Roche Virtuoso Manuale utente

Tipo
Manuale utente
Estrogen Receptor (SP1) Image Analysis Software User Manual, v. 5.1
Östrogenrezeptor (SP1) Handbuch zur Bildanalyse-Software-Anwendung, v. 5.1
Manuel d’utilisation de l’application logicielle d’analyse d’images du récepteur
d’œstrogènes (SP1), v. 5.1
Manual de usuario de la aplicación del software de análisis de imagen del receptor de
estrógeno (SP1), v. 5.1
Manuale dell’utente del software per l’analisi delle immagini
di Estrogen Receptor (SP1), v. 5.1
Uživatelská příručka softwarové aplikace pro analýzu obrazu estrogenového
receptoru (SP1), v. 5.1
Brugervejledning for Softwareapplikation til østrogenreceptor (SP1)-billedanalyse, v. 5.1
Εγχειρίδιο χρήσης της εφαρμογής του λογισμικού ανάλυσης εικόνας του οιστρογονικού
υποδοχέα (SP1), v. 5.1
Ösztrogén receptor (SP1) képelemző szoftveralkalmazás használati útmutató, v. 5.1
Gebruikershandleiding voor de oestrogeenreceptor (SP1)
beeldanalyse-softwareapplicatie, v. 5.1
Brukerhåndbok for bildeanalyseprogram for østrogenreseptor (SP1), v. 5.1
Podręcznik użytkownika oprogramowania użytkowego do analizy obrazu receptora
estrogenu (ER) (SP1), v. 5.1
Manual do utilizador para a aplicação do software para a análise de imagem do receptor de
estrogénio (SP1), v. 5.1
Priročnik za uporabo programske opreme za analizo slik estrogenskih
receptorjev (SP1), v. 5.1
Användarhandbok för programmet för bildanalys av östrogenreceptorn (SP1), v. 5.1
Not for distribution in the US
PS-001377/06449018001
Ventana Medical Systems, Inc. Part No.: 101407000 Rev. A
INTENTIONALLY BLANK
Companion Algorithm Estrogen Receptor (SP1)
Image Analysis Software User Manual, v. 5.1
Ventana Medical Systems, Inc. Part No.: 101407000 Rev. A
Companion Algorithm Estrogen Receptor (SP1) Image Analysis Software User Manual
Copyright
Copyright © 2014. Ventana Medical Systems, Inc. All rights reserved.
Trademarks
BENCHMARK, CONFIRM, COMPANION ALGORITHM, VENTANA ISCAN HT, ISCAN, VIRTUOSO,
VENTANA, and the VENTANA logo are trademarks of Roche. All other trademarks are the property of their respective
owners.
Companion Algorithm ER (SP1) image analysis software is licensed for use between Ventana Medical Systems, Inc. and
a licensee, and only users authorized there under are permitted to access and use the software. Unauthorized use and
distribution may result in civil and criminal penalties.
Open Source and Commercial Software
Refer to the Virtuoso Reference Guide for information on Open Source and Commercial Software programs.
Contact Information:
Ventana Medical Systems, Inc.
1910 E. Innovation Park Drive
Tucson, AZ 85755
USA
+1 520 887 2155
www.ventana.com
Ventana Medical Systems, Inc.
203 Ravendale Drive
Mountain View, CA 94043
USA
Roche Diagnostics GmbH
Sandhofer Strasse 116
D-68305 Mannheim
Germany
+49 621 7590
Part No.: 101407000 Rev. A i
Table of Contents
About the Companion Algorithm ER (SP1) image analysis software . . . . . . . . . . . .1
Topics Covered in this Chapter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Who Should Read this Manual . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Related Document . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Technical Support. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Connection Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Cyber Security . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
User Authorization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Securing Networks and Servers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Protecting Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Chapter 1: Intended Use and Indications for Use . . . . . . . . . . . . . . . . . . . . . . . .5
Intended Use and Indications for Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Summary and Explanation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Test Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Warnings and Precautions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Pre-Analytical Variables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Required Materials Not Provided. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Performance Characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Assay Cutoff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Chapter 2: ER Comparison and Reproducibility Studies . . . . . . . . . . . . . . . . . . . .9
ER Marker Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Staining Procedure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Study Devices and Samples for BenchMark XT Instrument and iScan Coreo Slide Scanner. . . 9
ER Concordance with BenchMark XT Instrument and iScan Coreo Slide Scanner . . . . . . . . . 9
Intra-System and Inter-System Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
ER Concordance with BenchMark ULTRA Instrument and iScan Coreo Slide Scanner . . . . . 12
Appendix A: Reagents (Antibody) Package Inserts. . . . . . . . . . . . . . . . . . . . . . .19
Reagents (Antibody) Package Inserts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21
ii Part No.: 101407000 Rev. A
Table of Contents ER (SP1) Image Analysis Software Users Manual
INTENTIONALLY BLANK
Part No.: 101407000 Rev. A 1
About the Companion Algorithm ER (SP1) image analysis
software
Welcome to the Companion Algorithm Estrogen Receptor (ER) (SP1) image analysis software User Manual.
