Women and HIV / AIDS Research: The Barriers to Equity

Women and HIV / AIDS Research: The Barriers to EquityAuthor(s): Carol LevineSource: IRB: Ethics and Human Research, Vol. 13, No. 1/2 (Jan. - Apr., 1991), pp. 18-22Published by: The Hastings CenterStable URL: http://www.jstor.org/stable/3563916 .

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Women and HIV/AIDS Research: The Barriers to Equity by Carol Levine

First impressions are hard to change. The Acquired Immunodeficiency Syn- drome (AIDS) has never been exclu- sively a disease of gay white men or black and Hispanic men who use intravenous drugs. That initial charac- terization-a media popularization of broad epidemiologic trends-continues to impede the development of effective education and prevention programs and appropriate health care and social services, including access to clinical trials of promising new drugs, for the growing number of women who are infected with the Human Immunodefi- ciency Virus (HIV).

From 1981 through October 1990, 14,816 cases of AIDS among women thirteen or older were reported to the Centers for Disease Control. Overall, this represented about 10 percent of the 152,231 adult and adolescent cases.' In 1989, 3,931 cases of AIDS among women were reported, out of a total of 35,238 cases for the year; that was an increase of 11 percent over the previous year.2

These statistics fail to capture the true prevalence of AIDS among women. One study in South Carolina found selective underreporting of AIDS cases among both blacks and women.3 AIDS itself is the final stage of a broad spectrum of illness related to infection with HIV. The number of HIV-infected women-the potential AIDS cases of the future-is unknown, but women, mostly infected in more recent years and therefore not yet ill, undoubtedly constitute a growing proportion of this category.

Women with HIV infection or AIDS are a significant pool of potential research subjects for the many new drugs being developed. The natural history of the disease may differ in women. A small study of twenty-four women with AIDS in Rhode Island found that Candida esophagitis (38%) rather than Pneumocystis carinii pneu- monia (13%) was the most common AIDS-defining event. Pneumocystis occurred less commonly during the illness than in men with AIDS. The authors suggest that "if more extensive

data from other geographic regions confirm the observations in this study, the optimal approach to prophylaxis against opportunistic infections in women with AIDS may be substantially different from that which is most appropriate for males."4

Despite the prevalence of the disease among women and the possibility that they may need different therapeutic strategies, to date drug trials have enrolled mostly men. As of August 28, 1989, of the 7,659 patients enrolled in federally funded AIDS clinical trials organized by the National Institute of Allergy and Infectious Diseases (NIAID), 6.8 percent were female. This overall statistic is misleading, however, since it reflects the inclusion of large numbers of women in a few academic centers. For example, in New York City, where women make up 13 percent of the AIDS cases, at Albert Einstein College of Medicine in The Bronx, 45.7 percent of the subjects enrolled in trials are women; by contrast, at Cornell University Med- ical College in New York, women make up 9.4 percent of the subjects. At the George Washington Medical Center in the District of Columbia and at Johns Hopkins Medical Center in Baltimore, 2.8 percent and 5 percent of the subjects were women.5 The panelists at a recent State-of-the-Art Conference on AZT (zidovudine), sponsored by the NIAID, acknowledged that "large groups of individuals, notably women, minorities, and intravenous drug users, were only modestly represented in the major studies on which [their] recommenda- tions are based." Nevertheless they concluded that "the same guidelines for initiation and management of zidovudine therapy be used in such HIV- infected individuals."6)

In drug trial recruitment, HIV- infected women suffer quadruple jeop- ardy: first, they may be excluded because they are women and either potentially or actually pregnant; second, they may be excluded because they are members of minority groups and lack access to the health care system in general, and to research in particular; third, they may be excluded because they are drug users and are presumed to be noncompliant subjects; and fourth, they may be excluded because most of the trials so far have focused on AIDS itself, and many of the women have been infected recently and are not sympto- matic or do not have a clinical diagnosis

of AIDS. Of the 7,659 patients enrolled in the NIAID trials, 20.4 percent were black or Latino; by comparison, about 42 percent of AIDS patients across the country are members of minority groups. Current or former drug users constituted 11.3 percent of the subjects, but 27.5 percent of the AIDS cases.

