Imagine this situation: you are stricken with a very serious and possibly fatal disease. There is a known drug that might cure your illness but, because of US government regulations, neither you nor your doctor is permitted to obtain it. "Impossible!" you say? According to numerous medical experts, economists, and at least 113 members of Congress, such a regulatory nightmare not only exists but is causing perhaps millions of Americans to suffer and even die from illnesses that might very well be cured—or at least alleviated.
The controversy centers around the restrictions imposed by Congress and implemented by the Food and Drug Administration (FDA) over the interstate pharmaceutical drug market. Most experts agree that before a drug is marketed, it should be proven safe to use. As far as the federal government is concerned, however, proof of safety is insufficient. Ever since 1962, drug manufacturers have been required to prove that their products are not only safe but also effective in combating illnesses, as claimed. Because effectiveness is very difficult and expensive to demonstrate, however, some observers maintain that the costs of clearing a new drug with the FDA often are greater than what the drug could possibly earn in profits. Consequently, many drug companies are reluctant to work on developing medicines that could be very useful for some patients but would not be likely to bring in hefty earnings.
Regulation of the drug industry was ushered in with President Franklin D. Roosevelt's New Deal. In 1938, after it was discovered that potentially poisonous drugs had been marketed without proper testing, Congress passed the Food, Drug and Cosmetic Act, giving the FDA authority to require proof of safety. Then, in 1962, Congress passed the Kefauver-Harris Amendments, requiring that drugs be proven effective as well before being licensed for commercial distribution. This action was taken in the wake of revelations that thalidomide, a sedative that had been very popular in Europe, could cause birth defects in the children of women who used the drug during pregnancy.
Critics argue that enactment of the efficacy legislation was illogical, since the issue that prompted it was purely a matter of safety (and, even so, thalidomide was never approved for use in the United States, having been screened out as a potential danger by FDA medical officer Frances Kelsey.) These experts claim that the effectiveness requirement has done little more than stifle innovation in the drug industry.
The FDA's drug approval process is very time-consuming and expensive. The first step in clearing a new drug for sale is to test it with animals. If animal tests indicate that the drug is likely to be safe for human consumption and might be effective in combating a disease, the FDA closely supervises three phases of extensive experiments with people: first with healthy subjects and later with actual patients. Using just a few patients for the early tests and as many as several thousand during the final phase, experimenters administer the drug to see if it causes the desired result without any serious adverse side effects. Upon completion of the tests, FDA scientists organize and analyze all of the accumulated data and make a final decision to approve or not approve the drug.
From beginning to end, this process takes years—usually over a decade, sometimes nearly two decades—and critics charge that much of the delay is caused by testing for efficacy. Prior to 1962, it took only two to four years for a drug to undergo FDA investigations. In particular, the final stage of approval (that of analyzing the data) is significantly slowed because determining effectiveness is much more complicated than determining safety.
Indeed, a number of experts contend that proving efficacy actually is impossible, because drugs cause different reactions in different people. It is seriously irresponsible, some say, to ban a drug that might be ineffective for most people but very helpful for a few. "We have seen cases where members of the same immediate family will react differently to a drug," claims Kern Smith, executive vice-president of the Health Industries Institute, a trade association for drug manufacturers. "And sometimes the FDA will keep a drug off the market even if it demonstrates efficacy in 20 percent of their own test subjects."
Moreover, during the drawn-out period when a drug is undergoing tests, patients with terminally fatal diseases are not likely to be overly concerned about "wasting their money" on a drug that might be ineffective (or even a little dangerous, for that matter).
But perhaps the most damaging argument against the efficacy amendments is this: The costs of the FDA approval process are paid by the company that wants to market the drug in question. When only proof of safety was required, these costs averaged about $1 million per drug. Today, mostly as a result of the efficacy amendments, some experts maintain that the figure has risen to nearly $40 million. Consequently, small drug manufacturers often cannot afford to develop new medicines, and even major firms are reluctant to do so because they might not earn sufficient profits to cover the enormous expense.
"This is a very clear-cut case where government intervention is warping the ability of private companies to serve consumers," asserts industry spokesman Smith. "The smaller companies, especially, are stifled by this because they don't have the financial resources to meet the FDA's standards. And it's the drug consumers—the elderly and the sick—who suffer because medicines which might help them cannot be made available."