Topics Covered in this Chapter
Who Should Read this Manual (page 1)
Introduction (page 1)
Related Document (page 1)
Technical Support (page 1)
Connection Requirements (page 1)
Cyber Security (page 2)
Who Should Read this Manual
System Administrators should read this user manual and use it for reference while operating the VENTANA Virtuoso software.
Introduction
The Companion Algorithm ER (SP1) image analysis software assists the pathologist in the semi-quantitative measurement of ER in
tissues stained with the Ventana Medical Systems, Inc. CONFIRM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary
Antibody (CONFIRM anti-ER (SP1)). This application generates an ER score that can be reviewed and accepted by the pathologist,
or if necessary, overridden by the pathologist. The image analysis application is an assist to the pathologist in the scoring and
interpretation of ER staining on breast cancer tissues.
The Virtuoso Estrogen Receptor Digital Read Application allows the pathologist to view CONFIRM anti-ER (SP1) stained slides
as images on a computer monitor, similar to what can be viewed under a microscope. While reviewing the image, the pathologist
may change magnification and move freely about the image.
Related Document
For additional information on the Virtuoso software, see the following Ventana document:
Virtuoso Reference Guide (PL-000123-EN)
Technical Support
Connection Requirements
Refer to the Virtuoso Reference Guide information on connection requirements.
Ventana Medical Systems, Inc.
1910 E. Innovation Park Drive
Tucson, AZ 85755
USA
Tel: +1 520 887 2155; for Technical Support, press 1
2 Part No.: 101407000 Rev. A
About the Companion Algorithm ER (SP1) image analysis software ER (SP1) Image Analysis Software User Manual
Cyber Security
Any device that is connected to a network (internally or externally) has the potential to be compromised by unauthorized access or
viruses. As with most devices, the software is designed to run on a computer utilizing Microsoft Windows and virus protection
software which requires the validation and implementation of the appropriate patches.
Some of the potential cyber security hazards are:
Malicious software that alters the device software (such as viruses)
Unauthorized access to the system that could compromise data safety
Security of data transmitted over the Internet
Cyber security involves protecting data by preventing, detecting, and responding to malicious cyber attacks. Cyber attacks could
involve computer viruses which can completely erase data or hackers who alter files or even use the device as a host to attack other
devices. As serious as these hazards are, steps can be taken to maximize cyber security.
User Authorization
All software users must login with a valid user name and password. The user name and password are securely transmitted in
encrypted form over the Internet or Intranet. Once a user has logged in, the user remains active in the application until the user
explicitly logs out, closes the browser, or because the application closes after a period of inactivity.
Securing Networks and Servers
Network security consists of the provisions made in the computer network infrastructure, policies adopted by the network
administrator to protect the network, and the network resources that prevent unauthorized access.
The following are critical steps for securing a network server:
Physical security (servers and network infrastructure behind locked doors)
Use of robust passwords
System and data backups (at regular intervals)
Data protection
Terminating unused services
Restricting access to used services
The following are critical steps and methodologies used to secure network and servers:
Data protection
Data backups (at regular intervals)
Refusal of automatic updates from off-the-shelf software
Antivirus software for computers and servers
Protecting Data
Establishment of a network firewall and protection of the network against viruses using anti-virus software are effective methods to
protect data. Virus definitions should be kept up to date and regular scans of computers for spyware should be performed using a
legitimate anti-spyware application. If viruses or spyware are found, remove them immediately.
ER (SP1) Image Analysis Software User Manual About the Companion Algorithm ER (SP1) image analysis software
3
Evaluate Your Software Settings
The default settings of most software enable all available functionality. However, hackers may be able to take advantage of this
functionality to access devices. It is especially important to check the settings for software that connects to the Internet (browsers,
email clients, etc.). Apply the highest level of security available that still provides needed functionality.
Backup and Recovery
In order to develop a successful backup and recovery plan, comprehension of data accessibility needs and the potential impact of
data loss is essential. Automatic backup procedures need to be adopted using a data backup utility.
4 Part No.: 101407000 Rev. A
About the Companion Algorithm ER (SP1) image analysis software ER (SP1) Image Analysis Software User Manual
INTENTIONALLY BLANK
Part No.: 101407000 Rev. A 5
Chapter 1: Intended Use and Indications for Use
This chapter shows comparison and reproducibility studies for the ER marker.
