Resource Considerations

Advocates for people with AIDS, government scientists, and physicians all agree that clinical trials should include a more balanced sampling of the population infected with HIV. In the early years of the AIDS epidemic, almost all trials of prospective AIDS drugs involved white gay men. Then scientists became concerned that the results of such trials might not be applicable to the growing population of individuals infected with HIV through intravenous drug abuse, many of whom were people of color. The latter tended to have more concurrent infections, poorer nutrition, and a different natural history of disease—for example, a lower incidence of Kaposi's sarcoma—all of which may alter how drugs work to fight HIV infection. Moreover, clinical trials represented the only access to potentially life-saving drugs; basic considerations of equity argued that they should not be restricted to one patient group.

Increased access for minorities was one rationale behind the Community Programs for Clinical Research on AIDS. In addition, NIAID created a program to support minority medical institutions in developing the necessary operational capabilities for an AIDS clinical trials unit (ACTU) and provided increased funding for existing ACTUs to help them recruit and retain previously underserved populations. The situation is improving. In 1987, only 6.5 percent of the subjects in protocols being run by the NIAID AIDS Clinical Trials Group were black, and 10.6 percent were Hispanic. By 1989, 13.9 percent were black, and 14.1 percent were Hispanic.

Some health care providers say, however, that it may be difficult to progress much beyond these levels. Most of the public hospitals and clinics that serve indigent patients are understaffed and over-crowded. Providing them with funds to conduct clinical trials enables them to hire special research staff, but it does not solve the space problem. In the absence of capital improvements, these institutions might have trouble meeting new expectations.

One of the common goals of community-based trials and expanded access protocols is to enable patients to receive investigational drugs through their own physicians. But many of these physicians are not equipped to determine eligibility for drug trials, to follow and monitor patients on new therapies, and to report on laboratory parameters and adverse reactions. For example, the director of the Boston AIDS Consortium reports that physicians from the city's neighborhood health centers are beginning to attend meetings of the consortium's Clinical Providers Group but that at this time they are more concerned with how to provide basic primary care than with the design and implementation of sophisticated clinical trials. He says:

Their concerns are about how to keep records confidential; where to get CD4 testing done reliably and at a reasonable cost; how to administer, bill, and get reimbursed for aerosolized pentamidine treatments; and how to get their neighborhood pharmacies to carry AZT.

I hope it is clear that if we are to be realistic, the issue of expanding access must be viewed from a broader perspective and has to be considered in the context of our capability to provide primary care generally, our preparedness to provide this for people with HIV infection, and the fact that even when we are doing this, unfortunately, to a great extent, we must weigh competing demands, offering detection, counseling, and initiation of standard antiretroviral therapy versus expanding access to clinical trials.

Programs to place clinical trials in primary care settings often fail to deal effectively with reimbursement issues. New York State has developed enhanced reimbursements for physicians seeing patients with AIDS in designated centers, but this is by no means universal. In most cases, time spent on clinical investigations is added to time spent doing routine care and, often, finding appropriate treatment for patients with drug abuse problems. All of these tasks together may be reimbursed at the same level as a routine office visit. Whatever the means that are finally adopted, government planners must deal effectively with these resource issues to enhance access to investigational drugs through the primary care providers that serve low-income minority patients.

Suspicion

Increasing minority enrollment in clinical trials also depends on greater understanding of the deep ambivalence that exists among people of color with regard to the premier academic research institutions in this country. An AIDS physician from Johns Hopkins University reports that he was greeted with hostility and suspicion when he first attempted to make contact with members of the black community in Baltimore. He discovered that some people growing up in the neighborhoods around the medical center had been told as children that scientists from the medical school snatched black people off the streets at night and put them in the basement to experiment on them. It was clear that the people who told these stories did not believe them in a literal sense, but the fact that they repeated them indicated a general level of unease with the medical establishment.

Individuals in the community also were extremely familiar with the details of the infamous Tuskegee study, in which members of the Public Health Service followed hundreds of poor black men with syphilis for four decades (1932–1972) without offering them treatment. The subjects neither knew nor consented to their role in this ''scientifically controlled experiment.''

Fears associated with both real and imagined abuses by the research community, combined with persistent memories of segregated care, will continue to hamper recruitment efforts for clinical trials unless they are discussed openly. Too often, there is a tendency to respond with a joke when a patient says, "So you mean I'm going to be a guinea pig, doc?" For people of color—as well as other patients—the question could mask a serious plea for reassurance.

