Controversy over a left-out member of the advisory committee for Lilly/Daiichi Sankyo's platelet inhibitor prasugrel illustrates the challenges that FDA continues to experience in ensuring the credibility of high-profile drug reviews.

While the meeting itself demonstrated that an FDA advisory committee's discussion of a tricky product application can be smooth and productive, it does not necessarily exclude the possibility of a backlash after the meeting is over.

FDA has acknowledged that it has work to do to increase its credibility in the eyes of the public. Center for Drug Evaluation & Research Director Janet Woodcock recently said that restoring FDA's position as the gold standard is a top priority for the agency (¹ Also see "FDA’s Team Mentality: Commish Search Should Avoid Single-Candidate Focus" - Pink Sheet, 15 December, 2008., p. 22).

But the publicity around the dismissal of an advisory committee member who has spoken out against the prasugrel application, in addition to the absence of any members of FDA's drug safety advisory committee, is evidence that once the agency has lost credibility with the public, every decision is put under a microscope.

Two Notable Absences

Agency observers noted two absences at the prasugrel advisory committee meeting. The first was the absence of any members of FDA's Drug Safety & Risk Management Advisory Committee despite prasugrel's well-documented risks of bleeding and cancer.

FDA's decision to convene only the Cardiovascular & Renal Drug Products Advisory Committee - and not to hold a dual committee meeting with drug safety nor invite any of those members to participate - was an early positive sign for Lilly (² The IN VIVO Blog, Dec. 31, 2008).

The addition of the Drug Safety & Risk Management Advisory Committee or some of its members would not have necessarily swung the vote one way or the other on prasugrel (the committee voted 9-0 in favor of approval).

But their presence could have focused the discussion even more on safety, and resulted in more significant labeling and use restrictions than what was recommended by the cardio-renal committee members (see ³ Also see "The Return Of The Blockbuster? Stage Is Set For Prasugrel Approval" - Pink Sheet, 9 February, 2009.).

FDA Explains Kaul's Dismissal

The second absence to raise questions was that of cardio-renal committee member Sanjay Kaul of Cedars-Sinai Heart Institute, who was recused from the panel at the last minute due to what FDA says is an intellectual bias.

Kaul is an outspoken critic of prasugrel and is considered by some as having a contrarian personality. He was tagged by Wall Street analysts in the days leading up to the meeting as the likely conservative voice on the cardio-renal advisory committee.

Some FDA observers suggested that Kaul's contrarian views made him a necessary voice on the advisory committee to ensure that all voices were heard. Another possibility would have been to allow him to participate, but as a non-voting member.

In a statement, FDA explained that Kaul's dismissal was because "the agency thought there was the possibility of an appearance issue."

FDA's guidelines on intellectual bias are outlined in a two-page document, and include cases where impartiality may be a concern based on comments made in public about a product under review (⁴ Also see "Nissen, Califf Absent From Prasugrel Panel" - Pink Sheet, 30 January, 2009.).

Addressing the last-minute nature of the decision, FDA said it had to bypass the typical review process due to time constraints. Typically, the determination of intellectual bias follows a course of review within FDA, with the final decision made by the commissioner or commissioner-designee after consultation with appropriate center officials.

In the case of prasugrel, FDA "did not receive sufficient information on a potential appearance issue until much later than what we would prefer, very late in the process, and the agency was unable to go through the review process in sufficient time in order to make a decision on the member's participation in the meeting."

"In this case, in order to enhance the credibility and transparency of the advisory committee proceeding and in an abundance of caution, the agency felt it was necessary for the member not to participate in the meeting," FDA said.

- Jamie Hammon (j.hammon@elsevier.com) and Kate Rawson (k.rawson@elsevier.com)

Prasugrel Advisory Committee Highlights FDA’s Continued Credibility Gap

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