Intended Use and Indications for Use
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 IHC ER (SP1) Digital Read and Image Analysis applications are intended for use as an aid to the pathologist in the detection
and quantitative measurement of estrogen receptor (ER) protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue.
ER results are indicated for use as an aid in the management, prognosis and prediction of therapy outcomes in breast cancer. When
used with Ventana Medical Systems, Inc. CONFIRM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody, it
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 (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 estrogen receptor 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-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody assay used to assure the
validity of the iScan System for IHC ER Digital Read and Image Analysis scores. The actual correlation of CONFIRM anti-Estrogen
Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody to clinical outcome has not been established.
Summary and Explanation
The Virtuoso system for ER SP1 is an instrument and software system designed to assist the qualified pathologist in the consistent
quantitative assessment of protein expression in immunohistochemically (IHC) stained histologic sections from formalin-fixed,
paraffin-embedded (FFPE) normal and neoplastic tissues. The Virtuoso system can be used for review of digitized images of
histologic sections with image analysis algorithms (Companion Algorithm Virtuoso image analysis applications), or without
Companion Algorithm image analysis algorithms (Virtuoso Digital Read applications).
Digital Read applications present images on the computer screen in the same manner as one would see with a manual microscope,
inclusive of the pathologist's ability to select any areas of interest and the option of various magnification levels. For the Companion
Algorithm image analysis applications, the pathologist may use the system software to select and outline one or several field of views,
(FOVs), and each FOV may be viewed at various magnifications and then analyzed by the software (analysis at 20x magnification);
a count of the total number of target cells and the number interpreted by the algorithm as positive and negative is generated. The
pathologist can accept the score provided by the algorithm, or may override the score with a different score. The system requires
competent human intervention at all steps in the analysis process, and the software makes no independent interpretations of the data.
The Virtuoso system consists of a slide scanner, computer, monitor, keyboard, mouse, Companion Algorithm image analysis
algorithms, and software with a user interface. Virtuoso is an end-to-end digital pathology software solution that allows pathology
laboratories to acquire, manage, view, analyze, share, and report on digital images of pathology specimens. Using the Virtuoso
software, the pathologist can view digital images at various magnifications (as previously stated), add annotations, make tissue section
measurements, perform image analysis, and generate reports.
For in vitro diagnostic (IVD) use.
6 Part No.: 101407000 Rev. A
Chapter 1: Intended Use and Indications for Use ER (SP1) Image Analysis Software User Manual
Test Principles
The Companion Algorithm for ER (SP1) image analysis software employs image analysis techniques to obtain ER scoring.
Pre-defined parameters are used to obtain ER scores. The identification of the nucleus is carried out automatically by the image
analysis algorithms. The steps involved in the analysis algorithms are:
1. Enhancing the image. This process increases the contrast to make the image more suitable for analysis.
2. Identifying the epithelial area. The epithelial area is the region of the image where there is the possibility of epithelial cells
being present.
3. Identifying the nucleus.
4. Classifying the cells based on extent, intensity, and thickness of nuclear staining.
5. Computing the score.
Warnings and Precautions
It is important that glass slides with acceptable staining quality be used.
Pre-Analytical Variables
Tissue preparation and staining should follow the recommendations provided in the CONFIRM anti-ER (SP1) assay package insert.
For optimal image capture using the Virtuoso software, it is recommended that the tissue be free of folds and be placed on the slide
with a minimum of 2 mm boundary from the edge on all sides. The cover slip and slide label (if present) should not overhang the
edges of the slide. For further information on scanning, please refer to the appropriate iScan slide scanner reference guide.
Procedure
Refer to Virtuoso Reference Guide.
It is recommended that at least three fields of view be selected for analysis when using the Companion Algorithm ER (SP1) software.
Required Materials Not Provided
The Virtuoso system for ER SP1 requires use of CONFIRM anti-ER (SP1), and any additional material or supplies listed in the
package insert, to stain tissues prior to analysis.
The iScan Coreo slide scanner or the VENTANA iScan HT slide scanner is required for scanning of the slides.
Results
The Companion Algorithm ER SP1 image analysis software produces the overlay images and a staining score. The pathologist views
the overlay image and the instrument score, makes an assessment, and reports a score which may not be the same as the instrument
score. Refer to Virtuoso Reference Guide for an example of a report.
