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Deirdre Imus

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FDA: Another Government Regulatory Disaster -- II of III

Posted: 10/01/08 12:14 PM ET

When the FDA grants approval on products marketed to consumers, the vast majority of Americans feel comfortable that the agency has performed its due diligence and the risk of injury or harm is non-existent.

Since its inception in 1906 as the Bureau of Chemistry, however, the FDA has been mired in an incestuous conflict-of-interest culture. Despite horrific reports on approved drugs harming and killing thousands of Americans, the public at large remains unaware of the agency's corrupt history.

According to its mission statement, "the FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation's food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health."

While operating under the illusion of a government regulatory agency responsible for ensuring products are safe, time and time again we have witnessed the FDA acting as an agency that has abandoned the public's interest and under the control of the very industries it is charged with regulating.

Over the past thirty years, there have been countless articles and books detailing startling revelations about the pervasive influence of industry on the regulatory process and exasperating attempts to change the strangle-hold that corporations have on the FDA.

Following three frustrating years as FDA Commissioner, Dr. Herbert Lay resigned and told the San Francisco Chronicle, "The thing that bugs me is that people think the FDA is protecting them. It isn't. What the FDA is doing and what the public thinks it's doing are as different as night and day" (January 2, 1970).

In a Wall Street Journal article, "Drug Firms Use Financial Clout to Push Industry Agenda at FDA" (Sept. 1, 2006), Anna Wilde-Mathews summarized how a heavily lobbied Congress allowed industry to seize more control over the under-funded agency.

Regulators usually don't negotiate their budgets with the industries they oversee... For most of its history, the FDA was funded entirely by Congress. But in the early 1990s, companies unhappy with the pace of drug approvals agreed to pay the FDA millions of dollars in 'annual fees to help speed its performance. Because the industry and the agency renegotiate every five years over the size of fees - and what they,' can be used for - drug makers can have considerable input, into which programs receive funding. Each time the arrangement has been renewed, the FDA has gained new funding. In return, industry has wrung concessions. In the 1997 deal, the review time for a standard application dropped from 12 months to 10 months. In 2002, the FDA agreed to a number of changes, including a new deadline for how fast the agency would respond to companies' requests for meetings about their drug applications.

And herein lies the problem. We have a government that sees nothing wrong with this meddling and is apparently incapable of correcting it. As if this insidious collaborative arrangement weren't bad enough, when well-intentioned FDA scientists attempt to bring safety concerns to the attention of their superiors, they are threatened and told to keep silent or worse, change their recommendations.

It would be impossible to chronicle the sordid history of collusion and corruption of the nation's premier regulatory agency. But a re-examination seems warranted in light of the FDA's recent declaration that bisphenol A (BPA) is "safe."

Although consumer watchdog organizations have always been critical of industry influence over government agencies and the "revolving door" relationship between the two, most Americans were not aware of the serious and systemic problems plaguing the FDA until 2003. This is when newspapers around the country reported that an FDA drug safety analyst, Dr. Andrew Mosholder, warned his superiors that children taking antidepressants like Paxil and Zoloft increased their risk of becoming suicidal.

When the Senate Finance Committee and the House Energy and Commerce Subcommittee on Oversight and Investigations began to hold hearings on Mosholder revelations, drug company executives began pointing the finger back at FDA officials and blaming them for withholding information from physicians and patients. A safe thing to do, since neither are held
accountable.

("FDA Urged Withholding Data on Antidepressants," Washington Post, Sept. 10, 2004). http://www.washingtonpost.com/wp-dyn/articles/A9802-2004Sep9.html

According to an article published in the Washington Post:

Regulators suppressed the negative information on the grounds that it might scare families and physicians away from the drugs, according to testimony by drug company executives. For at least three medications, they said, the FDA blocked the companies' plans to reveal the negative studies in drug labels, and in one case the agency reversed a manufacturer's decision to amend its drug label to say that the drug was associated in studies with increased hostility and suicidal thinking among children... More than two-thirds of all studies of antidepressant use among depressed children have failed to show the drugs are effective.

By the end of 2004, criticism of the FDA intensified both in Congress and in the press.

