Is the Use of Placebo Controls Ethically Permissible in Clinical Trials of Agents Intended to Reduce Fractures in Osteoporosis?

• Published in: Journal of bone and mineral research Vol. 18; no. 6; pp. 1105 - 1109
• Main Authors: Brody, Baruch A, Dickey, Nancy, Ellenberg, Susan S, Heaney, Robert P, Levine, Robert J, O'brien, Richard L, Purtilo, Ruth B, Weijer, Charles
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01.06.2003; American Society for Bone and Mineral Research
• Subjects: active controls; Bioethics; Biological and medical sciences; Clinical trial. Drug monitoring; clinical trials; Clinical Trials as Topic - standards; Controlled Clinical Trials as Topic - standards; Ethics; Fractures, Bone - ethnology; Fractures, Bone - prevention & control; General pharmacology; Human Experimentation - standards; Humans; Medical sciences; osteoporosis; Osteoporosis - ethnology; Osteoporosis - prevention & control; Pharmacology. Drug treatments; placebo controls; Placebos; Space life sciences; Human; Pathologic fracture; Diseases of the osteoarticular system; Controlled therapeutic trial; Bone disease; Trauma; Osteoarticular system; Prevention; Ethics; Osteoporosis; Treatment; placebo controls; Placebo; Clinical trial; clinical trials; Bone; active controls; Biomedical and Behavioral Research
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.2003.18.6.1105

Substantial progress has been made in developing treatments that reduce the risk of fractures in osteoporosis. However, available treatments are only partially effective, they are not widely used, and there is need to search for more effective means of fracture prevention. Currently known effective means of reducing fractures were found using randomized placebo‐controlled trials. The use of placebo controls in clinical trials has been a subject of significant controversy in recent years. The Declaration of Helsinki revision of October 2000 caused great concern among clinical investigators about the future use of placebo controls if known effective therapeutic agents are available. A working group of ethicists, clinical trial design experts, and clinical investigators examined the current state of knowledge of osteoporosis treatment and trials. They concluded that if placebo controls put subjects at substantial risk of serious outcomes, they are not ethically permissible. Placebo controls in osteoporosis trials with fracture as the measured outcome are permissible only under narrowly defined conditions. Placebo controls may be used if competent, well‐informed patients refuse approved therapies for sound reasons, there is a reasonable basis for substantial disagreement or lack of consensus among professionals about whether approved treatments are better than placebos, or subjects are refractory to known effective agents. Active control trials are permissible and desirable if they can be designed and conducted in ways that overcome the interpretive difficulties often associated with such trials.