Call it a case of bad news, then good news, then—distressingly—no news at all. In March 2004, FDA issued a white paper entitled
"Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Product Development." It painted a picture
of a drug-development system that was breaking down.
Janet Woodcock, FDA's deputy commissioner for operations
Not only had the arrival of genomics not created its expected bounty of new drugs, but there were signs that things were getting
worse. Spending by both the industry and NIH had more than doubled since 1993, but license applications for new drugs and
biologics were down worldwide. One might have expected that the cost of discovery was driving the change—but in fact, almost
all of the growth in the expense of developing a new drug came later, in the clinical phases of development that FDA labeled
"the critical path."
Douglas Throckmorton, deputy director of the Center for Drug Evaluation and Research
Worst of all, there were no signs that the industry and the agency were benefiting from their experience. "A new medicinal
compound entering Phase 1 testing, often representing the culmination of upwards of a decade of preclinical screening and
evaluation, is estimated to have only an eight percent chance of reaching the market," wrote the paper's authors. "This reflects
a worsening outlook from the historical success rate of about 14 percent. In other words, a drug entering Phase 1 trials in
2000 was not more likely to reach the market than one entering Phase 1 trials in 1985."
Lawrence Lesko, director of CDER's Office of Clinical Pharmacology and Biopharmaceutics.
That was the bad news. The good was that FDA planned an ambitious Critical Path Initiative to improve and accelerate drug
development by partnering with companies and academic institutions to discover and validate biomarkers, create innovative
protocols for clinical trials, and invent models and predictive tools—in short, to help create a robust science of drug development.
The white paper was written with a sense of urgency, and issued with fanfare. A list of research priorities was promised within
a matter of months. And then . . .
And then, seemingly nothing. The "research opportunities" list never appeared, and Critical Path seemed to drop off the radar
as public concern veered in the direction of drug safety, and politicians railed about the "too-cozy" relationship between
FDA and the industry. As recently as this fall, Critical Path looked dead or close to it.
But is it? The past few months have seen a flurry of announcements about projects related to Critical Path, and at several
meetings Acting Commissioner Andrew von Eschenbach called the initiative one of his highest priorities. At press time, FDA
said the long-awaited research opportunity list was (again) just days away from release.
The long silence, explains Deputy Commissioner for Operations Janet Woodcock, was not a period of inactivity, but a time of
serious conversations with stakeholders about sensitive issues, especially the problem of sharing data and scientific insight
while preserving intellectual property. "People shouldn't underestimate the difficulties of creating new models," she says.
"It involves a lot of lawyers and signing papers and agreements and working your way through questions: how would we do this,
and who would benefit if we discover something, and so forth. A lot of things that are worth doing can't happen quickly."