RU 486 is a synthetic drug with antisteroid hormone properties, synthesized by the Roussel-Uclaf Company, Paris, France, which owns a world-wide patent for all uses.

I have summarized the story of RU 486's discovery, testing and use in the Journal of the American Medical Association, in Science? and in a book entitled The Abortion Pill, also published in French as Génération Pilule.

Based on antiprogesterone action, RU 486 was first approved in France for voluntary pregnancy interruption (VIP), within the framework of the abortion law, as a medical method to replace the instrumental technique in use when the law was passed in 1975. Registration of RU 486 was obtained in September 1988.

Progesterone is essential both for ovulation and for the formation of the secretory endometrium which is required for nidation: it plays a central role in the establishment and maintenance of pregnancy. Given the multifaceted role of progesterone in the reproductive process, an anti-progestational compound such as RU 486 (Mifepristone, Roussel-Uclaf, Paris, France) could be expected to have a number of potential clinical applications in human fertility regulation including termination of pregnancy, induction of missed menses, postcoital contraception and inhibition of ovulation and implantation.

Our research and clinical evaluation have mainly been directed to termination of pregnancy and to inhibition of implantation. The aim of this presentation is to summarize briefly our experience with the use of RU 486 in these areas.

The development of antiprogestins and their use for early legally induced abortion have caused considerable heated debate concerning the appropriateness of this new technology for introduction into health care settings around the world. This debate is obviously complicated by broader issues such as abortion itself, women's rights and reproductive freedom, hormone-related medications, and other controversies. While these issues cannot be completely separated, this paper focuses on the management challenges that surround the introduction of new reproductive health technologies. This problem is central to the availability, accessibility, and applicability of new abortion technologies such as the RU 486/Prostaglandin combination.

Introduction of new contraceptive and abortion technologies has yielded important lessons that can guide decision-making regarding RU 486/Prostaglandin. Specifically, these experiences have highlighted the need to concentrate on quality of care concerns in introducing technologies, to ensure new services’ acceptability and, thereby, their effectiveness.

Antiprogestins represent a new class of promising drugs in fertility regulation, especially in early termination of pregnancy. RU 486 (mifepristone), manufactured by Roussel-Uclaf and marketed under the international trade name Mifegyne, is an antiprogestin tablet that is used sequentially with a prostaglandin for non-surgical termination of pregnancy. It has been chosen as a pregnancy termination method by over 100,000 women in France since its regulatory approval there in 1988. In addition, RU 486/prostaglandin was approved in July 1991 for use in the United Kingdom and an application for approval is being considered in Sweden. In Western Europe, it seems, RU 486/prostaglandin is increasingly accepted by medical experts, regulatory officials and women as an alternative to vacuum aspiration or dilation and curettage (D&C) for early pregnancy termination.

As the use of RU 486/prostaglandin becomes more established, health practitioners and women's health advocates are beginning to consider the feasibility of using this method for pregnancy termination in low-resource settings.

Although RU 486 has been the subject of extensive research and media coverage, in the United States the actual clinical use of the drug remains largely a theoretical possibility. California is the site of the only American clinical research on the use of RU 486 for termination of early pregnancy, and the California state legislature has adopted a strongly-worded resolution in favor of the testing and use of RU 486 in the state. However, the degree of physician awareness, the nature of physician opinion and the potential use patterns of this drug remain speculative.

To gain a better picture of what the physicians most likely to utilize RU 486 think about the drug, licensed California obstetricians and gynecologists were surveyed regarding their opinions about RU 486. The physicians were queried about their general awareness of the history of RU 486, their level of confidence in the existing data regarding the drug and their possible plans to administer the drug clinically if it were to become available.

Traditionally, fertility regulating methods were devised and offered in accord with the convenience of service providers and/or with their perceptions of the convenience of the population served. Generally, the focus was on a method's safety, efficacy, and affordability. It was not until a June 1972 planning meeting of the World Health Organization Human Reproduction Unit that the concept of acceptability was adopted as an additional criterion. The purpose was “to modify technology and programs to fit people, rather than modifying people to fit technology and programs.” A WHO Task Force on the Acceptability of Fertility Regulating Methods was established in January 1973 within what has now become the WHO Special Programme of Research, Development, and Research Training in Human Reproduction. Research conducted in the subsequent 17 years has had a profound effect on the field.

It is the purpose of this article to review the current status of early pregnancy interruption with mifepristone (RU 486) combined with a prostaglandin analogue from the standpoint of its acceptability to women.

“Acceptability research” is a term first coined to describe inquiries into individuals’ responses to family planning and contraceptive technology. As defined by WHO, “acceptability” is a “quality which makes an object, person, event, or idea attractive, satisfactory, pleasing or welcome.” In fact, the word “acceptable” in English is distinct from other issues that are also encompassed within “acceptability research.” “Acceptable,” to many, connotes faint praise. It may mean that something is tolerable only to the point of not being protested. On the other hand, the attributes “desirable” and “preferable” are more positive. In fact, all of these qualities are examined within the meaning of “acceptability research” as currently used by the Population Council.

Acceptability of a product or a medical procedure is most commonly studied in terms of patients or clients. Do those who will undergo the procedure or be the subjects of the technology find its use acceptable? But, in fact, acceptability can also be tested in relation to the providers of the technologies (i.e., the medical professionals), to the program managers or to policymakers.

In countries where abortion is performed safely in medical settings, the vast majority of up to several generations of women have come to identify early abortion as a surgical experience—whether on an inpatient or outpatient basis, whether with local or general anesthetic or whether in a freestanding clinic or a hospital.