Efforts to include women in HIV/ AIDS drug trials confront several barriers: the regulatory system, which has considered women of childbearing potential and their actual or potential fetuses as vulnerable subjects in need of special protection against risk; the pharmaceutical industry, which seeks to avoid potential liability for the possible teratogenic effects of experimental compounds by excluding women from drug trials; the health care system, which has failed to provide access to primary care for many of the poor, minority women most at risk for HIV infection; minority communities themselves, which are often suspicious of research that in the past has used (and sometimes abused) their members and failed to provide any compensating benefits.

Redressing the imbalance, however, is not simply a question of removing institutional or attitudinal barriers. Special ethical problems arise in HIV/ AIDS protocols that include women, and there may arguably be some protocols that should continue to exclude women. A brief review of the regulatory back- ground may help set the stage.

The Department of Health and Human Services regulations governing human subjects research do not exclude women, but they do place special emphasis on potential risk to fetuses. Among the "additional" elements of informed consent that must be disclosed to potential subjects when appropriate is "a statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unfore- seeable" (45 CFR 46.16(b)(1); 21 CFR 50.25(b) (1).

Furthermore, Subpart B of the DHHS regulations sets out "Additional Protec- tions Pertaining to Research Develop- ment, and Related Activities Involving Fetuses, Pregnant Women, and Human In Vitro Fertilization." No research involving fetuses and pregnant women can be undertaken unless:

(1) Appropriate studies on animals and nonpregnant individuals have been completed; (2) except where the purpose...is to meet the health needs of the particular fetus, the risk to the fetus is minimal and, in all cases, is the least possible risk for achieving the

Carol Levine is Executive Director of the Citizens Commission on AIDS. Her work on this article was partially supported by a grant from the American Foundation on AIDS Research. This article is adapted from "Women and HIV/AIDS Research: Barriers to Equality," Evaluation Review, October 1990, pp. 447-63. Reprinted by permission of Sage Publications, Inc.



January/April 1991

objectives of the activity (45 CFR 46.206). Furthermore, the regulations con-

tinue, (a) No pregnant woman may be involved as a subject in an activity covered by this subpart unless: (1) The purpose of the activity is to meet the health needs of the mother and the fetus will be placed at risk only to the minimum extent necessary to meet such needs, or (2) The risk to the fetus is minimal. (b) An activity...may be conducted only if the mother and father are legally competent and have given their informed consent after having been fully informed regarding possible impact on the fetus, except that the father's informed consent need not be secured if: (1) The purpose of the activity is to meet the health needs of the mother; (2) his identity or whereabouts cannot reasonably be ascertained; (3) he is not reasonably available; or (4) the pregnancy resulted from rape (45 CFR 46.207). Beyond the regulations governing

human subjects research, FDA guidelines for clinical evaluation of drugs state that women of childbearing potential should be excluded from large-scale clinical trials until the FDA Animal Reproduction Guidelines have been completed, except in cases of life- threatening illness. For Phase I studies "in general, women of childbearing potential should be excluded." For Phase II studies women may be included "provided segment II and the female part of segment I of the FDA Animal Reproduction Guidelines have been completed."'7

These guidelines were published in 1977 and have not been subsequently revised, although changes have been discussed.

The conservative stance toward including women in drug trials that became entrenched in the 1970s as a result of the experiences of Thalidomide and DES8 was reinforced by the litiga- tion that followed disclosures of harm. Pharmaceutical companies concluded that one way to avoid liability claims was to exclude women from research, even though the claims against them were based on injuries incurred when physicians used the drug in medical practice, rather than in research studies.

As a result of all these events, young women have been underrepresented in drug trials. In reviewing papers published in 1979 in two journals of the major organizations representing clinical pharmacology in the United States, Elvin L. Kinney, M.D. and colleagues found that only two of seventeen Phase

I studies included women. Even in these studies only women without childbearing potential were eligible. Among the twenty-eight published Phase II and Phase m studies (large-scale controlled efficacy trials), only six clearly included women under forty-five years of age. As additional evidence of underrepresentation, the researchers also found that about a third of the drugs listed in the Physicians' Desk Reference had been inadequately studied to ascertain their safety in pregnancy.9 The effect of menstrual cycles on drug metabolism is typically unknown, and forces physicians to use trial-and-error in establish- ing optimal dosages.10

The FDA conducted two surveys, in 1983 and in 1989, to determine actual participation of groups by sex, age, and race in studies that led to drug approval, and found no systematic discrimination against the inclusion of women. Overall, women represented 28 percent of the study population. In both surveys, "distribution generally followed disease incidence." More women received drugs used for arthritis, for example, and more men received beta blockers for angina and hypertension." (Although men are statistically at higher risk for heart disease, older women's risk increases, and heart disease remains the leading killer of women.)

