Fay Sawyier's "Clinical Trials of Cancer Therapy" raises at least four ethical issues. From the point of view of contemporary standards of ethical research in the United States, one of these issues is an (ethical) "no-brainer." Two more should be. Only the fourth, about which Professor Sawyier says nothing, is ethically complex.

The No-Brainer
The way in which the re-searchers dealt with Professor Sawyier (and her husband) during the informed consent process fell far short of ethical practice. Rather than actively educating the potential research subject about the proposed research -- what is known about the therapy to date, its likely risks and benefits, and so on -- the researchers simply handed Profes-sor Sawyier the consent form. She was not even invited to educate herself. Apparently, the research-ers thought that the purpose of giving Professor Sawyier the form was to have her sign it, not read it, understand it, or otherwise seek to resolve thoughtfully any questions she might have about participating in the research.

True, Professor Sawyier (or her husband) may already have communicated to the researchers that she viewed herself as having no real alternative to participation. But lack of any real alternative does not excuse researchers from making sure each research subject understands all the relevant information. For even if Professor Saw-yier were disposed to view any increased likelihood of life-extension from the research as of more benefit than any non-experimental medical alternative available to her, she might reasonably have concluded that, all things considered, entering the research program was not the best choice for her. She might, for example, not have wanted to suffer any of the therapy's possible side effects.

Professor Sawyier does indicate that she was already aware that the side-effects of the experimental regimen were not very burdensome; so, it might be argued that she already had learned of and weighed the risks involved. But a researcher's obligation to a potential subject is personally to educate or, at a minimum, to verify that the subject's previous education has been sufficient to weigh not only all the risks but also any factors that might limit possible benefits. Insum, the researchers, in winning Professor Sawyier's consent, failed to conform to the most elementary contemporary ethical standards regarding informing research subjects and receiving their informed consent.

The 50% Test
The eventual exclusion of Professor Sawyier from the research because her improvement did not pass the 50% test raises a different ethical issue. It was because of this issue that the previous paragraph stressed providing information about factors limiting the possible benefits. Unless specifically in-formed otherwise, few research subjects would guess that their continued participation in a Phase II trial could be limited by not improving fast enough. So, the absence of any reference to that limitation in the informed consent form was a serious ethical failure on the part of those who drafted it and of any IRB that reviewed it. The researchers' failure to alert Profes-sor Sawyier to the possibility of exclusion from the study if she did not improve fast enough only compounded the wrong inherent in the form itself.

At a deeper level, there is also the ethical question that Pro-fessor Sawyier poses about the 50% rule. Is the purpose of the rule simply to protect the pharmaceutical company by giving the public the impression that Phase II trials do more good than harm? There are serious ethical flaws with that basis for the rule. Could there be a good defense of the rule in terms of scientific methodology? Perhaps, but no one who interacted with Professor Sawyier seems have suggested one, not even those who finally offered her continued use of the experimental medication. Without more information about the reasons for the rule, making a final judgment is difficult. But the 50% rule surely deserves careful ethical analysis. If there is no good reason for the rule (that is, no reason related to its benefit to present or future users of the drug), then the rule itself is very likely unethical.

Professor Sawyier points out that because of her own (and her husband's) education, organizational savvy, and position (especially her husband's status as a corporate lawyer), she was eventually able to get the 50% rule set aside in her case. She asks what would happen to someone who was not so savvy or so well positioned. The answer is pretty obvious, raising questions of equity of access to treatment that affect all medical institutions. In addition, it is not clear whether the justification of the 50% rule was challenged even by those who eventually set it aside in her case. If restoration of her ac-cess to the drug was merely the effect of her leverage, those who authored or administered the rule never seriously considered the ethical question it raises, another ethical lapse.

Respect for the Patient
Beyond the issue of equity already raised here, there is an issue about the way in which both the individual researchers and their institution treated Professor Sawyier after she consented to become a participant in the research. They did not treat her as a patient, only as a potential source of scientific knowledge. But in fact Professor Sawyier would not have been a potential source of scientific knowl- edge for them if she were not already their patient. Both biomedical researchers and their institutions owe each potential subject the recognition that she is a patient first and only secondarily a research subject. Neither individual researchers nor their institutions may set aside the obligations that health care professionals have to patients because the patient in question is also a subject of research. It is only after a potential subject has freely chosen to become someone whose participation in the research is used for the benefit of others that any aspect of her treatment may be ethically viewed as secondary, and that only insofar as the secondary status is necessary for the successful conduct of the research and only if the patient-subject (or, in the case of a patient with compromised capacities, an appropriate surrogate) has freely consented to every such amendment to the standard physician-patient relationship.

There is hardly any resemblance between Professor Saw-yier's description of the way in which the researchers and their institution treated her and the way in which ethical physicians and an ethical hospital would treat a patient, especially a patient with a life-threatening illness. The ethical failings of the researchers and their institution are not strictly speaking failures to do research ethically but failures to provide medical care ethically. They are nevertheless fail-ures that all researchers who are health care professionals and whose research subjects are also their patients must attend to. Bio-medical researchers cannot es-cape their duty as health care professionals by claiming that those who are their subjects have physicians of their own and that they, as researchers, therefore owe them nothing beyond what any re-searcher owes any human subject.

An Overlooked Alternative
There is also a much subtler ethical issue in this narrative regading experimental treatments offer-ed to patients who are terminally ill and for whom there is no non-experimental medical intervention that offers any likelihood of life-extension. The ethical issue here parallels, but is even more complex than, that faced by health care professionals who must determine when to speak to a terminally ill patient about hospice care. In addition to the experimental and non-experimental treatment alternatives (and the alternative of doing nothing at all) likely to be explained to a potential research subject in Professor Sawyier's situation, there is also the possibility of palliative care alone. A fully in-formed patient needs to be able to weigh this alternative along with the others.

There is a growing understanding within the health care community that, for some terminally ill patients, there comes a time when the best course is to cease life-extending interventions and focus the patient's own efforts, and the efforts of those in supporting or caring roles, on the goal of dying well rather than on living longer. For such patients, appropriate palliative care is a valuable intervention. Since the potential subjects of biomedical research are the research-ers' patients already, a full discussion of alternatives should ordinarily include a caring and sensitive conversation about palliative care. True, such a conversation would be sharply counter-cultural in many research settings. Indeed, there are probably many biomedical re-searchers whose work and lives are so focused on life-extension that they would find it extremely difficult to offer mere palliative care as a reasonable option and would, therefore, do a bad job of explaining it. Nonetheless, we need to think about what a good conversation between a researcher and a research subject like Professor Sawyer might look like. It is in this spirit, rather than to find fault with the researchers in Professor Saw-yier's narrative, that I raise this fourth issue.