Article on U.S. RU 486 Test Gives More Details about Dangers to Women

On April 30, 1998, the prestigious New England Journal of Medicine (NEJM) published the results of a trial of the RU 486/Cytotec prostaglandin (RU 486/PG) abortion technique on 2,121 U.S. women. The test was conducted from September 1994 to September 1995 at 17 abortion facilities across the county as part of the effort to obtain a license to market the RU 486/PG here.

As would be expected, the abortionist-researchers proclaimed the safety and effectiveness of using RU 486/PG to abort women who were up to 49-days pregnant (that is 7 weeks since their Last Menstrual Period—or LMP). Unfortunately, journalists across the country followed their usual practice of uncritically parroting the pro-abortion researchers' claims about with scarcely any effort to offer the opposing Pro-Life or Pro-Family point of view.

Two aspects of the NEJM article are important for the Pro-Life and Pro-Family community.

First, media coverage of the publication provided a valuable update on the status of U.S. marketing of RU 486/PG, which has been stalled for over a year. Press accounts offered somewhat contradictory information, but apparently a manufacturer has come forward but not signed a contract. A spokesperson for the company that is handling the distribution and manufacture of RU 486 told the Associated Press that plans are being worked out to get RU 486/PG on the market in 1999.

And second, analysis of the data in the medical journal article reveals some additional ammunition that Pro-Family and Pro-Life advocates can use against RU 486/PG in the public policy debate. Of particular value is more information about how the drugs will be used and the risks of bleeding, nausea, vomiting, and pain.

Update on Marketing Plans

Press accounts about the NEJM article indicated that the Population Council and the companies that it is using to handle manufacturing and distribution, named Advances for Choice and Danco Laboratories, have revived plans for U.S. marketing, which has been stalled for over a year due to the lack of a manufacturer.

In September 1996, the U.S. Food and Drug Administration (FDA) declared RU 486/PG safe and effective for abortion but stated that final approval depended on additional information about labeling and manufacturing. In particular, the agency must inspect the manufacturer's facilities. Danco contracted with a Hungarian drug company, Gideon Richter, to make RU 486 for U.S. use. But Gideon Richter backed out in February, 1997, and Danco subsequently filed a lawsuit in May, 1997 to force the company to comply with the contract. Since then, plans for marketing have been on hold.

An April 29, 1998 Associated Press story reported that a spokeswoman for Danco, Heather O'Neill, “said the company has found a manufacturer, which she declined to identify, and is working out details with the FDA to get the drug on the market in 1999.” A similar report appeared in the April 30 Los Angeles Times.

But other media reports indicate that a manufacturer has not been definitely signed. In an April 30 New York Times story, O'Neill was quoted as saying that “We are focusing on identifying manufacturers, tableters, and distributors.” In addition, National Public Radio reporter Patricia Neighmond stated on April 29 that Population Council “officials say they're close to finding one, though they won't disclose any names.” Since Gideon Richter was not mentioned all, it appears that the lawsuit has not been settled and Danco is looking in other directions for a manufacturer.

Getting the production and distribution process underway is vitally important to the Population Council, its licensees, and their financial backers. Their patent rights to RU 486 expire in 2002. And at least $14 million has been raised so far from investors and spent without a single pill being sold. If RU 486/PG were to go on the market in 1999, Danco would have about three or four years to make a return on investment and show a profit while it controls the price.

One key factor is the price that Danco will charge. The Population Council's Internet website indicated on May 3, 1998 that no price has been set for an RU 486/PG abortion except that it “will be comparable to surgical abortion.” That probably sets a limit of about $350, an amount that has to cover not only the cost of the drugs but also additional staff expenses, special equipment such as an ultrasound machine, surgical treatment of the women who have an incomplete abortion, and surgical abortions when the drugs fail completely.

If past experience is any guide, the Population Council will publicize any breakthroughs in signing a manufacturer. But spokespersons have indicated that the name of the company will be not made public for fear of a consumer boycott of its other drug products.

More Complete Data on Dangers to women

Although the NEJM article was obviously slanted to put RU 486/PG in the best light, Pro-Life and Pro-Family supporters can use the research data about short-term adverse complications to inform the public, pregnant women, and the medical community about the dangers of the abortion technique.