However, the FDA surveys excluded Phase I trials, in which fewer women are enrolled. At present many HIV/AIDS drug trials are Phase I or combination Phase I/Phase II trials; while such trials are not designed to demonstrate efficacy and therefore the exclusion of women may not deprive them of benefit, it does deprive them of making auton- omous choices about participation and the results may not fully represent the potential side effects in women.

Dr. Robert Temple, head of the FDA's Office of Drug Evaluation, has stated, on the basis of the 1983 survey,

Women are thus not ignored in clinical trials. There is one area, however, where better information is needed yet difficult to obtain: the effects of drugs during pregnancy. There is considerable, but understandable, reluctance to carry out formal trials of drugs in pregnant women, unless the drug is specifically intended to treat a condition of pregnancy, even if animal data show no teratogenic effects.I believe this is not easily solved and that we will, as a rule, have to rely on spontaneous post-marketing experience for information on the effects of drugs in pregnancy.12 Recently several groups have begun

to challenge governmental and industry assertions that women are adequately

represented in drug trials. At the request of the Congressional Caucus on Women the General Accounting Office deter- mined that the National Institutes of Health (NIH) had made 'little progress in implementing its policy to encourage the inclusion of women in research study populations."'3 Subsequently Patricia Schroeder introduced the Clinical Trials Fairness Act (H.R. 5345), a bill on which no action has been taken.

While concern about the possibility of birth defects caused by drugs taken by pregnant women has increased dra- matically, there has been little concern that fathers' exposure to chemical agents may also contribute to birth defects. A chapter in a book on drug and chemical risks to the fetus and newborn published in 1980 begins by introducing a "new concept, namely that drug and chemical exposure of a male can affect his progeny." The authors reviewed animal and human studies in which only the male partner was exposed to the chemical or drug agent, mostly through occupational exposure. They found reports of "adverse effects on progeny of five species for lead, morphine, thalidomide, caffeine, and ethanol, including decreased litter size, birthweight, sur- vival, and learning ability in a T-maze." In humans, lead, anesthetic gases, cigarettes, and caffeine have been associated with a variety of adverse effects on reproductive outcomes.14

While it seems likely that maternal exposure remains a more significant factor, the possibility of male-mediated effects should not be overlooked. Fur- ther studies should be done on the male- mediated effects of pharmaceutical drugs as well as occupational exposure.

Implications of Underrepresentation

Excluding young women from drug trials may seem the most prudent course. After all, one might argue, why take any chances?

A categorical exclusion of young women is both unjust and unwise. Such a policy assumes that all women are alike, that all are sexually active, and that all are unreliable in their contraceptive practices. In fact, many young women- for example, those in professional education programs such as medicine, business, or law-are highly motivated to avoid pregnancy and would be excellent candidates for research.

Moreover, a policy that excludes women from research but then exposes them to risks-unknown because un- studied-through the more haphazard route of medical practice fails to protect their interests in obtaining the safest and

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most effective therapies. Women may react differently to drugs than do men, and pregnant women may react differently than do nonpregnant women. Without adequate scientific evidence to guide them, physicians are left to improvise on dosages and choices of drugs.

