1. A Health News Index poll sponsored by Henry J. Kaiser Family Foundation and Harvard School of Public Health Methodology, conducted by Princeton Survey Research Assoc. in August 2001 revealed that only 61% of women age 18_44 have heard of mifepristone (RU_486). Kaiser Family Foundation Press Release, "National Survey of Gynecologists and Family Practice Physicians," September 24, 2001. When asked if RU_486 was the same thing as "morning_after pills," 47% answered "don't know" and 36% [delete: wrongly] answered "true." When asked if RU_486 was the same thing as "emergency contraceptive pills," 52% answered "don't know" and 25% [delete: wrongly] answered "true" (Health News Index Poll [August, 2001], data provided by The Roper Center for Public Opinion Research, University of Connecticut). [Add: The most interesting part is that the groups conducting this survey treated *true* (that RU-486 is *the same thing* as emergency contraceptive pills and morning-after pills) as a wrong answer. Advertising and consumer product information about emergency contraceptive pills draw a distinction between them and RU-486, but in fact, RU-486 has been used as emergency contraception and even tested as a daily hormonal contraceptive pill.]
2. I. Spitz et al., "Early pregnancy termination with mifepristone and misoprostol in the United States," New England Journal of Medicine 1998, 338:1241-47.
3. Ibid.; L. Birgerson and V. Odlind, "Early pregnancy termination with anti-progestins: a comparative clinical study of RU-486 given in two dose regimens and Epostane," Fertil. Steril. 48:565-70 (1987).
4. The U.S. Food and Drug Administration (FDA) advises: "Do not take mifepristone [RU-486] if it has been more than 49 days since your last menstrual period [began] ...." (FDA Center for Drug Evaluation and Research, "Mifepristone Questions and Answers," available at http://www.fda.gov/cder/drug/infopage/mifepristone/mifepristone-qa.htm)
"During the first few weeks of a pregnancy, a woman's ovaries produce progesterone, but by the ninth or tenth weeks ... the placenta begins to produce progesterone in larger amounts, which is why anti-progestins like mifepristone are not as effective later in pregnancy" (Kaiser Family Foundation, "Issue Update: Mifepristone: An Early Abortion Option," July 2001,at 4, note 8).
5. I. Spitz et al., supra note 2, at 1242-1243.
6. Ibid. "The largest increase in failures was in failures representing ongoing pregnancy, which increased from 1 percent in the = 49 group to 9 percent in the 57-63 days group (p<0.0001)" (I. Spitz, et al., supra note 3, at 1241.
7. FDA Center for Drug Evaluation and Research ("CDER"), "Mifepristone Medication Guide," available at http://www.fda.gov/cder/drug/infopage/mifepristone/medguide.htm.
8. FDA CDER, "Medical Officer's Review of ... Final Reports for the U.S. Clinical Trials Inducing Abortion ..."("Medical Officer's Review"), Nov. 22, 1999, at 11.
9. See, e.g., Cytotec label, revised and approved by the FDA on June 22, 2000, which states in part: "Miscarriages caused by Cytotec may be incomplete, which could lead to dangerous bleeding, hospitalization, surgery, infertility, or maternal or fetal death."
10. RU-486 Canadian drug trials were suspended following the September 1, 2001 death of a woman from toxic shock brought on by a bacterial infection related to her abortion. She died just 10 days after taking RU-486. S. Schmidt, "Woman's death sparks abortion pill debate," National Post (Canada), Sept. 17, 2001, at A13.
11. An emergency room doctor, Mark Louviere, M.D., described treating a woman from Waterloo, Iowa who participated in RU-486 trials at the local Planned Parenthood clinic. Two weeks after her RU-486/misoprostol abortion, she was taken to a hospital emergency room where Dr. Louviere found her "in obvious shock" having "lost between one-half to two-thirds of her blood volume. ... It was my clinical opinion that she would die soon. ... Without even doing the routine preparation we normally do for surgery, I realized that I had to take her immediately to surgery to save her life" (Testimony of Dr. Mark Louviere before FDA Reproductive Health Drugs Advisory Committee, Hearing Transcript, July 19, 1996, at 224).
