There is no telling what is going to happen in Washington this summer, with the Prescription Drug User Fee Act (PDUFA) poised for renewal by a typically intemperate Congress and lame-duck President.

The final version of the legislation, like an exotic soup, is likely to have ingredients both savory and unsavory to industry. But there’s no doubt the FDA will have more authority to demand (not just suggest) post-approval studies.

With that in mind, we had a chat with Nayan Nanavati, VP in the Americas and head of the Peri Approval Clinical Excellence (PACE) group at Parexel. The contract research organization (CRO) set up the PACE group officially in 2001. It has completed 600 studies since then, using 61,000 sites that enrolled 516,000 patients.

Healthy Growth

The post-approval market is growing at 15-25 percent annually, Nanavati estimates, as the industry tries to manage patent expirations and new indications that are part of the life cycle of any drug. Nanavati’s not sure why, but demand for the company’s services in the space is healthy, perhaps because it’s been difficult for the sponsor community to build both the necessary technological infrastructure and hire the requisite staff.

One driver is the oft-reported figure about high percentages of post-approval studies that never get finished. Nanavati says the news media has bungled the reporting of that statistic, failing to note that studies categorized as incomplete may in fact be finished and awaiting a review at the overburdened FDA.

Says Nanavati: “The way the agency has defined completed, uncompleted or pending postmarketing studies has to be reviewed very carefully to get a true picture of it. The numerical values and metrics are media sensations, not meaningful.”

High Pressure

Even so, Nanavati concedes, there is real pressure on the industry to complete more post approval work. “It’s not necessarily just a public pressure or regulatory pressure or their self desire,” Nanavati says. “It’s a combination of all those pressures.”

“The amount of late phase research has grown so fast. Perhaps the research is growing faster than the ability to create the infrastructure,” he muses, noting that medical affairs departments at some sponsors are struggling to keep up with the workload.

Post-Approval SOPs

Working with investigators is one underappreciated challenge in post-approval work, he says. The trials blend both marketing and scientific objectives that have to be clearly understood and pursued. “You are representing a company, a product as well as managing research-naïve physicians. You are demanding from research-naïve physicians things they are not familiar with,” Nanavati says. Some companies struggle with balancing both roles.

Nanavati explains that one of the most valuable things his company can do for customers is supply a specialized set of standard operating procedures (SOPs). As gently as possible, he suggests that the industry may be a bit cavalier about applying practices from the pre-approval realm to what happens after a drug is approved. “Late phase studies are in fact regulated studies,” notes Nanavati. “But one must not force them to be Phase II-III studies.”

HR Nuances

Some of the differences in the pre- and peri-approval spaces, he says, have lead Parexel to recruit slightly different types of individuals for the post-approval segment. “One has to have the right mindset,” says Nanavati. “The worst thing we can do is carry out late phase research and apply the standards of investigational new drug (IND) research. It is interesting to me how many companies try to carry out research with that mindset. The person must be knowledgeable and totally flexible and not as rigid as someone would expect in Phase II.”

Says Nanavati: “A majority of pharmaceutical companies still would like to do a large Phase IV study and yet they think their SOPs require on-site monitoring. They would like to monitor 1,000 sites. We need to be able to fill their gap in knowledge.”

No Travel Necessary

Parexel often recommends “remote monitoring,” a concept that Nanavati says is not often widely understood. With the scale of many post-approval trials being so huge, the ability to scale such an effort may not be something that a sponsor’s internal IT department can handle easily.

Parexel has a facility devoted solely to remote monitoring in Centerville, Virginia where more than 100 monitors use the company’s web-based application for Phase IV research. Such efforts are extended by regional centers in Paris, Berlin and Buenos Aires. The teams can more or less run the program remotely, Nanavati says. “To carry out late phase research, you need different infrastructure,” he says. “It requires an appropriate IT platform that links the researcher in the field as well as our internal groups.”

Scaling The System

Technology, he says, is one reason Parexel can handle large projects with ease. And speed. One diabetes study, conducted only in the U.S., enrolled 12,000 patients and included 4,000 diabetologists, and endocrinologists and general practitioners. A cardiology trial enrolled 36,000 patients in six months.

Naturally, Nanavati is proud of the company’s tools for post-approval research. But technology can only take any organization so far, he adds: “The best technology in the world cannot guarantee success,” Nanavati says. “It’s the people, the knowledge, the experience.”