Undoubtedly physicians have tended to prescribe drugs liberally for women. In the nineteenth century male doctors prescribed drugs, including narcotics, more frequently for their female patients. According to surveys done in this period, two-thirds of people addicted to medicinal opiates, such as laudanum or morphine sulfate, were women.15 Perhaps physicians have been influenced by the need to appear to be "doing something" for their patients and perhaps in more recent years by pharmaceutical companies' promotional efforts. One British study conducted in the early 1970s found that 82 percent of 911 women had received prescription drugs during their pregnancy, with an average of four drugs prescribed for each woman, in addition to one or more over- the-counter drugs.16 A study in the United States during a comparable period found an even higher level of drug use; pregnant women ingested from three to twenty-nine prescription drugs, with a mean of 10.3.17

However, some physicians now with- hold potentially useful drugs from pregnant women or prescribe low and ineffective dosages.'8 One physician faced this dilemma in her own pregnancy. Dr. Agneta Philipson, a Swedish infectious disease specialist, developed bronchitis while pregnant. She responded poorly and slowly to the antibiotic ampicillin. Suspecting that inadequate amounts of the drug might be reaching the infection site, she measured the ampicillin in her blood after a usual dose and found that it was considerably below the "normal" level found in routine pharmacological studies in young, healthy men. After the pregnancy she took an identical dose, and found that her blood levels had returned to normal.'9

In 1975 Bernard L. Mirkin, professor of pediatrics and pharmacology at the University of Minnesota, posed the problem bluntly:

Society may choose to forbid drug evaluation in pregnant women and children. This choice would certainly reduce the risk of damaging individuals through research. However, this would maximize the possibility of random disaster resulting from use of inadequately investigated drugs. In the final analysis it seems safe to predict that more individuals would be dam-

aged; however, the damage would be distributed randomly rather than imposed upon preselected individuals... 20 The questions surrounding the inclu-

sion of women in research did not arise with HIV disease, but are-like so many issues-dramatized and highlighted by it. Similarly, some of the solutions that may be reached with respect to this one disease may affect future research affecting women with other diseases.

The central ethical issue is: How can the interests of society in developing safe and effective drugs for conditions that affect women, and the interests of individual women in obtaining access to experimental drugs that may prove of benefit to them, be balanced against the obligation to prevent harm, particularly to unconsenting future children that will be born?

Erythropoietin: A Case in Point

To illustrate the problem of enrolling women in research, consider erythropoietin (EPO). This drug, a genetically engineered analogue to a naturally occurring human hormone, has been approved for marketing in treating anemia in patients receiving dialysis for end-stage renal disease. AIDS patients who are anemic as a side effect of zidovudine (AZT) or because of their underlying HIV infection may also benefit from EPO. The drug was approved in January 1991 for marketing for this use. While this process was going on, the FDA had approved its use under a Treatment IND [Investigational New Drug], a mechanism to expand access to the drug for selected groups of patients based on the accumulated evidence. Few side effects had been reported in AIDS patients taking EPO. There are no animal or human data indicating that EPO has any mutagenic or teratogenic effects. Since it mimics a natural substance, such effects are unlikely.

Under the conditions of the original protocol and the extended-maintenance protocol for AIDS patients who took the drug in early trials, and the Treatment IND, pregnant women were specifically excluded by the drug's manufacturer, Ortho. At the same time Phase I trials of zidovudine in HIV-infected pregnant women are underway to determine whether that drug can be given safely This is the first step toward determining whether zidovudine given in pregnancy can prevent transmission of HIV from infected mothers to their fetuses.2' It seems quite possible that some of the pregnant women in that trial may develop anemia serious enough to

require transfusion. EPO would be a far more prudent therapeutic choice. Yet under the IND restrictions, investigators in this trial could not obtain EPO from the sponsor and offer this drug to their patients at no cost. Since EPO was approved for use in kidney patients, the drug could be obtained through a regular prescription at a cost of several thousand dollars a year, with no special consent or monitoring.

It is hard to see how excluding women from this protocol benefited them or future women patients whose physicians will have to prescribe on the basis of extrapolation rather than evidence. The drug company, however, did benefit: it incurred no expenses, no risks, or potential liabilities based on experimental use in women. The drug will be used in women now that it is approved so no marketing advantage was lost. The FDA could have avoided this situation by requiring changes in the Treatment IND protocol that would have allowed or required the inclusion of women.

Striking a Balance

In this article I have argued in favor of a shift in policy and practice toward redressing the injustice caused by excluding women from research. A logical conclusion might be that it is never justified to exclude women, regardless of their childbearing potential or state of pregnancy. I am reluctant to take that absolutist position.

