Food und Drang Administration

As one who has objected to a number of FDA actions, I approve of much of Alexander Volokh's article ("Clinical Trials," May). I have little love for the FDA.

But I have less for drug manufacturers who, with the FDA's connivance, claim exclusive rights to products developed with our money and charge exorbitant prices for some when their own R&D has been recovered a hundredfold. In seeking to reduce regulations, I should not want us to throw the baby out with the bathwater.

I remember why federal regulation was needed in the first place. When I took high school chemistry, our professor had a glassed-in cabinet of tainted, corrupted, even poisonous canned products sold as food before federal regulation came in earnest with the passage of the Pure Food and Drug Act of 1906. (It was only in 1931 that the FDA itself was created.)

Throughout recorded history there have had to be laws regulating food (especially adulteration) and drugs; we cannot do away entirely with them now.

Ralph Mason Dreger, Ph.D.
Baton Rouge, LA

Many libertarian authors become confused between good guys and bad guys. Just because government is bad, it does not follow that industry is good. The Bureau of Health Statistics notes that 125,000 people died in 1992 from adverse reactions to prescribed drugs. Alexander Volokh's "statistical" claim of all the lives that could have been "saved" if the FDA had permitted the marketing of various drugs and devices does not ring true. I suppose what he means by a "life saved" is a few more months of suffering at the cost of hundreds of thousands of dollars to insurance customers.

I dislike the FDA as much as anyone, but please don't assume that the pharmaceutical industry (or any other industry for that matter) is an altruistic institution. Let the buyer beware.

Gordon LaBedz, M.D.

Los Angeles, CA

Alexander Volokh's article presents hard evidence that the FDA causes the deaths of thousands of Americans every year by holding up the approval of lifesaving medical drugs and devices. The article is an excellent indictment of the FDA, but it doesn't go far enough.

The book Drugs Available Abroad by Jerry L. Schlesser (Gale Research Inc., Detroit, 1991) lists more than 5,000 safe and effective drugs available in countries around the world, but not in the United States. Many of these drugs, such as the neurostimulators Centrophenoxine and Piracetam, have been used safely and successfully throughout the world for decades, but will never be approved in the United States because the companies selling them have no incentive to seek approval. The patents on such drugs have long since expired and their widespread use makes them poor candidates for the huge expenditure of money and time needed to apply for FDA approval. The Center for the Study of Drug Development at Tufts University in Boston has calculated that it costs a company an average of $230 million and 10 years to obtain FDA approval for a new drug. These kinds of costs make it impossible for all but the largest pharmaceutical companies to get FDA approval for new drugs.

The agency's discouragement of off-label uses of approved drugs (such as aspirin) also causes many deaths. Although doctors are free to use approved drugs for any use they think appropriate, companies cannot advertise these uses, and most doctors are hesitant to prescribe off-label uses because of their lack of knowledge about these uses and because of their fear of malpractice suits. And, while the FDA has a policy that Americans may import unapproved drugs from foreign countries for their personal use, the agency does everything in its power to prevent them from doing so. The FDA orders U.S. Customs to seize such products at our borders and tries to destroy companies in other countries that sell unapproved drugs to Americans.

The agency is also responsible for deaths from highly dangerous drugs approved by the FDA. Thomas J. Moore's recent book Deadly Medicine (Simon and Schuster, 1995) documents the needless deaths of hundreds of thousands of Americans from the use of a single class of anti-arrhythmic drugs. Moore shows that the FDA approved these drugs without a shred of evidence that they provide benefits for anyone and with hard evidence that they kill people. The FDA knew that these drugs were killing people by causing the very same arrhythmias they were supposed to prevent, but the agency approved them anyway on the theory that they might save more lives than they cost. This theory was obliterated by a controlled clinical trial directed by the National Heart, Lung, and Blood Institute, which found that patients taking the drugs died at least three times as frequently as patients on placebos.

Finally, the agency has caused enormous damage to the health of the American people through its policies regarding vitamins, minerals, and other nutrient supplements. Although there have been thousands of studies showing that nutrient supplements can help to prevent heart attacks, strokes, cancer, and other lethal diseases, the FDA prohibits companies selling these products from informing the public about these studies.

