With more than two decades in the industry under his belt, Jeffrey Trotter had his own contract research organization (CRO) for more than a decade. He sold it—twice. And now he's helping to shepherd the late-phase strategy at PharmaNet Development Group, where his title is executive VP, Phase IV development. He supervises a 50-person group dedicated to such projects.
All of the large, global CROs routinely work in post-approval research, Trotter notes. They can all be competent. But only a few firms, his included, truly specialize in Phase IV studies and appreciate the nuances.
One respect in which his firm is different, he says, is in an immediate recognition that such projects are not simply carbon copies of Phase III studies. "This requires a different approach," Trotter says. "Most of the industry has been trained and shaped by traditional randomized clinical trials. Unless you can deploy those resources in a different way, you tend to over-engineer the study."
Even today, Trotter laments that the sponsor community may not truly appreciate the distinctions between pre- and post-approval studies. Some CROs may try to finesse the issue. PharmaNet can handle Phase II and III projects. But it tries to be clear about the requirements in both types of research.
Less Is More
"Companies have to challenge their processes to make sure they're not imposing Phase III practices on Phase IV," Trotter notes. "We will get, to this day, almost schizophrenic requests for proposals (RFP). The RFP wants to do an observational study, but the description will be almost contradictory. They'll talk about randomization. They'll talk about a visit schedule."
"We call patients 'patients' instead of 'subjects,' " he says. "It sounds like an innocuous thing. But it has truly important ramifications on how the study is done. Sweating those details is truly important to us."
Another example is in the monitoring visit schedule. Trotter says that out of habit or lack of understanding of the unique aspects of Phase IV projects, some CROs try to do too much. They may actually cause scientific problems by triggering the Hawthorne effect, he says. "You may be impacting what you're trying to observe in the first place by being out there and striving for clinical trial perfection. A lighter touch, a less intrusive touch, is generally appropriate for an observational study."
The Phase IV realm, he believes, requires the best CROs to work a bit more collaboratively with clients than may be the case in a typical preapproval study. PharmaNet tries to be sure that everything in the Phase IV project is necessary, and in alignment with what the sponsor really needs. "It's an opportunity for greater collaboration between CROs and their clients," Trotter says.
Technology, used appropriately, can enable monitoring without a personal face-to-face encounter at the clinical research site. Says Trotter: "I can do kinder and gentler remote monitoring, and I can have the assurance the data is going to be as good as I can possibly hope for."
Recent drug safety controversies, as readers know, have dented the industry's reputation with the public, academic physicians and regulatory agencies. Trotter says the post-approval arena is where the industry should redeem itself. One general recommendation is to proactively visit the FDA or European authorities and discuss early safety signals.
"The industry is recognizing that we have an obligation to follow products post-approval," he says. "If there are safety issues, a company is well advised to find out about it before the press finds out about it."
Trotter sounds fairly energized by the possibilities of electronic health records (EHR) in Phase IV. He is cautious and sounds the usual caveats. One of them is that the electronic health records may not contain crucial information needed by the FDA and industry scientists.
But assuming those issues can be worked out, and the industry can obtain access to the records it needs, there are interesting potential scenarios. "We might be able to snap our fingers and get a good representation of what the world looks like from just downloading a bunch of records," he says. "We're going to be planning on capturing information electronically and in a routine manner."
Combining its expertise in late phase research and its technology platform, PharmaNet is exploring networks of physicians that come close to having some of the attributes of a community in the scientific sense. Trotter says the effort is embryonic, but exciting in its potential to rapidly deliver answers for the sponsor community.
The company is planning announcements later this year, but Trotter says it hopes the doctors in the network view their relationship with the company as a valuable one. "We want to make this a two way street," he says. "This is our first initiative in this area. Ten years from now, I can see this as being much more routine."d9A2t49mkex