CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Granzow
Philips undertook an enormous task in its push for clearance, say Russ Granzow, general manager of Philips Digital Pathology Solutions, and Esther Abels, director of regulatory, clinical, and medical affairs at Philips Digital Pathology Solutions and chair of the DPA regulatory and standards task force.
“We’ve been working on this for so long, it’s become part of our DNA at Philips for the past five years or more,” Granzow says. “The FDA worked very hard with us. There was daily contact with Esther, reviewers, senior management. They wanted to make this decision and to make it the right way.”
That decision was largely dependent on a large clinical study of about 2,000 surgical pathology cases—one of the largest studies ever conducted to compare the use of digital pathology to optical microscopes.
Abels
“We used four different facilities [Cleveland Clinic, University of Virginia, Miraca Life Sciences, and Advanced Pathology Associates, Rockville, Md.], and four reading pathologists per hospital—16 pathologists, ranging from general pathologists to specialists—all reading the same cases at their institutions,” Abels explains. In total there were about 16,000 reads across 2,000 cases. “An adjudication committee—a panel of three independent pathologists—reviewed whether findings on these digital cases, including difficult cases, were different from sign-out cases,” Abels says.
Study results showed that diagnoses made based on Philips’ WSI system were comparable to those made using glass slides and demonstrated the point of non-inferiority.
“We tried to get full and representative coverage,” Granzow says. “The goal was to show non-inferiority between the microscope and all use cases for anatomic pathology, as opposed to simply biasing it toward just breast or prostate. Pathologists must feel confident that digital pathology can be adopted into daily practice.”
“One of the reasons it had not been adopted until today,” Abels adds, “is pathologists didn’t feel they could fundamentally adapt their workflow around digital pathology. Now they have the opportunity to do that.”
While news of the clearance has had its own level of energy, continuing excitement is found in the benefits to follow. Dr. Glassy says the FDA’s stamp of approval gives pathologists a new comfort level in enjoying those benefits. “Remote diagnosis is a liberating use of technology. The world is now a pathologist’s office, keeping in mind issues with CLIA licensure, of course. The FDA has lifted the travel ban that pathologists have been under, keeping them in offices or laboratories to read out cases. We have been untethered.”
Dr. Pantanowitz says the approval will make it easier to share cases, balance workload, and centralize services, and it will support subspecialty practice. “It will also allow us to embrace next-generation applications—such as image analysis, streaming analytics, and computational pathology—much sooner than anticipated. Once these digital pathology systems are ‘hooked up’ for clinical use and operational, they can even begin to be deployed within larger enterprise image ecosystems—for example, vendor neutral archives.”
Clinicians and patients stand to gain from greater access to experts, faster turnaround times, improved accuracy, and computer-aided diagnoses, Dr. Pantanowitz says. “I am hoping this milestone will drive down the cost of these systems, create new revenue opportunities for pathology labs, promote digital imaging specialists, and encourage innovation that will reshape pathology.”
Some worry that digital pathology approved for primary diagnosis could end up replacing pathologists, Dr. Becich says, but he doesn’t see it that way. “Today it is all about managing data drawn from imaging, longitudinal laboratory data, electronic health records, and so forth. Now more pathologists will embrace computational pathology; we will see pathology informatics as a discipline grow and diversify in ways to help us all. It will include the deeper research enrichment that comes from computational pathology’s ability to bring its own data. And that bodes well for precision medicine.”
In making its announcement, the FDA called for special controls to ensure “precision, reliability, and clinical relevance . . . safety and effectiveness for this digital imaging system.”
“DPA has been in discussions with the FDA regarding exactly what these are, what level of detail is required. It is a lot of work,” Dr. Pantanowitz says. “Before, it was not tangible, only hypothetical. Now we actually do have a class II device. As part of the submission, Philips was required to address a proposal of the special controls, and the FDA will provide final guidance. With the de novo authorization published in the FDA’s de novo database, the special controls are made public and apply to WSI devices. Finally someone is doing this.”
Pantanowitz
But he cautions that the regulatory challenge with WSI is not over. “How are we going to evaluate the safety and effectiveness of all the new devices on the market? There is work to be done, such as developing phantoms and related tools to aid with validation and regulatory evaluation.” And while FDA clearance for “one locked-down system is great,” he says, it raises questions about future interoperability—“will we be able to mix and match products?”—and the capacity to advance this field—“will open systems and artificial intelligence tools ever be permitted?” Moreover, pathology laboratories produce more than surgical pathology slides, he adds. “We still need FDA-approved digital pathology systems for cytology, non-FFPE hematology, and microbiology slides before we can claim to be ‘fully digital.’”
Granzow says Philips has seen widespread adoption by reference laboratories in Europe and expects the same will happen in the United States. He also says computational analysis is becoming more accepted overseas as companies roll out important algorithms. “Truly, digitalization is the first step, not the end,” he says.
Dr. Glassy knows the journey ahead is challenging but suggests the route already traveled has brought pathology to an important harbor. “We all knew this would happen and we would get here. But that it happened in my lifetime—that is truly fantastic.”
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Valerie Neff Newitt is a writer in Audubon, Pa.