Staff members of the Population Council, the sponsor of the test, presented preliminary information about the U.S. trial at the July 19, 1996 hearing of the FDA's Reproductive Health Drugs Advisory Committee, but the NEJM article is the first comprehensive presentation of the U.S. data. (According to a Population Council spokesperson, a companion article describing research on the “acceptability” of RU 486/PG will be published this summer.)

The article described the methodology, study design, statistical analysis, and results of the multicenter trial. According to the Population Council's Internet website on May 3, 1998, the U.S. trial focused on three goals. First, the American researchers sought to demonstrate that the abortion method could be used safely and effectively within the private U.S. health care system. Second, the U.S. test aimed to confirm the French data that RU 486/PG “was safe and effective” aborting women who were up to 49-days pregnant. And third, the experiment sought to gain experience and test safety and efficacy of using RU 486/PG on women up to 63 days pregnant.

The third objective represented a major departure from how RU 486/PG is used in France. There, drug company officials declined to license RU 486/PG beyond 49-days LMP because of the high incidence of on-going pregnancy.

Nevertheless, in this country, RU 486/PG was tested on women up to 63-days pregnant. Table I on the next page lists the key results of the trial on a total of 2,015 women and does not include the 106 dropouts from the study, which will be discussed in detail below.

The following points about the NEJM article are worthy of note:

Dropouts Initially, 2,121 women were enrolled in the study, but 106 (5%) of them dropped out. Table I on the next page lists the abortion rates for the remaining 2,015 women and excluded data for the 106 women who did not come back to the abortion facility for the third visit.

The article claimed that “evidence suggesting” a complete abortion was available for 92 of the 106 women, and “evidence for failure for 1.” The remaining 13 women were “lost to follow up,” and “5 of them had continuing [ongoing] pregnancies when last seen at visit 2,” stated the article.

The key issue is that 5% of the women dropped out of a carefully controlled study where the abortion facilities conducted extensive follow up. What is going to happen if RU 486 goes on the market? A similar dropout rate among the 650,000 women that abortion advocates project might use RU 486/PG annually would result in 32,500 women not returning for the third visit. Many of them might carry to term or need medical care to deal with the complications.

Increasing Rate of Ongoing Pregnancy As shown in Table I, as RU 486/PG was used progressively later into pregnancy, the rate of complete abortion declined significantly (from 92% down to 77%) while the rate of “ongoing pregnancy” increased dramatically (from 1% up to 9%).

Chemicals plus surgery As shown in Table I, 8% of the women had to have surgery in addition to the RU 486 and prostaglandin. If RU 486/PG were to be used by 650,000 as some abortion advocates have predicted, an estimated 52,000 women a year would require surgery.

Table I Results of the U.S. RU 486/PG Trial

Source: Irving M. Spitz, et al, Table 1, Results of Mifepristone and Misoprostol in Women Seeking Termination of Pregnancy, “Early Pregnancy Termination with Mifepristone and Misoprostol in the United States,” New England Journal of Medicine, vol. 338, no. 18 (Apr. 30, 1998), p. 1243.

Double Abortion As shown in Table I, 1% of the women had an “ongoing pregnancy,” which means that RU 486/PG did not cause an abortion. If the chemical abortion method is used on 650,000 U.S. women as projected, an estimated 6,500 women a year would have “ongoing pregnancies.” Would they all obtain surgical abortions or would some carry to term?

U.S. versus French Rates The rate of complete abortion in the U.S. trial (92%) was lower than the rate of complete abortion in the two French trials (95.5%) that the Population Council presented as the “pivotal” data in its application to the FDA for marketing. The researchers presented several possible reasons for this, including the difference in the design of the trial and the U.S. abortionists' lack of experience with chemical abortion which caused them to intervene with surgery more quickly than normally would be necessary.

Contraindications The researchers excluded women from the trial who had the following contraindications (medical conditions or diseases) (two in bold are for emphasis):

less than 18 years of age

more than 35 years of age who smoked over 10 cigarettes a day and had another cardiovascular risk factor

liver disease

respiratory disease

renal disease

adrenal disease

cardiovascular disease

thromboembolism

hypertension

anemia

insulin-dependent diabetes mellitus

coagulopathy

known allergy to prostaglandins

in situ intrauterine devices (IUD)

breast-feeding

receiving anticoagulation therapy

receiving long-term glucocorticoid therapy

adnexal masses

ectopic pregnancies

had signs that they might abort spontaneously

If RU 486/PG were to go on the market, many of these conditions or diseases could be latent among women seeking an abortion. Will there be sufficient screening to prevent such women from using the technique? If not, are those women putting their lives or health at risk? Will they be given true informed consent?