12. Agence France Presse, Aug. 29, 2001, reporting on an article in the British weekly, New Scientist, Sept. 1, 2001. The Mifepristone Medication Guide, supra note 7, warns that if the pregnancy has not ended, "there is a chance that there may be birth defects ... [and] your provider will talk with you about other choices you have, including a surgical procedure to end your pregnancy." Misoprostol is responsible for a "minor epidemic of birth defects" in developing countries, according to the New Scientist article. Poor women are taking this ulcer medication to induce abortion. Taken alone it results in abortion only 40% of the time. The referenced Agence France Presse English report (Aug. 29, 2001) states: "Doctors have discovered a high rate of birth defects among infants exposed in utero to misoprostol, such as fused joints, growth retardation and a paralysis of the face called Moebius syndrome. In Brazil, where up to 75 percent of the clandestine abortions involve misoprostol, studies suggest between a third and a half of infants born with Moebius had been exposed to misoprostol, New Scientist says."
13. Ectopic Pregnancy - United States, 1990-1992. Morbidity and Mortality Weekly Report 1995; 44:46-48. See also, F. Gary Cunningham et al., "Chapter 34: Ectopic Pregnancy," Williams Obstetrics, 21st ed., New York: McGraw-Hill, 2001; 883,at 885.
14. Mifeprex label, available at http://www.fda.gov/cder/foi/label/2000/20687lbl.htm.
15. FDA CDER, "Mifepristone Medication Guide," supra note 7.
16. Medical Officer's Review, supra note 8, at 8-9.
17. Kaiser Family Foundation, "Issue Update: Mifepristone: An Early Abortion Option," July 2001.
18. For example, the FDA advises those who have taken RU-486 to "contact your provider right away if you bleed enough to soak through two thick full-size sanitary pads per hour for two consecutive hours or you are concerned about heavy bleeding."
19. Danco Laboratories, LLC which distributes RU-486 in the U.S. has posted a sample Patient Agreement form on its website, http://www.earlyoptionpill.com.
20. O. Avrech et al., "Mifepristone (RU 486) alone or in combination with a prostaglandin analogue for termination of early pregnancy: a review," Fertil. Steril. 1991; 56:385-393.
21. S. Wu, "Medical Abortion in China," Journal of the American Medical Women's Assn. [JAMWA], Supplement 2000, 55:3, 197, 198-199; R. Hatcher et al., Contraceptive Technology, 17th rev. ed. New York: Ardent Media, Inc. 1998, at 649; F. Gary Cunningham et al., "Chapter 34: Ectopic Pregnancy," Williams Obstetrics, supra note 13, 885-886.
Regarding the use of ultrasound in China, Dr. Wu writes: |
"According to the SFPC [State Family Planning Commission]-recommended protocol, ultrasound scanning should be performed before administering mifepristone to confirm gestational age. It is not performed in all cases in practice, however, because there is not enough equipment, even in most of the large hospitals. ...
"Some recent adverse events resulting from ectopic pregnancies have led providers to pay more attention to ultrasound examination. ... One study found that 84% of providers in Beijing used ultrasound routinely, but only 57% in Hunan Province did." Wu, at 197.
22. Kaiser Family Foundation, "Issue Update: Mifepristone: An Early Abortion Option," July 2001, at 2.
23. R. Glasow, The RU 486 Report, Aug. 1995, at 2; I. Spitz, et al., supra note 2.
24. Mifeprex label, supra note 14.
25. Medical Officer's Review, supra note 8, at 9.
26. In Sweden, women are "supervised by the midwife for 4 to 6 hours at the outpatient clinic" (M. Bygdeman et al., "Medical Termination of Early Pregnancy: The Swedish Experience," Journal of the American Medical Women's Assn., Supplement 2000, 55:3; 195, at 196.
In France, the use of RU-486 is regulated by a 1990 directive jointly signed by the French Republic's Director General of Health, Director of Hospitals, and Director of Pharmacy and Medication, which states that whenever prostaglandins are given "in association with RU-486" the "following technical conditions ... are indispensable and are to be followed: ... b) The doctor must ensure that diagnostic instruments and machines are close by, such as electrocardiogram equipment and particularly resuscitative cardiopulmonary equipment (including nitrous oxide and injectable calcium antagonists and a defibrillator). ... c) [C]linical observations and blood-pressure readings every half hour are indispensable for several hours following the administration of these drugs. d) Whenever there is chest pain, an electrocardiogram should be taken on the suspicion of rhythm troubles and in case of significant lowering of blood pressure" (April 12, 1990 letter from the French Republic, Department of Solidarity, Health and Social Protection, "Amended Marketing Authorization for Mifegyne," April 13, 1990).