Limitations
The algorithms are designed to work for ER cell nuclei staining. The test results are only as good as the quality and accuracy of the
immunohistochemistry slide that is imaged, and the subsequent image that is analyzed. The pathologist must validate the CONFIRM
anti-ER (SP1) staining run by examination of the CONFIRM anti-ER (SP1) control images to verify that the expected results have
been obtained before images from patient slides are analyzed. The pathologist must follow the manufacturer's recommendations for
ER (SP1) Image Analysis Software User Manual Chapter 1: Intended Use and Indications for Use
Part No.: 101407000 Rev. A 7
CONFIRM anti-ER (SP1) including using all the positive and negative quality control materials for each staining run. If the control
slides are not acceptable, the patient tissues need to be re-stained with acceptable results. (See the CONFIRM anti-ER (SP1) package
insert for details about quality control recommendations.) The pathologist must follow the recommendations for surveying the
entire breast cancer specimen to assess any heterogeneity in the ER staining, the degree of background staining, cytoplasmic
staining, edge effect, etc. as recommended in the CONFIRM anti-ER (SP1) user's manual (available at www.ventana.com). If the
images captured have different staining (nuclear, cytoplasm, etc.), incorrect results will be generated. Incorrect results will also be
generated if the image quality cannot be analyzed. The software algorithms determine whether the quality of an image can be
analyzed, based on pre-defined parameters. Refer to the Virtuoso Reference Guide for more information.
The ER (SP1) image analysis algorithm will reject nuclei that are elongated regardless of the overall shape of the cell. For this reason,
tumors containing large numbers of cells with elongated nuclei may need to be evaluated manually. In addition, performance of the
Virtuoso system with the following types of breast cancers has not been evaluated: carcinoma in situ, carcinosarcoma, comedo
carcinoma, cystosarcoma phylloides, medullary carcinoma of the breast, mucinous variants of breast cancer, and spindle cell
carcinoma.
Performance Characteristics
Performance of the staining agent is described in the package insert for the CONFIRM anti-ER (SP1) staining process. See
Comparison and Reproducibility Studies in Chapter 2 for the description of the performance of the software.
Assay Cutoff
The performance of the Virtuoso system with ER SP1 was evaluated at the CAP/ASCO recommended clinical cutoffs: 0-0.99%
was considered a negative test result and 1-10% and >10% were considered positive test results.
8 Part No.: 101407000 Rev. A
Chapter 1: Intended Use and Indications for Use ER (SP1) Image Analysis Software User Manual
INTENTIONALLY BLANK
Part No.: 101407000 Rev. A 9
Chapter 2: ER Comparison and Reproducibility Studies
This chapter shows comparison and reproducibility studies for the ER marker.
ER Marker Studies
Staining Procedure
Refer to the CONFIRM anti-ER (SP1) package insert for the BenchMark XT, ULTRA and GX instruments, ultraView, and iView
detection kits.
Study Devices and Samples for BenchMark XT Instrument and iScan Coreo Slide Scanner
The ER comparison and reproducibility studies for the Virtuoso Digital Read and Companion Algorithm image analysis software
consisted of 120 de-identified archived breast carcinoma sections immunohistochemically stained with CONFIRM anti-ER (SP1).
Study test samples covered the ranges of 0-0.99%, 1-10% and >10%, and were interpreted at three different sites by three different
pathologists. All test slides were scanned at 20X magnification and all images were output in bif file format. For the image analysis
evaluation, a minimum of three fields of view were selected by each pathologist independently for each image.
ER Concordance with BenchMark XT Instrument and iScan Coreo Slide Scanner
The table below shows the concordance results for CONFIRM anti-ER (SP1) staining interpretation among three different sites:
1. Digital Read vs. Manual Method.
Table 2-1 Agreement - Digital Read vs. Manual (manual = true score).
Confusion Matrix
Digital
Site 1 Site 2 Site 3
(n = 114) (n = 116) (n = 114)
Neg Pos Neg Pos Neg Pos
Manual
Neg (0-0.99%) 52 7 49 5 45 11
Pos (1-10%, >10%) 0 55 2 60 2 56
% Agreement 94% 94% 89%
(95% CI) (88% - 97%) (88% - 97%) (81% - 93%)
10 Part No.: 101407000 Rev. A
Chapter 2: ER Comparison and Reproducibility Studies ER (SP1) Image Analysis Software User Manual
2. Image Analysis vs. Manual Method.
Intra-System and Inter-System Studies
The study was designed to demonstrate inter- and intra-Virtuoso system reproducibility for Virtuoso Digital Read and Companion
Algorithm image analysis applications. A designated subset of 40 cases that span the range of the ER scoring categories (0-0.99%,
negative, 1-10%, positive, and >10%, positive) were used.
