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Validation vs. Verification for Whole Slide Imaging (WSI) is it Really a Grudge Match?
Q: My practice would like to start using Whole Slide Imaging for Primary Diagnosis. Does my lab have to undergo verification or validation? What’s the difference between Validation and Verification for Whole slide imaging?
A: The CAP’s definition of validation is: “…Validation:…the process used to confirm with objective evidence that a laboratory developed or modified FDA-cleared/approved test method or instrument system delivers reliable results for the intended application.”
Their definition of verification is: “…Verification….the process by which a laboratory determines that an unmodified FDA- cleared/approved test performs according to the specifications set forth by the manufacturer when used as directed.”
So validation is the process for laboratory developed tests or FDA test systems that have been modified. Verification is the process for FDA approved systems used according to the manufacturer. There is only one WSI system that is FDA cleared in the USA, the Philips IntelliSite Pathology Solution. This system includes the Philips UF Scanner, Philips Display (Viewer), Philips Image Management System, and the monitors used by Philips in the FDA application (Barco, medical grade). **Note of importance - The Philips system is only approved for formalin fixed paraffin embedded H&E slides.
If a laboratory uses another viewer, image management system or monitor with the Philips scanner, it is now an FDA modified system and the laboratory must validate the same way as they would if they were using any other WSI system. The CAP’s definition of the modification of an FDA test is included at the end of this blog. But even if a laboratory uses the FDA approved system according to the manufacturer, it must still undergo a process to ensure the accuracy of the system within each laboratory. Philips states in its FDA letter that the “PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens.” Any of these specimens would still require a laboratory to validate the system for those specimen types the same as they would if they were to use any other WSI solution.
Q: What do the CAP Accreditation Checklists Say about Verification or Validation of WSI?
A: The CAP’s Lab General Checklist August 2018 revisions state:
“GEN.52920 Whole Slide Imaging System Validation/Verification Phase I
The laboratory validates or verifies whole slide imaging systems used for clinical diagnostic purposes by performing its own studies, including approval for use by the laboratory director (or designee who meets CAP director qualifications) before the technology is used for the intended diagnostic purpose(s).
NOTE: The specific components of validation or verification studies are left to the discretion of the laboratory. The approval or clearance of whole slide imaging systems by the FDA does not obviate the need for individual laboratories to verify the performance of these systems for the specific intended diagnostic purposes.
As general guiding principles, the validation or verification process should: “Closely emulate the real-world clinical environment and involve specimen preparation types and clinical settings relevant to the intended use(s); Be carried out by a pathologist(s) adequately trained to use the system; Assess intraobserver concordance between digital and glass slides; Encompass the entire whole slide imaging system, with reevaluation if a significant change is made to a previously validated or verified system. “
Summary for Implementing WSI Imaging for primary diagnosis is: The Checklist summarizes the CAP Guidelines for Implementing Whole Slide Imaging which are that a) the lab must conduct its own studies of accuracy, b) the Laboratory Medical Director must be involved and sign off on the studies, c) the study must emulate the intended use and clinical settings, d) that pathologists be adequately trained, e) that intra-observer concordance between glass and digital be assessed, f) that the study encompasses the entire system and g) revaluation takes place if there is a significant change, like a new scanner.
The complete CAP guidelines for implementing WSI can be found below.
Q: What does it mean to modify an FDA approved/cleared test or test system?
A: This is the CAP’s definition: “Any change to the manufacturer's supplied ingredients or modifications to the assay as set forth in the manufacturer's labeling and instructions. It may include a change to specimen type, instrumentation or procedure that could affect its performance specifications for sensitivity, specificity, accuracy, or precision or any change to the stated purpose of the test, its approved test population, or any claims related to interpretation of the results.”
For example, if a practice decided it was not necessary to purchase medical grade monitors to perform primary diagnosis on WSI, this would constitute a modification; and thus, a validation study would need to be performed.
Q: Is it easier to verify an FDA cleared test system for primary diagnosis with WSI or to validate a Lab developed WSI test system or a modified FDA cleared test system?
A: The verification procedure for an FDA cleared test system will depend upon the instructions from the manufacturer and will be depend on the Lab Medical Director’s determination that the test system is accurate. A Lab Medical Director may likely elect to follow the CAP Guidelines for WSI. In which case, the amount of effort for either verification or validation would be the same.
Q: In the event of a malpractice lawsuit involving a diagnosis performed WSI, is a pathologist better protected using an FDA cleared system?
A: In general, the pathologist or laboratory would still be responsible for a misdiagnosis, no matter the means the diagnosis was rendered. In the event of a misdiagnosis using an FDA cleared WSI system, it is unclear to what extent, if any, a pathologist would be protected.
