Fifteen years ago this fall, in September 2000, the US Food and Drug Administration (FDA) approved the sale of mifepristone for medical abortion in the United States. This action gave women in the US access to what is arguably the most important reproductive health innovation since the advent of the oral contraceptive pill several decades earlier.
While the availability of mifepristone was an exciting landmark for women and for medical advancement in the US, French women had had access to the same medication for 12 years before the year of approval in the US. A small nucleus of scientists and physicians in France, including, notably, Drs. Etienne Baulieu and André Ulmann, working for Roussel-Uclaf, had fought hard for mifepristone’s approval, achieved in 1988. British and Swedish women were able to use mifepristone in the early 1990s, and women in most of the rest of the European Union had access after 1999.
The US was thus not formally an innovator nation in this important technology. However, the complex history of the arrival of mifepristone in the US is something to celebrate because it reflected collaborations that ensured ownership of the technology well beyond the usual commercial interests in new drugs.
American women and women’s groups, including the National Organization for Women, played important roles in educating Americans about the existence of the drug and the need for advocacy strategies to secure its entry into the US, given the reluctance of the commercial entity that owned the patent to register the drug on this side of the Atlantic. The US nonprofit sector was also involved in creating an environment that enabled the registration and use of the drug. The Population Council bravely assumed the role of shepherding the drug through the FDA approval process, including the design and implementation of the US pivotal studies; the Reproductive Health Technologies Project embarked on key policy work in support of medical abortion with legislators and government officials; the National Abortion Federation undertook important publicity, education and training programs; Planned Parenthood leant its support and expertise to rolling out the use of the drug in its clinics, and various private foundations contributed resources for all these tasks.
The approval process was a historically lengthy one involving the creation of a new commercial entity, finding new producers of the drug substance and developing packaging and marketing. The FDA issued an “approvable” letter in 1996, 2 years after the rights to the drug had been donated by Roussel-Uclaf to the Population Council in New York. That letter indicated that the drug could be approvable in principle but that important manufacturing issues remained to be solved. The actual approval did not come until the year 2000. Throughout this interval, US clinicians were trying to provide medical abortion in other ways, for example, by using a regimen of methotrexate and misoprostol and by studying an unofficial copy of mifepristone commissioned by the philanthropist Lawrence Lader and approved for a clinical trial by the FDA.
During this same time, the US medical and research community began a still-ongoing process of innovation in clinical and programmatic use of medical abortion drugs. When a drug is legally the property of a pharmaceutical company, that company normally takes on the responsibility of developing the drug, including dosing recommendations, instructions for use, new indications and so forth. Over time, the company in charge usually revises labeling and creates promotional materials in concert with the new information that it develops. In the case of mifepristone, the drug was in some sense “owned,” at least in an emotional sense, by all those who fought hard for its US approval and who developed innovations in the delivery of medical abortion care. Some of the innovations that are now the standard of care (e.g., lower dose of mifepristone, higher dose of misoprostol, home use of misoprostol and use to 63 days last menstrual period) were, in fact, common practice even before the FDA approval. In this period, the pharmaceutical entity that took on the marketing and distribution tasks in the US was small and slimly capitalized, leaving room for others to fill roles normally reserved for the commercial owners of a new product.
Because the technology was owned by many actors, these individuals and groups were simultaneously doing research — both formally and informally — on new ways to provide mifepristone abortions including new doses and routes of administration, changes in service delivery (including greater participation of women in the process, for example by administering their misoprostol at home, taking mifepristone outside the clinic, etc.), use at later gestational ages and even new indications for the drug. This activity has resulted in a large body of accruing evidence, a lot from the US, that has informed practice and should be of interest to the US FDA — but none of this evidence has been incorporated (as yet) into the drug’s approved label.
The scenario of a drug label lagging behind knowledge is widespread in medicine but should be of special concern to the entire community invested in medical abortion, because abortion is subject to great scrutiny and, often, political interference. This situation has opened the door for nuisance laws, passed by several states, which compel providers to use the drug only in accordance with the approved label. Such laws ensconce inferior medical practice and have no redeeming value; indeed, as a commentary in this issue discusses, such laws are associated with worse outcomes for women than the evidence-based practices that are not part of the current label.
Keeping up with both the promise and the problems associated with medical abortion (sometimes also known as medication abortion) in the US means monitoring the environment for new difficulties and new opportunities. The discrepancy between label and practice has now shown itself to be both a more important problem and a bigger opportunity than we might have imagined a few years ago. It is urgent to update the mifepristone label so that label laws enacted by several states will no longer confound the choices of women and cause doctors to provide inferior medical care. At the same time, the body of research on service delivery in medical abortion has grown more expansive in its approach to task sharing and has generated new ideas that can be reflected in revised labeling. Thus, the moment is promising.
This issue of Contraception contains a selection of commentaries that look at what we have learned after 15 years of use of mifepristone and where we may expect to make changes in the future. Almost no pharmaceutical product has captured the public imagination with the force of mifepristone. Initially, predictions were both dire and ecstatic: women would run rampant, having more abortions than ever, boyfriends would slip mifepristone into their girlfriends’ tea, abortion would become simple and easy, women would have access to abortion without any medical interface and the politics of abortion would soften. Little of this set of predictions has become reality. On the other hand, medical abortion has now made a profound change in both the experience of abortion and the landscape of abortion provision: it seems poised to become even more important in the next decades. In the process, as Claude Evin, the then French Minister of Health, noted many years ago, the technology really has become “the moral property of women.” Fifteen years after approval in the US, mifepristone abortion really is just that — and must remain so.
Published online: July 02, 2015
Accepted: June 26, 2015
Received: June 26, 2015
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