1. Intra-pathologist/Inter-Day (pair-wise comparisons, Session1 vs. Session 2, Session1 vs. Session 3, Session 2 vs. Session 3).
Table 2-2 Agreement - Image Analysis vs. Manual (manual = true score).
Confusion Matrix
Image Analysis
Site 1 Site 2 Site 3
(n = 113) (n = 118) (n = 116)
Neg Pos Neg Pos Neg Pos
Manual
Neg. (0-0.99%) 56 2 56 0 52 3
Pos. (1-10%, >10%) 4 51 7 55 7 54
% Agreement 95% 94% 91%
(95% CI) (89% - 98%) (88% - 97%) (85% - 95%)
Table 2-3 Intra- Pathologist Digital Read.
Confusion Matrix
Intra-Pathologist Digital
Session 2 Session 3 Session 3
Neg Pos Neg Pos Neg Pos
18 20 17 22 17 22
Session 1
Neg 18 18 0 17 1
Pos 22 0 20 0 21
Session 2
Neg 18 17 1
Pos 20 020
% Agreement 100% 97% 97%
(95% CI) (91% - 100%) (87% - 100%) (87% - 100%)
ER (SP1) Image Analysis Software User Manual Chapter 2: ER Comparison and Reproducibility Studies
Part No.: 101407000 Rev. A 11
2. For Intra-Pathologist Image Analysis.
3. Inter-pathologist (pair-wise comparisons, Pathologist 1 vs. Pathologist 2, Pathologist 1 vs. Pathologist 3, Pathologist 2 vs.
Pathologist 3).
4. Inter-Pathologist Image Analysis.
Table 2-4 Intra-Pathologist Image Analysis.
Confusion Matrix
Intra-Pathologist Image Analysis
Session 2 Session 3 Session 3
Neg Pos Neg Pos Neg Pos
20 20 19 21 19 21
Session 1
Neg 20 19 1 19 1
Pos 20 1 19 0 20
Session 2
Neg 20 19 1
Pos 20 020
% Agreement 95% 98% 98%
(95% CI) (83% - 99%) (87% - 100%) (87% - 100%)
Table 2-5 Inter-Pathologist Digital Read.
Confusion Matrix
Inter-Pathologist Digital
Site 2 Site 3 Site 3
Neg Pos Neg Pos Neg Pos
51 65 47 67 47 67
Site 1
Neg 52 48 3 44 6
Pos 63 3 60 2 58
Site 2
Neg 51 41 8
Pos 65 558
% Agreement 95% 93% 88%
(95% CI) (89% - 98%) (86% - 96%) (81% - 93%)
Table 2-6 Inter-Pathologist Image Analysis.
Confusion Matrix
Inter-Pathologist Image Analysis
Site 2 Site 3 Site 3
Neg Pos Neg Pos Neg Pos
63 55 59 57 59 57
Site 1
Neg 60 59 1 55 4
Pos 54 2 52 3 51
Site 2
Neg 63 57 4
Pos 55 253
% Agreement 97% 94% 95%
(95% CI) (93% - 99%) (88% - 97%) (89% - 98%)
12 Part No.: 101407000 Rev. A
Chapter 2: ER Comparison and Reproducibility Studies ER (SP1) Image Analysis Software User Manual
ER Concordance with BenchMark ULTRA Instrument and iScan Coreo Slide Scanner
Study Devices and Samples for BenchMark ULTRA and iScan Coreo Slide Scanner
These ER (SP1) comparison studies for the Virtuoso Digital Read and Companion Algorithm image analysis software consisted of
120 de-identified archived breast carcinoma sections immunohistochemically stained with CONFIRM anti-ER (SP1) on the
BenchMark ULTRA instrument. Study test samples covered the ranges of 0-0.99%, 1-10% and >10%, and were interpreted by one
pathologist at one site. All test slides were scanned at 20X magnification and all images were output in bif file format. For the image
analysis evaluation, a minimum of three fields of view were selected by each pathologist independently for each image. 111 of 120
cases were able to be evaluated and were included in the analyses below.
The tables below shows the concordance results for CONFIRM anti-ER (SP1) assay stained on the BenchMark ULTRA instrument.
