What Ails the FDA? Payola – Marcia Angell Boston Globe

Thu, 10 Mar 2005

The Boston Globe reports that the FDA is scrambling to put out one drug crisis after another, doing a poor job in both its areas of responsibility: medicine and food.

FDA acting chief, Lester Crawford, cancelled testimony yesterday before members of Congress who will write the section of a bill that provides funds for the agency’s 2006 budget.

US Representative Maurice Hinchey (NY) said he would have pressed Crawford on poor leadership and allegations that Crawford silenced critics within the FDA who pointed to unsafe drugs while permitting inappropriately close ties to the drug industry.

“The consequences of that are being borne by the American people, including serious illness and death,” Hinchey said.

In an Op Ed in the Boston Globe, Dr. Marcia Angell, former editor of The New England Journal, puts the FDA squarely on the docks for its failure to ensure that the drugs it approves don’t pose greater risks of harm than benefits.

FDA’s hasty evaluation and approval process for drugs with lethal side effects and unproven clinically significant benefits has substantiallyt increased industr’s profits at a cost in sacrificed lives. Even when the FDA knew about a drug’s lethal adverse effects, it allowed it (e.g., Vioxx) to stay on the market for four years “after a clinical trial showed it was probably more likely to cause heart attacks or strokes than to prevent stomach ulcers.” Furthermore, FDA routinely allows drug manufacturer to misrepresent the risk/ benefit ratio of their products in beguiling advertisements that conceal the hazardous effects – “it’s a beautiful morning…”

“Why is the nation’s most important regulatory agency appeasing the pharmaceutical industry instead of protecting the public? One answer is that it is on the industry’s payroll. Literally.” When Congress passed the 1992 Prescription Drug User Fee Act, it put the FDA under industry’s control – “he who holds the purse strings holds the powerŠ.”

Congressman Hinchey has drafted legislation that would funnel drug industry funding for the FDA through the US Treasury to create distance between the industry and its regulator. And he would create a completely independent center to police drug safety with the power to pull unsafe drugs from the market. And he’ll seek higher overall drug safety funding so early warnings aren’t missed.

“What we’ve seen is often within these clinical trials… even though somebody in the FDA sees the red flag, they don’t look behind it to see what the problem is.”

Various members of Congress already are considering changes, including restrictions on drug advertising, requiring larger safety drug studies, and giving the FDA authority to immediately change labels for unsafe products.

Contact: Vera Hassner Sharav
212-595-8974

Boston Globe
MARCIA ANGELL
What ails the FDA? Payola
By Marcia Angell | March 10, 2005

LET’S FACE it. The FDA is doing a poor job of ensuring that prescription drugs are safe and effective. It approves drugs that offer only minimal benefit, and then sometimes leaves them on the market long after they’ve been shown to be dangerous.

Take Vioxx, the hugely popular arthritis drug that was taken off the market in September and now might return if an FDA advisory panel has its way. This is one of a class of drugs called COX-2 inhibitors (Celebrex and Bextra are the others) that are supposedly easier on the stomach than over-the-counter remedies like Advil or Aleve. It was rushed to market in 1999 even though it was never shown to be any better for relieving pain than the older drugs.

The FDA then let it stay on the market for four years after a clinical trial showed it was probably more likely to cause heart attacks or strokes than to prevent stomach ulcers. It could have insisted that the manufacturer, Merck, immediately conduct a large-scale study to better define the risks and that the company add a warning in its direct-to-consumer ads that made Vioxx sound like a miracle drug (think Dorothy Hamill skating effortlessly to “It’s a Beautiful Morning”). The FDA is now implying it doesn’t have that authority, but it does.

Why is the nation’s most important regulatory agency appeasing the pharmaceutical industry instead of protecting the public? One answer is that it is on the industry’s payroll. Literally.

