FDA turmoil
From Newark Star-Ledger
FDA criticized for promoting tenacious doc
He slowed blistering approval rate
01/16/00
By Edward R. Silverman
STAFF WRITER
Call it the end-of-the-millennium massacre.
A key division within the Food and Drug Administration is in turmoil over the recent transfer of Solomon Sobel, a long-standing and widely respected supervisor, who sometimes tangled with his superiors over drugs he thought shouldn't be approved.
Normally, personnel shuffles at a bureaucracy as large as the FDA draw little, if any, notice beyond the agency's nondescript headquarters in Rockville, Md., where hundreds of doctors work in virtual anonymity, reviewing reams of paperwork filed by drug makers.
But this instance is troubling some FDA employees, agency critics and doctors who serve as FDA advisers. As they see it, FDA supervisors are anxious to approve an increasing number of new drugs and want to remove a potential obstacle to that goal.
Sobel's admirers say he can be a particularly tenacious opponent. Since 1979, he has headed the agency's endocrine and metabolic division, an important unit that's responsible for approving drugs used to treat diabetes, obesity, osteoporosis and thyroid illnesses.
One notorious episode involving Sobel occurred four years ago, when he clashed with the FDA hierarchy over the Redux diet pill. Eventually, he offered qualified support for the drug's 1996 approval. It was withdrawn 18 months later after serious side-effects were reported.
"Sol Sobel is a central and competent figure," said Jules Hirsch, a professor emeritus at Rockefeller University and member of the FDA's endocrine and metabolic advisory committee, a group of doctors and medical specialists who meet voluntarily to review new drugs and recommend whether these should be approved by the agency.
"I'm really worried about removing someone who's been so effective. And I'm worried about a lot of the drugs being pushed along and I want to make sure they get the correct review," he continued. "In my area, which includes obesity, there have been problems. I wasn't on the committee when those occurred. But I wouldn't like to see that kind of thing happen again. I'm urging other members of my committee to write the FDA."
Last week, two FDA medical reviewers, both of whom worked for Sobel, took the unusual step of publicly criticizing the agency for moving their boss. Agency sources also suggest Sobel's transfer was precipitated by a fight he had last year with FDA brass over the approval of a new diabetes drug. In the end, agency managers made an uncommon decision by overruling FDA staff and outside advisers, who objected to the approval of the drug.
Officially, Sobel has been promoted to deputy director of the FDA's Office of Review Management, which oversees the endocrine and metabolic division, as well as four other divisions that review drug applications filed by drug makers. But his actual role is unclear, since the spot has been vacant for an extended period and its duties aren't formally defined.
In a Dec. 13 e-mail message to FDA personnel announcing the transfer, Murray "Mac" Lumpkin, who is the director of the Office of Review Management, wrote that Sobel will implement "policy mandates and develop new policy initiatives that impact on the drug development, review and post-marketing oversight processes."
Sobel, 65, declined to comment. Janet Woodcock, who heads the agency's Center for Drug Evaluation and Research, which is responsible for reviewing all drugs, declined to comment about Sobel, specifically, calling his job change a "personnel" matter.
"We expect scientific competency, good management and leadership from our division directors," she wrote in an e-mail. "There is no expectation that they agree on everything. Disagreement on sicentific matters is to be expected within a science-based process -- if everything was easy and evident, you wouldn't need experts to make the tough decisions."
Separately, an FDA spokeswoman denied Sobel was promoted in order to eliminate internal debate over drug reviews or that his promotion was tied to the agency's desire to increase the rate at which new drugs are approved.
FDA critics, however, maintain Sobel was shifted for that very reason. They note that the agency has been under continual pressure to speed drug reviews and approve more drugs, a controversial development that began several years ago and resulted in legislation that overhauled the FDA's apparatus for approving drugs.
The legislation spurred a growing number of approvals. But at the same time, there has been an accompanying increase in the number of newly approved drugs that have been recalled. Among them has been Redux; the Posicor heart drug; the Duract painkiller; and, just three months ago, the Rotashield infant diarrhea vaccine.
Meanwhile, serious health warnings have been issued about several other new medicines that have been approved recently, including Viagra, the impotence pill, and the Celebrex painkiller. Physicians also were told to restrict usage of the Rezulin diabetes treatment and the Trovan antibiotic.