In dramatic testimony before the U.S. Senate Finance Committee, Dr. David Graham, a senior official in the FDA's Office of Drug Safety, described the FDA as a "profound regulatory failure." In an illuminating and disturbing interview with PBS, Dr. Graham repeated some of what he told the Senate Committee. The scientist turned government whistle-blower explained how he was pressured by his superiors to change the conclusions of his study that found 30,000 to 55,000 deaths caused by Vioxx, Merck's blockbuster arthritis drug. When Graham refused, FDA officials withheld the public release of the full text but shared it with Merck.

"You have an agency that was completely oblivious to safety, completely insensitive to safety, that basically was willing to tolerate a 500% increased risk of heart attack with no demonstrable counter balancing benefit for the drug because it suits their clients to allow the drug to be marketed in America."

When asked, "who is the FDA working for?" Graham replied, "A former manager of mine from the Office of Drug Safety told me that industry was our client. And when I said to him, 'No, the public is my client' he said, I was wrong and it was industry."

"I would argue that the FDA, as currently configured, is incapable of protecting America against another Vioxx. We are virtually defenseless," said Dr. Graham.

After reviewing the Vioxx clinical trials, Dr. Richard Horton, editor of The Lancet, wrote a scathing article accusing Merck and the FDA "acted out of ruthless, shortsighted and irresponsible self-interest."

The Vioxx scandal outraged the scientific and medical community, members of Congress and the public, which brought greater scrutiny on the FDA but not much of anything else. If you think anything has changed after Dr. Graham exposed the dirty dealings within the walls of the FDA and the antidepressant and Vioxx investigations, think again.

In September 2005, citing "unwarranted interference in agency decision making" on the part of then Commissioner Lester Crawford, Susan F. Wood, assistant FDA commissioner for women's health and director of the Office of Women's Health, resigned from the position she had held for five years. In an email to FDA staff, Dr. Wood said, "I can no longer serve as staff when scientific and clinical evidence, fully evaluated and recommended for approval by the professional staff here, has been overruled."

Soon after Wood's exit, Dr. Crawford abruptly resigned as FDA Commissioner after the Wall Street Journal disclosed his stock ownership in companies regulated by the agency. Crawford later plead guilty to the conflict-of-interest charges.

Following Crawford's plea, Mike Adams, long time FDA critic and author of "Grocery Warning," told reporters, "Crawford's guilty plea now establishes as indisputable fact what myself and other FDA critics have been saying for years. The agency is headed by white-collar criminals who deliberately make regulatory decisions that are in the best interests of drug companies, junk food giants, rather than protecting the health of the public."

It is no secret that industry-funded studies were used for decades to hide the damaging affects caused by asbestos, tobacco, and lead. It is no secret that industry spends millions every year to make sure their interests are protected - at the FDA, other federal agencies and in the halls of Congress.

Whether we are talking about food, chemical or drug safety, FDA officials routinely rely upon industry-funded research as the convenient excuse for not taking action on dangerous products when safety concerns arise. This is called creating "scientific uncertainty," and has proven quite successful in thwarting regulatory action.

For years, Senator Chuck Grassley (R-IA) has been one of the FDA's harshest critics and a leader in pressing for FDA reforms, transparency and accountability. Having served as chairman of the Senate Finance Committee during the Vioxx and antidepressants hearings, Grassley began investigating the approval of the antibiotic drug Ketek after learning the drug was approved even though the agency knew "safety tests on the drug had been forged." Manufactured by Sanofi-Aventis SA, Ketek was linked to 12 cases of liver failure including four deaths.

In a press release, Grassley said, "The allegations of misconduct in this [Ketek] case are as bad as I've heard yet. It looks like the FDA caught the drug company red-handed and let them get away with it. On top of that, the FDA failed to set the record straight and, in fact, continues to cite a discredited safety study as a principle reason to feel okay about using this drug."

ABC News later reported Grassley "was sent home empty-handed" by FDA officials "who refused the powerful Republican access to information" and "wanted to speak to the FDA investigator who uncovered the fraud" about Ketek's approval.

"The study with the forged test results was conducted at a former weight loss clinic in Gadsden, Alabama. Dr. Maria Anne Kirkman-Campbell is serving five years in prison for falsifying safety test results on Ketek."

