitative assessment of marker expression in immunohistochemically stained histological sections digital images. The sample tissue is breast tissue prepared using the DAKO HercepTest Reagent Kit. The PATHIAM system consists of the BioImagene iScan slide scanner, computer with the PATHIAM Software, monitor, keyboard and mouse.

The PATHIAM System digitizes formalin-fixed, paraffin embedded normal and neoplastic tissue and provides semi-quantitative analysis of extent and intensity of stained tissue, providing the pathologist with an aid to interpretation of the level of expression of HER2/neu in breast cancer tissue. The pathologist is presented with a digital image of the tissue section and a suggested staining score (0 to 3). The pathologist then makes an assessment of the digital image and reports his/her score. Alternately, the pathologist can simply use the digitized image to perform his interpretation of the level of expression, without employing the software.

Hardware: The iScan slide scanning device captures digital images of formalin-fixed, paraffin-embedded tissues that are suitable for storage, viewing and visual analysis. The device includes a digital slide scanner, racks for loading glass slides, an Intel based PC, dual core, dual Xeon processor, PATHIAM Software, and a monitor.

Software: The PATHIAM Software requires competent human intervention at all steps in the analysis process. The system is designed to complement the routine workflow of a qualified pathologist screening the immunohistochemically stained histological slides with additional quantitative data to assist the reproducibility of the slide interpretation. It allows the user to select the area of interest on the breast tissue image. The user marks the area of interest for the analysis. The system software makes no independent interpretations of the data. The software will act as a tool for the user, to improve consistency and data recording. The image produced digitally may also be used independent of the software, by allowing the pathologist to count from the digital image, rather than from the microscope.

The provided document outlines the performance study for the PATHIAM™ System with iScan for HER2/neu, primarily focusing on its agreement with manual HercepTest methods and reproducibility.

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

1. Table of Acceptance Criteria and Reported Device Performance:

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

• Sample Size: 176 stained tissue specimens.
• Data Provenance: The document does not explicitly state the country of origin. The study appears to be prospective in the sense that the pathologists performed readings specifically for this study, first manually and then with the PATHIAM System. There is no indication of retrospective analysis of existing clinical data.

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

• Number of Experts: Three pathologists.
• Qualifications of Experts: The document states "trained pathologists" without specifying years of experience or sub-specialization.

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

• Adjudication Method: Not explicitly stated. For the "Comparison with Manual HercepTest method," pathologists observed digital images and the suggested score, then selected an appropriate tissue score. This suggests the pathologist made the final judgment for the PATHIAM System assisted score. For the manual scores, they read the slides manually. There's no mention of a consensus process or arbitration for discrepant scores.

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 form of MRMC study was conducted. Three pathologists (multiple readers) assessed 176 cases (multiple cases) both with and without the AI assistance (manual vs. PATHIAM-assisted).
• Effect Size of Improvement: The study demonstrates improved inter-reader reproducibility with AI assistance compared to manual reading.
  • Manual Inter-reader Agreement: Ranged from 67% to 81%.
  • PATHIAM-assisted Inter-reader Agreement: Ranged from 89% to 92%.
  • This represents an improvement in inter-reader agreement of 8% to 22% when using the PATHIAM system compared to manual reading alone (e.g., 92% vs 67% for Site 1 vs 2 comparison, an improvement of 25 percentage points; 89% vs 81% for Site 2 vs 3, an improvement of 8 percentage points; 91% vs 80% for Site 3 vs 1, an improvement of 11 percentage points). The "effect size" here is the increase in percentage agreement between pathologists.

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

• Standalone Performance: No, a standalone performance study of the algorithm without human-in-the-loop was not performed. The device description explicitly states: "The PATHIAM Software requires competent human Software: intervention at all steps in the analysis process. The system is designed to complement the routine workflow of a qualified pathologist..." and "The software will act as a tool for the user, to improve consistency and data recording." The "PATHIAM System values" are derived from the pathologist's review of the digital images and the software's suggested score.

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

• Ground Truth: The "ground truth" for evaluating the PATHIAM System's performance was the manual assessment by trained pathologists using the DAKO HercepTest package insert. This is implicitly assumed to be the "gold standard" against which the system-assisted readings are compared. The reproducibility study between pathologists also uses their independent assessments as the reference.

8. The sample size for the training set:

• Training Set Sample Size: The document does not provide information on the training set size or how the algorithm was developed. The studies described are performance validation studies.

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

• Training Set Ground Truth: As with the training set size, information on how the ground truth for any potential training set was established is not provided in this summary.

Ask a specific question about this device

Biolmagene PATHIAM is intended for use as an accessory to the Dako HercepTest® to aid a pathologist in semi-quantitative measurement of HER2/neu (c-erbB-2) in Formalin-fixed, paraffin-embedded breast cancer tissue. When used with the Dako HercepTest it is indicated as an aid in the assessment of breast cancer patients for whom Herceptin® (Trastuzumab) treatment is being considered.

The imaging software is intended to detect and classify cells of clinical interest by analyzing digitized images of microscope slides based on recognition of cellular objects of particular color, size and shape. The software can be used with a computer and image digitizer with features specified in the labeling.