"They don't think they make mistakes," said Sidney Wolfe, director of Public Citizen Health Research Group, a nonprofit consumer advocacy group that has repeatedly criticized the FDA drug-approval process and two years ago released a survey of agency medical reviewers who claimed agency standards for drug approvals had dropped since 1995.
"Sobel is very respected and revered. He was on the right side on a number of decisions, but just got beat up. But there's a lot of stuff in the pipeline in that division and they want to mow the resistance away," Wolfe said. "The FDA seems to be lowering even further the resistance by dedicated doctors against drugs that shouldn't be approved."
A recent episode in which Sobel argued against approving a drug may have been the last straw, according to sources. This occurred last spring during FDA staff discussions about a diabetes drug called Ergoset, which is being developed by a small New England company called Ergo Science Corp.
An FDA advisory committee in May 1998 voted against recommending agency approval. And later that year, the FDA wrote Ergo Science that the drug wouldn't be approved. But the company appealed and, despite an argument involving FDA managers, medical reviewers and advisory committee members, the agency reversed course last fall.
Such a step is unusual. Although it doesn't do it often, the agency can override its own advisory committees. Subsequently, Ergo Science was told its drug may be approved, conditioned on running further clinical trials. An Ergo Science spokeswoman said the company is evaluating whether it's feasible to conduct such studies.
Sources noted the reversal occurred shortly after Lumpkin transferred a pulmonologist, John Jenkins, to oversee the agency office that's responsible for the endocrine and metabolic division. In fact, Jenkins is now the acting head of that division as well, which means medical reviewers will lack an internal appeal process when disputing decisions, sources say.
Ergoset "hardly worked, and no one's offered a satisfactory explanation about the change," said a medical reviewer, who asked not to be named. "Now, we're not going to be able to make independent assessments of drugs and have them sustained. The basic driving force here is (FDA managers) are unhappy with us because we like to think for ourselves."
Separately, a veteran medical reviewer and physician in the same division, Robert Misbin, last week wrote to an industry newsletter that a recent story about Sobel's transfer unfairly suggested Sobel was to blame for the dissatisfaction among medical reviewers that was reported in the Public Citizen survey in 1998.
"Sol Sobel has dedicated his professional life to serving the public and has set an example for the rest of us to follow," Misbin wrote. "He had the ability to get the best out of his staff by creating an environment of mutual respect. The past productivity of the endocrine and metabolic division is a testament to his leadership."
Misbin declined to comment about the dust-up over Sobel. However, he's widely known in political circles for an unprecedented letter he wrote to The Washington Post. In the 1998 letter, he suggested the pressure on the FDA to review drugs was hurting the agency's credibility and its ability to maintain control over clinical trials.
Another long-time medical reviewer who worked for Sobel agreed the agency is moving too quickly to approve some drugs. Leo Lutwak, a physician in the endocrine and metabolic division who has similarly fought with FDA brass over some drugs, also charged the agency with preventing him from clarifying his position on the 1996 Redux approval.
"We have a great many drugs coming in (for review) and not enough time to review the applications and see the problems," said Lutwak. "These are allowed to move ahead without being able to evaluate the protocols properly. Because of all the pressure, we don't have the time to examine things."
Lutwak is also bitter that American Home Products Corp., which sold Redux and Pondimin, a related diet drug that was one-half of the fen-phen weight-loss combination, is mischaracterizing the meaning of a 1997 memo he wrote about the ability to foresee the problems with Redux. He's angrier still that the FDA won't let him testify in court.
Lutwak was against approving Redux over concerns it may cause brain damage, not the heart and lung damage that led to its withdrawal. But FDA unwillingness to let him testify -- a policy even former FDA commissioner David Kessler was recently quoted as saying shouldn't be upheld in this case -- has Lutwak wondering if FDA brass is trying to blame Sobel and other long-standing division members for the recent problem drugs.
"For some reason, I think blame is being put on reviewers retrospectively, but the problems were not divisional problems," he said. "The FDA gets a fee from each company to review a drug and, in return, the review has to be done in a fixed period. Statistics are kept on approvals, and the more approvals, the better the stats look."
¸ 1999 The Star-Ledger. Used with permission. |
