Lawmakers Go After Thugs at FDA Over Avandia

Evelyn Pringle June 2007

In one of the latest developments in the Avandia diabetes drug saga, on June 7, 2007, a bipartisan group of powerful lawmakers sent a letter to FDA asking Commissioner Andrew von Eschenbach asking for an explanation of the agency’s policy on conflicts of interest regarding hiring employees directly from drug companies regulated by the FDA.

At the center of the controversy, is the conduct of FDA spokesman, Douglas Arbesfeld, who has worked for several drug companies, in sending emails to journalists in what the lawmakers refer to as "smear campaigns" against cardiologist, Dr Steven Nissen, Chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, who recently waved the red flag about the risks associated with GlaxoSmithKline's Avandia.

Dr Nissen and Kathy Wolski, MPH, a statistician, evaluated the 42 studies involving nearly 28,000 patients and compared the 15,560 patients who were using Avandia to the patients who were not using the drug and found there were 86 myocardial infarctions in the Avandia group and 72 in the control group and there were 39 deaths from cardiovascular causes in Avandia patients compared to 22 in the control group.

"Cardiovascular disease is far and away the leading cause of death in diabetes," Dr Nissen said in the May 23, 2007 Wall Street Journal. "If you find a diabetes drug increases the risk of heart attacks," he warned, "the consequences are so grave that it warrants urgent action."

The June 7, 2007 letter to the FDA is signed by Senators Chuck Grassley, Max Baucus and Sherrod Brown, as well as Representatives John Dingell and Bart Stupak and they want a response to their inquiry by June 20, 2007.

At a June 6, 2007, hearing before the US House Committee on Oversight and Government Reform, Commissioner von Eschenbach testified that Arbesfeld had been formally reprimanded with a letter in his employment file but apparently the lawmakers believe his conduct warrants more than a slap on the wrist.

"We are concerned that Mr. Arbesfeld sent this message using his Government e-mail," the lawmaker's letter states, "which carried his FDA signature line and work-related contact information at the bottom."

"In several news articles on other matters," it says, "Mr. Arbesfeld is named as the spokesman for FDA."

"Given that he has acted in this capacity in the past," the lawmakers wrote, "this e-mail may have given journalists the impression that the United States Government actively encourages smear campaigns against independent scientists."

"The Committee finds it even more troubling that Mr. Arbesfeld may be using his position
with FDA to settle old scores with Dr. Nissen," the letters states.

"Certainly, Mr. Arbesfeld is familiar with Dr. Nissen, since the two have been on opposing sides of drug safety in the past," the lawmakers wrote.

The letter cites an April 26, 2005, New York Times article that reported quotes from Dr Nissen that were critical of Natrecor, a drug made by Johnson & Johnson

The Times noted that Dr Nissen cast the only vote against Natrecor when a FDA advisory panel recommended its approval in 2001, and the person defending Natrecor in the article was Mr Arbesfeld, as a spokesman for J&J at the time.

The lawmakers called Mr Aresfeld's emails to journalists, "a completely unacceptable use of Government time and equipment."

"In the Agency's response to this incident," the letter said, "it stated that Mr. Arbesfeld is a consultant and does not speak on behalf of FDA."

"Accordingly," the lawmakers pointed out, "this response may leave the media wondering how they should interpret future e-mails from FDA spokesmen and Mr. Arbesfeld, in particular."

In a June 7, 2007 press release announcing the letter, Senator Max Baucus stated, "I have some serious questions about Mr. Arbesfeld’s use of government resources, but I am even more concerned about whether his drug company connections led him, in any way, to seek to unjustly discredit Dr. Nissen."

"The FDA’s ultimate duty is to ensure the safety of the products it regulates," he added, "which includes sharing credible, potentially life-saving information from any trustworthy source.”

In summary, the lawmakers want answers the following: (1) What is the justification for use of taxpayer dollars for a communications consultant? (2) What is FDA's policy regarding the hiring employees who recently worked for the companies directly regulated by the Agency? (3) How does FDA ensure that consultants do not have relationships with companies in direct conflict with his role as FDA spokesperson? (4) Is Arbesfeld currently receiving, or has he received in the last year, income or other remuneration from companies directly regulated by FDA? (5) Does FDA have a policy regarding employees using their official e-mail accounts to express their personal opinions, which may not be FDA positions, to members of the press? (6) If there is such a policy, what is that policy?

Senator Grassley and the Senate Finance Committee is also investigating a matter involving the mistreatment by top FDA officials of Dr Rosemary Johann-Liang, the Deputy Director of the FDA's Division of Drug Risk Evaluation (DDRE), who was rebuked in March 2006, after she approved a recommendation by an FDA safety reviewer that the labels of both diabetes drugs, Avandia and Actos, should carry additional warnings.

On June 4, 2007, the Committee sent the FDA Commissioner a letter demanding a response to questions related to this matter by June 20, 2007.

In the letter, Senator Grassley cited an internal FDA memorandum, obtained by his Committee, dated February 22, 2006 that was prepared he said, by "a very seasoned safety evaluator" in the DDRE, that made several recommendations including that Glaxo should include macular edema, a condition that involves swelling of the retina and can cause blindness, as a "serious adverse event" on Avandia's label.

The memo also recommended that congestive heart failure be highlighted in a box warning. CHF is a condition where fluid builds up in the lungs causing severe shortness of breath and potential death and requires immediate attention.

To support the recommendation for a black box warning, the February 22, 2006 memo specifically quoted the FDA regulation that states in part that "…special problems, particularly those that may lead to death or serious injury, may be required by the Food and Drug Administration to be placed in a prominently displayed box…."

Senator Grassley called the fact that the FDA had not yet acted on the recommendations troubling. "But another allegation," he wrote, "has come to the Committee's attention that is simply unconscionable."

It has been alleged by multiple sources, he said, both in and out of the FDA, that the Deputy Director was reprimanded verbally for signing off on the memorandum.

"I also was informed," he wrote, "that the DDRE Deputy Director was advised that she would no longer be able to "sign off" on any matters related to Avandia in the future."

He also noted that she was told that, "in the future, she could no longer sign off on any recommendations for major regulatory actions, like box warnings, without first checking with the DDRE Director."

"I also sincerely hope that this is not standard practice within the FDA," Senator Grassley wrote. "Those FDA employees dedicated to post-marketing surveillance at the FDA should be able to express their opinions in writing and independently without fear of retaliation, reprimand, or reprisal," he said.

Post-marketing surveillance is critical to the health of this nation, he advised.