REFERENCES
1) Pantanowitz et al, Validating whole slide imaging for diagnostic purposes in pathology: Guideline from the College of American Pathologists Pathology and Laboratory Quality Center. ARPA, 2013 http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2013-0093-CP http://www.cap.org/apps/docs/membership/wsi_faqs.pdf
CAP WSI Validation Guidelineshttps://www.cap.org/protocols-and-guidelines/cap-guidelines/current-cap-guidelines/validating-whole-slide-imaging-for-diagnostic-purposes-in-pathology
Dear Clients, Partners, and Friends, As we close out 2024, I want to take a moment to reflect on the incredible milestones we’ve achieved together. At Gestalt Diagnostics, we remain committed to advancing digital pathology and supporting our clients in delivering the highest level of patient care. This year has been a remarkable journey, and I’m proud to share some highlights with you. Innovations and Product Enhancements This year, we introduced the PathFlow® AI Algorithm Evaluator , a tool enabling labs to test and integrate multiple AI algorithms seamlessly into workflows, driving precision and efficiency. We also expanded our Digital Pathology Education Module to include proficiency testing, credentialing, and management tools, empowering professionals with critical resources for growth. Thought Leadership and Industry Contributions Our team shared valuable insights through leading journals and platforms: Published in Medical Laboratory Observer on preparing labs for automation with digital pathology and AI . Shared findings on biomarkers in prostate cancer diagnosis and digital pathology adoption in MLO. Hosted engaging discussions like the Digital Pathology Today Podcast: A Fresh Start for Pathology and a Q&A on enhancing clinical labs through advanced data analytics. Strategic Partnerships and Collaborations We strengthened our partnerships globally, adding several AI integrations into PathFlow®. Notably, we were selected by Optum (Change Healthcare) as their digital pathology partner, complementing their Enterprise Imaging Suite. We also expanded into Africa with DataPathology , marking a key step in our international growth. Recognition and Advisory Excellence This year, we welcomed Dr. J. Mark Tuthill to our Strategic Advisory Board, whose expertise has already brought immense value to our mission. Our leadership team also took on influential roles, with elections as President-Elect of the API and as Co-Chairs of DICOM Working Group 26, further contributing to global pathology standards. Global Impact and Market Growth Gestalt celebrated substantial growth, increasing our customer base and revenue while earning accolades for innovation and market expansion. These achievements reflect our dedication to pushing the boundaries of digital pathology and delivering meaningful results for labs worldwide. As we step into 2025, I am filled with excitement and gratitude. Thank you for your trust, collaboration, and commitment to advancing pathology alongside us. Together, we are shaping the future of this vital field. Wishing you success and innovation in the year ahead,
Featured in CAP TODAY December 2024—Digital pathology in 2024—what’s the sentiment, the pace, the holdup, the worry? Five people spoke online with CAP TODAY publisher Bob McGonnagle on Oct. 9 about the state of play as the end of the year neared. “It’s an ongoing conversation and foregone conclusion that laboratories will be going digital,” said Lisa-Jean Clifford, president-elect of the Association for Pathology Informatics.
October 31, 2024 – Spokane, Washington and New York, New York – Gestalt, a leader in digital pathology solutions, and Paige, the leader in next-generation AI technology for pathology, are excited to announce a strategic partnership to integrate Paige’s advanced AI applications within Gestalt’s award-winning PathFlow® solution. This collaboration aims to streamline the delivery of integrated workflows, optimizing the pathologist’s experience while ensuring patient accuracy and safety by working in a single environment. Gestalt’s PathFlow is widely recognized for its robust capabilities in primary diagnosis, education, resident training, and research workflows. By incorporating Paige’s cutting-edge algorithms, the PathFlow solution will now offer an even broader range of tools to support pathologists in delivering precise and efficient diagnoses. All of Paige’s AI applications will be made available in PathFlow, enabling both current and new users to seamlessly access AI-powered diagnostic capabilities. This integration supports more efficient case reviews, accelerates diagnostic timelines, and promotes a comprehensive approach to cancer detection. Key Highlights of the Partnership: Enhanced Diagnostic Confidence: The integration of Paige’s AI applications will provide pathologists with powerful tools to improve diagnostic confidence and patient outcomes. Streamlined Workflows: The combined technologies will ensure seamless workflows, reducing the time and effort required for pathologists to reach diagnoses. Comprehensive Support: PathFlow’s expanded algorithm library will cater to a wide range of use cases, benefiting both current and future customers. Paige’s availability through PathFlow’s platform will allow easy access to Paige AI solutions for any Gestalt user. “By partnering with Paige to include their AI applications in PathFlow, we are reinforcing our commitment to providing pathologists with the best tools available,” said Lisa-Jean Clifford, COO & Chief Strategy Officer of Gestalt. “This partnership underscores our dedication to enhancing the pathologist’s experience and ensuring the highest standards of patient care.” “Leveraging Paige's AI-powered applications, PathFlow users can experience an enhanced workflow that supports efficient case