Grassley Calls for Safety Review /Unsafe Drugs Marketed to Consumers / FDA Lacks Leadership

Grassley Calls for Safety Review /Unsafe Drugs Marketed to Consumers / FDA Lacks Leadership

Sun, 19 Dec 2004

“We expect the FDA to not put a drug on the market that’s not safe. And you can’t compromise safety, regardless of how much pressure there is to get more drugs on the market.”

Senator Chuck Grassley who has taken the lead in investigating FDA’s performance is calling for “a comprehensive review of drug safety and of how federal government agencies oversee drug research and approve, license and regulate drugs” by an independent commission a la 9/11 commission. The following statement is indisputable: “At this point, no one can say with confidence whether the worst drug safety problems are behind us or ahead of us.”

A front page article in The New York Times focuses on the pernicious role direct to consumer marketing of drugs has had on exposing millions of people to hazardous drugs as if they wre “lollypops.” The rapid rise, “and now shaky future of this class [COX2 inhibotors] of drugs, some researchers say, is emblematic of the way drug companies’ efforts to spur the use of costly new medicines can distort the medical realities of safey and effectiveness.”

The FDA took only six months to review the applications for both Vioxx and Celebrex – “an accelerated process used only for drugs deemed medically important.” But, the Times points out, the FDA approved the drugs even though “in both cases, the FDA decided that the drugs had not sufficiently demonstrated that they reduced the rate of serious gastrointestinal prombelms compared with existing painkillers like aspirin and ibuprofen.”

Given its failure to satisfy scientific standards of evidence that Celebrex protects against gastrointestinal benefits, given that concerns about its cardiac damaging properties have not been resolved, shouldn’t the public be protected from an irresponsible massive direct to consumer promotional campaign that misinforms physicians and the public about the drug’s safety?

The Times notes that Celebrex has been one of the most heavily promoted prescription drugs in advertising aimed at consumers: Pfizer spent $7.2 million in advertising during the first nine months of this year, generating $3.3 billion in sales.

This collision between marketing hype and unresolved safety and efficacy concerns, led The Times reporters to note that the painkiller drug debacle is “perhaps the clearest instance yet of how the confluence of medicine and marketing can turn hope into hype.”

Merck pulled Vioxx when the death toll became public knowledge, Pfizer has indicated it has no plans to withdraw Celebrex.

Clearly, the public needs a drug safety agency that is accountable to the public.

The Washington Post focuses on the administration’s failure to fill FDA’s leadership slots, thereby reducing the agency’s status and ability to perform authoritatively when pressured by the pharmaceutical industry and their political allies in Congress.

Among the “acting” heads of the agency whose conduct has been the focus of heated controversy are: the agency’s Acting Commissioner, Dr. Lester Crawford, a veterenarian; Dr. Steven Galson, acting director of the Center for Drug Evaluation and Research; and Dr. Paul Seligman, acting director of the Office of Drug Safety.

NY Newsday Columnist, Saul Friedman, writes about a drug safety heroine: “When I last interviewed Dr. Frances O. Kelsey 10 years ago, she was 80, the director of the Office of Scientific Investigations for the Food and Drug Administration, and an authentic American hero.”

Indeed, Dr. Kelsey is the heroine who in 1961, fought off criticism within the FDA and pressure from a large American drug company and saved Americans from thalidomide.

In 1995, she had a warning for those who were about to weaken the FDA: “Let’s not go backwards. We’ve seen enough tragedy.”

However, a group of Republicans led by Speaker of the House Newt Gingrich embarked on a campaign to strip the FDA of some of its powers. Gingrich had called the FDA the country’s “number one job killer” and criticized its aggressive director, David Kessler (a Republican) as a “bully and a thug” for holding up approval of a number of potentially beneficial and profitable drugs. It would seem that though Gingrich and his posse are gone, they have succeeded in rendering the FDA ineffective in preventing tragic casualties of hazardous drugs.