In 1974, Professor Sam Peltzman of the University of Chicago's Graduate School of Business conducted an extensive study of the 1962 amendments. Publishing the results in a booklet of some 100 pages, Regulation of Pharmaceutical Innovation, he concludes that the efficacy requirement acts as a serious detriment to the development of potentially life-saving medicines. "Before I did this study my feeling was that a regulation of this kind could have both costs and benefits," Dr. Peltzman recalls, "and I didn't have any pre-conceived notions about it before I began. But it soon became clear to me that the magnitude of the costs and its very counter-productive effect on the drug market outweighed any conceivable benefits that regulations that are killing us this regulation could have."
Professor Peltzman discovered that, with the efficacy requirement, the cost of developing new drugs skyrockets, and in the process the availability of medicines falls by more than 50 percent. In the 10 years before the 1962 amendments, the pharmaceutical drug industry marketed an average of 43 new medicines each year. After the requirement for effectiveness was instituted, the number of drugs introduced in the United States began to decline sharply—at first, down to an average of 17 per year and, according to more recent statistics, it is now as little as 13 per year. When companies are determined to withstand the bureaucracy and promote their drugs until approved, the extra expense is usually passed on to consumers in the form of higher retail prices.
Measured against these negative aspects, the benefits of the efficacy amendments seem minimal, to be sure. Before they were enacted, Dr. Peltzman found, less than 10 percent (and possibly as little as 5 percent) of drugs sold on the market were deemed ineffective by the medical profession. "Even after the amendments were passed, there were still some ineffective drugs that managed to get through the FDA tests and onto the market," Peltzman observes. "So the advantages of the amendments could actually be less than it appears—and it appears that they are very small."
Other research tends to reinforce Professor Peltzman's conclusions. Two pharmacologists at the University of Rochester—William M. Wardell and Louis Lasagna—discovered that, of all drugs marketed in both the United States and Britain between 1962 and 1971, more than half were introduced in Britain first (an average of 2.8 years before the FDA permitted them to be sold in the United States).
"There are drugs which, in my judgement, have been proven effective for years in other countries," says Dr. Lasagna, "and yet they are not available in the United States because of the attitude at the FDA. You can hold off approval on a drug forever because it can always be argued that it hasn't been proven sufficiently effective or safe when, in fact, the same drug might have been used safely and effectively for decades—and this seems to be the way that some of the bureaucrats at FDA are thinking."
• Drugs to ease heart ailments, in particular, have suffered in the United States at the hands of FDA foot-dragging. US doctors are permitted to use only about one-eighth of the more than 45 new heart and circulatory medicines that have been introduced in other countries since the mid-1960s.
• For example, in recent years a new family of drugs for treating high blood pressure and a painful heart affliction called angina has come into wide use in Europe. Known as beta blockers, only one form of this medication, propanolol, is licensed by the FDA for use in the United States. Pharmacologists Wardell and Lasagna report that an elderly woman had to be treated in Britain with a different kind of beta blocker (which, of course, could not be obtained here) because propanolol made her ill.
• Heart disease patients have not been the only victims of the efficacy amendments. Cromolyn Sodium, a drug that in some cases greatly reduces the agony of asthma, was finally approved by the FDA in 1973, though it has been available in Britain since 1969 (where it is now the third most prescribed drug).
• Between 1967 and 1971, five new drugs to ease the effects of hypertension were introduced in Europe but, although hypertension burdens nearly one-eighth of all Americans, none of these drugs has been cleared by the FDA. In fact, there has not been an approval for any new general-purpose antihypertension drug since 1963.
• Sodium Valproate, viewed by many experts as one of the most effective drugs in preventing epileptic seizures, has been used successfully for more than a decade in 16 foreign countries. Although the FDA finally approved the drug in April, its foot-dragging caused up to a million needless seizures each year.
The 1975 Economic Report of the President of the United States came out with heavy criticism of the efficacy amendments, arguing that they not only have increased costs and caused unnecessary delays but also might be without any significant value at all. "It is not clear that the average efficacy of drugs introduced after 1962 is any higher than that of drugs previously introduced," the report concluded. In April 1976, the President's Biomedical Research Panel declared that the FDA "has become a formidable roadblock" to the development of "potentially useful drugs."
"It is indeed ironic," Dr. Lasagna remarks thoughtfully, "that what was supposed to be a program to protect consumers is actually increasing their exposure to greater disease by taking away possible cures."
