"When I went through this whole thing last year, and especially some of the discussions we had with the guys down at FDA,
I finally realized that I was thinking about drug development totally backwards," says Gombar. "We'd start with a homogeneous
population to control variability as much as possible so we got good data with a somewhat smaller number of patients, then
we went more real world in Phase III.
"They got me to realize that's the wrong way to think about it. Actually you want to use heterogeneous populations early on,
so you identify sources of variability—so that you can perhaps identify what patients are going to respond, and go to a more
homogeneous population in Phase III with some confidence that these are the patients that it's actually appropriate to use
the drug in."
A concept like Learn and Confirm needs to be more than just an idea—it has to be built into the structure of the R&D operation.
Toward that end, Wyeth has created a new team structure for R&D. Formerly, individual drug candidates were assigned to project
teams that handled both what would now be called Learn activities and Confirm activities. Now, Learn teams of a dozen people
are assigned not to individual drugs, but to the portfolio for a whole therapeutic area.
"Take Alzheimer's for example. We happen to have a lot of drugs in Alzheimer's development right now—maybe seven or eight
molecules," explains Schneider. "All of those are being overseen by a single team. We're trying to bring the people who have
the most expertise and scientific knowledge into those teams, with the idea of learning as much as we can and being able to
repeat learning from one molecule to the next."
Once a molecule gets to the Confirm phase—which for the moment will be equivalent to Phase III—it will be handled by a Confirm
team focused on operations and rapid execution.
The key to making this new organization work, however, is creating a structured dialogue between Learn teams and Confirm teams
to help them make practical decisions about how much learning is enough, and what, if any, additional practical steps need
to be taken before a drug can move forward.
"That's a discussion that didn't happen five years ago at all," says Stiles. "It was just this finger pointing: 'The drug's
not good enough.' 'Yes, it is. You're going to take it.' We haven't fixed it all, but we're getting there."
Where's the Saving?
There is little doubt that Learn and Confirm can produce better, more useful, clinical information that would serve the interests
of patients, physicians, and marketers alike. But in a time of massive patent expirations and pressures on margins, the question
remains: Will it save money?
There are reasons to be optimistic. Today, far too many drugs fail in Phase III because of inadequate data on dosing. If Learn
and Confirm is only moderately successful in improving the success rate (or, better yet, brings it back to the historical
rate of 80 percent or so, which has seemed like a pipe dream in recent years), it would be worth the effort.
The new system also promises the potential to save development time, which pays off both in lower costs and a longer period
of time selling on patent. There could well be additional savings just from collapsing Phase I and II together. But the real
savings, says Schneider, will come when regulatory agencies are willing to let the company go all the way to a seamless Phase
II/Phase III approach. "Right now, it's sequential," he explains. "You do Phase II. Say it takes a couple of years. Even if
you do interim analyses along the way, you have a transition zone, at least two and a half years, and then you have Phase