Learn & Confirm - Pharmaceutical Executive

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Learn & Confirm
At Wyeth, a sweeping set of initiatives is transforming the R&D operation—and spotlighting a possible futurefor drug development.


Pharmaceutical Executive


"If you combine those, that would be a huge saving," Schneider goes on. "If you collapse it all into a single sort of protocol concept—maybe dueling adaptive trials—you greatly collapse the time. That to me is the big win, if we can ever get ourselves to that point."

Getting to that point depends to a great extent on the comfort level of regulators, and they haven't shown themselves ready yet. But Schneider wonders whether there aren't other possibilities that would ease regulators into a new world. "Is there a halfway point that would allow us to do one adaptive, combined, seamless Phase I/II/III protocol, then somewhere along the way, you kick off a single confirmatory Phase III trial without waiting until the end? Maybe it's a little bit staggered, but you're still saving some time there and you're not creating two confirmatory studies. You're focusing on one."

Rethinking Operations

Still, there is reason to fear that Learn and Confirm will lengthen the old Phases I and II rather than shorten them. As Sheiner pointed out in his original article, learning is sequential, and we don't always control what we learn and when.

"Given the pressures for greater short-term rather than long-term thinking in our society in general and in the pharmaceutical industry in particular," he wrote, "the specter, even if unjustified, of longer total development time associated with sequential science based development may prove a formidable barrier to its acceptance. If so, then it will fall to a few brave (or foolhardy) research and development managers to judiciously choose from promising examples to demonstrate the value of fully science-oriented development."

Gombar agrees, but he takes the argument a step further: Managers need to seek efficiencies anywhere they can to make it possible to pursue a Learn and Confirm strategy. The long-term benefits are just too great to pass up.

More Springboard Initiatives

The search for new efficiencies makes Wyeth's other Springboard initiatives especially important. If they succeed, they will allow the company to afford the added work of acquiring more information about its drugs—without increasing overall costs.

Early Clinical Development Centers The Springboard team took an especially close look at recruitment for Phase II trials. There's a double-whammy to slow enrollment at this phase: On the one hand, it slows down the trial. On the other, it encourages companies to cope with slow enrollment by adding multiple additional research sites, many with very few patients, and accrue additional logistical costs for identifying sites, making qualifying visits, filing IRB paperwork, and monitoring performance.

What's more, explains Robert Maguire, vice president and chief of operations for clinical R&D, is the ample amount of waste built into the system. During a typical year, the company uses 400 to 500 sites for Phase II research—and 30 to 40 percent of them accrue either no patients or only one.

The team asked a question that hadn't really been asked before: Could they dramatically reduce the number of sites involved in a study while maintaining quality—and perhaps reducing cost? The company already did something similar with Phase I trials, which were mostly run out of large centers with cohorts of patients already lined up as volunteers. Could they build an equivalent mechanism for Phase II?

"One thing we saw over and over again was that 80 percent of our patients came from 20 percent of our sites," says Sheila Ronkin, assistant vice president for clinical development, who heads the ECDC program. "And we found that there were steps to take that could anticipate how they were going to enroll and conduct the study."

Was it possible, the team asked, to conduct Phase II trials in which 80 percent of the patients would come from a very limited number of sites—say, 10 or 20? They tried the process in Latin America, and received some encouraging evidence. In one trial, reports Ronkin, two Latin American hospitals provided 1,000 patients, about one-third for the entire trial.


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