The ethical obligation not to do harm carries particular force when the recip- ient of the potential harm is an unconsenting future child, who will be born and whose future health and welfare may be unalterably affected. (Many HIV-infected women will choose to continue a pregnancy; those who elect termination of the pregnancy should have timely access to abortion services.) On grounds of beneficence and the harm principle, parents have moral obligations to enhance, insofar as is reasonably possible, the health and welfare of children they have conceived and that will be born to live independent existences. (Society too has obligations to provide the education, medical care, and support that is necessary for parents to fulfill their responsibilities.) Although both parents have this obligation, and there are limits to what either parent can be expected to do or forgo, mothers have particular obligations because of their biological connection with the developing fetus.

The vast majority of women see their own primary interests as identical with those of their future child. Women do not lightly undertake any medical



January/April 1991

intervention that might have an adverse outcome on their future child; many women in fact may deny themselves optimal medical care in order to avoid risk. Some, however, may exercise their right to choose validated medical treat- ments despite known or unknown risks to the fetus.

Research, unlike treatment, has as its primary goal the acquisition of knowledge. Approval by an IRB of a protocol is not an ethically neutral stance: it is an affirmative statement that the choices to be offered to potential subjects, while perhaps difficult to make, are ethically justifiable. Exposing a fetus to known serious risk when there are alternatives or when the potential benefits to the mother are modest is not, in my view, an ethically justifiable choice.

Most HIV/AIDS protocols do not present any known or foreseeable risks to future children; for these protocols, there are, as has already been pointed out, no reasons to exclude women, especially those who are not pregnant or do not plan to become pregnant. Some HIV/AIDS protocols may carry the possibility of minimal or even moderate risk to future children but also offer the possibility of great benefit to the woman. An obvious example would be a life-saving drug or a cure. Another example might be a study involving a drug to treat a debilitating opportunistic infection for which there are no accept- able alternative therapies. In these cases women should not be excluded auto- matically but should be given the opportunity to make that calculus for themselves, with careful explanation of the risks and benefits to themselves and their future children.

There remains, however, the small but worrisome category of studies involving drugs that present known high risk to future children and minimal or unknown benefit to women. Some would argue that risks to future children, as unconsenting participants, must always outweigh considerations of the woman's autonomy. Others would argue that there are never any grounds to override a woman's autonomy and to deny her the choice of whether to participate. In this view valuing a future child's welfare more highly than a woman's autonomy is objectionable in principle and is yet another example, like forced cesareans and arrests of drug- using pregnant women, of treating women solely as "fetal containers."

Is there a middle ground? Protocols in other diseases may fail to gain approval on grounds of excessive risk to subjects, even when there are potential benefits. Risk to future children cannot simply be dismissed as irrele-

vant, even if one does not grant them "rights." But what would constitute "serious" or "excessive" risk? Opinions differ. The administration of zidovudine to pregnant women to see whether it reduces HIV transmission might strike some as posing serious risk to the more than two-thirds of fetuses who will receive a toxic substance in utero but who will be uninfected. Yet such a study has been approved and federally funded. (Although the pregnant woman might benefit from receiving the drug, that is not the purpose of the study. In fact,

according to the protocol, zidovudine will be discontinued after delivery. Of course the woman may receive it under different auspices.)

Consider this hypothetical scenario. Thalidomide, already described as a drug that causes devastating birth defects when taken early in pregnancy, is a good treatment for a serious complication of Hansen's disease (lep- rosy) known as erythema nodosom leprosum (ENL). Thalidomide prevents permanent damage from the fever, nerve inflammation, and eye and skin

CALENDAR

MARCH 4: The American Society for Healthcare Risk Management invites you to submit a one-page abstract and detailed outline of an original article on any area of health care risk management and bioethics, to be published in the Fall 1991 issue of Perspectives in Healthcare Risk Management. Abstracts are due by this date, in duplicate to Margaret Veach, American Society for Healthcare Risk Management, 840 N. Lake Shore Dr., 10 East, Chicago, IL 60611.

MARCH 4-5: A two-day program on the issues related to the protection of human subjects in research will be sponsored by the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) and hosted by the University of North Carolina at Chapel Hill and the Shaw University. The conference will be held at The William and Ida Friday Continuing Education Center, Laurel Parkway, Chapel Hill, NC. For registration information, call or write: Mr. Al Dawson, Manager of Operations, The William and Ida Friday Continuing Education Center, Laurel Hill Parkway (C.B. 1020), Chapel Hill, NC 27599-1020; (919) 962-1106.