Informed Consent

Reassurance takes on even greater importance for patients who feel they have no alternative to participation in a clinical trial. Chapter 2 explores the difficulties of obtaining genuine informed consent in AIDS-related drug trials. Poor patients may not have the option of forgoing randomization and obtaining a desired drug through some other mechanism.

Some patients also may be at a disadvantage because they do not have the educational skills necessary to understand the complex details of a research protocol. One way to make protocols more responsive to the needs of such patients is to broaden membership on local institutional review boards (another option discussed in Chapter 2). This would provide a forum for members of the community to educate clinical investigators about the best ways to present new treatment options.

The Gender Perspective

In fact, the problems go much deeper than resource issues. The AIDS epidemic among women differs in almost every respect from the AIDS epidemic among men. For example, the growth of the epidemic among women is very different. One scientist suggests that the majority of men who will develop HIV-related illnesses in the next 10 to 20 years are already infected; moreover, a significant proportion have progressed to the symptomatic stages of disease. In contrast, most HIV-infected women are in the early stages of disease and there is a large population of high-risk women who have yet to become infected. (This situation has arisen because of the transmission patterns in the United States; early in the epidemic, most transmission occurred through male homosexual activity and intravenous drug abuse—about 70 percent of IV drug abusers are men. Heterosexual transmission did not become a major factor until later.) Physicians who provide health care to women are concerned that too much emphasis on enrolling women in clinical trials could overshadow the tremendous opportunities that still exist for prevention.

A New Approach

Efforts to increase access to clinical trials for women will be most successful if they are part of a new gender-specific approach to HIV education and therapy. Such an approach might include greater support for research on the natural history of HIV infection in women, a commitment to include physicians who are knowledgeable about women's health issues in the design of clinical trials, and a unified approach to the scientific, medical, and ethical issues surrounding clinical trials in pregnancy. Women should be viewed as primary recipients of care, and every effort should be made to repudiate the characterization of HIV-infected women as vectors, transmitters, or vessels of disease.

Today, an HIV-infected woman with an infected child is often required to broker her care among four different providers: her routine provider, her clinical trial site, her child's routine provider, and her child's clinical trial site. Even a woman with extraordinary financial and emotional resources would find such a task difficult. For the average woman with HIV infection, who must worry about feeding, clothing, and housing her healthy children as well as her sick children, it is almost impossible. Future efforts to increase access to investigational drugs for women will be most effective in centers that integrate clinical trials with routine medical care for both women and children.

Scientific Issues

The scientific problems result primarily from lack of experience in conducting clinical trials in newborns and young children and from the paucity of information about the natural history of HIV infection in this age group. In fact, three-quarters of the drugs that are now part of standard formularies were never tested in children; they are simply used by extension. Because pharmaceutical companies have very little incentive to produce formulations specifically for the pediatric population, the pace of future clinical trials in children will depend in part on developing such incentives and increasing the availability of appropriate substances.

Scientists also need more information about the progression of HIV-related diseases in children with perinatal infection. As noted earlier, more HIV-infected children survive infancy than was previously expected, and some children do not develop symptomatic disease until well after their fifth birthday. Investigators cannot completely assess the efficacy of drug candidates until they understand the factors that determine the onset and pace of disease in the absence of drugs.

Social Issues

Earlier sections have alluded to the fact that most children with perinatal HIV infection come from severely impaired families. In some cases, the day-to-day demands of poverty and drug abuse may prevent parents from taking an active role in their children's care; in other cases, parents may be severely ill themselves. Pediatric clinical trials among this population must offer much more than investigational drugs and research-related medical care. Compliance with trial regimens depends on the availability of a broad range of services to provide physical and emotional support for the entire family. The multidisciplinary teams developed for pediatric clinical trials could become a model for pediatric AIDS care in other settings.

HIV-infected children who have no family support usually enter the foster care system, a circumstance that raises additional issues. Foster care agencies vary from city to city in their policies on investigational therapies. The implementation of AIDS-related clinical trials may be difficult in areas where the foster care system does not recognize the importance of access to experimental drugs.

In addition to infants born to high-risk women, one other pediatric population is at great risk of HIV infection: adolescent runaways (officials estimate that there are about a million teenage runaways across the United States). In large cities, such as New York and San Francisco, runaways often use sex as a way of earning a living, which places them at enormous risk of infection from all types of venereal diseases. Providing regular health care for these homeless children is extremely difficult; the potential for including them in clinical trials is limited. The most urgent task with regard to teenage runaways is AIDS prevention education; communications skills developed to help adolescents avoid HIV infection might be used later to promote long-term care for this very challenging target group.