THE ABORTION PILL: FINALLY AT HAND?

his was to have been the year that would change abortion in America.

With the anticipated arrival of the abortion pill, mifepristone, or RU-486, American women were to have gained an alternative to surgical abortion that, most health experts believe, would make abortion safer, more accessible and more private.

But this is the United States, and nothing about abortion is predictable.

After a decade of use by women in France, England and many other countries and after approximately 500,000 abortions worldwide, mifepristone is still not available in this country. Instead, RU-486 has encountered a daunting obstacle course strewn with antiabortion politics, bureaucratic red tape and missteps by the abortion rights group that is shepherding efforts to get the drug on the U.S. market.

Now, as a crucial Sept. 30 federal deadline nears, the fate of the abortion pill remains uncertain. Abortion rights advocates fear that the Food and Drug Administration may delay approving the drug or so severely restrict it that women and their doctors will be reluctant to use it as an alternative to surgical abortion.

(The FDA earlier this year set Sept. 30 as its deadline for deciding whether to approve mifepristone. The agency could also decide to set a new deadline.)

“I don’t think the public understands that because of politics, we are falling way behind other countries in terms of access to medical abortion,” says Francine Coeytaux, co-founder of the Pacific Institute for Women’s Health in Los Angeles.

Coeytaux and other abortion-rights supporters say that a window of opportunity for approving mifepristone may be slipping away, especially if the Republicans take control of the White House next year. Mifepristone, used to terminate pregnancy, differs from the “morning-after” pill, which is used within days of unprotected intercourse to prevent pregnancy.

Though Al Gore supports abortion rights and opposes restricted access to abortion, George W. Bush would allow abortion only in cases of rape, incest or to save the life of the mother. Bush’s father, former President George Bush, banned importation of RU-486 in the late 1980s.

Abortion rights supporters fear that if the FDA fails to act in September and Bush wins in November, the drug may never be available in this country.

“It’s clear that mifepristone would increase access to abortion,” something that Republicans have traditionally opposed, says Marie Harvey, an associate professor of public health at the University of Oregon and a researcher on reproductive health issues.

Access has been a hot-button issue for both sides of the abortion debate. Throughout the 1980s and ‘90s, legislatures across the country passed laws that required parental consent for minors seeking abortions, mandatory counseling and waiting periods and other limitations. An estimated 86% of U.S. counties, the majority of them rural areas, lack abortion providers, and the number of abortion providers fell 14% from 1992 to 1996, according to surveys from the Alan Guttmacher Institute, a New York-based reproductive rights group.

About 49% of pregnancies among U.S. women are unintended, and about half of those--an estimated 1.37 million per year--are terminated by abortion, according to the institute.

An abortion pill, many reproductive health experts believe, would increase access because many doctors who don’t perform surgical abortion would be more likely to offer the pill because it is relatively simple to use and could be given in the privacy of doctors’ offices.

Taken early in a pregnancy, the abortion pill is expected to be less costly and less traumatic for a woman than surgical abortion, says Dr. Bryna Harwood, a reproductive health researcher at USC. “For many, many women in this country,” she says, “access is a real problem.”

Two-Drug Regimen Early in Pregnancy

Mifepristone, which is the chemical name for the French medication, is prescribed during the first seven weeks of pregnancy as part of a two-drug regimen. (The second drug used to trigger the abortion is misoprostol, already available for the prevention of ulcers.) Women undergoing a mifepristone abortion typically experience severe cramping, bleeding and nausea. However, the most serious potential side effect, heavy bleeding, is rare, researchers say. About one to three women per 1,000 required a blood transfusion, according to data from clinical trials of the drug in the United States.

In contrast, surgical abortion is typically performed no earlier than six weeks into pregnancy, requires anesthesia and carries risks, such as infection, associated with any surgery.

Mifepristone was developed in 1980 by the French pharmaceutical company Roussel Uclaf. France approved the pill in 1988, followed by England, Sweden, China, Israel, Russia, Spain and other countries.

