Ethics in the design and conduct of clinical trials.

Received for publication August 21, 2001, and accepted for publication February 12, 2002. 1 Center for the Study of Medical Ethics and Humanities, Duke University, Durham, NC. 2 Departments of Medicine and Philosophy, Duke University, Durham, NC. Correspondence to Dr. Jeremy Sugarman, 108 Seeley G. Mudd Building, Duke University Medical Center (Box 3040), Durham, NC 27710 (e-mail: [email protected]). The history of medicine reveals the need for clinical research. All too frequently, interventions thought to be safe and effective by clinicians prove to be otherwise. The current emphasis on “evidence-based medicine” enunciates the need for carefully obtained data from carefully conducted clinical research; yet the history of medical research in general, and clinical research in particular, has been an unfortunate and littered one in which some physician-scientists have undermined the rights and interests of the participants. While some of the most frequently cited examples of unethical research are clearly egregious, such as the dangerous experimentation on unwilling concentration camp prisoners by Nazi physicians, others are more subtle and involve the misuse of commonly employed, rigorous methods of study design such as randomization and use of placebos. While underrecognition of these issues may be the norm, recent headlines demonstrate that ethical issues associated with certain types of study designs can animate substantial debate. Witness, for example, the controversy over the use of placebo controls in trials aimed at decreasing vertical transmission of human immunodeficiency virus infection (1). Regardless of whether such ethical issues are overt or subtle, it is critical that persons designing, sponsoring, overseeing, conducting, reviewing, and reading the results of clinical research understand these issues so as to ensure that all persons who agree to participate in research are adequately protected. In this article, I outline some of the important ethical issues in the design and conduct of clinical research. To set the appropriate context, I first sketch some of the most notorious examples of unethical research and explain how the ethics of research came to be recognized and articulated, especially in public declarations. Next I describe the basic ethical principles that can be of assistance in understanding the relevant ethical issues encountered in clinical research. I then outline the ethical implications associated with selected issues in research design: randomization, use of placebos, confidentiality, and selection of participants. Finally, I discuss some of the ethical considerations involved in the research process: obtaining valid informed consent, dealing with interim results, and the responsible conduct of research. Although the scope of this article does not permit a detailed analysis of any of these particular issues, I have attempted to provide a sense of the relevant concerns and to point the reader towards literature appropriate for further discussion of them.