During her 60 year tenure at the FDA, Dr. Kelsey helped remove or keep medicines that were worthless or, worse, that maimed and killed, off the shelves. Today, Dr. David Graham is following in her footsteps.

Contact: Vera Hassner Sharav
212-595-8974

Excerpts:

1. http://www.channelnewsasia.com/stories/afp_world_business/view/122988/1/.html
Lawmaker calls for FDA review amid drug safety troubles
18 December 2004 2254 hrs (SST)

WASHINGTON : The latest revelation that a blockbuster drug may not be safe for patients is putting the US Food and Drug Administration (FDA) in the hot seat.

With alarm bells ringing over several drugs in recent months, a leading senator who has accused the FDA of being too close to the pharmaceutical industry has called for a panel of experts to evaluate its performance.

“It seems the time has come for a comprehensive review of drug safety and of how federal government agencies oversee drug research and approve, license and regulate drugs,” said Senator Chuck Grassley, chair of the Senate finance committee, which oversees the FDA.

“Today, Pfizer released information about an increased risk of heart attack for its drug Celebrex, and Eli Lilly issued a new warning about liver problems with the drug Strattera. The last year revealed serious problems involving children and anti-depressants, painkillers like Vioxx, Bextra and Celebrex, the flu vaccine, and the AIDS drug nevirapine,” Grassley said Friday.

“At this point, no one can say with confidence whether the worst drug safety problems are behind us or ahead of us.”

US drug giant Pfizer said Friday that a trial had found a sharp rise in heart attacks for patients using Celebrex, its arthritis and pain medicine, but that it would not immediately withdraw the treatment.

2. The New York Times
December 19, 2004 A-1
Medicine Fueled by Marketing Intensified Trouble for Pain Pills
By BARRY MEIER

This article was reported by Barry Meier, Gina Kolata and Andrew Pollack and written by Mr. Meier.

In the mid-1990’s, the medical community reached an inescapable conclusion. Researchers at the Stanford University Medical School and elsewhere who had long been monitoring arthritis and rheumatism patient records had found that thousands of patients, perhaps as many as 16,500, were dying annually from bleeding ulcers and other problems caused by widely used painkillers like ibuprofen.

Within a few years, a new class of pain relievers, the so-called COX-2 inhibitors, burst onto the market with the promise they might reduce that toll. Sales of the best known products, Celebrex and Vioxx, quickly skyrocketed – thanks in part to changes in federal rules in 1997 that made it much easier for drug makers to advertise medications directly to consumers on television, in newspapers and in magazines.

Now, though, the flight path of these blockbuster drugs has been aborted. On Friday, Pfizer the maker of Celebrex, which is expected to end up with sales of $3.3 billion this year, disclosed that a patient trial by the National Cancer Institute had found significant risks of heart attacks. Vioxx, which was made by Merck and had sales of $2.5 billion last year, was pulled from the market in late September after similar findings.

In some ways, the story of the COX-2 drugs, a class that includes another troubled Pfizer medication, Bextra, is part of an age-old search for safer pain treatments. And some doctors say that they have helped. But it is also perhaps the clearest instance yet of how the confluence of medicine and marketing can turn hope into hype – and how difficult it is for the Food and Drug Administration to monitor the safety of drugs after they have been approved for the market. Celebrex and Vioxx, after fast-track approval from the F.D.A., hit the nation’s pharmacies as revolutionary drugs that could not only treat arthritis patients’ pain, but potentially save their lives.

But having spent hundreds of millions of dollars to develop their drugs, the makers of Celebrex and Vioxx, cheered on by Wall Street, had every motivation to expand their markets beyond the older people most at risk of ulcers to encourage the drugs’ use by millions more people of all ages. That was so even as, at least in the case of Vioxx, there was evidence as early as 2000 that a COX-2 drug could cause heart problems.

“You have to realize that these medications, they are not candies, they are not placebos,” said Dr. Gurkirpal Singh, a Stanford professor who has worked on the arthritis database project. A big problem with the COX-2 drugs, he said, has been the tendency of doctors to use them indiscriminately. “Like all medications, you have to identify which people will benefit the most, and which won’t.”

