FDA Commissioner Andrew C. von Eschenbach

The Food and Drug Administration (FDA) must change to respond to innovations in cancer therapies, FDA commissioner Andrew C. von Eschenbach, M.D., said at AEI on March 13. But he cautioned that regulators must maintain safeguards on drug approval. Much of the recent public scrutiny of the FDA has concerned the agency's handling of drug safety, but too little attention has been given to the apparent decrease in the number of innovative new cancer therapies being brought to market in the past several years due to the higher regulatory burdens being placed on new cancer products.

Von Eschenbach joined academics, medical researchers, and former FDA commissioners at a conference to evaluate and critique the FDA review process for cancer drugs. He offered the agency's perspective on the institutional changes he is making to better address growing challenges, such as developing better scientific tools for evaluating new drugs, improving the agency's ability to recruit and retain scientific staff, and taking new steps to give better assurances that the products the FDA approves are safe.

"We have to address the fact that in order to change the process of cancer we may need to change the process of how we go about discovery, development, and delivery," he said. "And those changes in that process include changes that have to occur within the regulatory framework."

Although oncology drugs often receive "accelerated approval" and "orphan drug" designations to accelerate their entries into the market, U.S. clinical development took one and a half times longer on average for oncology drugs than other drugs approved from 1990 to 2005, according to data presented at the conference. Only 8 percent of oncology drugs that enter the first phase of review are actually approved, compared to 20 percent for drugs in other therapeutic categories.

Conference speakers attributed these trends to regulatory shortcomings, such as the use of outdated statistical methods in clinical trials; a reluctance to use measures of tumor progression rather than measures of survival, which often require clinical trials to be longer and to enroll many more patients; too few patients willing to enter clinical trials; and the FDA's movement away from making more robust use of accelerated approval, which enabled products to come to the market more quickly in the past.

Von Eschenbach stated that although there may be some advantages to using progression-free survival as an "endpoint"--that is, a particular target in clinical trials--the science must be developed to ensure that the endpoints are meaningful, not arbitrary. He said that the regulatory process does not need to be a "retardant" to progress and the development of safe and effective new products--as long as regulators rely on good scientific tools for evaluating new products. He affirmed the FDA's "openness to examine new endpoints, new ways of arriving at those endpoints, and new scientific tools that will give us the certainty that's required to make a regulatory decision."

AEI's John E. Calfee and Scott Gottlieb, M.D., organized the conference. During the final panel of the conference, former FDA commissioners David Kessler, M.D., and Mark McClellan, M.D., a visiting senior fellow at AEI, joined current FDA official Douglas Throckmorton, M.D., and former FDA chief counsel Nancy Buc for a discussion of the agency's past and future.

For a video, podcast, and report on this conference, visit www.aei.org/event1666/.