review, accelerates time to diagnosis, and allows for a more comprehensive approach to cancer detection, enabling pathologists to focus on what matters most—delivering precise and actionable insights for patient care,” said Peter Hamilton, General Manager for Diagnostics at Paige. For more information about this partnership and the respective solutions, please visit Gestalt at booth #107 and Paige at booth #113 during the Pathology Visions Conference November 3-5, 2024. About Gestalt Gestalt Diagnostics transforms pathology through an intelligent, configurable, vendor-neutral, and AI-driven digital workflow that provides true interoperability enabling pathologists to diagnose* diseases faster and more efficiently. Our PathFlow solution consists of professional, education, and research modules for ease of mixing and matching the digital needs of your facility in a single solution, freeing pathologists from tedious, repetitive, and manual tasks, allowing them to focus on their expertise – providing invaluable experience where it matters most. To learn more, visit www.gestaltdiagnostics.com and follow @Gestalt on LinkedIn About Paige Paige is pushing the boundaries of AI to solve cancer’s most critical issues, revolutionizing cancer care with next-generation technology. By leveraging exclusive access to millions of digitized pathology slides, clinical reports, and genomic data, Paige gains a holistic understanding of cancer, encompassing diverse factors such as gender, race, ethnicity, and geographical regions. This comprehensive data enables Paige to create advanced AI solutions that redefine cancer detection, diagnosis, and treatment. With a unique, intricate understanding of tissue, Paige sets new standards in precision diagnostics, earning the distinction of being the first FDA-approved AI application in pathology. Paige has also developed the first million-slide foundation model for cancer, continuing to lead the way in uncovering novel insights and transforming them into life-changing products. For more information, visit www.paige.ai. *Research use only unless following CAP guidelines for LDT. CE-IVD certified for use in Europe.
September 16, 2024 – Spokane, Washington – Gestalt, a leader in AI-driven digital pathology solutions, is excited to announce its international expansion with the onboarding of its first client in Africa, DataPathology. This partnership marks a significant milestone as Gestalt continues to extend its global footprint, leveraging its innovative PathFlow digital solution with the new PathCloud platform to provide streamlined cloud-based digital access. DataPathology, a pioneering MedTech startup, operates five laboratories across Morocco and Djibouti. This collaboration aims to create a robust ecosystem that addresses two critical challenges in North Africa: the severe shortage of anatomic pathologists and the accessibility to specialized medical expertise. Addressing the Pathologist Shortage Africa faces a daunting shortage of pathologists, with an estimated ratio of 1 pathologist per 500,000 people. Given the continent’s population of approximately 1.2 billion, this translates to around 2,400 pathologists. In stark contrast, the United States boasts about 22,000 pathologists, resulting in a ratio of 1 pathologist per 15,000 people. This disparity underscores the urgent need for innovative solutions to bridge the gap in medical diagnostics and care. Enhancing Accessibility to Medical Expertise Through the integration of Gestalt’s PathCloud platform and the 3DHistech and Roches scanners, DataPathology will be able to connect its laboratories seamlessly, facilitating the rapid and accurate diagnosis of pathological samples. This technological advancement not only enhances the efficiency of diagnostic processes but also ensures that patients in remote and underserved regions have access to high-quality medical expertise. A Vision for the Future “We are excited to partner with DataPathology and bring our leading-edge technology to Africa,” said Lisa-Jean Clifford, COO & Chief Strategy Officer of Gestalt. “This collaboration is a testament to our commitment to improving healthcare accessibility and addressing critical shortages in medical expertise. Together, we aim to revolutionize the field of pathology and make a significant impact on patient care in North Africa.” DataPathology’s co-founder, Dr. Hicham El Attar, added, “Our partnership with Gestalt is a game-changer for pathology services in Morocco and Djibouti. By leveraging advanced digital pathology solutions, we can provide faster, more accurate diagnoses, ultimately improving patient outcomes and saving lives.” About DataPathology Founded in 2020, DataPathology is a MedTech startup specializing in pathology diagnostics. With a network of laboratories across Morocco and Djibouti, the company leverages artificial intelligence and digital technology to provide quick and accurate pathological diagnoses, addressing critical healthcare challenges in Africa. Gestalt Diagnostics, Inc. Gestalt Diagnostics transforms pathology through an intelligent, configurable, vendor-neutral, and AI-driven digital workflow that provides true interoperability enabling pathologists to diagnose diseases faster and more efficiently. Our PathFlow solution is a cloud-based digital pathology enterprise platform that can easily be customized based on your specific preferences. Our platform consists of professional, education, and research modules for ease of mixing and matching the digital needs of your facility in a single solution, freeing pathologists from tedious, repetitive, and manual tasks allowing them to focus on their expertise, providing invaluable expertise where it matters most. *Research use only unless following CAP guidelines for LDT. CE-IVD certified for use in Europe.
