Painful FDA?

The Food and Drug Administration has just yanked or restricted all but two of the nation's top painkilling drugs, throwing patients requiring regular anesthesia into what Dr. Joshua Prager, head of the UCLA Pain Center, called "great confusion, not only among patients, but for physicians" about how to treat severe and chronic pain.

The only painkillers the FDA will recommend as working without long-term high-risk are aspirin and acetaminophen (Tylenol). If these do not work to control your pain, you are on your own. Popular non-prescription drugs, ibuprofen (Advil, Motrin, etc.) and naproxen (Aleve), will now require warnings against use for longer than two weeks. The prescription COX-2 inhibitor drug Bextra will be removed from the market and Celebrex (and Vioxx, if its manufacturer is willing to go back on the market) will require the maximum "black box" warning that its use could cause heart attacks and strokes.

By an interesting coincidence, Dr. Joel Kent, director of the University of Maryland Pain Center, Dr. Leza Leal, a pain physician and author of "Live Well With Chronic Pain," and RN Micke A. Brown of the American Pain Foundation were on NPR radio the day before the decision and, without knowledge of it, criticized the FDA for its bureaucratic ways that resulted in insensitivity to patients in pain. Dr. Leal, who suffers constant pain herself, specifically said that Celebrex was the only such medicine that helped her and that she would continue to use it if she could no matter what the FDA decided on the issue.

What is going on at the agency that supposedly protects American patients? Two days before the decision, Senators Hillary Rodham Clinton, Patty Murray, and Edward Kennedy confronted Dr. Lester M. Crawford, who was named by George W. Bush to become permanent FDA Administrator, and announced they would place his nomination on "indefinite hold" unless he followed their desires to make the "emergency” contraceptive “Plan B" available without a prescription. While the hold had limited practical effect since the longtime medical bureaucrat and professor is already acting head of the agency, it did make an already politically pressured bureau even more nervous about making decisions not popular with the activist medical constituencies of the Democratic left.

Led by the liberal Public Citizen's Health Research Group, backed by the trial lawyers and endorsed by senators like Kennedy and Barbara Boxer, their mission is to promote absolute safety through maximum bureaucratic regulation, unlimited access to health litigation against drug businesses and, ultimately, the elimination of private medicine in favor of government-run health care -- not surprising since the organization was originally founded by Mr. Left, Ralph Nader. Unfortunately some Republicans such as the normally sensible Sen. Charles Grassley have jumped in too. The recent panic began in late 2004 by a self-described “whistleblower” FDA bureaucrat named David Graham who made the claim that the risk-adverse agency actually ignored safety matters and was in the pocket of business. While he presented no evidence on this, Graham noted that the FDA earlier had said Vioxx may have caused 28,000 heart attacks or sudden cardiac deaths. He told a Congressional committee there actually were 55,000 deaths based on his calculations. Despite the fact that estimation is a tricky business, this frightened the manufacturer, Merck, into almost immediately removing the drug from the market, just ahead of the lawyers, and leaving the patients in the lurch, even those who were willing to take some risks with the drug to get relief from their pain.

Rule number one for bureaucratic regulators is, what you do can get you in trouble, what you deny no one can see. The ideal would be to approve no drugs at all so that no one could get hurt using them and could not blame the bureaucrat who approved them. That is impractical so the next best is to test them to death over the longest period possible in an effort to eliminate all risk. FDA regulation has very little to do with patient health but everything to do with their fears. The regulators, being statisticians, know it is impossible to eliminate all risk but they can always rule on the side of caution. The only little problem is that people die during the endless approval process. But no one can tell for sure they died from not having a drug no knew was available.

The FDA bias toward endless testing is most noticeable for patients suffering from incurable diseases. The bureau insists experimental drugs for these patients meet the tightest standards, called Phase IV testing, to obtain a full Tier or accelerated Tier approval, requiring thousands to be tested under statistical methodology utilizing "blind" controlled experiments with some patients receiving the full dose and some with little or no dose at all. The so-called controlled experiment may make some sense for everyday drugs but even FDA should recognize the true control for patients with terminal diseases is that all will die with the no treatment regime the test imposes on some. When a father started the advocacy group Abigail Alliance and tried in 2003 to save his little Abigail Burroughs' life by proposing a new Tier 1 expedited procedure without large numbers or controlled tests, as is done in early phase testing, for patients who had no other recourse and were terminally ill, the bureaucrats denied the request and defended the existing system for its efficiency, specifically mentioning the colon cancer drug Eloxatin .

