The Ethical Challenges of Human Research Selected Essays

The use of human beings as research subjects poses distinctive ethical issues. Subjects of medical research are exposed to risks of harm for the sake of generating scientific knowledge that can benefit future patients and society. Ethical analysis of the challenges posed by research involving human subjects requires careful attention to the contextual details of scientific experimentation. This book contains 22 essays by Franklin G. Miller on research ethics written over a 15-year period. With the exception of the first essay, all have been previously published in bioethics and medical journals. The book is arranged into four parts. Part One addresses a general ethical perspective on the protection of human subjects in clinical research, including paternalism in research regulation and acceptable limits to research risks. The essays in Part Two examine ethical issues in study design. It includes ethical analyses of controversial types of medical experimentation-studies that provoke psychiatric symptoms, induce infections, provide patients with placebos that withhold proven effective treatments or administer fake invasive procedures, test experimental treatments in cancer patients who have exhausted all standard treatment options, and employ the use of deception to generate scientifically valid data. Part Three offers a systematic critique of "the therapeutic orientation" to clinical trials and the principle of clinical equipoise, which is widely regarded as a fundamental norm for randomized treatment studies. Part Four takes up a range of ethical issues relating to informed consent for research participation, including examination of "the therapeutic misconception" and presentation of a novel approach to the validity of consent: "the fair transaction model." An abiding theme, developed in many of the essays is that the ethics of clinical research is importantly different from the ethics of medical care.

Preface; Acknowledgments; Part One: Protecting Human Subjects in Clinical Research: A General Perspective; 1. Miller FG. Situating research ethics: revisiting Beecher and Jonas; 2. Miller FG, Wertheimer A. Facing up to paternalism in research ethics. Hastings Center Report 2007;37(3):24-34.; 3. Miller FG, Joffe S. Limits to research risks. Journal of Medical Ethics 2009;35:445-449.; Part Two: Study Design; 4. Miller FG, Rosenstein DL. Psychiatric symptom-provoking studies: an ethical appraisal. Biological Psychiatry. 1997;42:403-9.; 5. Miller FG, Grady C. The ethical challenge of infection-inducing challenge experiments. Clinical Infectious Diseases. 2001;33:1028-33.; 6. Miller FG. Placebo-controlled trials in psychiatric research: an ethical perspective. Biological Psychiatry. 2000;47:707-16.; 7. Miller FG, Brody H. What makes placebo-controlled trials unethical? The American Journal of Bioethics. 2002;2(2):3-9.; 8. Miller FG, Emanuel EJ, Rosenstein DL, Straus SE. Ethical issues concerning research on complementary and alternative medicine. JAMA 2004;291:599-604.; 9. Miller FG. Sham surgery: an ethical analysis. American Journal of Bioethics 2003;3(4):41-8;; 10. Miller FG, Joffe S. Benefit in phase 1 oncology trials: therapeutic misconception or reasonable treatment option? Clinical Trials 2008;5:617-23.; 11. Miller FG, Wendler D, Swartzman L. Deception in research on the placebo effect. PLoS Medicine 2005;2(9):e262.; 12. Miller FG, Gluck JP, Wendler D. Debriefing and accountability in deceptive research. Kennedy Institute of Ethics Journal 2008;18:235-51.; Part Three: Therapeutic Orientation and Equipoise; 13. Miller FG, Rosenstein DL, DeRenzo EG. Professional integrity in clinical research. Journal of the American Medical Association. 1998;280:1449-54.; 14. Miller FG, Rosenstein DL. The therapeutic orientation to clinical trials. New England Journal of Medicine. 2003;348:1383-86.; 15. Miller FG, Brody H. A critique of clinical equipoise: Therapeutic misconception in the ethics of clinical trials. Hastings Center Report. 2003;33(3):19-28.; 16. Miller FG, Brody H. Clinical equipoise and the incoherence of research ethics. Journal; of Medicine and Philosophy 2007;32:151-65.; 17. Miller FG, Joffe S. Equipoise and the randomized clinical trial dilemma. New England Journal of Medicine 2011;364:476-80.; Part Four: Consent; 18. Miller FG, Joffe S. Evaluating the therapeutic misconception. Kennedy Institute of Ethics Journal 2006;16:353-66.; 19. Miller FG, Wendler D. Is it ethical to keep interim findings of randomized controlled trials confidential? Journal of Medical Ethics 2008;34:198-201.; 20. Miller FG. Research on medical records without informed consent, Journal of Law, Medicine & Ethics 2008;36:560-66.; 21. Miller FG, Pearson SD. Coverage with evidence development: ethical issues and policy implications. Medical Care 2008;46:746-57.; 22. Miller FG, Wertheimer A. The fair transaction model of informed consent: an alternative to autonomous authorization, Kennedy Institute of Ethics Journal 2011;21:201-18.

Department of Bioethics, National Institutes of Health. Co-editor of The Oxford textbook of Clinical Research Ethics, and The Ethics of Consent