There is a simple solution to stop the carnage, initially proposed by Durk Pearson and Sandy Shaw: Just take away the FDA's power to stop Americans from using the products they wish to use by providing for a split label (including promotional literature). Half the label would be written by the company selling the product and half by the FDA. Anyone who wants FDA protection could stay away from unapproved products, while those who want freedom of choice could waive FDA protection whenever they wish to.

Such a change would force the FDA to compete for the consumer's ear. If the FDA gave consumers good advice based upon solid research, most health-conscious Americans would follow it; if the FDA's advice was bad and unsupported by evidence, most health-conscious Americans would ignore it.

Saul Kent
Life Extension Foundation
Ft. Lauderdale, FL

The obvious question that the average citizen usually faces is, "When is my lifesaving product going to be approved?" However, a far larger foundational issue Mr. Volokh touched on merits a different discussion here.

The more paramount question is whether there will be any small medical manufacturing companies left in business by the end of the decade that will be in a position to manufacture these life-saving devices. The monolithic billion-dollar conglomerate medical manufacturers with the means and manpower will simply shuffle money, people, and plants across international borders at a faster and faster rate. Most of the rest of the medical manufacturing industry will likely be stuck in the United States, struggling to survive. The firms that are too small or too financially strapped will suffer and be eaten alive (i.e. acquired) by the multinational firms. Likewise for firms that may be too cautious—a very preventable but unfortunate trait of most American corporate managers today.

In the not-too-distant future, firms that require large masses of research will regularly conduct it in China, India, Korea, and other developing countries. These are countries with well-educated researchers and scientists who can conduct basic research at fractions of the prices in the United States.

Some of this may sound like overstatement and oversimplification, since there will almost certainly always be medical manufacturing companies in the United States. The total number of U.S. medical manufacturers has tripled since 1980, according to FDA statistics. Having reported on the medical industry since 1980, though, I can readily testify that the trend toward more companies is in critical danger of reversing at the same rate.

Another eye-opening experience is to read the list of products being exported overseas. Every month, several dozen are approved by the FDA for export, even though they have not been cleared by the FDA for sale in the United States. This totals many hundreds of products per year that are not available to U.S. medical practitioners and their desperate (but usually unaware) patients.

It is also worth noting that at least 95 percent of these products will at some point receive FDA "clearance," according to FDA officials and outside legal counsel, since they have to meet FDA requirements in order to be OK'd for export. Because of that level of certainty, Biomedical Market Newsletter now trumpets that it can predict which products the FDA will approve, months or even years beforehand. It is an embarrassingly simple but extremely accurate crystal ball that is only possible because the bureaucrats are so predictable.

However, to lay the blame for all of these incidents and others solely at the feet of the FDA, and claim that virtually all the troubles of U.S. medical manufacturers would disappear if the FDA were eliminated is not true. The FDA product-approval process is faster than it was two years ago and additional improvements were announced in recent weeks. It is a mistake to swallow the logic of those who claim the FDA can and should be replaced.

It cannot, and should not, be replaced. Improved? Absolutely. This year? A must. Will it happen? A safe bet. Make a difference? For sure. Save U.S. jobs? No question. Worth trying? Our future depends on it.

David G. Anast
Biomedical Market Newsletter
Costa Mesa, CA

While we agree with the thesis presented in Alexander Volokh's article, we consider the statistics used at the beginning of the article to be misleading at best.

The numbers provided are baseless within the context of the article. Without any sources accompanying them, they are no better than the endless litany of "scare" statistics for such things as the now-infamous Super Bowl domestic violence statistics. Even if the withheld products were available to those people cited in the "statistics," there is no evidence presented that all of the deceased people (or even a large percentage of them) would actually have benefited from those products.

It would have been better to focus the article on the simple fact that the FDA disallows our citizens and their selected health care providers freedom of choice in determining what's best for their individual health care needs. This simple fact is what can lead to preventing many tragic and preventable deaths. Numbers aren't important.

We also feel that for the purposes of the article, it would have been much more illustrative to focus on examples in which the FDA approved/licensed drugs or devices, and yet problems resulted anyway, showing that the FDA really doesn't make much of a difference, safety-wise, with its present level of excessive regulatory intrusion. One example would be the drug Felbamate, an initially promising anti-epileptic drug which was recommended for approval in late 1992 and actually licensed for use in July 1993. In mid-1994, scarcely a year following licensure of Felbamate, a warning was issued to physicians, noting that Felbamate was linked to risk of aplastic anemia, and that some fatalities had resulted.

