The Approval of Mifepristone (RU486) in the United States: What's Wrong With this Picture?

Paul Blumenthal, MD, Jane Johnson, and Felicia Stewart MD

Disclosures

Introduction

Since its approval in France in 1988, the abortifacient mifepristone (RU486) has proven to be a safe, effective, acceptable option for millions of women seeking abortion during the first several weeks of pregnancy. More than 500,000 women in Europe and millions of women in Asia have used the mifepristone/misoprostol regimen.[1] Women in the United States have waited long enough for this safe and effective early abortion option.

After more than 5 years and at least 1 false start, the Population Council, a nonprofit entity which holds the US rights to mifepristone, was able to identify a private industry partner, Danco, willing to confront threats of economic boycotts and protests to bring mifepristone to American women. In the meantime, violent acts and protests meant to intimidate women and healthcare providers have continued, culminating in the murder of Dr. Barnett Slepian in October 1998.

Women's health advocates have recently learned of yet another development in the ongoing saga regarding final approval of mifepristone. At a meeting of early abortion providers and abortion rights advocates, the Population Council and Danco revealed that the U.S. Food and Drug Administration (FDA) had made a series of proposals regarding the labeling and distribution of mifepristone that would severely limit women's access to the drug if and when it is approved.

The labeling and distribution restriction described by Danco would be unprecedented and without any clinical or scientific merit. More than 8000 women in the United States have had a medical abortion using mifepristone in combination with misoprostol in clinics, doctors' offices, and their own homes.[2,3,4,5]

In 1996 and again in February 2000, the FDA had declared mifepristone safe and effective for use as a very early abortion method. So why don't American women have access to this drug? Given the safe and efficacious profile that has been established for mifepristone and misoprostol, the answer apparently lies neither in science nor the practice of medicine, but in the politics of abortion and women's reproductive health.

Mifepristone can be administered safely by a wide array of healthcare providers. As a result, mifepristone availability not only could expand the options available to women who want to terminate their pregnancy early, but it could expand the number of providers willing to offer safe and accessible abortion services. A recent national survey by the Kaiser Family Foundation found that more than 1 in 3 gynecologists who do not now perform abortions would offer mifepristone.[6]

In addition, 31% of family practice physicians -- most of whom do not perform abortions now -- say they would also offer the drug. Rather than have to face a barrage of angry or even violent protestors outside an abortion clinic, women potentially could access abortion services in the privacy of their own doctor's office.

Unfortunately, the distribution limitations being discussed would virtually eliminate that possibility. One provision, limiting sale of the drug only to physicians trained in 3 procedures -- surgical abortion, mifepristone abortion, and the use of ultrasonography -- would mean that few new providers would be likely to begin providing medical abortion services. Another provision being considered, limiting its use to physicians who have admitting privileges to an emergency room within an hour's distance of their office or clinic, would make many current abortion providers ineligible to use this option.

These restrictions might be appropriate if mifepristone was a dangerous drug. But it is not. No woman has died as a result of using mifepristone. In fact, a blood transfusion, the most severe adverse outcome, has been required in only 0.1% of cases (or 8 out of more than 8000) in the United States[2,3,4,5] (Schaff EA, et al. Randomized trial of vaginal misoprostol at 24, 48, and 72 hours after mifepristone for abortion up to 56 days pregnant. Submitted for publication).

By comparison, Viagra -- known to have caused far more serious health consequences, including at least 60 reported deaths -- carries no such training or certification restrictions.[7]

Furthermore, the proposals' scope translates into an unprecedented and unwarranted intrusion in the nature of clinical practice. Midwives, for example, can and do deliver babies without having to be certified in backup procedures such as cesarean sections. Cardiologists routinely provide medication for chest pain without being trained and certified in cardiovascular surgery should medication fail. Ultrasonography is certainly not an essential part of early abortion care. In fact, a recent study in Lancet shows that a majority of women can accurately predict for themselves when they became pregnant.[8]

Even if one accepts ultrasound as a prerequisite to eligibility for a mifepristone abortion, isn't a consultant radiologist perfectly competent to perform this test and relay the results to the clinician providing the abortion procedure? Isn't such consultation an established, proven pattern for the safe and expeditious practice of medicine in the United States and elsewhere?

While final US approval of mifepristone continues to languish, clinical trials have been under way that clearly demonstrate that a variety of healthcare providers, including obstetricians/gynecologists, family physicians, and nurse/midwives, can and do provide safe medical abortions using mifepristone without any certification procedures. When an optometrist in rural Montana can write a prescription for Viagra -- no questions asked -- but a family practice physician in suburban Maryland has to jump through multiple certification hoops to offer the far safer mifepristone, something is clearly wrong.

Organizations such as the American College of Obstetricians and Gynecologists, Physicians for Reproductive Choice and Health and the National Abortion Federation are in strong agreement that mifepristone should be made available to women without imposing any unnecessary, unprecedented, or politically motivated restrictions that are not supported by scientific data (Physicians for Reproductive Choice and Health, personal communication).

Although disappointing, the slow and cautious pace to final approval for mifepristone is not altogether surprising. In 1998 and again in 1999, the House of Representatives approved an amendment to the Agriculture Appropriations bill that would prohibit the FDA from using any public funds to review and approve mifepristone. As long as social conservatives remain in power, review and approval process at the FDA will continue to come under heavy partisan scrutiny. Allowing decisions about medical science to be delayed by political pressure or fear of pressure, however, is surely not appropriate. This is especially unacceptable when such significant clinical issues are involved for women and their families. Indeed, the FDA's principal role in the drug-approval process is as a regulatory agency and, as such, is mandated to be concerned solely with the science and medicine of new drugs and devices.

In the past, despite political pressure, the FDA has relied on supportive scientific information to make courageous regulatory decisions. We urge that in determining how this regimen will be approved and regulated in the United States, the FDA should consider the enviable safety and efficacy record of mifepristone and misoprostol and make it's recommendations solely on the basis of the scientific data without being influenced by partisan political pressures.

Mifepristone, formerly known as RU486, is an antiprogesterone drug that blocks progesterone receptors that are key to establishing and sustaining a pregnancy. When administered within 49 days of a woman's last menstrual period and used in combination with a prostaglandin such as misoprostol, mifepristone is very effective (over 95% success) at inducing abortion.

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