MARCH 20: Applied Research Ethics National Association (ARENA) will hold its annual animal issues conference for research administrators at the Park Plaza Hotel in Boston. Contact PRIM&R, 132 Boylston St., Boston, MA 02116; (617) 423-4112 for information.

MARCH 21-22: Public Responsibility in Medicine and Research (PRIM&R) will sponsor a meeting on Animal Care and Use Programs: Regulatory Compliance and Education in an Age of Fiscal Constraints. The meeting will take place at the Park Plaza Hotel in Boston. For additional information, contact Joan Rachlin, PRIM&R, 132 Boylston St., Boston, MA 02116; (617) 423-4112.

MARCH 24-28: The Kennedy Institute of Ethics, Georgetown University announces a course entitled Ethical Issues of Animal Experimentation to be held on the campus, Washington, DC. For details, contact Ms. Michelene Sheehy, Course Administrator, Kennedy Institute of Ethics, Georgetown University, Washington, DC 20057; (202) 687- 6766.

APRIL 4-5: The second of the workshops sponsored by NIH, OPPR on implementing the Public Health Service Policy on Humane Care and Use of Laboratory Animals will be held in Charleston, SC. The topic of this workshop will be Surgery and Post- Surgical Care. The meeting is sponsored by the Medical University of South Carolina, Carol Reed, Registration Coordinator, Dept. of Comparative Medicine, 704 BSB, Charleston, SC 29425-2216. For information contact Dr. M. Michael Swindle, (803) 792- 3625.

APRIL 11-12: PRIM&R will hold a conference entitled The Role and Responsibility of the Institutional Ethics Committee. Included in the agenda is a discussion of the history, current status, and future of the institutional ethics committee, as well as an analysis of its role and responsibilities within both the hospital and the surrounding community. The meeting will be held at the Park Plaza Hotel in Boston. Contact PRIM&R for further information: 132 Boylston St., Boston, MA 02116; (617) 423-4112.

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problems of ENL. Studies of cancer patients suggest that thalidomide can prevent many of the side effects, such as the sometimes fatal graft-host reac- tion, of radiation therapy given to bone marrow transplant recipients. The drug may also be useful in treating patients with autoimmune disease who cannot tolerate steroids or who are unrespon- sive to these drugs.2'

Suppose an investigator wished to study the effect of thalidomide on immunosuppression in HIV/AIDS. The benefits would primarily be the acquisition of knowledge, although if the hypothesis is correct, subjects' immune status might be enhanced. Should women of childbearing capacity be excluded? In such a case I would argue that sexually active, fertile women should be excluded because the potential harm to future children is well known, severe, and permanent and the knowledge is attainable through other means. Because no contraceptive is foolproof, the harm would occur at a point when the woman might not even know that she is pregnant. Moreover, even under the best of circumstances, informed consent is not perfect. Any subject's understanding of risks may be colored by the common misperception that research is designed for individual benefit rather than to gain generalizable knowledge. Furthermore, concern about risks may diminish over time. A woman who has no intention of becom- ing pregnant at the beginning of a study may fail to appreciate the risks or remember the warnings if her life situation changes.

A woman who was enrolled in such a study and became pregnant would be faced with the option of abortion (which

she might find morally unacceptable) or carrying the potentially severely dam- aged fetus to term. If the results of early studies showed that thalidomide or an experimental drug with known similar teratogenic properties had a good chance of providing substantial benefits for the woman and there were no alternatives, the drug might be offered off protocol through any one of a number of mechanisms. In this way the decision can be made on a case-by-case basis, with treatment of the individual as the primary goal, rather than as part of a research study.

Fortunately, most protocols do not present such stark choices. In the vast majority of cases women can be offered the same options as men, with full explanation of the risks and benefits to themselves as well as to their fetuses.

Beyond the Protocol Barrier: Increasing Access

Even if exclusionary barriers related to gender or substance abuse were totally removed, women would still face problems in access to research because of their lack of access to primary health care and their special needs for assist- ance with child care, transportation, and family responsibilities. Recruitment efforts will have to take account of the multiple roles HIV-infected women play as family caregivers and employees (often in marginal jobs with few oppor- tunities for flexibility). Meeting their own health care needs may not be their highest priority; enrolling in research, an alien concept to many, may seem even less important.