Since the drugs’ release, the companies have spent hundreds of millions of dollars on television, newspaper and magazine advertising for them and, by some estimates, at least as much on marketing and promoting the drugs to doctors. As a result, many medical experts now say that Celebrex and Vioxx, selling for $2 or $3 a pill, have been too widely prescribed to patients who could safely obtain the same pain benefits from over-the-counter drugs costing pennies apiece.

Potentially wasted money, though, is not the main point about the sales push, now that there is clinical evidence that all the COX-2 drugs on the market can, in some circumstances, increase a user’s likelihood of strokes or heart attacks.

On Friday, Pfizer characterized the cancer trial findings as an anomaly requiring further study and said it was not ready to withdraw the drug. But the news of the trial results was enough to send drug stocks plummeting and to cast grave doubts on the future of the entire COX-2 drug category. Only a few weeks ago, the F.D.A. ordered Pfizer to put a label warning on Bextra, noting that it could pose cardiac risks to patients recovering from heart surgery.

Pfizer and Merck have repeatedly said that their marketing has been accurate and responsible. “We market all of our medicines consistent with regulation,” said a spokeswoman for Pfizer. “Doctors and patients are in the best position to say which drugs are most appropriate for them.”

But the rapid rise and now shaky future of this class of drugs, some researchers say, is emblematic of the way drug companies’ efforts to spur the use of costly new medicines can distort the medical realities of safety and effectiveness.

Too often, marketing can drown out medical science, said Dr. James F. Fries, the director for the Stanford arthritis database project, which receives funding from the National Institutes of Health. “Here, it was not a fair battle.”

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3. http://www.washingtonpost.com/wp-dyn/articles/A10775-2004Dec18.html

FDA’s Reliance On Unconfirmed Chiefs Is Faulted
By Marc Kaufman
Washington Post Staff Writer
Sunday, December 19, 2004; Page A01

The Food and Drug Administration, which regulates almost one-quarter of the U.S. economy, has been without a permanent chief for almost two-thirds of the time that President Bush has been in office. The agency also has had a high number of temporary appointees administering its centers, offices and divisions, including the key positions running the offices that evaluate new drugs and monitor the safety record of approved medications.

To many agency observers, the absence of settled leadership has become a significant problem. The agency, they say, is less able to respond quickly and effectively to emerging problems and has been weakened in the face of political, industry and sometimes consumer pressures to stray from the agency’s science-based public health mandate.

In recent months, the FDA has been sharply criticized for its laissez-faire stance in the withdrawal of the arthritis drug Vioxx, its oversight of the company that was to provide half of the nation’s flu vaccine this winter, and its handling of the sensitive issue of when and whether antidepressants should be prescribed for children. Friday’s announcement that another popular arthritis drug, Celebrex, may also pose serious risks has raised the stakes further.

The White House says the situation at the agency is no reason for concern, and FDA officials said their work has not been hampered by the lack of permanent leaders. Deputy Commissioner Janet Woodcock, who herself has served in an acting capacity for more than a year, said, “Our programs are set up to carry on. . . . Transitions for us are pretty frequent and inevitable.”

But others, including Sen. Charles E. Grassley (R-Iowa), who has held hearings into recent controversies at the FDA, are particularly concerned about the prevalence of “acting” leadership.

“Recent events make it obvious there’s no time to waste in securing stronger leadership at the Food and Drug Administration,” he said. “Permanent people need to be appointed to these jobs posthaste. . . . Leadership is hampered by the term ‘acting.’ ”

While the FDA’s top job has been filled by temporary appointments for months at a time in previous administrations, the duration of the situation under Bush is unprecedented in modern times. Of the 48 months in Bush’s first term, then-Commissioner Mark B. McClellan’s 17-month tenure was the only period during which the position was permanently filled.

