Improving Clinical Trial Efficiency and Accuracy

By Dr. Steven Potts, Worldwide Director, Biotech/Pharmaceutical, Aperio

Oncology clinical trials are expanding internationally while laboratory tests become increasingly complex. Pathology is a key diagnostic component of clinical trials used to measure efficacy signals that are decipherable by expert, credentialed pathologists. As more trial sites are added and fewer patients are enrolled at each site, global pathology test standardization is critical.

Digital pathology facilitates international clinical trials by allowing the pathologist instant access to histopathology data globally, as well as quantitative image analysis tools to standardize test results. Pathologists working remotely can support international enrollment and the expansion in test complexity, making their test results more quantitative and reproducible.

Digital pathology utilizes whole slide images from a computer monitor rather than glass slides from a microscope. The entire tissue section on a glass slide is scanned and becomes a single, large image viewable from anywhere via the internet. Software enables multiple pathologists to view and discuss the same tissue result concurrently in a digital slide conference, or to simultaneously view and align a series of histology slides stained with different biomarkers. Because digital slides are simply large image files, image analysis programs can help make quantitative, computer-generated measurements of tumor response across entire tissue sections.

Eleven of the thirteen largest pharmaceutical companies use Aperio's digital pathology solution in biomarker discovery and preclinical research. In outsourced toxicity studies, nearly all of the major preclinical CROs offering pathology services have adopted Aperio's digital pathology solutions. Slides are scanned at the histology lab location, and then viewed by one or more veterinary pathologists from any location

Pathology working groups, informal peer reviews, archiving and other essential collaborative activities can be conducted remotely with a full electronic record. Because the entire tissue section is scanned as one large image, computer analysis can be run to quantitate toxicology lesion size or measure protein expression.

New product

In response to the clinical needs in drug development, Aperio has recently launched a new product, Digital IHC (immunohistochemistry) for oncology clinical trials. Digital IHC is being offered by select industry-leading contract research organizations, as it leverages their existing large immunohistochemistry test menus. Slides are scanned at remote clinical sites, and then uploaded to a secure HIPAA and 21 CFR 11 compliant database.

Pathologists can conduct confirmatory diagnosis during enrollment, discuss results with distant colleagues or study directors, or complete full electronic pathology workflow from slide to case report. Aperio's recently lauched Genie histology pattern recognition technology can be used to measure protein expression specifically in the cancerous cells of interest, automatically ignoring adjacent stromal tissue. Even with patients from hundreds of locations and dozens of international sites, the pathology assessment is centralized and standardized across all study participants.

Instant access

Instant global secure access to pathology data will revolutionize oncology clinical trials and study design. Digital pathology provides today what the pharmaceutical industry took for granted several decades ago - access to pathologists. Logistics will improve, with the ability for an anatomic pathologist at a pharmaceutical company to do confirmatory reading during patient enrollment at a remote international location without the costs of time and travel. Communication improves between the pathologists at the CRO and the study directors and oncologists at the pharmaceutical sponsor.

Searchable whole-slide pathology databases post-study will become a standard tool in the near future, similar to how virtual compound databases are used in computational chemistry today. Quantitative results are derived from the entire tissue section, not small 'representative' areas photographed using a microscope. For example, Targeted Molecular Diagnostics, a CRO recently acquired by Quintiles, uses Aperio's Digital IHC to multiplex downstream phosphomarker measurements as efficacy readouts in kinase inhibitor clinical trials.

Digital pathology addresses the dual challenges of international patient enrollment and test complexity in oncology clinical trials. The adoption in early stage tissue-based research and preclinical safety studies has been remarkable. Clinical oncology project teams at leading pharmaceutical companies will expect the same advantages from their CRO clinical pathology service providers.

Dr. Steve Potts is Worldwide Director for Biopharma at Aperio, rapidly expanding digital pathology in GLP and non-GLP studies. He previously was Head of Bioinformatics at Quest Diagnostics Nichols Institute. He earned a bioengineering doctorate and MBA from UC Davis, and a B.S. in Physics from Wheaton College, Illinois.