Digital Read vs. Manual
Image Analysis vs. Manual
Table 2-7 Agreement (ULTRA Instrument) - Digital Read vs. Manual
Manual Microscope Read
Digital Read
Positive Negative Total
Positive 69 1 70
Negative 1 40 41
Total 70 41 111
Positive Percent Agreement (PPA) n/N (%) (95% CI) 69/70 (98.6%) (92.3-99.7%)
Negative Percent Agreement (NPA) n/N (%) (95% CI) 40/41 (97.6%) (87.4-99.6%)
Overall Percent Agreement (OPA) n/N (%) (95% CI) 109/111 (98.2%) (93.7-99.5%)
Table 2-8 Agreement (ULTRA Instrument) - Digital Read vs. Manual
Manual Microscope Read
Digital Read
Positive Negative Total
Positive 64 4 68
Negative 6 37 43
Total 70 41 111
Positive Percent Agreement (PPA) n/N (%) (95% CI) 64/70 (91.4%) (82.5-96.0%)
Negative Percent Agreement (NPA) n/N (%) (95% CI) 37/41 (90.2%) (77.5-96.1%)
Overall Percent Agreement (OPA) n/N (%) (95% CI) 101/111 (91.0%) (84.2-95.0%)
ER (SP1) Image Analysis Software User Manual Chapter 2: ER Comparison and Reproducibility Studies
Part No.: 101407000 Rev. A 13
ER Concordance with BenchMark XT/ULTRA Instruments and VENTANA iScan HT Slide Scanner
Study Devices and Samples for BenchMark XT/ULTRA Instrument and iScan HT Slide Scanner
The ER comparison and reproducibility studies for the Virtuoso Digital Read and Companion Algorithm image analysis software
consisted of 30 de-identified archived breast carcinoma sections immunohistochemically stained with CONFIRM anti-ER (SP1).
Study test samples covered the ranges of 0-0.99% (negative), 1-10% (positive) and >10% (positive), and were interpreted at by one
pathologist. All test slides were scanned at 20X magnification and all images were output in bif file format. For the image analysis
evaluation, a minimum of three fields of view were selected by each pathologist independently for each image.
Digital Read vs. Manual
Image Analysis vs. Manual
Table 2-9 Agreement - Digital Read vs. Manual Microscopic Read
Manual Microscope Read
Digital Read
Negative Positive Total
Negative 13 1 14
Positive 1 14 15
Total 14 15 29
Positive Percent Agreement (PPA) n/N (%) (95% CI) 14/15 (93%) (70-99%)
Negative Percent Agreement (NPA) n/N (%) (95% CI) 13/14 (93%) (69-99%)
Overall Percent Agreement (OPA) n/N (%) (95% CI) 27/29 (93%) (78-98%)
Table 2-10 Agreement - Image Analysis vs. Manual Microscopic Read
Manual Microscope Read
Digital Read
Negative Positive Total
Negative 13 1 14
Positive 1 13 14
Total 14 14 28
Positive Percent Agreement (PPA) n/N (%) (95% CI) 13/14 (93%) (69-99%)
Negative Percent Agreement (NPA) n/N (%) (95% CI) 13/14 (93%) (69-99%)
Overall Percent Agreement (OPA) n/N (%) (95% CI) 26/28 (93%) (77-98%)
14 Part No.: 101407000 Rev. A
Chapter 2: ER Comparison and Reproducibility Studies ER (SP1) Image Analysis Software User Manual
ER Concordance with BenchMark GX Instrument, iScan Coreo, and iScan HT Slide Scanners
Study Devices and Samples for BenchMark GX Instrument, iScan Coreo, and iScan HT Slide Scanners
The ER comparison and reproducibility studies for the Virtuoso Digital Read and Companion Algorithm image analysis software
consisted of 30 de-identified archived breast carcinoma sections immunohistochemically stained with CONFIRM anti-ER (SP1)
Rabbit Monoclonal Primary Antibody. Study test samples covered the ranges of 0-0.99% (negative), 1-10% (positive) and >10%
(positive), and were interpreted by two pathologists. All test slides were scanned at 20X magnification and all images were output in
bif file format. For the image analysis evaluation, a minimum of three fields of view were selected by each pathologist independently
for each image.
The results were analyzed for each pathologist individually and also averaged across the two pathologists. The average overall percent
agreement (OPA) was determined as the weighted average for the two pathologists who independently scored the same cases, where
the weight of a pathologist's individual OPA rate was determined by the number of cases considered evaluable by that pathologist.
Digital Read vs. Manual Microscopic Read, iScan Coreo Slide Scanner
The average OPA for Digital Read vs. Manual Microscopic Read for iScan Coreo slide scanner was 96.5%.