"A former nurse, Michelle Snedeker, told ABC News she was ordered to forge documents and report data on people who had not even been given Ketek. The doctor was paid $400 for each of the 407 subjects that she enrolled for the study."

As Grassley pressed for the denied documents, a defiant Dr. Andrew von Eschenbach, acting director of the FDA, refused to provide the information to the Senate Committee on Finance.

So much for the power of congressional oversight.

On February 12, 2007, the FDA finally announced that Ketek would get a "black box" warning. "The changes include the removal of two of the three previously approved indications -- acute bacterial sinusitis and acute bacterial exacerbation of chronic bronchitis -- from the drug's label. The agency has determined that the balance of benefits and risks no longer support approval of the drug for these indications." The warning also states that "Ketek is contraindicated (should not be used) in patients with myasthenia gravis, a disease that causes muscle weakness."

Years later The New England Journal of Medicine published an article written by a former FDA physician, David B. Ross, M.D., Ph.D., who participated in the Ketek review:

The review of Ketek was thus marked by pronounced departures from accepted review practices. In addition to the use of fraudulent data, the substitution of uncontrolled postmarket safety reports for controlled clinical trial data, and the acceptance of trials that could not show efficacy, there was also overt internal pressure brought to bear on FDA reviewers to alter their conclusions.

But did any of these revelations change the way the FDA evaluates internal dissent regarding safety concerns? Did congressional investigations result in the agency cleaning up its act? Did von Eschenbach's refusal to cooperate with a congressional investigation prevent him from becoming FDA Commissioner? Absolutely not.

Senior officials continue to censor and intimidate honorable scientists trying to do their jobs and committed to protecting the public.

Two years following Dr. Graham's testimony before Congress, another FDA scientist, Rosemary Johann-Liang, was reprimanded when she recommended GlaxoSmithKline's diabetes drug Avandia be given a "black box" warning label to alert physicians and consumers about its heart failure risks. Again, Johann-Liang's supervisors refused to act on her report.

"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," Johann-Liang told USA Today one day before leaving her job as deputy director of the Division of Drug Risk Evaluation.

Only after the New England Journal of Medicine published a study that found patients using Avandia doubled their risk of heart failure compared to individuals not taking the drug, did FDA officials finally accept Dr. Johann-Liang's report and give the drug the strongest "black box" warning label. By that time, the drug had already been prescribed for millions of Americans.

In a speech on the senate floor, Senator Grassley told his colleagues that as many as 20 heart attacks a day might be caused by Avandia. Grassley has been angry and frustrated by the attitude and actions of senior FDA officials and has introduced legislation aimed at establishing an independent drug safety review board.

In reality, the last thing industry wants is FDA reform... unless it is on their terms. And this is where all the lobbyists and campaign contributions are most effective. The political influence of the dirty money bestowed on lawmakers, partnered with industry's bankrolling of the FDA from user fees, has led to catastrophic consequences to hundreds of thousands of Americans.

In response to on-going congressional attacks, FDA officials blame a myriad of agency failures on the lack of funding. But the problems at the FDA are not because of lack of money. Good scientists like Andrew Mosholder, David Graham, and Rosemary Johann-Liang were doing their jobs and reporting safety concerns to their superiors. Warnings could have saved thousands of lives. The problem is a lack of accountability and conscience in the FDA hierarchy who so casually turn a blind eye to dangerous and deadly drugs, chemicals and food products.

When large financial institutions fail, people lose their investments. But when the FDA fails, people lose their lives. Children lose parents. Parents lose their children. Had Dr. Graham not come forward, it is very probable the FDA would still be telling Americans Vioxx is "safe," just as they are now proclaiming BPA "safe," and the arthritis drug would still be on the market, quietly injuring and killing tens of thousands of unsuspecting Americans.

Federal officials who intentionally deceive the public and mislead physicians through the illegal practice of hiding data that shows children taking antidepressants have a greater risk of committing suicide, because they are concerned that the public would lose confidence in antidepressants are not regulators are criminals. They should be treated as such.

Besides a complete overhaul, a few prosecutions might be just the medicine the FDA needs.