White House spokesman Trent Duffy acknowledged that the FDA had been without permanent leadership for a significant portion of the past four years. But Duffy said Bush believes that acting commissioner Lester M. Crawford is doing an “excellent” job and that he has all the “authorities and responsibilities” of a permanent commissioner. Duffy said the White House prefers having a permanent leader at the FDA, but there is no statutory or policy reason to rush the process.

Some speculate, however, that there may have been political considerations. Edward M. Kennedy (Mass.), ranking Democrat on the Senate health committee, has said he would strongly oppose any nominee from the pharmaceutical industry; that stand may have made the administration less interested in filling the position before the election.

Paul C. Light, a New York University professor who works on the Brookings Institution’s presidential appointments initiative, said the absence of permanent FDA leadership may be in part intentional. “There are some in the administration and in the industry who would rather have vacancies at FDA than an aggressive regulator,” Light said. “The theory is that it is better to have no one there than someone who favors a proactive stance that might slow down the industry or raise hard questions about profitable drugs.”

In four years, the Bush administration has sent only one name to the Senate for confirmation as food and drug commissioner — McClellan’s in October 2002. Early this year, he was shifted to oversee the Medicare program as it implements a new prescription drug benefit.

Since then, Crawford, who was trained as a veterinarian and pharmacologist, has served as acting commissioner, taking on for the second time a role he and another FDA veteran filled for more than a year and a half before McClellan’s confirmation. (Bush fired Clinton appointee Jane Henney immediately after taking office.) Naming permanent FDA commissioners became more complicated in 1988, when Congress required Senate confirmation as a way to make the job more powerful.

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NY Newsday
GRAY MATTERS FDA’S sad slide: warnings went unheeded
Saul Friedman
December 18, 2004

When I last interviewed Dr. Frances O. Kelsey 10 years ago, she was 80, the director of the Office of Scientific Investigations for the Food and Drug Administration, and an authentic American hero. She had a warning for those who were about to weaken the FDA: “Let’s not go backwards. We’ve seen enough tragedy.”

What has happened since to the once-proud, independent FDA is tragedy enough for the millions who depend on safe, effective and reasonably priced medicines. But its recent record of anti-consumer malfeasance – its campaign to prevent the purchase of cheaper and safe Canadian drugs, the shortage of flu vaccine and the failure to act on the deadly dangers of Vioxx – has posed a particular risk to older Americans.

Kelsey knew what she was talking about in 1995, for during more than 60 years as a physician and pharmacologist, she helped remove or keep from druggists’ shelves medicines that were worthless or, worse, that maimed and killed.

In 1961, Kelsey fought off criticism within the FDA and pressure from a large American drug company. She refused to grant the company a U.S. license to market a sleeping pill widely used by women in Europe to relieve morning sickness during the early stages of pregnancy. Kelsey had read about disturbing reports of the pill’s side effects on fetuses and stopped the drug from coming to the U.S. market.

The drug was thalidomide. Women who took the pill in the early stages of pregnancy gave birth to more than 5,000 deformed babies, most in Germany and Britain. A few were born in the United States to mothers who had gotten the drug from abroad. But Kelsey and the FDA saved thousands of American families from grief. President John F. Kennedy gave her a medal and signed legislation strengthening the FDA.

Kelsey, now retired, personified what the American public then thought of the FDA.

It was the gold standard of trustworthiness, both for the patient and the prescribing physician. Even drug manufacturers impatient with the long process coveted FDA approval, for it meant their drugs were safest; American drugs were the safest in the world.

Lately, however, the FDA’s credibility has fallen on hard times. According to a recent CNN-USA Today-Gallup Poll, nearly 40 percent of 1,015 adult respondents said their confidence in the FDA has slipped during the past year. The reason: the FDA failed to anticipate the need for flu vaccine, and the United States was forced to get the vaccine from abroad. At the same time that the agency OK’d emergency importation of flu vaccine from Canada and Germany, saying it was sure the vaccine was safe, the FDA joined U.S. drug companies in warning against the purchase of Canadian drugs, which were made in the United States.

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