APA Newsletters
Fall 1999
Volume 99, Number 1

David B. Resnik
East Carolina University School of Medicine

Questions about access to experimental drugs in terminal illness figure prominently in current controversies in bioethics. Proponents of unrestricted access argue that competent patients should be allowed to try all new drugs that may offer them some benefits, while opponents counter that this choice can be constrained in order to promote safety, public health, and scientific and medical progress. In the last decade, HIV/AIDS activists have given this issue international exposure by lobbying for unrestricted access to experimental drugs. In response to this intense political pressure, government agencies, such as the Food and Drug Administration (FDA), have revised their procedures in order to expedite the review, approval, and availability of new and experimental medications to treat AIDS and other terminal conditions. However, these policy changes have not satisfied proponents of unrestricted access, and the debate continues.

Udo Schuklenk’s book, Access to Experimental Drugs in Terminal Illness: Ethical Issues, is a very thoughtful, provocative, and timely contribution to this important debate. Schuklenk develops a rigorous philosophical and ethical analysis of the policy debate that is founded on a well-informed and compassionate understanding of the medical, social, legal, economic, and scientific issues in HIV/AIDS research. Although he focuses on access issues in drugs used to treat HIV/AIDS, his work has implications for other terminal conditions. The book delivers a careful and convincing defense of increased access to experimental drugs in terminal illness and challenges many of the paternalistic and idealistic assumptions that govern drug approval. It is a must read for anyone who cares about these issues.

Schuklenk considers two of the main arguments used to defend restricted access. According to the first argument, restricted access can be justified on the grounds that it prevents people from harming themselves. This paternalistic viewpoint seeks to restrict access because 1) experimental drugs are potentially harmful, and 2) most people are not capable of making intelligent and responsible decisions regarding these risks. According to this view, decisional capacity is often impaired in terminal illness. People who have terminal illnesses are "coerced" by circumstances to make decisions that they would not make under different conditions. People with terminal illnesses are "grasping at straws" and will try anything to have some hope. Hence, according to this argument, the government is justified in restricting their marginal autonomy in order to prevent people with terminal illnesses from making unwise, inauthentic, and harmful choices.

In order to evaluate this line of argument, Schuklenk discusses several different approaches to autonomy and the justification of paternalism, including the views of John Stuart Mill, Immanuel Kant, Gerald Dworkin, Tom Beauchamp, James Childress, Ruth Faden, and Robert Young. He concludes that none of these theories offer sufficient justification for restricting access to experimental drugs in terminal illness. Using HIV/AIDS as his case study, Schuklenk claims that the harms or risks created by taking experimental drugs for HIV/AIDS are no worse than the harms or risks associated with having HIV/AIDS. People who have AIDS will eventually die of this disease, since we do not yet have a cure for AIDS. If they do not try experimental drugs, they have little hope for a cure. If they try experimental drugs, then they have at least a chance of getting well.

Schuklenk also presents some evidence that people with HIV/AIDS usually do not lack the ability to make intelligent and responsible choices about experimental treatments. According to Schuklenk, many people with HIV/AIDS know and understand a great deal about their disease and possible treatments. Schuklenk also argues that people can still make voluntary choices even when circumstances or conditions, such as AIDS, lead them to "grasp at straws." Schuklenk claims that since all people face different pressures and coercive conditions in decision making, no choice is purely voluntary. Since voluntariness is an ideal that cannot be achieved, it may be morally acceptable to allow people who face coercive conditions to make decisions and act on them. If we are justified in letting a person choose a career or a mate, then we are justified in allowing a person to choose an experimental drug to treat a terminal illness.

However, Schuklenk also recognizes the practical limitations of this point of view, since social and economic circumstances can compromise a person’s ability to make free and informed choices. He acknowledges that many people with HIV/AIDS often lack the educational or financial resources to make intelligent and responsible choices. Schuklenk considers some policy solutions to this problem, such as increased funding for health care and medical education.

The second main argument that Schuklenk evaluates is the defense of restricted access in order to promote clinical trials. If experimental drugs are available outside of a clinical trial, then patients will try these drugs and it will be impossible to conduct sound clinical trials because subjects may refuse to participate, or those who agree to participate may already be taking experimental drugs. In order to conduct a controlled clinical trial, potential subjects should be denied access to experimental drugs. Since we need to conduct clinical trials in order to develop reliable knowledge about possible treatments for terminal conditions, we are justified in denying access to experimental drugs in order to promote scientific knowledge and public health. According to this point of view, some individuals may be required to sacrifice their interests (and health) in order to promote the interests (and health) of other individuals.

