Perceptive Informatics is gearing up to go into overdrive on imaging.

The technology division of Boston-area contract research organization (CRO) Parexel recently announced that it had amassed an A-list of imaging advisors, including big names from Georgetown University to Harvard Medical School.

The goal: To keep its imaging-centric operations on the bleeding edge of a rapidly expanding area of clinical trials, and to move into new therapeutic realms.

Promising Pictures

That way, the firm’s already robust Perceptive Informatics Medical Imaging unit—currently one of the largest among the major CROs—will be positioned to win even more contracts as the field gets hotter, says Mark A. Goldberg, president of Perceptive (in his spare time, he’s also president of the largest division at Parexel, clinical research services). He joined Parexel in 1997 and quickly started the imaging group. He helped start Perceptive in 2000, and the imaging unit became part of that.

Traditionally, imaging in clinical trials has been used in oncology. Goldberg says that tumor size, measured via imaging, may constitute an expedient end point that may be discernible before, say, a change in survival rates.

Faster, Better

Indeed the main goal in imaging right now, says Goldberg, is “to achieve a surrogate end point that a regulator would accept as proof that a drug is having a desired effect.”

Goldberg added that surrogate end points aren’t meant to replace clinical outcomes, but rather to enhance the whole process.

“Clinical outcomes are the gold standard,” he says. “Surrogate end points, to determine safety and efficacy of new treatments in clinical trials, should be predictive of clinical outcomes and provide the answer faster, potentially years faster.”

But imaging is also beginning to transcend pictures of solid masses or arthritic bones, dubbed “anatomic” imaging. Newer functional imaging—which allows researchers to view markers like changes in metabolic activity—can help researchers make critical decisions on a potential drug well before they submit a protocol to regulators.

Go, No-Go

“We’re seeing imaging be of interest to pharmaceutical companies earlier and earlier in the developmental life cycle of a compound,” says Goldberg, a radiologist himself. “Increasingly, the science is being used to make no-go decisions about a compound. It can be used to weed them out.”

An example? Think positron emission tomography, or PET scans. And take, for instance, angiogenesis compounds, which are designed to target blood vessels in order to cut off blood supply to tumors. Early in the life of such a compound, researchers can now use imaging to see whether the compound in fact reduces blood flow. If it doesn’t, it can be scrapped early. Not going any further saves drug companies a lot of money, says Goldberg, who adds that the industry failure rate at the Phase III level is 50 percent, which is “hugely expensive.”

Academics Necessary

The recent push toward using imaging in this way makes Perceptive’s new list of advisors even more key, says Goldberg.

“The more you push back to toward this cutting edge technology, the more you need academic expertise,” he says. “The best way for us to offer that is through a marriage of internal experts and external experts in a particular therapeutic area.”

Perceptive’s new advisors are imaging experts in the fields of cardiovascular, musculoskeletal, oncology and the central nervous system.

Market Size

No solid numbers exist on imaging in clinical trials. But those that are commonly bandied about, said Goldberg, indicate that $300-$400 million is currently being spent. And the field is expected to grow about 15 percent annually, he estimates.

Despite all the exciting technology out there, Goldberg says the most frequently used forms of imaging for trials right now are CT scanners and MRIs. And even plain old radiographs are employed for trials on ailments like arthritis. But following quickly on the heels of those more familiar modes are PET scans.

Reconciliation Nightmare

Services the company provides as a core lab include preparing a “charter,” the imaging equivalent of a protocol. That ensures the study’s imaging is done in a consistent fashion across all sites, and that such data is compiled in a way that can be digested by regulators. This can be a challenge. Image data has to be appropriately matched up with other data in the case report forms from a trial. If not managed properly, the reconciliation process can be a nightmare.

That’s where being part of Parexel comes in handy, says Goldberg, as CRO personnel from the parent company and technology folks from Perceptive can work together closely and regularly on integration projects. In one project for a large pharma, it extended the familiar idea of “edit checks” to the imaging arena, allowing radiologists to review measurements and calculations taken by nonphysician technicians.

“It’s a lot of stats moving around,” Goldberg says. “It takes very good project management so you don’t end up in a situation where you sit down with the regulators and you have some but not all of the information. Whether a tumor has progressed may be based on a lab test or an image or something else. We have to integrate and combine that data from the clinical and imaging sides.”

Tight Regs

Speaking of regulators and regulations, they seem to be getting tighter, Goldberg says.

“The FDA has become increasingly specific about how these trials are run,” he says. He added, though, that instead of wanting to see all images from a trial that’s using imaging, regulators now seem to be satisfied with spot checks.

But interestingly, Goldberg adds, while imaging is still new, many sponsors seem bashful about sitting down with regulators to discuss their imaging charters in an up-front manner.

Face The Agency

“There is a lack of enthusiasm [among sponsors] for engaging with the regulators as much as they should,” he says. “The FDA really wants to talk to the sponsors about how the images are going to be used in the trial, review the charter and provide feedback. We’ve seen companies get into a real quagmire, launching imaging programs without asking regulators as much as they should. Sponsors are often just afraid of sitting around a table with regulators.”

Fortunately, as imaging use in trials grows and matures, Goldberg reports he is seeing a decline in that behavior among sponsors.

Like the rest of the industry, imaging is going global. “An increasing number of images are being reviewed internationally,” says Goldberg. “In theory, radiologists from any geography could be used if they have the appropriate credentials and are experts in their field.  As medicine and drug development becomes more global, the international review of medical images will also grow as a trend.”

FDA guidance on imaging in trials can be found here, here and here.

—by Suz Redfearn

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