We are pleased to announce the election of Brian Napora from Gestalt and Dr. Mustafa Yousif from the University of Michigan as the new co-chairs. Both began their duties on June 1, 2024.
Featured in Medical Laboratory Observer - MLO Written By Lisa-Jean Clifford Incorporating digital pathology and AI solutions and workflows into your organization is an exciting opportunity to enhance your operational efficiency, positively impact your diagnostic accuracy, and increase the overall automation of your laboratory practice. It is essential for maintaining your competitive position in the industry with adoption of leading technology occurring at an ever-increasing rate. It is also important to understand your current technology infrastructure and workflows and to work closely with your digital pathology solution provider to ensure that you are taking full advantage of the benefits of deploying these technologies —both today and setting the foundation for further adoption of new technologies into the future. Things to consider 1. Understand your initial goals and your long-term goals. These two may be the same or very different, depending upon your adoption strategy and reasons. The most common goals for digital pathology solution adoption in the clinical setting today are: Reduce the need for transportation of glass between labs Access to geographically distributed facilities and pathologists The ability to recruit and retain pathologists Support the technical component (TC), professional component (PC), and global workflows for outreach clients Instant access to consultations for subspecialties and/or complex cases Tumor boards The ability to use artificial intelligence When considering the above, you may have one or more initial reasons or objectives in adoption with the understanding that you would like to achieve more of these goals, or additional ones, moving forward. 2. The implementation of digital pathology needs to be an organizational goal and not just one of the lab’s. The process starts with the technical side of the workflow — from the understanding of what the scanner(s) you choose to deploy require for ‘clean’ slides. This is something that can have a significant impact on the usability, speed, and value of digital. You must start with proper identification of your lab process for creating slides and know that things like misaligned slipcovers, smudges, fingerprints, substances on the glass, folds in tissue, bubbles, and other artifacts are going to cause scanned images (WSI’s) to be unusable. This will create inefficiencies and increased time by having to redo and rescan slides in order to get usable images to the pathologists. This is the first step in quality in, quality out.... Read More
Featured in Medical Laboratory Observer - MLO Written By Lisa-Jean Clifford Biomarkers serve as critical navigational tools, guiding physicians on their patients’ journey through the diagnosis, treatment, and management of their specific cancer. In oncology, a biomarker may be a molecule secreted by a tumor or a specific response of the of the body to the presence of cancer. It can help in identifying early-stage cancers, forecasting how aggressive a cancer might be, or predicting how well a patient will respond to treatment. Biomarkers are also used to predict or monitor cancer recurrence. Prostate cancer often begins its journey with the detection of prostate-specific antigen (PSA) in the blood. This biomarker, a protein produced by both normal and malignant prostate cells, can be elevated in the presence of prostate cancer. PSA testing has become a keystone in the early detection of prostate cancer, offering insight into the biological state of the prostate. If a person has been diagnosed with cancer, biomarker testing may show whether the cancer is more likely to grow and spread, if certain cancer treatments are likely (or unlikely) to be helpful, and whether the cancer treatment is working.1 Determining treatment: Predictive biomarkers Once prostate cancer is diagnosed, the next step involves predictive biomarkers, which help in predicting the cancer’s behavior and potential response to treatments. Genes like ER, PR, and HER2/neu, although more commonly associated with breast cancer, have parallels in prostate cancer research, where molecular markers can predict the effectiveness of therapies such as hormone treatments or chemotherapy. One of the biggest areas of research is in immunotherapy, this is a treatment that manipulates the patient’s immune system to fight cancer with drugs or modified immune T cells. In the past several years, immunotherapy has had great success in some patients with certain types of cancer, but not all patients respond to this type of treatment. I have written about this in previous articles I have done on cancer and treatments — I believe this type of treatment has great potential with further development.2 There is a significant amount of research focused on discovering biomarkers that could identify which patients are likely to respond to immunotherapy. In some types of cancer, the presence or absence of immune molecules in cancer cells has been associated with determining whether a patient will have a better or worse response to immunotherapy. Biomarkers can also be used to help physicians determine if there are clinical trials available for their patients. Some trials, called basket studies, are based on the biomarkers in tumors and/or cells instead of the primary body site of the cancer. There are other trials that are using biomarkers to match treatments based on the gene characteristics or genetic changes in the patient’s cancer. Monitoring treatment: Prognostic biomarkers ... Read More
Gestalt’s Advisory Board guides the development of Gestalt’s digital pathology platform,
PathFlow® – made by pathologists for pathologists