The goal is not to convince women to become research subjects, either for

their own good or for the good of society, but to make more equitable the selection of subjects who will undertake the risks and share in the benefits of research.

REFERENCES I Centers for Disease Control: HIV/AIDS Surveil-

lance Report. November 1990, pp. 1-18. See also Centers for Disease Control: Update: Acquired Immunodeficiency Syndrome-United States, 1981-1988. Morbidity and Mortality Report 1990; 38(14):232-33.

2 AIDS cases in U.S. rose 9 percent in 1989. New York Times, 11 February 1990, p. A 43.

3 Conway, G.A., et al.: Underreporting of AIDS cases in South Carolina, 1986 and 1987. Journal of the American Medical Association 1989; 262(20):2859-63.

4 Carpenter, C.C., et al.: Natural history of Acquired Immunodeficiency Syndrome in women in Rhode Island. The American Journal of Med- icine 1989; 86:771-75.

5 Steinbrook, R.: AIDS trials shortchange minorities and drug users. Los Angeles Times, 25 Septem- ber 1989, pp. 1, 19.

6 State-of-the-Art Conference on AZT: Recommen- dations for zidovudine: Early infection. Journal of the American Medical Association 1990; 263(12):1606-09.

7 Food and Drug Administration: General Consid- erations for the Clinical Evaluation of Drugs. Washington DC: U.S. Government Printing Office, 1977.

8 Apfel, RJ., and Fisher, S.M.: To Do No Harrm DES and the Dilemmas of Modern Medicine. New Haven: Yale University Press, 1984.

9 Kinney, E.L., et al.: Underrepresentation of women in new drug trials. Annals of Internal Medicine 1981; 95:495-99.

10 Cotton, P: Examples abound of gaps in medical knowledge because of groups excluded from scientific study. Journal of the American Medical Association 1990; 263(8): 1051, 1055.

I Temple, R.: Memo on studies of older patients in NDAs [New Drug Applications] for NMEs [New Molecular Entities] approved in 1988. Office of Drug Evaluation, FDA. 8 September 1989.

12 Temple, R.: Letter, I April 1987. 13 Cotton, P.: Is there still too much extrapolation

from data on middleaged white men? Journal of the American Medical Association 1990; 263(8): 1049-50; Statement of Mark V. Nadel, General Accounting Office, June 18, 1990.

14 Soyka, L. E, and Joffe, J. M.: Male mediated drug effects on offspring. In Drug and CehmicalRisks to the Fetus and Newborn, ed. R. H. Schwartz and S. J. Yaffe (New York: Alan R. Liss, 1980), pp. 64-65 [49-66].

15 Courtwright, D., Joseph, H., and Des Jarlais, D.: Addicts Who Survived: An Oral History of Narcotic Use in America, 1923-1965. Knoxville: University of Tennessee Press, 1989, p. 3.

16 Forfar, J. and Nelson, M.: Epidemiology of drugs taken by pregnant women: Drugs that may affect the fetus adversely. ClinicalPharmacology and Therapeutics 1973; 14:633.

7 Hill, R.: Drugs ingested by pregnant women. Clinical Pharmacology and Therapeutics 1973; 14:654.

18 Mitchell, J., M.D., chief of perinatology, Harlem Hospital. NIH Workshop on Ethical Issues in Research. Bethesda, MD. August 16, 1989.

19 Sabath, L.D., Philipson, A., and Charles, D.: Ethics

and the use of drugs during pregnancy. Science 1978; 202:540-41.

20 Mirkin, B.L.: Drug therapy and the developing human: Who cares? Clinical Research 1975; 23:110-11.

21 National Institute of Allergy and Infectious Diseases: NIAID to evaluate safety of giving AZT to pregnant women. Press release, 10 July 1989.

Cumulative Index

A cumulative index of IRB: A Review of Human Subjects Research covering volumes 1-12 (1979-1990) is now available through the Publications Department, The Hastings Center, 255 Elm Road, Briarcliff Manor, NY 10510. $7.50/copy inclusive of postage and handling. We request that orders be prepaid.



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Women and HIV / AIDS Research: The Barriers to Equity