Table 2-11 Pathologist #1 Agreement - Digital Read vs. Manual, iScan Coreo Slide Scanner
Digital Read
Manual Microscope Read
Negative Positive Total
Negative 16 1 17
Positive 0 10 10
Total 16 11 27
Overall Percent Agreement (OPA) n/N (%) (95% CI) 96.3%
Table 2-12 Pathologist #2 Agreement - Digital Read vs. Manual Microscopic Read,
iScan Coreo Slide Scanner
Digital Read
Manual Microscope Read
Negative Positive Total
Negative 18 0 18
Positive 1 11 12
Total 19 11 30
Overall Percent Agreement (OPA) n/N (%) (95% CI) 96.7%
  • Page 1 1
  • Page 2 2
  • Page 3 3
  • Page 4 4
  • Page 5 5
  • Page 6 6
  • Page 7 7
  • Page 8 8
  • Page 9 9
  • Page 10 10
  • Page 11 11
  • Page 12 12
  • Page 13 13
  • Page 14 14
  • Page 15 15
  • Page 16 16
  • Page 17 17
  • Page 18 18
  • Page 19 19
  • Page 20 20
  • Page 21 21
  • Page 22 22
  • Page 23 23
  • Page 24 24
  • Page 25 25
  • Page 26 26
  • Page 27 27
  • Page 28 28
  • Page 29 29
  • Page 30 30
  • Page 31 31
  • Page 32 32
  • Page 33 33
  • Page 34 34
  • Page 35 35
  • Page 36 36
  • Page 37 37
  • Page 38 38
  • Page 39 39
  • Page 40 40
  • Page 41 41
  • Page 42 42
  • Page 43 43
  • Page 44 44
  • Page 45 45
  • Page 46 46
  • Page 47 47
  • Page 48 48
  • Page 49 49
  • Page 50 50
  • Page 51 51
  • Page 52 52
  • Page 53 53
  • Page 54 54
  • Page 55 55
  • Page 56 56
  • Page 57 57
  • Page 58 58
  • Page 59 59
  • Page 60 60
  • Page 61 61
  • Page 62 62
  • Page 63 63
  • Page 64 64
  • Page 65 65
  • Page 66 66
  • Page 67 67
  • Page 68 68
  • Page 69 69
  • Page 70 70
  • Page 71 71
  • Page 72 72
  • Page 73 73
  • Page 74 74
  • Page 75 75
  • Page 76 76
  • Page 77 77
  • Page 78 78
  • Page 79 79
  • Page 80 80
  • Page 81 81
  • Page 82 82
  • Page 83 83
  • Page 84 84
  • Page 85 85
  • Page 86 86
  • Page 87 87
  • Page 88 88
  • Page 89 89
  • Page 90 90
  • Page 91 91
  • Page 92 92
  • Page 93 93
  • Page 94 94
  • Page 95 95
  • Page 96 96
  • Page 97 97
  • Page 98 98
  • Page 99 99
  • Page 100 100
  • Page 101 101
  • Page 102 102
  • Page 103 103
  • Page 104 104
  • Page 105 105
  • Page 106 106
  • Page 107 107
  • Page 108 108
  • Page 109 109
  • Page 110 110
  • Page 111 111
  • Page 112 112
  • Page 113 113
  • Page 114 114
  • Page 115 115
  • Page 116 116
  • Page 117 117
  • Page 118 118
  • Page 119 119
  • Page 120 120
  • Page 121 121
  • Page 122 122
  • Page 123 123
  • Page 124 124
  • Page 125 125
  • Page 126 126
  • Page 127 127
  • Page 128 128
  • Page 129 129
  • Page 130 130
  • Page 131 131
  • Page 132 132
  • Page 133 133
  • Page 134 134
  • Page 135 135
  • Page 136 136
  • Page 137 137
  • Page 138 138
  • Page 139 139
  • Page 140 140
  • Page 141 141
  • Page 142 142
  • Page 143 143
  • Page 144 144
  • Page 145 145
  • Page 146 146
  • Page 147 147
  • Page 148 148
  • Page 149 149
  • Page 150 150
  • Page 151 151
  • Page 152 152
  • Page 153 153
  • Page 154 154
  • Page 155 155
  • Page 156 156
  • Page 157 157
  • Page 158 158
  • Page 159 159
  • Page 160 160
  • Page 161 161
  • Page 162 162
  • Page 163 163
  • Page 164 164
  • Page 165 165
  • Page 166 166
  • Page 167 167
  • Page 168 168
  • Page 169 169
  • Page 170 170
  • Page 171 171
  • Page 172 172
  • Page 173 173
  • Page 174 174
  • Page 175 175
  • Page 176 176
  • Page 177 177
  • Page 178 178
  • Page 179 179
  • Page 180 180
  • Page 181 181
  • Page 182 182
  • Page 183 183
  • Page 184 184
  • Page 185 185
  • Page 186 186
  • Page 187 187
  • Page 188 188
  • Page 189 189
