The BEAST: Buffalo's Best Fiend

The staff at the Food and Drug Administration may not actively hate you and want you to die, but a study of the agency's sordid history suggests that they don't really care if you live either. Lucky for us, drug companies are kind, conscientious, and self-regulating. For example, in late September Merck and Co, makers of Vioxx, agreed to voluntarily recall their famous drug, now that a new study suggests it may put people at increased risk for heart attack. Isn't that nice of them? How thoughtful…. Unless four years doesn't qualify as "new" to you.

The findings leading to the drug's recall originally came out in a Merck-sponsored study, the results of which were first published in The New England Journal of Medicine in late 2000. It found that people over 40 with rheumatoid arthritis who took Vioxx had four times the risk of heart attack as comparable subjects who took a similarly acting painkiller.

Hhhmm. Four years, four times, maybe there's something esoteric here. Perhaps the FDA people have joined Madonna in the study of Kabala and now know something we don't know. After all, on October 15h they announced the new requirement that all antidepressants carry a "black box" warning. The government's strongest safety alert was decided appropriate since the publication of studies linking the drugs to increased suicidal tendencies among children and teens taking them. Beyond the questionable practice of putting children on antidepressants-I had to suffer the horrors of adolescence armed with only Clearasil and Twinkies-warning label strategies to prevent harm from drugs have failed miserably in the past.

Ugly details surround Lotronex, a drug approved to treat irritable bowel syndrome in women. The FDA approved Lotronex in February 2000. In late November of the same year, the FDA requested that the drug manufacturer, Glaxo Wellcome, voluntarily withdraw Lotronex. In those eight months, 49 cases of reduced blood flow to the intestine (ischemic colitis) and 21 of severe constipation, including instances of obstructed and ruptured bowel were reported. 34 patients required hospital admission, and 10 needed surgery. Five died.

Prior to the Lotronex recall, concerns were raised about risks of the drug. By June, three patients had already required surgery, and newly collected data confirmed risks suspected at pre-approval review. Rather than recall the drug or halt sales until more testing could be done, the FDA chose to issue a medication guide warning patients of escalating risks. Then people died. Silly FDA, medication guides are for safe drugs.

All of this begs the question: Why did the FDA approve Lotronex in the first place? Well to paraphrase the FDA website: We got a shitload of money from the Glaxco Wellcome people! And we helped develop this filthy drug and we spent a whole bunch of money advertising it too, and somebody has to give us all that money back!

The Center for Drug Evaluation and Research (CDER) is the arm of the FDA charged with ensuring that drugs are safe and effective. The CDER does not test drugs. They are a review team of physicians, statisticians, chemists, pharmacologists, and other scientists, who evaluate a sponsor's new drug application.

A company develops and tests a drug, including clinical trials--you know, where they pay grad students twenty-five dollars to take these pills and see if they die. The company then approaches the FDA for approval. New drug applications must include the drug's chemical composition and pharmacology, results of animal studies, how it's manufactured and packaged, and how many grad students died.

The inherent flaw with this system is that it relies on the market to investigate the drug. But a market-based testing approach is only going to look at the positive aspects of a drug. It is unlikely to consider or investigate the possible negative consequences. A Frontline interview with Dr. Raymond Woosley, the then-vice president for Health Sciences at the University of Arizona, included a perfect example of how such an arrangement could backfire.

In the 1980s, oral lidocaines were being developed to prevent major complications of heart disease. It was known that irregular heart rhythms placed individuals at very high risk for sudden death, and these drugs showed vastly improved electrocardiogram in their users. A market approach would be likely to stop there. Better EKGs means fewer sudden deaths. Only that wasn't the case. In a study specifically designed to check, it was discovered that despite better heart rhythms, more people died suddenly while on these medications than in the group treated with placebo.

Treating the symptoms, e.g. assuming that better cardiograms means fewer deaths, is called addressing surrogate endpoints or biomarkers. But as demonstrated in the oral lidocaine tests, a cause-effect relationship cannot be assumed. If you're developing a drug, you have to scrutinize the final result, in this case death and heart attack.

Yet the FDA website, on a page titled: Benefit Vs. Risk: How FDA Approves New Drugs states the following: " FDA has…taken steps to make urgently needed drugs available sooner…Under the accelerated approval rule, the agency can rely as a basis for drug approval on a reasonable 'surrogate' endpoint--that is, an effect of a drug on a marker of the disease, rather than an actual effect on survival or illness…."

So the FDA is flying in the face of science? Oh yes. On the wings of greed. In September 2000, USA Today reported that more than half (54%) of the experts hired to advise the government on the safety and effectiveness of medicine have financial relationships with pharmaceutical companies. The conflicts typically included stock ownership, consulting fees or research grants, and manifested as scientists helping a pharmaceutical company develop a medicine, then serving on an FDA advisory committee that reviews the drug.

Federal law prohibits the FDA from using experts with financial conflicts of interest, but the FDA has waived the restriction more than 800 times since 1998, waivers presumably allowed because bribes and pressure don't stop within the FDA. The Foundation for Taxpayer and Consumer Rights (FTCR) reported that no U.S. governor or federal official raised more money than Governor Schwarzenegger from the pharmaceutical industry over the last year-other than President Bush. "The Governator" came in at over $337,200 in campaign contributions from pharmaceutical companies, while Dubya was clocked at $870,000 since the 2000 election. So as not to be partisan, let's also mention Kerry's $349,312 from drug companies since 2000.