Since 1992, by an act of Congress, drug companies pay the FDA “user fees,” which are earmarked almost entirely for speeding up drug approvals. Consequently, the agency now behaves as though that were its main job, not ensuring safety and effectiveness.

Even worse, the 18 standing advisory committees of outside experts who help the agency decide whether drugs should be approved include paid consultants to drug companies. They are supposed to recuse themselves from decisions that directly affect the companies they work for, but that rule is regularly waived on the dubious grounds that their expertise is uniquely valuable. (Imagine judges not recusing themselves from cases in which they have a financial stake on the grounds that their expertise is invaluable!) The advisory committee that originally recommended approval of Vioxx, for example, consisted of six people, four of whom had received waivers because of their “potential for a conflict of interest.”

Last month a special advisory panel (two of the standing committees combined) held public hearings on the safety of COX-2 inhibitors and decided that the benefits outweighed the risks. What was not publicly disclosed was that at least 10 of the 32 panel members (we don’t yet know the exact number) were paid consultants for the companies that make the drugs. If their votes had been discounted, the panel would have recommended that Vioxx and Bextra be removed from the market. No wonder drug companies hire members of FDA advisory committees.

Drug companies and the FDA sometimes respond to critics by reminding them that nearly all prescription drugs have side effects. Even so, one of the FDA’s most important jobs is to make sure the risks don’t outweigh the benefits. When potential benefits are great, as with many cancer treatments, it is acceptable to run substantial risks. But when there are few benefits over drugs already sold, as in the case of the COX-2 inhibitors, it is not.

Vioxx is estimated to have caused tens of thousands of heart attacks or strokes. It is hard to see how the panel could have concluded that the benefits were worth those risks, especially given the fact that taking over-the-counter Prilosec in addition to an older pain reliever would probably have provided as much protection from stomach ulcers. The fact is, this was a public health disaster.

To prevent such disasters in the future, the FDA must be made independent of the industry it regulates. First, the legislation that authorized user fees should be repealed and the money replaced and augmented by appropriations that restore a better balance between drug approval and safety monitoring. The public is the primary “user” of the FDA, not the industry, and funding should reflect that. Second, FDA advisory panels should not include paid consultants for drug companies. Their conflict of interest is real, not “potential.” The excuse that they are indispensable is not only self-serving but insulting to the experts who don’t consult for industry.

The FDA is vital to our public health. We need to strengthen it as an independent watchdog, not an industry lapdog.

Dr. Marcia Angell is a senior lecturer in social medicine at Harvard Medical School and author of “The Truth About the Drug Companies: How They Deceive Us and What to Do About It.”

© Copyright 2005 The New York Times Company

FDA piles initiatives on the back burner
Pressing drug safety problems divert the agency’s attention from longer-term issues awaiting action
By Diedtra Henderson, Globe Staff | March 10, 2005

WASHINGTON — Acting Food and Drug Administration commissioner Lester Crawford has been so busy putting out fires on drug safety that other unfinished business has piled up.

For months, the agency has been finalizing a drug safety plan to identify people most at risk for serious side effects while keeping a drug on the market. In a National Press Club speech in August, Crawford set a six-month deadline for such goals as providing instructions to the food industry for labels on low-carbohydrate products and strengthening restrictions on animal feed to protect against mad cow disease.

Those efforts, some former agency officials and consumer advocates say, have fallen victim as FDA resources were diverted to more pressing issues.

“Whenever you have a series of crises, as they’ve had this year in the drug safety area, they tend to overwhelm and attract the attention of all the senior management,” said William W. Vodra, a former FDA attorney now with the Washington, D.C., office of Arnold and Porter. “So keeping on with longer-term initiatives is a real challenge.”

The agency acknowledged its unfinished business includes significant initiatives that it expects to complete shortly.

The “FDA is diligently working on each of these important issues,” said Kathleen K. Quinn, FDA’s media relations director.

Quinn declined to comment further and said Crawford was not available for an interview.