Eloxatin was on the FDA accelerated approval list but it was not endorsed until 2003. By that time, 56 nations had already approved it. France, the epitome of rigid bureaucracy, had approved it way back in 1996, saving colon cancer lives for seven years it was unavailable in the U.S. While your reporter has been writing on this subject for years (although the Wall Street Journal has long been the leader in this lonely battle), it has now become personal. Someone very dear to me has been recently diagnosed with melanoma and while it is presently under control, she cannot try the vaccines that have been in clinical tests for years without traveling across the country to a "blind" trial where she might receive sugar pills rather than effective treatment. The government says one must wait until the tests are completed if she wants to be sure she will receive the full dosage.

I have a 1997 report showing a melanoma vaccine proving in a Phase III test that it was more effective than the alternative debilitating combination chemotherapy treatment. Another test with peptide vaccine and interleukin-2 was conducted in 1998 where 42 percent of those receiving the treatment had a fifty percent or greater shrinkage of their tumors. Further double-blind testes were ordered but it was cancelled due to side effects that were questioned by several involved who said it was called off too soon to know for sure. Another test in 2002 showed a similar shrinkage of tumors from vaccines. In order to protect her, however, the FAA will not let her try the therapy. On what moral reasoning does that decision rest?

In fact, the FDA method is scientifically flawed as well as morally objectionable. For fourteen years, I was the lead professor teaching social statistics to political scientists at the University of Maryland, and can testify that there is no perfect or "objective" means to make decisions between control and test groups using statistical methodology. Once the notion of probability enters -- and it is the essence of statistics -- certainty leaves. As Dr. Prager noted, "There is no black and white on these matters." There is a Type I and a Type II error in statistics that are inversely related to each other. The more one reduces one type of error, the more one increases the other. Of course, statistics can help improve such judgments but drawing the line is a subjective decision at the end.

Human beings desire certainty. That is why the myth of purely objective science and absolute safety are so popular, even among scientists. Politicians trying to please constituencies rely upon the myth even more and expect their bureaucrats to do so too, but the methodology does not allow it. So there is a great deal of smoke and mirrors in government health decision-making all hidden behind scientific-sounding terminology. It is not surprising that FDA acts the way it does. It must deal with a Congress and public that want certainty over science, so it insists on double-blind tests and statistical methods but knows they can only result in partial safety. Almost any substance will not be safe for some people under some circumstances. This may make little difference with aspirin but when it denies available drugs to those who have no other possible solution to like-threatening situations, it is not only scientific nonsense but morally reprehensible.

Congressman Dan Burton is a politician tough enough to stand up to the myth and confront the bureaucrats and the left wing extremists. He is reportedly producing a bill to incorporate aspects of the Abigail Alliance Tier I as an alternative to patients with potentially terminal diseases. The Abigail plan would allow patients who have no other alternatives to obtain experimental drugs that have only been proven in Phase I tests (which do not require blind statistical testing). Actually, that language is too restrictive in my opinion because it requires that every other alternative be exhausted without allowing the patient and the doctor to decide whether to skip a more highly invasive procedure. Why should a patient in such conditions not be able to make such a choice? Still, even that would go further than anything else and has already faced a bureaucratic and political firestorm as it is.

Actually, pain sufferers would not even have aspirin if it were tested under FDA procedures. As Dr. Prager told NPR the day following its decision "aspirin would never be able to get through the FDA process today." For, you see, aspirin existed before FDA and was not required to pass through its sole and perfectionist approval process. As Dr. Prager noted, aspirin although extremely helpful is not perfect: it creates stomach problems for some and that is why other drugs (now restricted by the FDA) were developed. If the FDA had existed when aspirin was developed, there would be no unrestricted pain medicine on the market today!

This nonsensical governmental monopoly approval process must be taken away from the exclusive hands of politicians, activists and bureaucrats. A more rational process can only be attained by much more liberal FDA rules or, better, by offering an alternative process, perhaps through a private Underwriters Laboratories-type approval certification process where patients have a choice, so that drugs are truly available to the sick people that need them most.

Donald Devine, Editor.

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