Of special significance, “no one under 18 was admitted to the [U.S.] trial because of informed consent issues,” stated Beverly Winikoff, a Population Council official at the FDA Advisory Committee hearing in July 1996. But the Population Council plans to use it on women of any age if it goes on the market.

Excessive Bleeding Excessive bleeding is the most severe and potentially life-threatening short-term adverse complication from RU 486/PG. One women in the trial in Des Moines, Iowa almost bled to death before emergency surgery and transfusions saved her life. A Population Council spokesperson cynically and callously told the FDA Reproductive Health Drugs Advisory Committee on July 19, 1996 that “there have been no adverse events, no serious, unexpected adverse events, during the course” of the U.S. trial. Did the Council really expect a woman to almost die?

The NEJM article reported that “excessive bleeding necessitated blood transfusions in four women and accounted for 25 of 27 hospitalizations (including emergency room visits), 56 of 59 surgical interventions, and 22 of 49 administrations of intervenous fluid.” The median duration of bleeding for the women who were 7-weeks-or-less pregnant was 13 days.

“Adverse Events” “Almost all the women (99 percent) reported at least one adverse event during the study period,” reported the article. Among the women who were 7-weeks-or-less pregnant, 96% had abdominal pain, 61% had nausea, 25% had vomiting, and 20% had diarrhea. (This hardly seems like an “easy” abortion technique.)

Abortion as Birth Control In the U.S. trial, 51% of the women who took RU 486/PG had at least one prior abortion. An FDA official indicated at the July 19, 1996 FDA hearing that there is no information about the effects of repeat use of RU 486/PG abortion.

Use in Developing Countries Abortion advocates plan to expand use of RU 486/PG into developing countries. In the opening section of the NEJM article, the researchers claimed that the availability of chemical abortion such as RU 486/PG in the United States and developing countries “could lead to greater access to safer abortion services.” The Population Council's Internet website expanded on this point and asserted that RU 486/PG “might be easier to provide in many developing country settings than safe surgical abortion services.” Almost as an afterthought, the article admitted that “medical emergency backup would still be required,” which is major understatement. Women in so-called “Third-World” countries who often are malnourished, anemic, and miles (and hours) from good medical treatment hardly seem candidates for an abortion technique that always causes severe bleeding.

Abortion Sites The names of the abortion facilities and lead researchers who participated in the experiment were published in full for the first time. Only 12 of the 17 sites had previously been identified.

The abortion facilities were the following (listed alphabetically by state; sites not previously identified are underlined): University of Southern California School of Medicine, Los Angeles, CA; Planned Parenthood of San Diego and Riverside Counties, San Diego, CA; Planned Parenthood of the Rocky Mountains, Denver, CO; Feminist Women's Health Center, Atlanta, GA; Planned Parenthood of Greater Iowa, Des Moines, IA; Johns Hopkins Bayview Medical Center, Baltimore, MD; Planned Parenthood of Greater Boston, Boston, MA; Washington University School of Medicine, St. Louis, MO; Planned Parenthood of Central New Jersey, Shrewsbury, NJ; Columbia University College of Physicians and Surgeons, New York, NY; Planned Parenthood of Westchester and Rockland, White Plains, NY; Preterm, Cleveland, OH; Oregon Health Sciences University, Portland, OR; University of Pittsburgh, Pittsburgh, PA; Planned Parenthood of Greater Houston and Southeast Texas, Houston, TX; Planned Parenthood of Northern New England, Burlington, VT; and Aurora Health Services, Seattle, WA.

Conclusion

In conclusion, Pro-Life and Pro-Family advocates should be use the data in the NEJM article to prepare for the next barrage of publicity about the RU 486/PG test, which will probably come during the summer. Whether the plans to market the dangerous abortion technique in 1999 actually come about remains to be seen. Abortion advocates have been making such projections for at least 10 years.