The results of such conflicts of interest have been well-documented. Numerous news outlets report a long history of scientists who raise safety questions about the drugs being dismissed by FDA officials and subsequently marginalized. The culture of drug review within the FDA presents an overall expectation that most drugs will be approved. To research a perceived problem means facing hefty obstacles within the agency, requiring enormous effort and justification. Conversely, approval is seldom, if ever, challenged. Finally, since nay-saying scientists are ignored, post-approval monitoring is not nearly as vigilant as it should be.

Another major contributing factor to the pharmaceutical industry's stranglehold on the FDA is marketing. In 2001, Merck spent roughly $170 million promoting Vioxx. Let me put that in perspective for you: That's more than the Coca-Cola Company spent advertising Coke, and more than Anheuser-Busch spent advertising Budweiser. It was the first year in history that the pharmaceutical industry spent more money advertising drugs than developing new ones.

Marketing of such proportions has two major consequences: first, the company wants that money back, and the only way to make it back is to sell their junk-I mean medicine. Second, pharmaceutical companies get the public on their side. People are pretty easy to entice; we want to be thin, happy and healthy, and we don't want to work very hard to achieve that. Remember the Fen-Phen fiasco? People were angry when it was recalled. Many would gladly have risked heart attack in order to be thin.

In many cases, selling a pill means convincing people they are sick. "Ask your doctor about the purple pill…." "Do you ever feel tired? Not yourself?" "Did you wake up this morning? You might need a pill for that…." Part of this strategy is response to the FDA: In 1962, FDA rules were overhauled in an effort to improve drug safety. As part of this, companies have to develop products targeted to specific diseases rather than general conditions such as "stress." So companies now market not just pills, but the diseases that they are supposed to cure. And if you think you're sick, you'll push your doctor, and if he says no you'll find another doctor.

If FDA approval means, as claimed, that benefits outweigh risks, antidepressant drugs like Prozac should never have been approved. In most company-controlled clinical trials, the drugs failed to show a benefit greater than placebo. The drug label claims there were 5,600 Prozac-exposed individuals, but this apparently includes patients given the drug under a variety of conditions other than actual clinical trials, like sold on the street corner or out of a Lexus. Oh wait, that's OxyContin…. The actual number of patients in the trials reviewed by the FDA turns out to be less than 300. But hey, what's 5,300 test subjects between a government agency and a drug corporation?

FDA's allowing Eli Lilly to use the placebo wash-out method dilutes their supposed positive findings even further. It's been found in most studies that nearly 50 percent of depressed patients improve on the sugar pill. In some studies, nearly 90 percent improved on placebo. But with the wash-out method, patients responding to a placebo within 4-14 days were dropped from the study and the trials restarted. Obviously, this technique makes a drug seem more effective than it is. Apparently though, it's commonly used in drug studies.

It is not only antidepressants that don't get fully reviewed, or monitored once approved, or reigned in after long-term studies confirm negative consequences of a drug. Pfizer has been accused of misleading heath care professionals as to how often patients need to take Celebrex. Merk was pushing their now-recalled Vioxx for unapproved uses, such as the prevention of cancer, and the treatment of Alzheimer's disease and gout.

Granted, even at four-times increased risk, the chances of Vioxx causing a heart attack are still pretty low: This equates to a real-world number of four heart attacks per 1,000 patients. Low, but not insignificant, and it joins an already extensive list of warnings, contraindications, precautions, and possible side effects on the Vioxx label. It is known, for example, that Vioxx and other COX-2 inhibitors (like Celebrex, Vioxx's main competitor) can cause reduced kidney function in elderly patients and diabetics. Additionally, a number of cases of aseptic meningitis were linked with the use of Vioxx.

Combine these risks with the fact that Vioxx doesn't fix anything--it doesn't rebuild cartilage or provide a simple hysterectomy--it just gets you high enough that you don't really care. You may as well smoke pot or shoot heroin, either one of which is significantly cheaper.

If you hang out in the wrong (or right, depending on your perspective) parts of town, people will come and give you things to try. Try it once for free, see if you like it. Maybe even more than once, maybe the first three times. Then you gotta pay, see. After you're hooked, it's not free anymore. If you go to the doctor's office, you will see stacks and stacks of sample packages of pharmaceuticals the drug companies give to doctors to give to you. All you have to do is ask, and you know how to ask because they told you on TV. More scrupulous doctors are tightfisted with them, or give them to low-income patients in lieu of an expensive prescription they could not afford to fill.

FDA approval suggests an assurance of safety. But these assurances are not based on testing or experiments; they are being purchased. The price? A few million dollar bills, y'all. And, we can only hope, the souls of the sick, greedy bastards at the drug companies and within the FDA. The FDA's history of payoffs, rollovers and perjuries makes that bad CEO Kenneth Lay look less like an economic serial rapist and more like that big kid that took my lunch money every day. At least he wasn't taking my life, just my dough.

No other government administration can boast of such a long and thick chain of corruption. To document it all would take volumes. Numerous major news outlets have done investigations and exposés on the FDA, with no consequent changes. The corruption is so systemic that there is no obvious practical way to alleviate it. So face it: your health is in your own hands. It's best to acknowledge that, every time you take a drug, you're experimenting on yourself. Kind of like being at a rave, only way more expensive.

My advice? Become a Meals-on-Wheels volunteer. Find an especially cute and endearing old person who doctors can't help but want to give away drugs to. Chat them up about their pain, convince them it hurts more than ever, and take them to a doctor (preferably a fresh, young, still-idealistic doctor). Then raid their supply. Hey, Merck, Glaxo, Lilly and their ilk are sending us all to hell anyway; you may as well feel good on the trip down.