Data Safety and Monitoring Boards
http://www.100md.com
《新英格兰医药杂志》
To the Editor: The original purpose of the data safety and monitoring board, as reported by Slutsky and Lavery (March 11 issue),1 was to protect subjects from the poor judgment of investigators who may have been so committed to advancing science for the good of humanity (or for their own potential gains) that they put subjects at risk. Currently, the mission of data safety and monitoring boards includes ensuring the safety of subjects and the quality and integrity of the trial.2 Once a data safety and monitoring board takes on the task of advancing science, it has the same potential for conflict that investigators have. This conflict is compounded when only the data safety and monitoring board reviews interim data. The interim data are "blinded" because disclosure might influence the decision of subjects to withdraw from or not enter a trial in which the data safety and monitoring board believes they should participate.3 Blinding denies the investigator and the institutional review board (IRB) the opportunity to conduct a risk–benefit analysis that could be the basis for early termination of a trial. This violates the provisions of the Nuremberg Code, the Helsinki Declaration, and the Code of Federal Regulations (45 CFR 46) for fully informed consent and investigator- or IRB-mandated termination of scientific research, and it erodes the protection of subjects from poor judgment by the investigators or the data safety and monitoring board.4,5
Robert J. Wells, M.D.
University of Texas M.D. Anderson Cancer Center
Houston, TX 77030
rjwells@mdanderson.org
References
Slutsky AS, Lavery JV. Data safety and monitoring boards. N Engl J Med 2004;350:1143-1147.
Ellenberg SS, Fleming TR, DeMets DL. Data monitoring committees in clinical trials: a practical perspective. Chichester, England: John Wiley, 2002.
Green SJ, Fleming TR, O'Fallon JR. Policies for study monitoring and interim reporting of results. J Clin Oncol 1987;5:1477-1484.[Abstract]
Jonsen AR, Veatch RM, Walters L, eds. Source book in bioethics: a documentary history. Washington, D.C.: Georgetown University Press, 1998:11-5.
Protection of Human Subjects, 45 C.F.R. 46. OPRR reports. Rockville, Md.: Office for Human Research Protections, March 15, 1994.
The authors reply: Dr. Wells is correct that there is an inherent conflict for data safety and monitoring boards with respect to optimizing protection of human subjects and optimizing a trial's scientific value. If the only mandate of the data safety and monitoring board was to ensure that subjects were not harmed, then the optimal approach would be for the data safety and monitoring board to cancel the trial at its inception in order to ensure that no subjects are enrolled in the study. Although this option represents a perfect strategy for eliminating research-related risk, it has been squarely rejected by modern societies, which have benefited enormously from ethical scientific research.
Despite Dr. Wells's assertion to the contrary, the Nuremberg Code does not provide a simple solution to the conflict between protecting subjects and optimizing the scientific value of the research. In fact, its first two principles, on voluntary consent and valuable science, clearly lay out the nature of this conflict, and its preamble recognizes explicitly that these requirements can be successfully balanced.1 The Declaration of Helsinki and the regulatory requirements of the U.S. Common Rule contain similar statements.
Arthur S. Slutsky, M.D.
James V. Lavery, Ph.D.
St. Michael's Hospital
Toronto, ON M5B 1W8, Canada
arthur.slutsky@utoronto.ca
References
Brody BA. The ethics of biomedical research: an international perspective. New York: Oxford University Press, 1998:213.
Robert J. Wells, M.D.
University of Texas M.D. Anderson Cancer Center
Houston, TX 77030
rjwells@mdanderson.org
References
Slutsky AS, Lavery JV. Data safety and monitoring boards. N Engl J Med 2004;350:1143-1147.
Ellenberg SS, Fleming TR, DeMets DL. Data monitoring committees in clinical trials: a practical perspective. Chichester, England: John Wiley, 2002.
Green SJ, Fleming TR, O'Fallon JR. Policies for study monitoring and interim reporting of results. J Clin Oncol 1987;5:1477-1484.[Abstract]
Jonsen AR, Veatch RM, Walters L, eds. Source book in bioethics: a documentary history. Washington, D.C.: Georgetown University Press, 1998:11-5.
Protection of Human Subjects, 45 C.F.R. 46. OPRR reports. Rockville, Md.: Office for Human Research Protections, March 15, 1994.
The authors reply: Dr. Wells is correct that there is an inherent conflict for data safety and monitoring boards with respect to optimizing protection of human subjects and optimizing a trial's scientific value. If the only mandate of the data safety and monitoring board was to ensure that subjects were not harmed, then the optimal approach would be for the data safety and monitoring board to cancel the trial at its inception in order to ensure that no subjects are enrolled in the study. Although this option represents a perfect strategy for eliminating research-related risk, it has been squarely rejected by modern societies, which have benefited enormously from ethical scientific research.
Despite Dr. Wells's assertion to the contrary, the Nuremberg Code does not provide a simple solution to the conflict between protecting subjects and optimizing the scientific value of the research. In fact, its first two principles, on voluntary consent and valuable science, clearly lay out the nature of this conflict, and its preamble recognizes explicitly that these requirements can be successfully balanced.1 The Declaration of Helsinki and the regulatory requirements of the U.S. Common Rule contain similar statements.
Arthur S. Slutsky, M.D.
James V. Lavery, Ph.D.
St. Michael's Hospital
Toronto, ON M5B 1W8, Canada
arthur.slutsky@utoronto.ca
References
Brody BA. The ethics of biomedical research: an international perspective. New York: Oxford University Press, 1998:213.