A FREEDOM ISSUE
In 1972, 22 leading medical experts, disturbed by the consequences of the efficacy amendments, combined forces and protested to Paul G. Rogers, chairman of the Health Subcommittee in the House of Representatives. This unofficial but distinguished group—led by anesthesiologist Robert D. Dripps and including Dr. Lasagna, heart surgeon Michael DeBakey, and cardiologist Irving H. Page—complained to Congressman Rogers that the FDA approval process is "causing us to fall behind in…medical science" and "may be depriving the practicing physician of agents beneficial to patient care."
Though coolly received by Congressman Rogers, this communication prompted outrage elsewhere on Capitol Hill. Representative Steven D. Symms introduced legislation to repeal the efficacy amendments altogether. The proposed Medical Freedom of Choice Bill would, he claims, "lessen the price and increase the availability of safe pharmaceutical drugs to the American public." Symms has been one of the FDA's strongest critics since he was elected to Congress in 1972. "There is a tremendous and totally unnecessary additional cost of medicines burdened upon the public by the efficacy amendments," he says. "This is particularly burdensome for the elderly senior citizens who really need these drugs."
"In this country, we have a system of professional medical care, where we have well-trained physicians who have to meet very high standards before they can practice medicine. And in each individual case, the doctor and the patient should have the freedom to decide which drugs might be useful, which might be dangerous or ineffective in that particular case—and you don't leave that decision up to a bunch of bureaucrats who aren't skilled physicians."
At first, Symms's bill had difficulty attracting supporters. Even some of the academicians most vocal in their criticism of the 1962 amendments were reluctant to endorse complete abolition of all requirements for efficacy (in fact, a few still are). Symms himself was viewed as a very conservative politician (which he is) whose motivation might be to terminate all government regulations. Indeed, Symms's political campaigns are dominated by his unswerving support for the limited government/free enterprise system, and he concedes that the Medical Freedom of Choice Bill is largely an outgrowth of his economic philosophy. "The issue here is freedom," he says emphatically—"the right of citizens to decide their own destinies." Thus Symms probably had more trouble obtaining support for the bill than if it had been proposed by a political figure of more moderate standing.
Nevertheless, Symms persisted in promoting the legislation, and his efforts have begun to meet with some success. What emerged as an unlikely proposal endorsed by only a handful of Symms's fellow conservatives on Capitol Hill now has at least a chance of being passed (though probably not in the immediate future). At present, the bill has 113 House cosponsors from all corners of the political spectrum, including Republican moderates such as Guy A. Vanderjagt (one of the GOP's leading dissenters in the House) and liberal Democrats like Thomas J. Downey (the youngest and one of the most reform-minded members of Congress) and Leo J. Ryan (who often finds himself taking positions left of the already liberal Democratic leadership)—and even Shirley Chisholm, the practically radical black congresswoman whose unsuccessful bid for the 1972 Democratic presidential nomination was based on a platform more liberal than that of the senator who finally won the candidacy, George McGovern. (More recently, however, some of the liberals have begun to favor an administration-backed reform bill [see box].)
As a matter of fact, Representative Chisholm has done more than just offer her vote of support: last year she and Symms coauthored a letter to their colleagues urging them to help pressure the FDA to expedite the approval of Sodium Valproate. "The harmful results of the efficacy amendments are so clear," notes Symms, "that support for this legislation cuts across traditional political boundaries."
And what about repealing the 1938 requirement that drugs be proven safe before they are marketed? Of course, proving safety is not nearly so time-consuming nor expensive as proving efficacy. Still, because different patients vary in their reactions to drugs, medications that are dangerous for many may be completely safe for others and possibly helpful in curing disease. Though he acknowledges that this argument may have some legitimacy, Representative Symms opposes an extension of his bill to abolish the FDA's safety provisions. "The American public is not prepared to embrace a concept of freedom that is of such a drastic nature," he suggests cautiously, adding, "Besides, the safety requirements have actually had an important beneficial effect and I think that repealing them could put the public in some danger."
THE LAETRILE SPECTER
Though partially related in certain respects, Congressman Symms stresses that the Medical Freedom of Choice Bill should be distinguished from the highly explosive laetrile controversy. Hard-line laetrile advocates are demanding that this purported cancer-curing drug, made from an abstract of apricot pits, be licensed for distribution throughout the country. Already, laetrile has been cleared for use by a number of individual states, but interstate sales of the drug are still forbidden by the FDA.