The above example and others like it should be well documented in medical and pharmaceutical journals, and would have proved a much more solid argument for the author than his use of "might-have-been" alarmist estimated statistics, like those used at the beginning of the article. The misuse of statistics is not needed to illustrate this case of government gone bad.

Alicia Oakley
Greenville, IL
Eric Tellefsen
Elberon, NJ

Alexander Volokh replies: For the benefit of Ralph Dreger and Gordon LaBedz, let me make clear that I, too, am not in love with drug and medical-device manufacturers. Neither the government nor industry is in the medical business for kindness alone. The true question, though, is how to avoid the FDA making an already risky situation worse.

Mr. LaBedz suspects that my estimated "lives saved" will be short and low-quality. I suspect that the folks whose lives are saved may think differently. Some of the treatments may cost hundreds of thousands of dollars, but I assure you that the FDA has quite other criteria in mind.

Mr. Dreger's question of drug patents is a thorny one, but FDA reform can proceed independently of patent law, and patent law can be changed regardless of what the FDA looks like. The two questions are connected, but independent. As for his second point, if all the FDA did was guard against fraudulent labeling, there would be no problem.

Saul Kent's proposal, which would allow consumer choice, is a good one. I wouldn't lay the blame for the antiarrhythmic drug deaths, though, on the FDA. Until we become all-knowing, science will be tricky and intelligent folks will disagree. Given this, the true public health policy is not to ban things that don't work, but to empower people to choose what they think might work and to take the risks that may save their lives.

I agree with David Anast that we should be concerned about the survival of the device-manufacturing industry. I wouldn't be too concerned, though, about the number of companies that are actually inside the United States. If, regulation aside, it's really cheaper to do the same work in India, then we may be better off if companies go there. And if mom-and-pop plants go under but a multinational acquires them, then we consumers may not lose anything.

As to my statistics, I refer the reader to Sam Kazman's "Deadly Overcaution: FDA's Drug Approval Process" (Journal of Regulation and Social Costs, August 1990). Here's how they work. In 1988, the FDA approved the ulcer drug, misoprostol. The FDA estimated that gastric ulcers caused 10,000 to 20,000 deaths a year, and misoprostol was reportedly 94 percent effective. FDA review took 9.5 months (.79 years), which makes a death toll of about 7,500 (10,000x.94x.79) to 15,000 (20,000x.94x.79).

Naturally, these are just crude approximations. Of course, if the FDA had approved misoprostol immediately, not everyone would have used it. There are methodological questions—do we count FDA delay from the moment of the application or from the moment the drug is sold anywhere? But the FDA hasn't admitted that the FDA could be responsible for any deaths. If we can start arguing over the numbers, the FDA debate will have made a great leap forward.

Alicia Oakley and Eric Tellefsen claim that such numbers are useless and that I should have focused on FDA-approved drugs and devices that killed people anyway. I disagree. The "simple fact that the FDA disallows our citizens and their selected health care providers freedom of choice" is a powerful fact for libertarians, but isn't enough for most people. When people die from bad drugs and devices, they already make headlines. Folks like Sid Wolfe of Public Citizen latch onto such examples and use them to advocate vastly expanding the FDA. But drug-lag victims, even when there are thousands of them, are invisible. We need to put faces on the victims.

Regulation Blues

"Slash and Burn" by Rick Henderson (May) was a well-reasoned analysis of the frustrations that have fed the growing regulatory reform movement. The difficulties the Kahle family experienced using a well that provided fresh water cleaner than government standards required is symptomatic of the rigidity that has given the United States the most costly regulatory system of any industrialized nation.

This state of affairs could be alleviated by regulatory reform legislation containing risk assessment and cost-benefit analysis. These procedures, which the U.S. House has passed and the Senate will be considering in June, would bring about a reallocation of resources to more cost-effective programs. They "could save an additional 60,000 lives per year" at no increased cost to taxpayers or the private sector, according to the Harvard Center for Risk Analysis.

Arthur E.F. Wiese Jr.