"We're beat up for not approving things that ultimately prove to be beneficial because we're uncertain about the benefits,"
she says. "We're beat up if we approve something and then a subgroup turns out to be harmed by it. It's a no-win situation
for the regulators, because there are always going to be people who benefit and people who are harmed."
She explains that the industry and the agency need to move from a population-based model, in which drugs are tested on broad
pools of patients, to a more targeted approach in which clinical development focuses on patients most likely to benefit from
a drug. But to do that will require new libraries of biomarkers, new models for clinical trials, and other tools—all of which
Critical Path hopes to develop. FDA does not fund research, Woodcock acknowledges, but it has a responsibility to improve
its rules and evaluation processes.
The potential payoff? A solution to falling R&D productivity, new tools for improving safety, and in the long run, a chance
to make drug development more predictable and manageable. "I think we bring a knowledge of where the issues are." says Douglas
Throckmorton, deputy director of FDA's Center for Drug Evaluation and Research (CDER), "because we sit at the intersection
between basic science and product development and marketing. "We know where the critical lesions are, if you will—the things
that if made better could materially affect drug development. We also bring the regulatory piece. At the end of the day, we
can say, 'Yes, this is acceptable. This biomarker is useful in this setting. We'll use it as a surrogate.' That clarity, of
course, is terribly important for sponsors.
"What we can't bring are monetary resources and personnel resources. So what we can offer is to work with the people that
can do those things—clearly identify the tasks, the tests, and the research, so at the end of the day, we, in fact, can make
that regulatory decision."
Science Plus Process
"For me," says Lawrence Lesko, director of CDER's Office of Clinical Pharmacology and Biopharmaceutics, "Critical Path is
two broad things. One is the science—the innovations that would improve productivity and success. That's what most people
have focused on. But it's just as important to focus on the process by which FDA interacts with industry and vice versa, because
you could have all the innovative science you want, but if you don't have venues to have conversations about that science,
I believe it would be business as usual."
As an example of what he means, Lesko points to FDA's Voluntary Genomic Data Submission program (VGDS), which began in 2004.
Created to provide an avenue for the use of innovative science, the program offers companies a safe harbor to discuss genomic
data with the agency without fear of repercussions in the review phase.
Companies apply to participate in VGDS, and FDA selects the applications most likely to yield new insight. The company submits
a packet of data—perhaps a validation package about a genomic expression, or data related to the selection of a biomarker
that the company thinks might be associated with an adverse event. FDA reviews the data, and meets with the company to discuss
how to move forward.
"Because it's exploratory data, we're free to explore all possibilities," says Lesko. "The strength of the meeting is the
ability to dialogue in a way that everyone knows is nonbinding." FDA has conducted about 30 VGDS meetings involving a dozen
companies in the past year—about as many as the agency can handle, Lesko says.
Working with individual companies, however, is much easier than collecting data from multiple companies or working with consortia.
FDA has projects under way that will help it gain experience in sharing selected data while maintaining the intellectual property
of the companies that produced it.