In China "the emphasis on close medical supervision is well accepted. ... It is stressed that misoprostol should be taken in the clinic and followed by several hours of observation" (Wu, supra note 19, 197 and 199). The long observation is one reason staffs in some large hospitals in China are growing reluctant to prescribe the drug combination: "The number of medical abortions has decreased recently in some of the large hospitals. The staffs were too busy to handle the procedure (more counseling, more visits, and observation), and they also have to manage the referred cases with serious side effects and complications" (Id. at 199).
In England, regulations concerning the use of RU-486 state: "The use of mifepristone must be followed, 36 to 48 hours later, by a prostaglandin analogue, [unless the abortion is already completed]. ... There is a risk of profound hypotension, related to the administration of prostaglandin, occurring during this period. Hence, the patient must be observed in the treatment centre for at least 6 hours or until any bleeding or pain have diminished to an acceptable level, whichever is the longer. It is imperative that suitably experienced medical personnel and resuscitation equipment are available during this period" (Mifegyne label, [United Kingdom]).
27. Wu, supra note 20, at 198: "The common complications of [RU-486] abortion are profuse bleeding and allergy. ... Allergic reactions to mifepristone and misoprostol were not uncommon, manifesting in facial edema [swelling of the face], skin rash and itching, numbness of feet and hands, and even a serious case of allergic shock. The potential for such reactions is one reason to keep clients for observation."
28. See note 26 supra.
| ||"In a large study in France, serious cardiovascular side effects following prostaglandin administration (sulprostone injection) were reported in 4 out of 16,000 women treated after sulprostone injection. (Ulmann et al., 1992). These included one acute myocardial infarction and three cases of severe hypertension. By now, over 60,000 women have used RU 486 for abortions. Two more myocardial infarctions have occurred, one of which was fatal. ... Roussel-Uclaf recommends that mifepristone plus any prostaglandin not be used in women who smoke over 10 cigarettes a day, who are older than 35, or who have any cardiovascular risks. ...|
. . . . Although one patient death was reported during the first trial of mifepristone plus misoprostol (Aubeny and Baulieu, 1991), a much larger study has documented the safety of this protocol" (Institute of Medicine, Clinical Applications of Mifepristone (RU 486) and Other Antiprogestins, 1993, at 27-28).
29. See note 27 supra.
30. National Abortion Federation, "Making Your Choice," available at http://www.earlyoptions.org.
31. I Spitz et al., supra note 2.
32. Mifeprex label, supra note 14.
34. S. Schmidt, "Woman's death sparks abortion pill debate," National Post, Sept. 17, 2001, at A13.
35. See note 11 supra and text related thereto.
36. Mifeprex label, supra note 14.
37. Medical Officer's Review, supra note 8, at 11-12.
38. Id. at 11.
39. Medical Officer's Review, supra note 16, at 13.
40. Medical Officer's Review, supra note 8, at 13.
42. S. Schmidt, "Woman's death sparks abortion pill debate," National Post, Sept. 17, 2001, at A13; R.K. O'Bannon, "Woman Dies in Canadian RU486 Trials," available at http://www.kcrtl.org/National_News/RU_486/Woman_dies_in_ru486.htm ; C. McGovern, "Woman Dies in Canadian Abortion-Pill Testing," available at http://www.ru486.org/wiebe2001.html.
43. S. Schmidt, supra note 34.
44. World Health Organization, "Pregnancy Termination with Mifepristone and Gemeprost: A Multicenter Comparison Between Repeated Doses and a Single Dose of Mifepristone," Fertility and Sterility, 56:1, 1990, at 40.
45. P.W. Ashok et al., "An Effective Regimen for Early Medical Abortion: A Report of 2000 Consecutive Cases," Human Reproduction, 1998; 13:2962-2965.
46. H. von Hertzen, "Research on Regimens for Early Medical Abortion," Journal of the American Medical Women's Assn., Supplement 2000, 133, at 136.
47. Medical Officer's Review, supra note 8, at 12.
48. I. Spitz et al., supra note 2, at 1244.
49. FDA Reproductive Health Drugs Advisory Committee, Hearing Transcript, July 19, 1996, at 224).
50. U.S. Embassy Beijing, "Family Planning in China: RU-486, Abortion and Population Trends," November 2000.http://www.usembassy-china.org.cn/english/sandt/ru486.html.
