Opening the Floodgates

FDA's guidance on expanded-access programs--revised earlier this month in response to mounting pressure from patient advocates and federal courts to increase access to experimental drugs for the terminally ill--set new standards for admitting patients and for cost recovery, allowing pharmacompanies to charge for the drugs they provide to these patients. The new guidance, however, doesn't address the murky liability issues involved in compassionate-use drug programs.

"What we've tried to do with this proposal is strike the proper balance [between safety and access]," said Janet Woodcock, FDA's deputy commissioner for operations.

Agency officials refused to comment on whether the revisions announced last week are related to an ongoing lawsuit from Abigail Alliance for Better Access to Developmental Drugs, which is arguing that terminally ill patients have a constitutional right to unapproved therapies. Instead, regulators insisted that the changes are more clarification than modification.

Many companies already have compassionate-use programs in place, spurred by philanthropic motives as well as the opportunity to collect additional data from patients who were ineligible for clinical trials.

But there are also a number of unanswered questions that need to be addressed.

"While we support approaches to make experimental drugs available...our concern [has always been]: Would this discourage patients from enrolling in clinical trials?" said Alan Goldhammer, associate vice president of regulatory affairs at PhRMA. "I don't think anyone wants to short circuit the clinical trial process."

There are also concerns about informed consent, and whether treating physicians should have a certain level of expertise to administer the therapy. And there are questions about which reactions--positive or negative--must be reported to FDA, and at what point expanded access will be permitted. "Phase I is simply looking at safety and dosing," Goldhammer said. "It might get patients hopes up."

FDA emphasized that the new "clarifications" are intended to make it easier for individuals--including those in emergency situations--and small groups to access information about experimental treatment options as well as the drugs themselves. "These [expanded access] programs in fact existed, but they were not recognized by our regulations," said Rachel Behrman, deputy director in FDA's Office of Medical Policy Center for Drug Evaluation and Research, in a press conference. "Our regulations only recognized large-scale populations toward the end of" drug development.

The revised guidelines also update the original 1987 rule to suggest that the agency will grant expanded access based on a proportional scale that takes into account the risk/benefit profile of the drug, the seriousness of the disease, and the number of patients that will be exposed to it. "There's always a tension between the need for information and the need for access," Behrman said. The larger the group, for instance, the more safety and efficacy data will be needed to grant access to an investigational drug.

The new guidelines also address the issue of cost recovery. Most companies, FDA points out, don't charge for their compassionate-use programs. The agency doesn't expect that to change, but the revisions to the guidelines provide more detail about the issue of payment. The clarification should ease the burden on small, start-up companies that want to participate in these programs.

Manufacturers would have to get written permission from FDA before charging for a treatment, and would have to provide "reasonable assurance that charging will not interfere with developing the drug for marketing purposes," such as when a large-scale compassionate-use program prevents sufficient enrollment in clinical trials.

Abigail Alliance and public interest firm Washington Legal Foundation sued FDA in 2003, arguing that seriously ill patients have a constitutional right to unapproved therapies when they've exhausted other available treatments. Although a federal appeals court's three-judge panel ruled in May in favor of the group, it agreed last month to rehear the case with all ten DC circuit court judges present.