What the FDA Should Learn From the RU-486 Marathon

The Food and Drug Administration did something truly surprising late last month: It made a cautious decision that put strong safeguards in place to protect the health of patients using a newly approved drug.

Unfortunately, that hasn't been the norm at the FDA lately. For years, Congress has gradually stepped up pressure on the agency, complaining that it blocked or delayed the sale of useful and profitable medications. In 1997, a new law directed the FDA to speed up the approval process, at the same time weakening the agency's resources and authority to protect consumers. Chastened, the FDA today approves more medical products and does so more quickly than ever before--but far too many of these drugs are approved before they have been adequately tested and scrutinized.

Last month, however, the FDA approved RU-486--mifepristone, the abortion pill--and its example has turned out to be instructive. The process of approving this controversial drug was agonizingly slow and obviously politicized, resembling a battle between warring ideologies more than a scientific review. But the outcome makes scientific sense and protects consumers.

In that way it reminds me of the kind of careful review and internal battles that once gave the FDA the reputation of a fierce watchdog--a reputation it earned when it kept thalidomide off the U.S. market 40 years ago, saving thousands of American babies from deformities.

Lately, the FDA has become more of a consumer adviser than a watchdog. FDA decisions have often saved lives; but the agency's efforts to please the companies that make drugs and medical devices--as well as Congress--have sometimes undermined its mission to protect consumers.

I have watched the FDA for years: first as a university researcher, later as an investigator for the House subcommittee that oversees the agency, and now as the head of a think tank that focuses on health issues. I have seen firsthand how often the FDA approves medical drugs and devices whose benefits are questionable compared to their risks--and claims that it has fulfilled its responsibility by pointing to the often-unintelligible warnings written in fine print on package inserts.

The few FDA watchdogs that are left share my concerns. For example, a report by the General Accounting Office early this year publicly stated what FDA insiders have admitted for years: The FDA lacks the ability to track problems caused by medical products once they are approved. That means that drugs and devices continue to be sold long after dangers have become obvious.

The FDA is not supposed to make moral judgments. It is supposed to approve medications and devices solely in terms of how well they do what they promise, and what risks they pose to the people who take them.

By those standards, RU-486 should have been approved long ago: It had been safely used for years in France and other countries, and there was solid research evidence that it was effective at ending a pregnancy. Extensive data showed that it is at least as safe for pregnant women as the alternatives, which are surgical abortion or pregnancy and childbirth. And yet, while the abortion pill languished in FDA limbo, many more questionable products were quickly approved.

The reason was the intense ideological battle over abortion, and the fact that many members of the Republican congressional leadership--which has power over FDA funding and programs--are opposed to abortion. So the final FDA decision on RU-486 was a compromise: It approves the drug, but spells out very detailed rules for how it can be prescribed, by whom, and under what circumstances it can be used.

Under these rules, a woman must make three visits to the doctor or clinic. During the first, she must be examined to determine that she is no more than 49 days into her pregnancy; she must receive counseling and get a printed document with information on the drug; and she must sign an agreement saying that she understands the procedure and its potential risks. Then the doctor provides the mifepristone pill.

Two days later, she must return to the doctor to take the second drug in the abortion procedure, misoprostol (a drug previously approved by the FDA for other uses). Twelve days later, she must return to the doctor, who will confirm the end of the pregnancy or, if there are complications, arrange for her to see a surgeon.

Such restrictions are extremely rare. The FDA usually backs off from telling doctors what to do, saying it can only approve or reject medical products, not regulate how physicians use them.

For example, our think tank, as well as the National Women's Health Network and other health advocates, has repeatedly asked the agency to require that clearly worded informed consent forms be signed before patients receive long-acting contraceptives, breast implants and several other medical products, but the FDA has refused.

Patients will benefit from the RU-486 rules that require both the informed consent form and the patient information brochure be written by the FDA rather than the manufacturer. Instead of tiny print or unintelligible jargon, these materials clearly explain how the drug works, and describe possible side effects and warning signs of problems to watch for.

Abortion-rights advocates say this process will restrict the availability and affordability of RU-486. That's true. For example, doctors who cannot find surgeons to back them up will be unable to prescribe the abortion pill. (Although the FDA lacks the resources to ensure that all doctors abide by the rules, doctors could certainly be vulnerable to lawsuits by any patient harmed when they do not.) But the process also protects women from potentially serious adverse reactions and thus provides safeguards for patients that we have not been able to obtain for other medical products that lack the politically supercharged atmosphere surrounding the abortion pill.

Rezulin was approved by the FDA in 1997 to treat Type 2 diabetes only six months after its manufacturer submitted it for approval. That same year, Rezulin was taken off the market in England because it was linked to serious and sometimes fatal liver damage. The deaths due to liver damage of at least 61 Rezulin patients were reported before the agency finally concluded earlier this year that other available drugs were safer and just as effective. Even then, the FDA did not take Rezulin off the market: As is its usual practice, it requested that the manufacturer "voluntarily" withdraw the drug, which the manufacturer did in March.

Propulsid was a popular heartburn medication that was approved by the FDA in 1993. After more than 80 deaths from cardiac problems were linked to the drug in the United States, the FDA and the manufacturer announced in March that this drug also would be voluntarily removed from the market. Even then, the FDA allowed it to be sold for several more months.

Saline breast implants provide an especially dramatic comparison with the RU-486 process. Because they were first sold before the FDA was authorized to regulate medical devices, several hundred thousand women received such implants before the manufacturer was required to submit safety data and go through the approval process earlier this year. Saline implants were not widely used until a few years ago, but already more than 65,000 serious adverse reactions have been reported to the FDA. This is an amazingly high number of complaints.

Because of the highly publicized court settlements and multimillion-dollar public relations efforts of implant manufacturers, few medical products have been as controversial as breast implants. So, you might expect that the FDA would take extra care in reviewing the safety of the newly popular saline implants. You'd be wrong.

The FDA advisory panel considering approval was never given information about the 65,000 adverse reactions already reported. The FDA required no long-term safety data and made its decision without waiting for the not-yet-published results of long-term cancer and mortality studies conducted by the National Cancer Institute. Meanwhile, the manufacturers' studies reported extremely high complication rates within the first three years--affecting approximately three out of four mastectomy patients, for example. And yet, the FDA approved saline implants, with no restrictions on which doctors could use them under what circumstances and no requirements that patients receive clear warnings about risks in a consumer brochure or informed consent form.

How could this happen? The purpose of the approval process is supposed to be to determine whether a product is safe. The FDA that I used to respect, and that consumers have counted on, had a dual mandate--to warn consumers of possible risks and to keep products off the market that were not proven safe. And the lack of proof that a product is deadly is not the same as proof that it is safe. That's why long-term research is important for products that may have long-term risks.

The FDA's review of RU-486 took too long and was much too influenced by political pressure. But the final decision showed that the FDA still knows how to think through the risks of a medical product, and put safeguards in place to protect patients while giving them an informed choice.

Women choosing RU-486 will be protected from most potential risks and will understand the choice they are making. But the rest of American consumers--like the patients harmed by Rezulin, Propulsid and implants--had better beware.

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