In Europe, more than half of women who have a choice between RU-486 (sometimes called a medical abortion) and surgical abortion opt for the abortion pill, according to a 1996 survey.

The drug’s safety record is part of its appeal for women seeking early abortions. Studies in Europe and the United States have shown the pill to be effective about 92% to 95% of the time. The mifepristone regimen fails to cause an abortion in 2% to 4% of women; those women can either opt to undergo a surgical abortion or to continue their pregnancies. For women who choose to continue their pregnancies after mifepristone fails, there is an increased risk of birth defects.

“Medical abortion is about physicians being able to give women a pill and then managing the effects of that pill, which is a miscarriage,” says Sandra Waldman, a spokeswoman for the Population Council. The council is the nonprofit reproductive rights group that holds the U.S. patent on mifepristone and has been trying to gain its approval.

The acceptance of RU-486 in Europe and elsewhere did not smooth the way for its debut in this country. The senior Bush’s import ban on RU-486 was not lifted until 1993, when President Clinton directed the FDA to investigate the drug. Shortly afterward, Roussel Uclaf donated U.S. patent rights for mifepristone to the Population Council.

From 1994 to 1996, mifepristone followed a fairly typical path through the federal drug approval process. U.S. research studies involving about 2,000 women produced results similar to those of earlier European studies.

Based on those findings, the FDA notified the Population Council in 1996 that it had given the drug an “approvable” designation. Approvable is agency jargon for a drug deemed safe and effective but for which there are still concerns about manufacturing, distribution or labeling. Most new drugs reach the market within a year, or sometimes just a few months, after receiving an “approvable” designation.

But an unusually rocky path lay ahead for the drug and its sponsor. In 1997, the company chosen to manufacture the drug backed out, leaving a trail of lawsuits and bad publicity. The council and its partner, Danco Laboratories, then had to convince the FDA that its new manufacturer could produce a quality substance.

Locating a new manufacturer “created a substantial delay,” said Heather O’Neill, a spokeswoman for Danco, which would distribute the pill.

But more recent setbacks have been harder for abortion rights advocates to comprehend. There is lots of speculation about the reasons for the delays--from political pressure by abortion opponents to bureaucratic timidity of FDA officials worried about job security in an election year--but few hard facts.

“There is growing resentment,” said Coeytaux of the Pacific Institute, noting that four years have passed since the FDA cleared the drug for safety and effectiveness. “Every step of the way has been marked by delays and more delays.”

Despite accusations from some abortion rights groups, there is no evidence that the FDA is bending to political pressure to keep mifepristone from U.S. women. The FDA declined to discuss the drug approval process for mifepristone, citing agency policy.

The FDA approval process for mifepristone has been unusually rigorous given the scientific evidence of the drug’s safety and effectiveness, says Harwood. But the latest delay was the most unexpected. And it has prompted some abortion rights supporters to consider a future without mifepristone.

FDA Questions Dog Approval Process

In February, the FDA issued a second approvable letter, asking for detail on a few final issues.

“Those questions were fewer in number and narrower in scope” than the ones in the 1996 letter, says Danco’s O’Neill, adding that responses were sent to the agency by late March.

Danco and the Population Council were so encouraged that they called a meeting on June 2 in New York to update health and reproductive rights leaders. The meeting was a turning point--but not the one they had hoped for.

On the eve of the meeting, the FDA unexpectedly issued a new list of questions and demands that had to be resolved before the drug would get final approval.

“The reaction was shock and confusion because we all thought we were moving in the same direction” as the FDA, says Coeytaux, who attended the meeting. “The Population Council was floored.”

According to several people who attended the June meeting, the FDA proposed:

* That mifepristone be distributed only by health professionals trained in surgical abortion, medical abortion and sonography, a condition that would appear to limit the service to doctors and exclude nurse practitioners and physician’s assistants who could help expand the pool of abortion providers.

* That doctors be situated within one hour of emergency rooms where they have admitting privileges.