For years, most of the medical profession has alleged that laetrile is completely worthless as a cure for cancer or anything else. Moreover, recent incidents involving the drug have raised questions about its safety. As a result, the FDA continues to issue stringent warnings against using laetrile—particularly when it is purchased from manufacturers who are operating illegally. Although Congressman Symms would like to see laetrile eventually cleared by the FDA (after a method is developed to produce it in a form that meets with federal safety requirements), he urges those who might be suspicious of laetrile not to deny the benefits of his bill. "Laetrile is not by any means the most important drug I'm concerned about," he says. "There are numerous other drugs, which have the strong support of the medical community, that are being kept off the market by the efficacy amendments."
Mr. Symms charges that some opponents of the Medical Freedom of Choice Bill are behaving irresponsibly by trying to link the laetrile issue directly with the drive to repeal the 1962 amendments and thereby discredit his entire legislative effort—particularly in the eyes of medical experts who have not yet made up their minds about the drug effectiveness debate. Last May, the Washington Post editorially condemned the bill as "scary," claiming that it is "being advanced in the emotional atmosphere generated by laetrile." In a reply printed two weeks later, Symms charged the newspaper with following the "policy of a great deal of the media" to ignore the potential benefits of his bill and added that, if anything, it is the Post that permits its editorial opinions to be "advanced by the laetrile issue."
FDA FIGHTS BACK
Whether or not they use the laetrile issue irresponsibly, opponents of the Medical Freedom of Choice Bill are firm in their criticism of efforts to repeal the efficacy amendments. Not surprisingly, FDA bureaucrats, who stand to lose a lot of authority if Symms is successful, are bitterly opposed to the proposal and maintain that federal control over the drug industry should be enforced more aggressively, not weakened. Some FDA officials even hint that supporters of deregulation simply are trying to promote their own political or academic careers with a fraudulent cause.
"The efficacy amendments are a basic form of consumer protection," declares FDA spokesman Wayne L. Pines, "and they provide the public with an ability to have at least some confidence in this country's drug system—in how drugs are developed and marketed to ensure that an average consumer is not deliberately cheated or put in any unnecessary danger. I don't think the co-sponsors of Symms's bill are supporting it out of any kind of hysteria, but I do think that they are taking the wrong approach."
As FDA officials see it, the requirements for effectiveness and safety are interrelated to such a large extent that to abolish one would seriously weaken the other. "You can't separate safety from efficacy," claims Mr. Pines, "because all drugs that have any kind of an effect also pose some kind of safety hazard. There's no such thing as a completely safe drug—if a drug affects your disease it's also going to affect other functions in your body. What we do at FDA is try to make a basic decision—we call it a benefit/risk decision—as to whether a certain drug is likely to have sufficient advantages to make it worth the possible risks it's going to impose."
Mr. Pines acknowledges that the FDA'S drug approval process requires an enormous amount of time and money but maintains that such inconvenience is necessary to ensure public protection. "Before we let a drug go on the market," he says, "we want to be as sure as we can that it's safe and will do the job that it's supposed to do." At the same time, however, Mr. Pines maintains that federal health officials are not insensitive to the problems created by FDA foot-dragging. He points out that the FDA presently is formulating its own legislative proposals to enable critically ill patients to obtain certain drugs that are still undergoing experimentation. "We are concerned," he insists. "We are concerned that we do not have strong enough ties with the private medical community, we are concerned that keeping drugs off the market too long can sometimes do more harm than good, and we are concerned that the laws might need up-dating to make them more workable in the present."
GOING TOO FAR?
While very few observers expected to find the FDA in support of the Medical Freedom of Choice Bill, it does seem a little odd that some of the efficacy amendment's strongest critics also are against complete repeal. This is a hurdle that Symms will have to overcome if he hopes to see his legislation enacted. For if the bill is opposed by a large number of medical experts, Congress will be very reluctant to pass it.
