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Human Subjects/Clinical Research

Research involving humans entails a rigorous responsibility for the well being of the research subjects, as well as a delicacy and sensitivity not required when working strictly with test tubes and reagents. Patients make an important contribution to science and society by participating in research protocols. This commitment must invite in return the utmost in respect and diligence from the researcher. In practice, that respect and diligence should include planning studies so that the potential benefits (to both the subject and society) outweigh the potential risks. In addition, steps must be taken to guarantee that subjects are selected equitably and that they make an informed decision about participating. This last concept is known as the principle of informed consent. Informed consent requires that patients be fully informed of the risks and benefits of the protocol and be competent to evaluate this information. Not only must consent be informed, it must also be free of coercion.

Obtaining informed consent is not always a straightforward issue. For example, the most appropriate method of obtaining informed consent may not be clear. Ensuring that patients fully understand the risks and benefits of a procedure can be a complicated matter as well, particularly where the competency of the patient is in doubt -- a situation dealt with in Case H1. The role of what might be termed "deferred consent," or seeking consent from next-of-kin or guardians is also explored in this case.

Although there is general agreement that a patient's well being should be paramount, the level of risk to which he or she may be subjected is less clear. Even under the best of circumstances, researchers may not be able to anticipate every eventuality of the study. Thus, although patients have been informed at the outset of possible events, unanticipated risks or benefits may arise during the course of the protocol. Researchers must inform patients of these events and make appropriate determinations about whether and how to proceed. For example, even in a double-blinded study, the experimental drug may prove so promising that its therapeutic effects break the blind. At that point, physicians must consider whether it is ethical to continue to utilize a placebo in seriously ill patients when an apparently effective agent is available. This issue is dealt with in Case H2.

Case H3 also deals with the ethics of denying patients possibly therapeutic agents. In this instance, the alternative is a standard therapy with modest clinical effectiveness in an ultimately fatal disease. Patients who perceive that their prospects for survival are grim may be willing to subject themselves to greater levels of risk in seeking new therapies than would normally be scientifically and ethically acceptable. The reader must consider whether scientists should make exceptions for terminally ill patients, or whether the patient's condition represents a coercive influence. Another consideration is whether expanded access to unproven therapeutic agents jeopardizes efforts to obtain scientifically valid, generalizable data of value to society.

Another issue pertinent to clinical investigation concerns the role of the physician as investigator. In the context of double-blinded clinical trials, some argue that there is a conflict between the fiduciary responsibility of physicians and the objectivity required of the researchers. In Case H4, the investigator has definite, yet unproven, opinions about the efficacy of a certain course of treatment. On the basis of his subjective opinion alone, he might be inclined, and even have a responsibility, to provide the drug he believes is most effective. Yet, as a researcher, he understands that certain knowledge of the drug's efficacy cannot be obtained without administering to some patients a drug he believes is less effective.

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