Pharma strives to aid companion diagnostics

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For its part, Clarient had discovered that the positivity rate for ALK varied dramatically between clients. “So while there was an average ALK positivity rate, if you looked at it by client, almost nobody was at the average,” Dr. Bloom says. “Clients were either higher than average or lower than average, but the average was quite rare. So we worked with Pfizer looking for the cause of the variation.”

Initially it was suspected that preanalytical variables such as humidity or temperature might be playing a role since the positivity rates were lowest in Florida. Instead, “what we discovered was that the positivity rate was very tightly correlated with the age of the patient,” Dr. Bloom says. “So when we were looking at places like Florida, where most of the patients averaged more than 70 years of age, the positivity rate was less than one percent. But in other areas of the country, where the patient population averaged, let’s say, less than 45 years of age, their positivity rate was eight percent. That data significantly aids pharma, but each of the pharmas has a different approach to what they do with the data. In the end, they all want to ensure that testing is being performed appropriately and correctly.”

“It’s important,” Dr. Bloom continues, “to educate pathologists that they might be performing or interpreting a test incorrectly. If, in the case of ALK, their positivity rate was three percent, but the average age of their population was in their 40s, they shouldn’t be feeling good about their test results. That rate is too low for that population. Assessing statistics is critical for labs, because many of these molecular abnormalities are so rare, how do you know you’re doing the test correctly? How do you ensure accurate testing in your laboratory when positive samples are so rare? Understanding statistics and understanding the distribution of the analyte is turning out to be a very important business.”

PhenoPath in Seattle, too, has begun collaborating with Pfizer to analyze de-identified testing results for biomarkers such as ALK, EGFR, and KRAS for lung tumor specimens, says Harry Hwang, MD, director of molecular pathology. “We share those results so they can do statistical work on what rates of positivity the pathology testing community is getting on actual patient samples,” he says. “I do think this type of data exchange is good for pathology and patient care, as it lets a third party examine whether we are seeing expected rates of positivity in different settings. They have given us preliminary feedback on their analysis and are going to give us more feedback as they continue.”

A third institution, St. Joseph Hospital in Orange, Calif., has also begun partnering with Pfizer, but in a different way. As Lawrence Wagman, MD, explains, “The regional leadership at Pfizer originally contacted the chief medical officer here in 2013 to talk about doing a project to examine how molecular testing fits into the practice of medicine in oncology.” Dr. Wagman, an oncologic surgeon, is executive medical director at the hospital’s Center for Cancer Prevention and Treatment.

Gathering stakeholders, mapping the existing molecular testing process, identifying opportunities for improvement, and applying Lean methodology were the start of the project. It soon became clear, Dr. Wagman says, that one of the hospital’s primary challenges was determining how and by whom tissue would be acquired. “Is it done by surgeons? By interventional radiologists? In a hospital setting? In an outpatient setting associated with a hospital or in one not associated with a hospital?” he says.

“The other area identified was the timing of the patient process. Is this testing something that should be done initially and becomes part of the initial workup? Or should it be done selectively, at a later time when we are certain it would apply to that patient’s specific situation?” They also looked at the process for reflex testing and the incorporation of specific molecular testing in the evaluation of tissue. “And another component of it was the interaction with therapy. We reviewed how the physician made a decision using the information in patient care.”

Dr. Wagman

Two years later, with the process mapping completed, Pfizer and St. Joseph have shifted their focus to measurement. “For example, we’re measuring how often a specimen that’s obtained is adequate to perform the testing and how often a patient might need additional testing,” Dr. Wagman says. “We’re measuring the time between the acquisition of the tissue, the reporting back to the practicing physician, and the time until the patient begins personalized therapy. This is a true, real-world turnaround time that includes the multiple components in the pathway. So that’s the kind of thing we’re in the process of now, and that’s where a lot of the detail starts to emerge. Maybe you go back and say, ‘OK, well, the 18-gauge needles are adequate 50 percent of the time, and the 16-gauge needles are adequate 90 percent of the time. Can we switch from 18 gauge to 16 gauge?’ And then you look at the potential complications of each of them.”
In his view, working with Pfizer has improved conversations between pathologists, oncologists, surgeons, and radiologists. “We had a cancer conference last week, and we were talking about testing specimens and what they were going to get tested for, and there was a really interesting discussion among the pathologists and the oncologists about the process,” Dr. Wagman says. “We were able to put into context some of the things we have done to improve the process in terms of reflex testing and unique results that would or would not drive therapy.”

The next step of the project, he says, will entail modeling, “where we take these processes that we’ve outlined and start manipulating some of the key parameters. Right now we’re biopsying patients when they relapse. What would happen if we move that analysis to the beginning? What if we tested all lung cancer patients at the time of surgical resection on their primary tumors? How many of them would never need that information? How many of them would benefit when they had their first relapse and that information was available immediately? We want to create some theoretical models.”
Not surprisingly, Dr. Wagman characterizes St. Joseph’s relationship with Pfizer as “very valuable.”

“They have an understanding of drug utilization and the epidemiology of the different markers,” he says. “They can do the arithmetic at the corporate level and know what the marketplace is like. By helping us develop these very appropriate evidence-based flow diagrams of our processes, they’re helping ensure that more people will get the right treatment in a timely fashion. It’s good for them from a marketplace point of view, and it’s good for us because we’re doing the right thing for the at-risk patient population.” Echoing Dr. Hammond’s sentiment, he adds, “Everyone wins on this one.”

Anne Ford is a writer in Evanston, Ill.