PATHIAM software is a standalone software application that will work on a system with the following features required but not provided:

Computer

• Processor: 2.4 GHz, Pentium IV equivalent
• Memory: 512 MB RAM
• Operating System: Windows 2000 or later
• Hard Drive: minimum 100MB for software installation, 20GB for image storage
• LAN connectivity, minimum 100 MBPS (recommended), support for USB interface, support for HTTP, TCP/IP protocols (using the Operating system)
• High Speed Graphic Accelerator Card (1024 X 768)
• 17" High resolution display monitor
• 24 bit color depth
• Font Setting: Small font (DPI setting: 96 DPI)

Digitizing Equipment: Camera

• Resolution: at least 2048 x 1536 pixels
• Frame rate: 20 fps@1200 x 768 resolution (6 fps @ 2048 x 1536 resolution)
• Sampling Frequency of 6.26 square/um
• Compression format: JPEG 2000, BMP, TIFF, JPEG
• Color: 24-bit (R. G. B)
• Connection to computer

Digitizing Equipment: Digital Side Scanner

• Input Format: 25X75mm microscope slides
• Resolution: 54,000 pixel/inch with 20X objective
• Method: Line-scanning
• File Format: TIFF/JPEG2000; compliant with TIFF 6.0 standard.
• Color: 24-bit (R.G. B)
• Connectivity: 100/1000 MBPS Ethernet
• Compression format: JPEG 2000, BMP, TIFF, JPEG

The software allows both archiving of the digital image, and semi quantitative analysis of extent and intensity of stained tissue, providing the pathologist with an aid to interpretation of level of expression of Her2/neu in breast cancer tissue. The pathologist is presented with a digital image of the tissue section and a suggested staining score (0 to 3). The pathologist then makes an assessment of the digital image and reports his/her score.

Here's a breakdown of the acceptance criteria and study details for the BioImagene PATHIAM Image Analysis Software for Her2/neu, based on the provided 510(k) summary:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for the PATHIAM software are implicitly defined by comparison to the established predicate device (ACIS Her2/neu software component) and through performance studies demonstrating inter-laboratory and inter-reader agreement. While explicit numerical acceptance criteria for overall agreement are not stated as "target thresholds," the demonstrated high levels of agreement strongly support the device's performance.

Study Details

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

   • Test Set Sample Size: 176 stained breast cancer tissue specimens.
   • Data Provenance: The study was conducted in the US at three different sites. There is no explicit mention of the data being retrospective or prospective, but the description of "analyzed images of the same set of 176 stained breast cancer tissue specimens" suggests a retrospective analysis of existing samples.

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

   • Number of Experts: Three different pathologists.
   • Qualifications: They are referred to as "trained pathologists," but no specific experience levels (e.g., years of experience, board certifications) are provided.

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

   • The study involved multiple pathologists providing scores, and comparisons were made between their scores. However, there is no explicit mention of an adjudication method to establish a single, definitive ground truth score for each case through consensus or a tie-breaker. Instead, the study focuses on agreement between the individual scores of the device, manual readers, and device-assisted readers across different labs.

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, implicitly, an MRMC comparative effectiveness study was performed in the sense that multiple readers (pathologists) evaluated multiple cases with and without the PATHIAM assistance, and across different laboratory setups.
   • Effect Size of Improvement:
     • Manual Scores (Inter-lab agreement): 76% - 97% overall agreement (Table 3).
     • Pathologist Assisted by PATHIAM Scores (Inter-lab agreement): 81% - 96% overall agreement (Table 2).
     • The summary states: "Consistency is improved when the PATHIAM score assists the pathologist in their interpretation (Table 2)."
     • While not quantified as a single "effect size" number, comparing Table 3 (Manual Scores) to Table 2 (PATHIAM-Assisted Scores) suggests an improvement in agreement. For instance, Lab 1 vs Lab 3 manual agreement was 76%, while with PATHIAM assistance, it was 81%. Lab 2 vs Lab 3 manual agreement was 78%, and with PATHIAM assistance, it was also 81%. This indicates a trend towards improved inter-reader consistency with AI assistance.

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

   • Yes, a standalone performance assessment was conducted. This is evidenced by the "Between-Lab Agreement for Raw PATHIAM- Scores" (Table 1), which shows the consistency of the algorithm's output across different laboratories without direct pathologist modification of the software's initial score. The study also compared "PATHIAM raw scores and Manual Scores" (Table 5), which is a comparison of the algorithm's output against human interpretation.

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

   • The primary "ground truth" or reference for comparison in this study is the pathologist's interpretation, both manual (microscopic assessment) and PATHIAM-assisted. The study focuses on agreement between these interpretations rather than against an external, independent gold standard like pathology results or clinical outcomes. The device is an aid to a pathologist, implying its performance is assessed by how well it aligns with or improves human expert interpretation.

7. The sample size for the training set:

   • The document does not provide information on the sample size used for the training set. The performance data presented relates exclusively to the test set used for validation.

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

   • Since the training set size and details are not provided, it is also not stated how the ground truth for any potential training set was established.

Ask a specific question about this device