House and Senate Committees are requesting documentation from FDA officials on what and when they knew about a possible link between antidepressants and suicidal behavior.

Senate Finance Committee Chairman Chuck Grassley (R-Iowa) is requesting meetings with FDAers to investigate allegations that the agency suppressed the disclosure of internal data analyses pointing to a link between antidepressant drugs and suicidality in children. The investigation was announced March 22.

In addition, the House Energy & Commerce/Oversight Subcommittee is seeking documentation of data reports submitted by manufacturers to FDA and the agency's subsequent action on those reports.

The requests for information from Congress follow FDA's decision to request a stronger warning on pediatric suicide in labeling for 10 antidepressant drugs (see ¹ Also see "FDA Requests Antidepressant Labeling Add Suicidality Warning" - Pink Sheet, 29 March, 2004. ).

The House Oversight Subcommittee previously requested the submission of unpublished pediatric study reports from several manufacturers (² [A#00660060029], p. 34).

Based on data from GlaxoSmithKline concerning the use of Paxil in children, FDA requested that several other companies submit data regarding pediatric use of their antidepressants beginning in July and November 2003, a March 24 letter from the Energy & Commerce Committee to outgoing FDA Commissioner McClellan notes.

"Two important factual questions of interest to the committee are the following: (1) What did the FDA know about issues of safety and efficacy of anti-depressants in children after these companies submitted their data form these clinical trials? and (2) When was the FDA provided a complete set of pediatric clinical data from the respective companies?" the letter states.

The letter seeks clarification on what actions were taken within the agency to analyze the pediatric data submitted by manufacturers. "The committee is interested in learning who at FDA undertook this analysis and the results thereof."

The letter suggests concern that FDA did not take appropriately speedy and strong action based on the data, particularly citing the U.K.'s decision to require an extensive relabeling, including the addition of contraindications, for antidepressant (³ Also see "GSK Discussing Paxil Pediatric Suicide Link With FDA; Label Change In U.K." - Pink Sheet, 16 June, 2003., p. 23).

House and Senate investigators are also looking into allegations discussed in a Feb. 1 San Francisco Chronicle article that an analysis prepared by FDA Office of Drug Safety Epidemiologist Andrew Mosholder, MD, was suppressed.

Mosholder was one presenter at a Feb. 2 advisory committee meeting on antidepressants and suicide, (⁴ Also see "Antidepressant Warnings On Pediatric Suicide Need Immediate Strengthening" - Pink Sheet, 9 February, 2004., p. 35).

"In recent weeks, my staff has gathered information about whether" Mosholder "was barred form presenting his findings," a March 24 letter from Grassley to HHS Secretary Thompson says.

"I am concerned that Dr. Mosholder did not present his findings and that his prepared and completed report was and continues to be withheld from the public."

"My committee staff reports to me that Dr. Mosholder was told he would not be allowed to present his report at the" advisory committee meeting, the letter states.

"Further, he was given a so-called script to read," and "was even provided with prepared questions and answers to any questions posed to him at the meeting."

"It is also reported that one or more FDA employees are presently being investigated by the FDA Office of Internal Affairs with regard to an alleged 'information leak' related to Dr. Mosholder's findings."

Grassley is asking FDA to provide investigators with a copy of all drafts of the "script," any Q&A remarks prepared for Mosholder, and a copy of his original report.

The letter also requests a detailed account from FDA of any internal investigation being undertaken regarding the Mosholder report and "each and every OIA investigation, review, evaluation, or audit...initiated by OIA in the last five years where an 'information leak' was the primary target of the review."

The ⁵ House committee letter also asks for an explanation of why the agency asked Columbia University to conduct an outside analysis of the reports submitted by manufacturers.

"The committee is interested in learning who at FDA was knowledgeable about Dr. Mosholder's conclusions, and whether his conclusions were a factor in the decision to involve an outside group...in conducting another data analysis before the FDA decides whether to take further regulatory action on the matter."

House investigators are requesting that FDA provide extensive documentation on the issue, including records relating to communication between the agency and antidepressant manufacturer and records concerning the advisory committee meeting.

In addition, the letter requests copies of individual employees' documents, including those of Mosholder, Neuropharmacologic Drug Products Division Director Russell Katz, MD, and Office of Drug Safety Deputy Director Anne Trontell, MD. The submissions are due April 5.

The letter also requests interviews with 18 agency employees, including Mosholder, Katz, Trontell, and Office of Drug Safety acting Director Paul Seligman, MD.

The Finance Committee said its investigation will also focus on getting information from FDA but not involve manufacturers.

Grassley's letter requests interviews with Mosholder, Trontell, ODS Division of Drug Risk Evaluation Medical Officer Mark Avigan, MD, and Office of Internal Affairs Special Agent Horace Coleman. The Senate letter sets April 12 as a deadline for FDA's response.

FDA's handling of dissenting opinions among reviewers is a frequent subject of attention in the context of product safety issues.

During a recent interview with "The Pink Sheet," acting CDER Director Stephen Galson maintained that the agency has sound procedures for handling internal disputes. "The fact that there may be a loser in a scientific dispute doesn't mean that certain parties are being squelched," he said (⁶ [A#00650470015], p. 19).

FDA Action On Antidepressants Questioned; Congress Widens Investigation

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