* That a third party--such as the National Abortion Federation, a private accreditation group that trains health professionals--certify that the providers possess these qualifications and maintain a list of such providers.

The FDA often places conditions on a medication’s use, and mifepristone does produce unusually severe side effects. However, the agency’s proposals for the drug, particularly the suggestion of keeping a list of certified providers of a drug, is highly unusual, say industry experts.

None of the parties involved will discuss the negotiations in detail, but the Population Council’s Waldman said: “We’re really in the last stage, but it’s a tricky stage. This is a safe drug.”

And, Waldman adds, “the conditions the FDA has raised are not for safety reasons but because of politics.”

Some observers suggest that the recent setback may simply reflect a changing FDA. Agency Commissioner Jane Henney is considered more cautious than her predecessor, David Kessler, who first approved mifepristone. And the agency is still feeling shock waves from the recent controversy over Rezulin, the diabetes drug that was pulled from the market after it was linked to dozens of deaths.

Opponents of abortion, however, praise the proposed restrictions, saying that mifepristone is dangerous and that women are being misled about what medical abortion is like.

“Mifepristone is killing life. We don’t want to diminish that aspect of it. But it isn’t good medicine, either,” said Heather Cirmo, a spokeswoman for the Family Research Council in Washington, D.C. “There are complications associated with the drug that are similar with miscarriage. You can have the abortion at home. There is bleeding, severe cramping, and sometimes the woman doesn’t come back for follow-up if the abortion isn’t complete.”

Advocates of the method, says Cirmo, “are painting this as a miracle pill and the child vanishes.”

Whatever the FDA’s reasons, abortion rights advocates say that the proposed restrictions would significantly lessen the appeal of RU-486 to women and doctors.

“It would disqualify some current abortion providers, let alone other clinicians who want to add this to their practice,” Vicki Saporta, executive director of the National Abortion Federation.

Requiring doctors who prescribe the drug to be certified and listed could dissuade physicians concerned about the personal safety of themselves or their patients, says Coeytaux.

“More and more physicians [providing abortions] fear for their lives,” she says. “And if there is anything close to sounding like a registry or a list, they could be targeted.”

Danco says it has not established a price for the pill, and whether insurance companies would cover the drug is not known. But there is evidence that more doctors would offer abortions if they could do so with an FDA-approved pill in the privacy of their offices.

According to a recent survey of 767 doctors by the Kaiser Family Foundation, a nonprofit health care philanthropy based in Menlo Park, Calif., 44% of gynecologists and 31% of family practice doctors said they were very likely or somewhat likely to offer mifepristone. But some of those doctors would reconsider their decisions if, for example, they had to be certified to prescribe the drug.

Abortion rights advocates acknowledge that, with or without restrictions, mifepristone will not dramatically change abortion services in America, says Saporta.

“Improving access is very important,” she says, “but mifepristone is not a magic solution [for] ending the abortion debate in this country.”

(BEGIN TEXT OF INFOBOX / INFOGRAPHIC)

More interest in early abortion

Access to RU-486 in clinical trials or through “off-label,” or non-approved, use of the drug methotrexate has allowed more women and medical clinics to consider these alternatives to surgical abortion.

Doctors’ offices and clinics that offered abortion pills to women who were less than six weeks pregnant as part of clinical trials or in “off-label” uses of the drugs

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1992 1996 33% 42%

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Women who said they had abortions using pills seven or fewer weeks into their pregnancies:

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1992 1996 30% 33%

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FEWER ABORTION PROVIDERS

The number of U.S. doctors, hospitals and clinics providing abortion services has declined in the past 15 years, with most of the drop among hospitals and doctor’s office.

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1996 2,042 1988 2,582 1982 2,908

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ABORTION RATES DECLINE

The abortion rate among women ages 15 to 44 has declined from a peak in 1980.

(Number of abortions per 1,000 women)

1980: 29.3

1985: 28.0

1990: 27.4

1996: 22.9

Source: The Alan Guttmacher Institute