51. On October 22, 2001, Cybercast News Service reported that China has "banned all pharmaceutical sales of abortion pill RU-486, citing safety concerns about the drug. 'In order to guarantee patients' safety and protect their health, it is decided that no matter whether patients have a doctor's prescription or not, retail drug stores are forbidden to sell mifepristone (RU-486) tablets,' read a notice from China's state drug administration reported in international news agencies" (Christine Hall, "China Bans Abortion Pill," CNSNEWS.COM, October 22, 2001).
52. "Excessive bleeding necessitated blood transfusions in four women, and accounted for 25 to 27 hospitalizations (including emergency room visits), 56 of 59 surgical interventions, and 22 of 49 administrations of intravenous fluId. Hospitalizations, surgical interventions and intravenous-fluid administration were reported for 2 percent of the women in the = 49-days group and for 4 percent of those in each of the other groups [50-56 days group and 57-63 days group] (P=0.008)" (I Spitz et al., supra note 2, at 1243).
53. Medical Officer's Review, supra note 8, at 13.
55. Medical Officer's Review, supra note 8, at 14.
56. I. Spitz, et al., supra note 2.
57. A. Davis et al., "Bleeding Patterns After Early Abortion with Mifepristone and Misoprostol or Manual Vacuum Aspiration," Journal of the American Medical Women's Assn., Supplement 2000, 141, at 143.
58. Sachs, "Abortion Pills on Trial," TIME, Dec. 5, 1994,at 45.
59. Mifeprex label, supra note 14.
60. Wu, supra note 20, at 198.
61. Medical Officer's Review, supra note 8, at 14-15.
62. A. Ulmann, et al., "Medical Termination of Early Pregnancy with Mifepristone (RU 486) Followed by a Prostaglandin Analogue," 71 Acta Obst. Gyn. Scand. 278 (1992); Anonymous, "A Death Associated with Mifepristone/Sulprostone," 337 Lancet 969 (1991); See also, Institute of Medicine, Clinical Applications of Mifepristone (RU 486) and Other Antiprogestins 27 (1993), reporting one patient death during the first trial of RU 486 with oral misoprostol.
63. Interview, "Drug firm defends marketing strategy on abortion pill," Guardian Weekly (U.K.), August
19, 1989, at 16.
64. F. Vrazo, "In Europe, 'Abortion Pill' Has Not Met Expectations," Philadelphia Inquirer, August 25, 1996, at A01.
65. Louise Levathes, Hippocrates, February 1995, at 45.
66. "One Woman's Experience," London Evening Standard, December 4, 1993.
67. Lisa Rarick, M.D., of the FDA's Reviewing Division, testimony before the Reproductive Health Drugs Advisory Committee, Hearing Transcript FDA, July 19, 1996, at 134.
68. Letter to the Editor, signed W. Wilson Downie, International Medical Operations, G.D. Searle, The Lancet, vol. 338:247 (July 27, 1991).
69. Letter from Michael Cullen, MD, Searle's U.S. Medical Director, dated August 23, 2000, available at http://www.fda.gov/medwatch/safety/2000/cytote.htm.
70. L. Szabo, "Not Many Dispense Pill that Was Expected to Revolutionize Abortion," The Virginian-Pilot, September 24, 2001.
71. J. Duin, "Just 7% of U.S. Doctors Prescribe Abortion Pill': Poll Cites Controversy, Low Demand," The Washington Times, September 25, 2001, at A3.
72. L. Reisberg, "College Health Centers Face a New Abortion Question," The Chronicle of Higher Education, Dec. 15, 2000, at A53.
73. S. Russell, "Survey Shows Low Demand for RU-486 Abortion Pill," SF Gate (San Francisco Chronicle, on-line edition), September 24, 2001.
74. G. Kolata, "Doctors Looking at Abortion Pill Are Often Unaware of Obstacles," The New York Times, September 30, 2000, at A1, A11.
75. L. Szabo, "Not Many Dispense Pill that Was Expected to Revolutionize Abortion," The Virginian-Pilot, September 24, 2001; R. Padawer, "Abortion Pill Hasn't Had Impact that Was Expected," The Record (Bergen County, N.J.), September 25, 2001.
77. R. Padawer, "Abortion Pill Hasn't Had Impact that Was Expected," The Record (Bergen County, N.J.), September 25, 2001.