In this context, the introduction of RU 486 with prostaglandin (RU 486/PG) as an alternative method of early abortion will once more alter women's experience of abortion.

The first part of this paper explores the similarities and differences between an abortion with RU 486/PG and vacuum aspiration from a women-centered perspective. This comparison is limited by the fact that only women in France have so far had access to both methods, along with those who have participated in clinical trials, and that very few in-depth women's experiences and reactions to this method have been published.

There is little experience with, and virtually no documentation of, adolescents’ use of RU 486 as a means of terminating pregnancy. While this void is understandable presently, it must be filled in order to determine how best to apply this new medical method to a special population—teenagers. It is imperative to know how adolescents might react differently from older women physiologically and psychologically, how they would accept this method of abortion and how health service providers should respond to their special needs. Counseling, for example, is particularly important for adolescent use of any family planning or abortion service.

Although it is not possible to review directly adolescent experience with RU 486, it is instructive to examine related attitudinal and behavioral patterns to assess the potential for adolescent use of a medical method of abortion. Documented experience with contraception and surgical abortion underscores the major challenges—present and new—for adoption of a new approach.

There is little experience with, and virtually no documentation of, adolescents’ use of RU 486 as a means of terminating pregnancy. While this void is understandable presently, it must be filled in order to determine how best to apply this new medical method to a special population—teenagers. It is imperative to know how adolescents might react differently from older women physiologically and psychologically, how they would accept this method of abortion and how health service providers should respond to their special needs. Counseling, for example, is particularly important for adolescent use of any family planning or abortion service.

Although it is not possible to review directly adolescent experience with RU 486, it is instructive to examine related attitudinal and behavioral patterns to assess the potential for adolescent use of a medical method of abortion. Documented experience with contraception and surgical abortion underscores the major challenges—present and new—for adoption of a new approach.

Does the prospect of introducing RU 486 into the United States pose any unique ethical issues? Or are the ethical questions raised by antiprogestins similar to those that arise when any new medical technology comes along? The short answer is that the ethical issues are not new or different, but the politics of abortion can seduce us into thinking that antiprogestins bear ethical hazards of a novel sort.

One transcending ethical question stands before us: Would it be the right thing to do to introduce RU 486 into the United States today? The deceptive simplicity of that question requires further analysis.

Some pharmacists who believe that abortion is immoral are troubled by the thought that they might be required to fill prescriptions for abortifacient drugs like mifepristone. Do pharmacists have the right to refuse to fill such prescriptions?

Questions about the rights of professionals have both moral and legal dimensions. I will assume—although this assumption is by no means axiomatic or uncontested—that the rights and responsibilities of persons in general and professionals in particular ought to be grounded in morality and not the law. For example, a person who breaks the speed limit to bring a critically ill friend to a hospital's emergency room violates the law, but may be morally justified in doing so. There is no legal duty to rescue a person in danger, but many moral communities hold that our moral duty of beneficence requires us to prevent harm to others, at least if in so doing we are not placing ourselves and others at great risk of harm.

One key legal question on everyone's mind is whether RU 486 can meet the standards for Food and Drug Administration (FDA) approval for a drug indicated for abortion. It would seem that it can. Under the Food, Drug, and Cosmetic Act, a sponsor must show that a drug is safe and effective for its intended use. Efficacy must be demonstrated by substantial evidence, which means evidence consisting of adequate and well-controlled investigations, including clinical investigations by experts qualified by scientific training and experience to evaluate the effectiveness of the drug. If on the basis of the clinical trials it could fairly and responsibly be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions of use prescribed in the labeling, and if the drug is safe, the FDA will approve it.

Prospects for the introduction of RU 486 into the United States in the foreseeable future are not good. Despite the drug's proven value in inducing abortion safely and effectively in early pregnancy without the need of surgery or anesthesia and its potential value in the treatment of many other diseases, it has been held hostage by the controversy over abortion. Because of opposition to abortion from the current administration and the threat of boycotts by antiabortion groups, Roussel-Uclaf, the drug's manufacturer, has expressed its resolve not to become embroiled in the abortion debate and has postponed indefinitely plans to market RU 486 in the United States.

The contrast between this situation and that accompanying the introduction of RU 486 into France and England, the two countries where it has so far been approved, is striking. Rather than blocking access to RU 486, the governments of these countries moved forward expeditiously with testing and approval of the drug.

Grants of exclusive rights to inventors are not a modern phenomenon. In some early civilizations such grants were at the pleasure of the ruler. In 1474 the senate of the Republic of Venice introduced what is believed to be the first law that provided a systematic procedure for obtaining patents for inventions. That system disappeared with the decline of the Venetian Republic. During the 17th and 18th centuries the English developed a system which has survived in its fundamentals, and that system has been adopted, with variations, by the great majority of countries. The justification for the system is the encouragement that it provides to invest in research and development and to publish one's accomplishments rather than try to preserve secrecy.

On July I, 1992, I received a phone call from a reporter asking for my response to Leona Benten's choice to defy the U.S. Food and Drug Administration's ban on RU 486 by bringing a single personal dose of the abortifacient drug into the U.S. on a flight from Europe. By the end of the day, my colleagues and I at the New York-based Center for Reproductive Law and Policy had been asked and had agreed to represent Leona and her companions, Dr. Louise Tyrer and Lawrence Lader, in their legal challenge to the import ban and, more urgently, in their effort to retrieve the RU 486 pills that were confiscated from Leona by U.S. Customs officials at the airport. Leona, who was 6 weeks pregnant and who desperately wanted to terminate her pregnancy by a non-surgical abortion method, had only two more weeks in which to use the drug according to prevailing medical protocol.