Dr. Rosemary Johann-Liang thought she'd be able to leave her job Friday at the Food and Drug Administration, where she worked for 6½ years, without much fanfare.
"I was trying to leave peacefully," she said in a telephone interview on the eve of her last day as deputy director of the Division of Drug Risk Evaluation, part of the Office of Surveillance and Epidemiology (formerly the Office of Drug Safety). "I had nice parties last week."
But then the popular diabetes drug Avandia began making headlines because a prestigious medical journal aired concerns about its safety. Johann-Liang found herself in the media spotlight.
The reason: She took her staff's advice and recommended in February 2006 that Avandia get a "black box" warning about congestive heart failure. For doing so, FDA staffers told Senate Finance Committee investigators, Johann-Liang was verbally reprimanded and told to talk to her director before making any major recommendations related to drug safety.
FDA spokeswoman Susan Cruzan said Friday that the agency is looking into whether Johann-Liang was reprimanded for her opinion. "We don't know if that's actually the case," Cruzan said.
A pediatrician and expert in infectious diseases, Dr. Johann-Liang joined the agency in December 2000 and rose through the ranks. For four years, she reviewed drug applications as a medical officer and then team leader.
Two years ago she became a deputy division director in the agency’s office of surveillance and epidemiology, the group that examines the safety of already-marketed drugs.
In February 2006, one of her safety reviewers, Lanh Green, went to her with a problem. The agency’s Office of New Drugs had asked Ms. Green to determine whether eye problems that sometimes resulted from taking Avandia and a similar drug, Actos, were a serious issue. But Ms. Green noted that visual deficits were just one part of a drug-induced swelling problem that could lead to weight gain, ankle swelling and, if left untreated, heart failure.
Alerts about some of these problems were scattered throughout the two drugs’ labels. Ms. Green suggested consolidating them and highlighting the heart risks with a boxed warning, the agency’s most severe. After a weeklong review, Dr. Johann-Liang agreed.
“There’s no doubt these problems are caused by these drugs, and there’s no doubt that patients are continuing to suffer bad outcomes,” Dr. Johann-Liang said.
A week later, top officials from the new drug office walked by Dr. Johann-Liang’s office and into the office of her boss, Dr. Mark Avigan, she said. Nearly an hour later, she said, the door opened, the officials left and Dr. Avigan called her in.
“Mark told me that they were upset with our recommendation,” Dr. Johann-Liang recalled. “They decided to act like the review never happened.”
Dr. Avigan took over the supervision of the safety review of Avandia and Actos and told Dr. Johann-Liang that she could no longer approve strong safety recommendations without his say-so, she said. Over the next year, she was increasingly excluded from crucial safety reviews and meetings, which contributed to her decision to leave the agency on Friday, she said.
In an interview, Dr. Avigan said that he did not intend to punish Dr. Johann-Liang.
“My view was simply that when there were conversations going on about important safety issues that were likely to garner a lot of attention, that I needed to be in the loop,” he said.
On Wednesday, the F.D.A. commissioner, Andrew C. von Eschenbach, announced that the agency had asked for boxed warnings on Avandia and Actos, more than a year after Dr. Johann-Liang’s recommendation.
Last week, Commissioner Andrew von Eschenbach, in written remarks for a House panel hearing, said the FDA is now asking for a black-box warning about congestive heart failure on the labels of Avandia and its cousin, Actos.
"It is our goal to not just make the right decision about a drug like Avandia, but, more important, to always do the right thing by patients," von Eschenbach told the House Committee on Oversight and Government Reform.
Longtime FDA critic Sen. Chuck Grassley, R-Iowa, ranking member of the Senate Finance Committee, is asking von Eschenbach to make sure no agency scientist is ever reprimanded for raising safety questions. "Those FDA employees dedicated to post-marketing surveillance … should be able to express their opinions in writing and independently without fear of retaliation, reprimand or reprisal," Grassley wrote in a letter dated June 4.
Von Eschenbach told the House panel that the FDA "is committed to appropriate scientific dialogue and discussion."
But, Johann-Liang says, "I really advocate for drug safety, and a lot of times the agency doesn't want to hear that there are problems. I think, in general, there is a culture of 'The drug is always innocent.' "
Part of the problem, she says, is that the Office of Surveillance and Epidemiology can only recommend how to manage risks linked to drugs. The Office of New Drugs, the same office that approves drugs, is the one that decides whether to take action.
With Avandia, Johann-Liang says, "when we recommended this black box, they said they wanted to look at it further." But the Office of New Drugs never got around to it, she says, because they were pressed to meet deadlines for acting on new drug applications.
In her two years in the Office of Surveillance and Epidemiology, Johann-Liang says, "I worked really hard to institute systematic safety meetings" with the Office of New Drugs. She says Congress needs to increase staffing in the surveillance and epidemiology office and give it the authority "to take action in a timely manner."
Johann-Liang speaks of a convoluted system in which the FDA requires a higher level of proof of risk than of effectiveness.
The FDA approves diabetes drugs such as Avandia if clinical trials show they meet the "surrogate endpoint," or goal, of lowering blood sugar, she says, but then doesn't require makers to do follow-up studies of whether patients actually feel better and live longer.
On the other hand, Johann-Liang says, "if there is a safety issue with the drug, it must be confirmed. I just don't think that that's appropriate." As a result, "we're not doing things in a timely way."
Meanwhile, Johann-Liang says, "people are continuing to be hurt."
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