Healthy Skepticism Library item: 447

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Publication type: news

Senator Says FDA Put Pressure On Staffer Over Antidepressants
The Wall Street Journal 2004 Jun 17

Full text:

Food and Drug Administration officials tried to get an agency staffer to alter his recommendations about how to deal with the risks some antidepressant drugs may pose to young people, according to a letter to the agency from Senate Finance Committee Chairman Charles Grassley.

The letter, sent yesterday, may provide the fullest account so far of the experience of Andrew Mosholder, an FDA epidemiologist whose finding of a tie between antidepressants and suicidal tendencies in young patients is the center of two congressional investigations into why his conclusion wasn’t publicly revealed at an FDA advisory committee meeting in February. Dr.
Mosholder repeatedly has declined to comment publicly about his analysis of clinical trials of the antidepressants; he was interviewed for about 10 hours by finance-committee investigators. He declined to comment about the new letter.

An FDA spokesman, who said he hadn’t yet seen the letter, said the agency “has acted and will act in the future in the best interests of the public health.” The agency, which in March issued a high-profile warning that adults and young people taking antidepressants should be watched closely for signs of depression and suicidal tendencies, made its “decision based strictly on the best science at hand,” he said.

The letter from Sen. Grassley, an Iowa Republican, is addressed to the heads of the FDA and its parent agency, the Department of Health and Human Services. It says that interviews conducted as part of his staff’s investigation, including with drug-safety employees, have provided “a trove of information to consider.” Among the findings, the letter says, was that Dr. Mosholder was pushed to say things he didn’t agree with. The FDA staffer was “advised at one point that if he were willing to modify his recommendations, perhaps he could present his analysis” to the advisory committee, the letter says. The epidemiologist “refused to accept new, alternative language, stating that the alternative language misconstrued his recommendations,” the letter says.

According to a later report by Dr. Mosholder, he recommended that the FDA take steps to discourage pediatric use of the drugs, except in the limited cases mentioned on the labels of some of the drugs. Only one, Prozac, is labeled to treat depression in young people.

The letter also raises broader questions about the FDA’s handling of findings by its drug-safety office. The drug-safety office, which is part of the Center for Drug Evaluation and Research, focuses broadly on safety issues, including reports to the agency about serious side effects and other problems possibly caused by a drug. Much of the therapeutic expertise about specific medicines is in another part of the center, the office of new drugs, which reviews new-drug applications. These drug-review divisions tend to spearhead the FDA’s oversight of specific drugs even after the approval process is complete.

The letter says the office of new drugs and the drug-safety office “exist in a relationship that is best described as ‘separate but unequal,’ “ with the safety office “subservient.” Interviews “suggest” that when the new-drug office consulted with drug-safety staffers, their recommendations were “neither encouraged nor wanted,” the letter says.

The FDA spokesman said that was “an untrue portrayal of a collegial relationship that works very well on behalf of the public health.”

In the case of Dr. Mosholder, who worked for the drug-safety office, high-ranking officials in the drug center and the review division that oversaw psychiatric drugs felt his findings were premature and based on limited data, and risked causing an unjustified overreaction. They decided not to reveal the findings to the advisory committee. The FDA commissioned a new examination of the clinical-trial data analyzed by Dr. Mosholder, and the committee will re-examine the issue this summer.

Sen. Grassley’s letter also says Dr. Mosholder was asked to present reporting rates of suicidal thoughts and behavior by young people taking antidepressants, using figures based on reports made to the FDA’s adverse-event reporting system measured against estimated prescription numbers for that drug.

The letter says such rates, which would likely be low partly because the number of reports to the system typically represents an incomplete picture, would be “deceptively false and misleading and would provide a ‘false sense of security’ to the public.” The letter asks, “in how many other instances has the [office of new drugs] manipulated its advisory committee meetings to withhold from the public and misrepresent safety information about marketed drugs of critical importance to patient safety?”

The FDA spokesman said agency advisory-committee meetings are “open and transparent,” and they “deal with very complicated and nuanced scientific issues, and to characterize any meeting, including this one, differently, is untrue and unfair.”

According to a transcript of the committee meeting, Dr. Mosholder did present data from the adverse-event reporting system, but didn’t give those numbers in terms of rates comparing reports to prescriptions. In the same meeting, a different FDA official, from the pediatric-drugs division, presented adverse-event data for two drugs, but noted that “we could not really estimate true incidence rate of events or exposure risk for many of these medications that we have reports for.”

Russell Katz, the director of the division that oversees psychiatric drugs, told the committee that adverse-event data couldn’t “reasonably inform our judgment” about a tie between the drugs and suicide, so the FDA must rely on data from controlled clinical trials — the type of information Dr.
Mosholder had analyzed.

Dr. Mosholder didn’t present that data, which instead were offered by a different FDA official, who raised questions about their completeness and meaning.