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

Baruch A. Brody, Nancy Dickey, Susan S. Ellenberg, Robert P. Heaney, Robert J. Levine, Richard L. O'Brien, Ruth B. Purtilo, Charles Weijer

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1105-1109
Number of pages5
JournalJournal of Bone and Mineral Research
Volume18
Issue number6
DOIs
StatePublished - Jun 1 2003

Fingerprint

Osteoporosis
Placebos
Clinical Trials
Therapeutics
Helsinki Declaration
Research Personnel
Ethicists
Randomized Controlled Trials

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Is the Use of Placebo Controls Ethically Permissible in Clinical Trials of Agents Intended to Reduce Fractures in Osteoporosis? / Brody, Baruch A.; Dickey, Nancy; Ellenberg, Susan S.; Heaney, Robert P.; Levine, Robert J.; O'Brien, Richard L.; Purtilo, Ruth B.; Weijer, Charles.

In: Journal of Bone and Mineral Research, Vol. 18, No. 6, 01.06.2003, p. 1105-1109.

Research output: Contribution to journalArticle

Brody, BA, Dickey, N, Ellenberg, SS, Heaney, RP, Levine, RJ, O'Brien, RL, Purtilo, RB & Weijer, C 2003, 'Is the Use of Placebo Controls Ethically Permissible in Clinical Trials of Agents Intended to Reduce Fractures in Osteoporosis?', Journal of Bone and Mineral Research, vol. 18, no. 6, pp. 1105-1109. https://doi.org/10.1359/jbmr.2003.18.6.1105
Brody, Baruch A. ; Dickey, Nancy ; Ellenberg, Susan S. ; Heaney, Robert P. ; Levine, Robert J. ; O'Brien, Richard L. ; Purtilo, Ruth B. ; Weijer, Charles. / Is the Use of Placebo Controls Ethically Permissible in Clinical Trials of Agents Intended to Reduce Fractures in Osteoporosis?. In: Journal of Bone and Mineral Research. 2003 ; Vol. 18, No. 6. pp. 1105-1109.
@article{409a7c7b694246cab9b1010bd199e658,
title = "Is the Use of Placebo Controls Ethically Permissible in Clinical Trials of Agents Intended to Reduce Fractures in Osteoporosis?",
abstract = "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.",
author = "Brody, {Baruch A.} and Nancy Dickey and Ellenberg, {Susan S.} and Heaney, {Robert P.} and Levine, {Robert J.} and O'Brien, {Richard L.} and Purtilo, {Ruth B.} and Charles Weijer",
year = "2003",
month = "6",
day = "1",
doi = "10.1359/jbmr.2003.18.6.1105",
language = "English",
volume = "18",
pages = "1105--1109",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Is the Use of Placebo Controls Ethically Permissible in Clinical Trials of Agents Intended to Reduce Fractures in Osteoporosis?

AU - Brody, Baruch A.

AU - Dickey, Nancy

AU - Ellenberg, Susan S.

AU - Heaney, Robert P.

AU - Levine, Robert J.

AU - O'Brien, Richard L.

AU - Purtilo, Ruth B.

AU - Weijer, Charles

PY - 2003/6/1

Y1 - 2003/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0142122896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142122896&partnerID=8YFLogxK

U2 - 10.1359/jbmr.2003.18.6.1105

DO - 10.1359/jbmr.2003.18.6.1105

M3 - Article

C2 - 12817764

AN - SCOPUS:0142122896

VL - 18

SP - 1105

EP - 1109

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 6

ER -