Crawford canceled testimony yesterday before members of Congress who will write the section of a bill that provides funds for the agency’s 2006 budget.

US Representative Maurice Hinchey said he would have pressed Crawford on what Hinchey says is poor leadership and allegations that Crawford silenced critics within the FDA who pointed to unsafe drugs while permitting inappropriately close ties to the drug industry.

“The consequences of that are being borne by the American people, including serious illness and death,” Hinchey said.

The New York Democrat has drafted legislation that would funnel drug industry funding for the FDA through the US Treasury to create distance between the industry and its regulator.

Currently, companies pay fees directly to the FDA for drug approval expenses.

In addition, Hinchey said he would create a completely independent center to police drug safety with the power to pull unsafe drugs from the market. And he’ll seek higher overall drug safety funding so early warnings aren’t missed.

“What we’ve seen is often within these clinical trials, red flags are raised. Frequently, many of them. But even though somebody in the FDA sees the red flag, they don’t look behind it to see what the problem is,” he said.

Various members of Congress already are considering changes, including restrictions on drug advertising, requiring larger safety drug studies, and giving the FDA authority to immediately change labels for unsafe products.

Unilateral authority would shift power to the FDA as it revises labels for such painkillers as Bextra, Celebrex, and Vioxx, linked to heart attacks and strokes.

Right now, such changes occur after lengthy negotiations with manufacturers, which critics say weakens warnings.

The FDA, however, could sidestep such problems if it knew earlier which patients were likely to suffer serious side effects. A trio of draft plans to reduce such drug risks have languished since last summer as the FDA grappled with pressing safety issues linked to antidepressants used by kids and painkillers popular with millions of Americans.

“If we can identify the patients who are most at risk of gastrointestinal problems and least at risk for cardiovascular problems, they’re the ideal ones for” painkillers like Celebrex, Vodra said. “That’s what this whole risk-management initiative is about.”

He said FDA senior management has been so consumed with immediate crises that such long-term solutions have been delayed.

“It’s hard to think about draining a swamp when you’re up to your butt in alligators,” he said.

One potential solution is knowing precisely why some drugs are more dangerous.

Moving in that direction, the FDA signed an agreement with Applied Biosystems, the company said yesterday, for molecular sleuthing on five diabetes drugs, including Rezulin, to reveal the reason for liver toxicity that forced that drug from the market.

With food, as with prescription drugs, safety experts say the FDA has made scant progress on significant initiatives.

Last August, Crawford said the FDA was considering barring from all animal feed risky material, like cow’s blood, thought to harbor the agent that causes mad cow disease.

The FDA’s move would provide “an added assurance of safety for our food supply and other products we all use that are manufactured with bovine-derived materials,” Crawford told a National Press Club audience.

Seven months later, FDA’s improved protections for animal feed have neither been proposed nor implemented.

“The failure of FDA to move forward on the animal feed improvement might have been a waiting game,” said Caroline Smith DeWaal, food safety director at the Washington, D.C.-based Center for Science in the Public Interest. “It’s clear the industry pressure on this issue has really paid off.”

The National Cattlemen’s Beef Association has few concerns about the delay, said Gary Weber, executive director of regulatory affairs for the trade group.

He added that the industry has not pressured the FDA to delay.

Food safety experts pointed to a number of recent FDA actions that bolster food safety and security, including registering American food processors, requiring prior notice of foods to be imported, detaining suspect food until inspectors clear it, reducing hazards posed by fresh juice, and, for the first time, spelling out activities on farms to ensure fresh fruit and vegetables are safe.

But other initiatives await action. In his August speech, Crawford said that consumers are confused by the term “low carb.”

As the low-carb craze ebbs, however, the FDA has still not given industry guidance that Crawford said would “demystify” carbohydrate claims on food labels.

“We are still waiting for that,” said Robert Earl, senior director of nutrition policy at the Food Products Association, which represents the $500 billion food-processing industry.

© Copyright 2005 The New York Times Company

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