In critiquing this perspective, Schuklenk argues that it would still be possible to conduct valid research even if people in the study population have access to experimental drugs. It may still be possible to conduct randomized, controlled trials or to employ alternative study designs, such as retrospective case-control studies or epidemiological studies. He also points out that the current situation of restricted access often leads subjects to cheat in order to obtain treatments they want or need. Subjects who cheat in clinical trials deviate from the protocol by taking additional medications, by attempting to unblind the trial, or by lying about their medical history. Cheating occurs because the restricted access approach requires people to be unreasonably altruistic: people with terminal illnesses are sometimes forced to sacrifice their own health and well-being for the sake of future patients. As long as experimental subjects believe that they are receiving free access to a new and effective therapy, then they will not regard participation in a research study as a sacrifice. However, if terminally ill people believe that they are being denied access to a new and effective therapy, then they will view their plight as a sacrifice. People who are unwilling to make this sacrifice will be tempted to break the rules of research protocols in order to obtain access to new treatments. Schuklenk also discusses a number of other scientific and ethical problems in clinical trials, including the use of placebo-controls when treatments are available, the concept of clinical equipoise, and the use of alternative endpoints in studies.

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Before reading Schuklenk’s book, I accepted most of the arguments and assumptions for restricted access to experimental drugs in terminal illness. Contemplating the points he makes in his book has made me reconsider these views. I find the book highly compelling and persuasive, and I am much more sympathetic to the unrestricted access viewpoint. However, I would like to point out some practical problems with unrestricted access. While I think that unrestricted access might work under some very idealized conditions, there are some real difficulties with unrestricted access in practice. Schuklenk understands and is concerned about these practical issues, but I would like to discuss some of these in the remainder of this review.

The first problem is the issue of risk in terminal illness. Granted, people with terminal illnesses will die eventually, but death is often not the worst outcome. Some experimental drugs can cause pain, suffering, and dysfunction and can accelerate death. Sometimes it may be a good gamble to take an experimental drug when one has a terminal illness, but sometimes it may be a very poor choice. The nature of this risk varies from one condition to another. Thus, while it may be a good gamble for a person with full-blown AIDS to try a variety of experimental drugs, this decision would be a poor choice for a person with HIV. In many cases, HIV is a manageable, chronic illness. HIV is still a terminal condition in some sense, but it is far different from full-blown AIDS. The same point holds for different kinds of cancer, such as brain cancer, liver cancer, and prostate cancer. A person with inoperable brain cancer has more to gain (and less to lose) from taking an experimental drug than a person with prostate cancer. The case for unrestricted access is the strongest when a person is likely to die soon with a poor quality of life, but this argument is much weaker when a person has a better prognosis. As a practical matter, how can we decide which patients with terminal conditions should be allowed to have access to experimental drugs?

The second problem is the broader question of controlling access to experimental drugs in society. In the United States, the FDA’s procedures for approving drugs are designed to protect the health and safety of all people who make take drugs, not just people with terminal illnesses. If we loosen restrictions on access to experimental drugs in order to benefit people with terminal illnesses, how can we prevent other people from getting access to these same drugs? Once a drug is available to the public, it is very difficult to control prescribing practices to insure that only patients with specific conditions, such as terminal cancer, obtain to the drug. We need look no further than the use of Viagra, Fen-Phen, Prozac, and Ritalin to see how difficult it is to control prescribing practices once a drug reaches the market. Admittedly, most nonterminal patients will have little interest in taking drugs that are appropriate for people with terminal conditions, but it is possible that some of the drugs used to treat terminal illnesses, such as marijuana, may have some desirable benefits or effects. Although it is important to be sensitive to the needs of people with terminal conditions, we still should not forget the need to promote drug safety in the entire population. Once again the safety/risk issue presents itself: a person without a terminal condition has a great deal to lose and not much to gain by taking an experimental drug. What is an acceptable risk for a terminal patient may be an unacceptable risk for a nonterminal patient.