FDA Panel Rejects New Rule For Psychiatric Drug Testing

With a unanimous 12-0 vote, members of the U.S. Food and Drug Administration (FDA) Psychopharmacologic Drugs Advisory Committee (PDAC) told the agency to reverse its recently implemented requirement calling on drug companies to submit both short-term (eight to 12 week) and longer-term (more than six months) efficacy data as part of an initial application for approval to market a psychiatric medication.

The PDAC members expressed concern that the requirement would slow drug development and timely approval of new medications for the treatment of mental illness. In addition, they expressed concern over how longer-term data should be collected and by whom.

“We'll likely follow your advice,” said Thomas Laughren, M.D., acting director of the FDA's Division of Psychiatry Products. Laughren officially spoke for the agency at a day-long public hearing late last month.

Legally, the FDA is not bound by the votes of its advisory panels. Historically, it has nearly always followed its committees' leads, although there have been notable exceptions recently in areas other than psychiatric drug products.

The unanimous “no” vote was in response to the first of a list of 12 questions Laughren had submitted to the PDAC for its consideration. Of the 12 questions (some multipart), formal votes were requested for four, with the remainder of the questions intended only to generate discussion. The PDAC's answer to the first question, “Is it a reasonable expectation that a sponsor would have accumulated data for both acute and longer-term efficacy trials at the time of filing of an application for a drug treatment for major depressive disorder?” seemed to be a foregone conclusion nearly from the outset of the hearing. Indeed, of those speaking throughout the hearing, Laughren seemed to be the only one who supported the notion.

Yet, several members of the PDAC expressed concern over how the public might view the panel's “no” vote. Some members said they feared that the panel's vote would be considered a rebuke to the FDA for attempting to require “a higher standard of evidence” for approval of psychiatric medications.

In an unusual move, the PDAC unanimously voted to approve the release of a public statement saying: “The advisory committee recognizes the need for evidence to inform clinical practice regarding long-term treatment efficacy, without potentially slowing progress of new drug development. We encourage collaborative efforts by industry, the National Institutes of Health, and the FDA to further research on long-term treatment.”

At the end of the day, the remaining questions that the FDA had presented to the PDAC were not directly addressed, and no further votes were taken.

An unusual coalition involving 10 pharmaceutical companies (all of which are direct competitors in the psychiatric drug market) provided nearly three hours of joint testimony on how the requirement for long-term data at the time of initial filing would effect the drug-development process. The overwhelming message was that the requirement would significantly slow down drug development, perhaps obstructing it altogether. Bringing psychiatric medications to the market would take longer and be more costly, the companies said.

“Both acute and long-term efficacy data are needed for psychiatric disorders that are recurrent or chronic; everyone agrees with that,” said Frederick Goodwin, M.D., a professor of psychiatry at George Washington University, who introduced the companies' joint testimony. “But [an indication to treat an acute episode and an indication for maintenance treatment] are very different indications and should not be made interdependent.”

Yet, FDA's Laughren argued throughout the day for requiring“ longer-term data,” saying at the outset that “most psychiatric illnesses are chronic, and all psychiatric illnesses for which psychiatric drugs have approved indications in the U.S. are chronic.”

Even so, he emphasized, all of the drugs currently approved for psychiatric illnesses gained their approvals with short-term efficacy data (generally eight to 12 weeks). In contrast, he noted, “most treatment guidelines for chronic psychiatric illness” recommend between four and six months of medication treatment.

“Clinicians,” he said, “have generally not had sufficient evidence base to support what is the standard of practice.”