  • Page 190 190
  • Page 191 191
  • Page 192 192
  • Page 193 193
  • Page 194 194
  • Page 195 195
  • Page 196 196
  • Page 197 197
  • Page 198 198
  • Page 199 199
  • Page 200 200
  • Page 201 201
  • Page 202 202
  • Page 203 203
  • Page 204 204
  • Page 205 205
  • Page 206 206
  • Page 207 207
  • Page 208 208
  • Page 209 209
  • Page 210 210
  • Page 211 211
  • Page 212 212
  • Page 213 213
  • Page 214 214
  • Page 215 215
  • Page 216 216
  • Page 217 217
  • Page 218 218
  • Page 219 219
  • Page 220 220
  • Page 221 221
  • Page 222 222
  • Page 223 223
  • Page 224 224
  • Page 225 225
  • Page 226 226
  • Page 227 227
  • Page 228 228
  • Page 229 229
  • Page 230 230
  • Page 231 231
  • Page 232 232
  • Page 233 233
  • Page 234 234
  • Page 235 235
  • Page 236 236
  • Page 237 237
  • Page 238 238
  • Page 239 239
  • Page 240 240
  • Page 241 241
  • Page 242 242
  • Page 243 243
  • Page 244 244
  • Page 245 245
  • Page 246 246
  • Page 247 247
  • Page 248 248
  • Page 249 249
  • Page 250 250
  • Page 251 251
  • Page 252 252
  • Page 253 253
  • Page 254 254
  • Page 255 255
  • Page 256 256
  • Page 257 257
  • Page 258 258
  • Page 259 259
  • Page 260 260
  • Page 261 261
  • Page 262 262
  • Page 263 263
  • Page 264 264
  • Page 265 265
  • Page 266 266
  • Page 267 267
  • Page 268 268
  • Page 269 269
  • Page 270 270
  • Page 271 271
  • Page 272 272
  • Page 273 273
  • Page 274 274
  • Page 275 275
  • Page 276 276
  • Page 277 277
  • Page 278 278
  • Page 279 279
  • Page 280 280
  • Page 281 281
  • Page 282 282
  • Page 283 283
  • Page 284 284
  • Page 285 285
  • Page 286 286
  • Page 287 287
  • Page 288 288
  • Page 289 289
  • Page 290 290
  • Page 291 291
  • Page 292 292
  • Page 293 293
  • Page 294 294
  • Page 295 295
  • Page 296 296
  • Page 297 297
  • Page 298 298
  • Page 299 299
  • Page 300 300
  • Page 301 301
  • Page 302 302
  • Page 303 303
  • Page 304 304
  • Page 305 305
  • Page 306 306
  • Page 307 307
  • Page 308 308
  • Page 309 309
  • Page 310 310
  • Page 311 311
  • Page 312 312
  • Page 313 313
  • Page 314 314
  • Page 315 315
  • Page 316 316
  • Page 317 317
  • Page 318 318
  • Page 319 319
  • Page 320 320
  • Page 321 321
  • Page 322 322
  • Page 323 323
  • Page 324 324
  • Page 325 325
  • Page 326 326
  • Page 327 327
  • Page 328 328
  • Page 329 329
  • Page 330 330
  • Page 331 331
  • Page 332 332
  • Page 333 333
  • Page 334 334
  • Page 335 335
  • Page 336 336
  • Page 337 337
  • Page 338 338
  • Page 339 339
  • Page 340 340
  • Page 341 341
  • Page 342 342
  • Page 343 343
  • Page 344 344
  • Page 345 345
  • Page 346 346
  • Page 347 347
  • Page 348 348
  • Page 349 349
  • Page 350 350
  • Page 351 351
  • Page 352 352
  • Page 353 353
  • Page 354 354
  • Page 355 355
  • Page 356 356
  • Page 357 357
  • Page 358 358
  • Page 359 359
  • Page 360 360
  • Page 361 361
  • Page 362 362
  • Page 363 363
  • Page 364 364
  • Page 365 365
  • Page 366 366
  • Page 367 367
  • Page 368 368
  • Page 369 369
  • Page 370 370
  • Page 371 371
  • Page 372 372
  • Page 373 373
  • Page 374 374
  • Page 375 375
  • Page 376 376
  • Page 377 377
  • Page 378 378
  • Page 379 379
  • Page 380 380
  • Page 381 381
  • Page 382 382
  • Page 383 383
  • Page 384 384
  • Page 385 385
  • Page 386 386
  • Page 387 387
  • Page 388 388
  • Page 389 389
  • Page 390 390
  • Page 391 391
  • Page 392 392
  • Page 393 393
  • Page 394 394

Roche Virtuoso Manuale utente

Tipo
Manuale utente