Post-Marketing Study Deadlines Urged As House Tackles FDA Safety Effort

FDA should revisit the post-marketing studies that firms have outstanding, eliminate many of them, and set firm deadlines for the remaining trials, academics suggested at a March 22 hearing by the House Energy and Commerce/Oversight and Investigations Subcommittee.

Many of the studies "aren't well-designed, and probably 20 percent don't deserve to be done," Bruce Psaty, University of Washington, said. FDA should look at the studies and "decide which ones need to be done, drop the rest, assign a start date for all of them."

Curt Furberg, Wake Forest University, added that studies should also have a firm completion date.

Sponsors should be held responsible for the deadlines, he said. "If they don't produce these studies on time, there should be consequences ... eventually drug withdrawal if these studies are not done."

The suggestions came in response to a query by Subcommittee Chair Bart Stupak, D-Mich., about how FDA can pressure sponsors to complete pending Phase IV trials, which numbered 1,200 according to FDA's latest count (¹ (Also see "Phase IV Commitments Are Increasingly Delayed, FDA Report Finds" - Pink Sheet, 12 Feb, 2007.), p. 22).

Psaty pointed out that Phase IV study requirements often are proposed close to the NDA action deadline. And many drug reviewers do not know what sort of post-market commitments to request, he said.

Epidemiologists are needed "to help medical officers to think about the proper design" for the studies. The current process "really contributes to the weakness of the U.S. drug safety system."

FDA Commissioner Andrew von Eschenbach emphasized the agency's efforts to improve the process of developing post-marketing commitments.

As part of its proposal to renew the Prescription Drug User Fee Act, FDA has pledged to set a schedule for resolving labeling and post-marketing commitment issues earlier in the review process (² (Also see "User Fee Hike Will Give Sponsors Clarity On Label, Postmarketing Discussions" - Pink Sheet, 15 Jan, 2007.), p. 4).

Earlier consultation between FDA and drug sponsors "to define and determine both the need for a post-market study, as well as the content of that post-market study," will make the process "much more effective," von Eschenbach said. The agency now has tools to conduct "much better oversight," he said.

Rep. Henry Waxman, D-Calif., questioned whether FDA currently can force companies to do what they promise. "The only thing you can do is to take a drug off the market. ... That's a pretty harsh sanction."

But von Eschenbach insisted "that the opportunity for compliance is ultimately there. The effective way of achieving compliance ... is to get much better studies in the first place."

New safety authorities for FDA are expected to be included in the renewal of the Prescription Drug User Fee Act (³ (Also see "Rx Safety Bill Would Require Renegotiation Of User Fees, FDA Tells Senate" - Pink Sheet, 19 Mar, 2007.), p. 3).

Proposals would give the agency leverage to get firms to conduct post-marketing studies allowing the agency to fine companies for non-compliance.

Waxman, along with Rep. Ed Markey, D-Mass., introduced legislation that would give FDA authority to mandate post-market studies, as well as labeling changes, and to restrict a drug's distribution and use.

H.R. 1561 is similar in this respect to a Senate bill (S. 484) sponsored by Sens. Edward Kennedy, D-Mass., and Michael Enzi, R-Wyo.

H.R. 1561 differs from the Senate bill in that it authorizes a higher minimum civil fine - $50,000 - for violations and creates more risk management procedures that may be required of firms (see chart ⁴ Waxman vs. Kennedy: A Side-By-Side Comparison of Drug Safety Bills From The House And Senate).

Another piece of legislation would enact more substantial revisions to the way FDA operates. H.R. 788, sponsored by Reps. John Tierney, D-Mass., and Jim Ramstad, R-Minn., would create a post-market safety center within FDA that is separate from CDER and CBER. The bill is identical to S. 468, introduced by Sens. Chuck Grassley, R-Iowa and Christopher Dodd, D-Conn. (⁵ , p. 3).

- Cathy Dombrowski ([email protected])