Home >> ALL ISSUES >> 2017 Issues >> New scope for trial drives FDA verdict

New scope for trial drives FDA verdict

image_pdfCreate PDF

Valerie Neff Newitt

June 2017—The new FDA-enabled milestone in pathology—approval in April of whole slide imaging for primary diagnosis—allows pathology to dip its toe into the technological revolution that has already transformed other fields. Widespread adoption will take time, training, and money, but it no longer awaits breakthrough approval.

“It allows us to say there is a competent device that, when we give it a slide, will give us back an image consistent with what we would see through light microscopy,” says John Gilbertson, MD, director of pathology informatics, Massachusetts General Hospital. “And when one slide is scanned by many different scanners, will those images be the same? The answer is yes. And that is a big deal.”

Having worked in digital pathology for almost 20 years, Dr. Gilbertson predicts “a golden age of pathology,” one that unleashes driving forces.

“We will be able to apply computational power and network our activity, both driving forces behind innovation, discovery, and productivity in the modern world in virtually every industry. Now we can also apply that to pathology for the very first time.”

Dr. Taylor

Dr. Taylor

This noteworthy moment is due in part to an exhaustive Philips study that paved the way to the FDA’s approval of the Philips IntelliSite Pathology Solution for primary diagnosis. Clive Taylor, MD, PhD, a professor of pathology at Keck School of Medicine of USC, was involved in the design of the study, which was much broader in scope than earlier whole slide imaging investigations.

Comparing it to a 2013 study by Bauer TW, et al. (Arch Pathol Lab Med. 2013;137[4]:518–524), Dr. Taylor explains, “The Philips study was intended to be a very large comparison of primary diagnosis by glass slide versus whole slide digital imaging, using the same pathologists to look at both diagnoses and to make the comparison against the original reference diagnosis of record. The Bauer study did some of those things as well, but it was a much smaller study—about 600 cases—and was limited to only subsets of disease.”

Dr. Taylor says one key differentiator of the Philips study is that it was designed with input from the FDA regarding the specifics required before broad approval could be granted. The study had to hit almost all organ systems, with the exception of non-formalin-fixed, paraffin-embedded hematopathology cases, frozen sections, and cytology, across 2,000 cases.

“While diagnostic subcategories in pathology are similar in terms of diagnostic principles, they also have significant differences in diagnostic applications. The FDA felt, and most people agree, there needed to be a validation to prove this process works for breast, prostate, lung, and so forth—not just one or two organ systems,” Dr. Taylor explains.
There were also discussions about what the case mix should look like, which led to agreement on a required number of cases for major organ systems and a smaller number of cases for smaller organ systems that may be encountered less commonly and considered less critical.

Asked if validation guidelines for the study differed from the CAP’s validation guideline published in 2013 (Pantanowitz L, et al. Arch Pathol Lab Med. 2013;137[12]:1710–1722), Dr. Taylor says, “The CAP guideline study was different in the sense that a consensus panel reviewed the literature on digital pathology diagnosis and came up with a series of 12 recommendations. Yet I should say that in putting the Philips study together, those guidelines were essentially all embraced in the proposal, in terms of how the process was introduced into each of the reading institutions for the purpose of the study and in the intended use of the digital slides once they get out there into practice.” The value of the CAP guideline is credibility, Dr. Taylor says. “They reflect the work of a broad group of experts who enumerated sensible steps to be taken before embarking on digital pathology. Validation of the device itself was an additional dimension. Again, Philips reviewed that same literature that CAP reviewed in considering what they had to do to create a device that is safe and reliable and consistent.”

The clinical study design required that there be
four clinical sites (Cleveland Clinic, University of Virginia, Miraca Life Sciences, and Advanced Pathology Associates, Rockville, Md.) to read the 2,000 cases. There were 27 pathologists involved: four to complete case enrollments, four to oversee validation, 16 to read cases, and three to adjudicate. In total there would be 16,000 reads with four pathologists reading both glass slides and digital slides for each case, with a four-week wash-out period in between.

CAP TODAY
X