Already, the FDA's most vocal critics are refusing to endorse Symms's proposal. "I feel that the efficacy amendments are an important concept and can be made to work more in the public interest," remarks Dr. Lasagna, a long-time opponent of FDA policy. "My basic criticism is of the way that the bureaucrats have interpreted the law. Right now, I would say that most people at the FDA feel that it's their job to keep drugs off the market. And I think this negative interpretation should be transformed into a positive interpretation so that the FDA helps a proponent of a drug—whether it be an industrial proponent or anyone else—to find out if it is effective or not and get it on the market if it is. But repeal the efficacy amendments? No—I think that's going too far."
Congressman Rogers, who heads the House panel with authority over the Medical Freedom of Choice Bill, is fiercely opposed to repeal of the amendments. Though willing to consider modifications of the FDA's approval process, Rogers refuses even to hold hearings on Symms's legislation until it has more than 50 percent of all representatives as cosponsors (at which point House rules would force him to hold hearings).
Sen. Edward Kennedy, chairman of the Health Subcommittee in the Senate, has proposed compromise legislation that would enable critically ill patients to obtain some partially tested drugs, but only under the FDA's close scrutiny. This proposal is approved by the FDA (see box) but is opposed by those who favor total repeal of the efficacy amendments on grounds that it would result in giving the FDA direct control over an ever-increasing number of medical cases that should be left in the hands of private practitioners. "If we go down this road, we're going to have cook-book medicine in America," Congressman Symms remarks sharply, "where decisions regarding medical care will be made by bureaucrats who are not qualified to do so."
At present, the future for the Medical Freedom of Choice Bill is uncertain. Opposition to the legislation may grow enough to prevent enactment—notwithstanding the bill's 113 cosponsors. Congressman Symms, however, remains confident and is seeking to take his argument for the bill to the general public. He predicts, "If the American people decide that they have had enough bureaucracy, enough ill health and high-priced medical costs, then Congress will have to consider this legislation seriously."
"In the end," the congressman concludes thoughtfully, "it will be up to average Americans to push for their own rights in health and medicine."
Mr. Silver is a commentator and correspondent for the Trans-World News Service. He has produced several TV and radio shows and has written for various magazines.
FDA Reform: Alternatives
Almost no one is now satisfied with the FDA's performance in the area of drug regulation, particularly when it comes to proving the effectiveness of drugs. Congressman Steve Symms's bill (HR 12371) is in competition with one sponsored in the Senate by Edward Kennedy (S 2755) and an identical one sponsored in the House by Paul Rogers (HR 11611). The Kennedy-Rogers proposal is backed by both the Carter administration and the FDA.
The Symms bill would:
• Abolish the efficacy requirement, keep the safety requirement, and require labeling that a drug's efficacy has not been judged by the FDA.
• Abolish the requirement that raw data on (safety) testing be submitted by drug companies and require submission only of certified summaries of methods and results, with raw data available for FDA inspection.
• Limit the FDA to only one 180-day extension of the processing deadline.
• Require the FDA to report semiannually to Congress, covering the status of each drug-approval application and providing a list of foreign countries where the drug has been introduced.
• Require the FDA to show administrative costs and economic implications for consumers of any proposed new regulations.
• Allow either house of Congress to block new FDA regulations.
• Require the FDA to provide technical assistance to small firms.
The Kennedy-Rogers bill would:
• Maintain the efficacy and safety requirements and, in addition, authorize HEW to require efficacy tests if a drug is "known" or "expected" to be put to uses not claimed effective by the manufacturer.
• Authorize the FDA to refuse approval of a drug if it is not statistically safer and more effective in its use than any drug already on the market.
• Require that all (raw) drug-testing data be available to the public (with apparently unenforceable provisions against a manufacturer's competitors' obtaining the information).
• Set up a National Center for Clinical Pharmacology to develop drugs with limited market potential—drugs currently neglected by manufacturers because of the cost of meeting regulatory requirements.
Symms's approach is to alleviate the problems generated by the 1962 efficacy amendments by removing the issue of efficacy from the FDA bureaucracy and leaving it to the drug companies and to consumers and their physicians. Symms would also exert more congressional control over the FDA, so that the costs of FDA regulation-delays in drug approval, the paperwork burden, and increased drug prices—might be kept in public focus. The Kennedy-Rogers-Carter-FDA plan is hardly comparable. It would not attempt to cut back the government's costly and time-consuming role in drug matters but would increase that role by maintaining and expanding the FDA's and HEW's mandate with respect to drug efficacy.
This article originally appeared in print under the headline "Regulations That Are Killing Us".