Ethical Issues in HIV Vaccine Trials

 

Chapter 14

Informed consent (1)

 

The principle of informed consent has become almost the cornerstone of medical ethics discussions in the West. Sometimes it seems as if no other principle in medical ethics can hold a candle to the supremacy of this principle. The principle derives its validity from the more basic principle of autonomy, which in turn is based on the even more fundamental principle of respect for persons. In fact the simplest and most profound conclusion of Annas' and Grodin's lengthy 1992 study of the Doctors' Trial at Nuremberg is that "the need to respect the humanity and self-determination of all humans is central to the ethos not only of medicine and human experimentation but of all civilized societies". Even though in recent years ethicists have more and more recognized that there are some limitations on the principle of autonomy, it is still recognized as one of the most important imperatives in all medical ethics decision-making, both in clinical situations and in human subjects research. Many ethicists would argue that, as Annas, Grodin, and Katz put it, "without the informed consent of the competent subject, there really is no defensible justification for using human beings as research subjects". Our focus in these following pages will be on the use of informed consent in biomedical research settings.

In its simplest terms, the principle requires that you tell potential volunteers what the proposed research is about, what you hope to learn by it, what will be expected of them, and what they can expect will happen to them during (and even after) the experiment. Prospective volunteers should also be told what their rights are as participants in the trial, and what their responsibilities are as well. They should probably be given a written "Bill of Rights and Responsibilities" to keep. (I have written, and included in Appendix III, a sample Bill of Rights and Responsibilities for volunteers in HIV vaccine trials.) Prospective volunteers must also be assured that they can quit their participation in the study anytime they wish, without any kind of penalty or cost. Some ethicists have suggested that subjects should also be told what company, institution, or government agency is sponsoring the research, so they can decide whether or not they wish to support that agency's or company's research. Although this is not standard practice right now, it does not seem like an unreasonable recommendation.

At least as important as the content of what they must be told, subjects must also be able to competently deliberate and freely choose, "without the intervention of any element of force, fraud, deceit, duress, overreaching, or other ulterior form of constraint or coercion".

In its simplest terms, this is what the principle requires. In practice, things are rather more complex. And when investigators are doing research in developing nations, yet another layer of complexity is added to an already troublesome tangle of issues.

Several functions are intended to be served by application of this principle. The principle is partly intended to promote self-reflection in the biomedical research community and to promote self-scrutiny and rational decision-making among investigators. But the principle's primary function is to promote the autonomy of individuals and to insure the protection of vulnerable subjects.

Applying this principle to each individual volunteer may be much more difficult in developing nations, where levels of literacy are much lower than in developed nations, where beliefs about the nature and causation of disease may be different from those held by the researchers, and where the notion and value of personal identity and individuality may be strikingly different than that held in western nations. Because of these factors the principle of informed consent, which has been one of the cornerstones of biomedical ethics since its origins in The Nuremberg Code, will be problematic in developing nations.

And yet the ethical guidelines are very clear: ethical standards governing human subjects research must be no less stringent in developing nations than they are in developed nations. International Ethical Guidelines #15 is quite explicit: When a sponsoring agency submits its research proposal to ethical review in the country of origin (as it is required to do), the "ethical standards applied [to research in developing nations] should be no less exacting than they would be in the case of research carried out in that country [of origin]".

This single sentence alone underlines one of the key problems faced by research sponsors: conditions in some underdeveloped communities may be significantly different than in developed communities, yet the ethical standards must be applied just as stringently as they are anywhere. This is good ethics, but it presents researchers with some almost insurmountable problems. There must be utmost regard for individual autonomy in decision making. Every single subject must be fully informed and must give free consent. "The investigator is required to ensure that each prospective subject is clearly told everything that would be conveyed if the study were to be conducted in a developed community."

"Everything?" the intelligent reader might ask. "Everything," emphasizes the Guidelines. That will include a variety of kinds of information, including "the aims and methods of the research; the expected duration of the subject's participation;... any foreseeable risks or discomfort to the subject;... the extent to which confidentiality of records in which the subject is identified will be maintained;... whether the subject or the subject's family or dependants will be compensated for disability or death," and all the possible harms and hazards that may be attendant on participating in the research.

In the case of HIV vaccine research specifically, this principle requires informing prospective subjects about what a vaccine is and what an immune system is, as well as about

 

the concepts of randomization, blinding [and double-blinding], placebos, informed consent, and risk/benefit, concepts which [may not be] easily understood in the cultural context of many developing countries.

 

Ethical guidelines require that prospective research subjects be fully informed of all these aims, purposes, methodologies, and hazards associated with their participation in research protocols for which they are considering volunteering.

 

* To see the citations associated with material in this chapter, see a published printed copy of the book, or contact the author directly.

 

 

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