When the Senate Finance Committee held hearings in November 2004 to investigate whether the US Food and Drug Administration had ignored safety warnings about the painkiller Vioxx, David Ross was, by his own account, "furious." Not that he had any personal involvement with Vioxx; he was a scientist and midlevel manager overseeing other drug reviews at the agency. But he was furious that anyone would speak badly of the FDA—"my organization," as he called it—in public.
A lot can change in two years. In 2006, Ross left "his organization" in frustration, after higher-ups ignored his repeated warnings of serious liver problems with the antibiotic Ketek. In the past, "people tended to be very invested in the agency and its mission and feel very proud of it," says Ross, now an associate clinical professor at George Washington University. "But there was more and more pressure to just get the review done. There's been extremely public criticism of the agency now. Who wants to work for an agency where everyone is saying, 'these people aren't doing their jobs?'"
Historically, scientists like Ross came to work at the FDA because they felt a sense of civic mission, and they stayed for decades. "They know they're serving the public health. They really are the most dedicated people I've ever known," says Raymond L. Woosley, chief executive of the Critical Path Institute, a Tucson, Az.-based nonprofit that works with the FDA and industry to redesign drug testing and get drugs to market faster. Of course, FDA staff face constant scrutiny from Congress, the press, and the public: They are criticized for either taking too long to approve drugs that patients desperately need, or for rushing to approve drugs that have dangerous side effects. But the sense of public mission has generally outweighed the criticism. Until now.
In the past several years, in-house pressures and public criticism have
eroded morale, according to former agency scientists and other health care experts
who deal regularly with the FDA. In recent surveys conducted by the Union of
In mid-July, about a half-dozen current and former employees launched the Web site Thoreau-fda.com to air complaints of "unwarranted top-down intrusions and retaliations," according to Randall Woods, a former FDA investigator and one of the site's cofounders. Woods says that less than two months after the site went live, 31 people had sent FDA Commissioner Andrew von Eschenbach the site's form protest letter. "Problems used to get resolved behind closed doors," says Ira Loss, who specializes in health care and is an executive vice president of Washington Analysis, a Wall Street research firm. "Now the losing side is starting to talk publicly."
Sources of stress
Woods, Loss, and other observers cite a number of reasons for the deteriorating mood, including congressional micromanagement, industry influence, overwork, and political pressure. "They're getting it from all sides," says Alastair Wood, a professor of medicine and pharmacology at Weill Cornell Medical College in New York who talks regularly with FDA staff and who, along with Woosley, was a contender to become the FDA commissioner in 2002. (Wood is also an editorial board member at The Scientist.) Frank M. Torti, the agency's chief scientist and principal deputy commissioner, says he's not aware of problems related to either congressional overload or management ignoring safety warnings. But he admits that "the FDA has been under some extraordinary stresses."
The agency has over 800 scientists who review drugs or oversee reviews. (There are also 31 advisory committees of outside physicians, professors and other scientists who analyze the most controversial and cutting-edge drug applications.)
Morale takes time to erode, but the biggest plunge probably began with the Vioxx investigations in 2004. Then came arguments over the agency's handling of the diabetes drug Avandia, the antibiotic Ketek, the cholesterol-lowering drugs Vytorin and Zetia, and teenage use of certain antidepressants. In addition, it seemed as though every month there was another alert about contaminated drug or food imports. Turnover among the professional staff rose by about 10% in 2004 and stayed at roughly that level for the next two years.
During that time, at least six government-ordered reports criticized the FDA's ability to oversee drug and food safety or to keep up with scientific advances, including one report from the Institute of Medicine in 2006 that found "a suboptimal work environment?an underestimation of and poor handling of scientific disagreement and differences of opinion." Meanwhile, Congress hauled agency officials in for 18 hearings.
Ross says he spent nearly two years warning agency officials about serious liver problems and fraud in the Ketek clinical trials. After they repeatedly ignored him, he took his complaints to congressional investigators; Commissioner von Eschenbach told him and other whistleblowers to keep their disagreements "inside the locker room." (Three months after Ross left the agency, the FDA rescinded approval of the drug for its two most common indications.) "In my office, the philosophy became, 'let's not ask too many questions' about suspicious trial data," Ross says.
FDA veterinarian Victoria Hampshire says that agency officials ignored her warnings about side effects of a heartworm drug, and even transferred her to another part of the agency in 2004 after pressure from the drug's maker, Wyeth. (Wyeth has publicly admitted to telling the FDA about a Web site Hampshire ran—and is now shut down—that could be a conflict of interest.) "There was a chilling effect on everyone else," says Hampshire, of the colleagues who worked with her on veterinary safety. "People just stopped doing their job, they didn't complete assignments on time. They were very reluctant to take any action that was viewed as rocking the boat."
Recently, FDA scientists' workload has also mushroomed. After dropping steadily for 10 years, the number of new drug applications rose 20% in 2007 (the latest statistics available), and the agency foresees more growth, based on the number of drugs under development. The 2002 Bioterrorism Act requires more rigorous food inspections, while globalization has increased the number of countries exporting food, drugs, and drug ingredients to the United States.
A brighter future?
Some observers, including David Flockhart, chief of the Division of Clinical Pharmacology at the Indiana University School of Medicine, and Woosley of the Critical Path Institute, say conditions have recently improved, in part because reviewers are excited about the new scientific research projects that Torti and Woosley are working on. For instance, the FDA just got $150 million to bring in 50 academics on two-year fellowships to learn about the agency and help redesign some of its processes. Torti also hopes to create sabbaticals where FDA staff can work in university labs. In response to the Institute of Medicine report, the FDA's drug center brought in management consultants to conduct workshops on "people skills," and also created new positions to coordinate safety and clinical review. Torti, who joined the agency in May, says he hasn't been there long enough to see any drop in morale. But in reference to the changes he's implemented, he admits, "Here's what I've done to enhance the culture, which will of necessity enhance morale. You can read into that."
To prevent scientists from being muzzled Woods says the FDA should establish a noninterference principle that "in no case shall a higher-level official attempt to dictate the outcome of a lower-level review." Also, people like Hampshire point out that morale is better in some parts of the FDA, such as oncology.
"Come back and talk to me a year from now," Torti vows. If people are still talking about bad morale, "I'll give you a nickel."