Data and Safety Monitoring Boards: Some Enduring Questions

These are also known as Data Safety Committees (DSCs), Independent Data Monitoring Committees (IDMCs), Data Monitoring Committees (DMCs) and Data Review Boards (DRBs).

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Ellenberg S. S. Fleming T. R. and DeMets D. L. , Data Monitoring Committees in Clinical Trials (New York: Wiley, 2003).

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Edwards S. J. L. Lilford R. J. and Hewison J. , “The Ethics of Randomized Controlled Trials from the Perspectives of Patients, the Public and Healthcare Professionals”, BMJ 317, no. 4 (1998): 1209–1212.

See Ellenberg , supra note 3. One reason for this is that the NIH requires that a DSMB monitor every phase III trial.

Food and Drug Administration, Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical Trial Data Monitoring Committees, Rockville, MD, 2005.

See Ellenberg , supra note 3.

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Lilford R. J. Braunholtz D. Edwards S. S. and Stevens A. , “Monitoring Clinical Trials – Interim Data Should Be Publicly Available”, BMJ 323, no. 7310 (2001): 441–442.

They cite the ISIS 2 example, where initially skeptical physicians moved into equipoise.

Both the NBAC and Beecher are quoted in Michels R. , “Are Research Ethics Bad for Our Mental Health?” New England Journal of Medicine 340, no. 18 (1999):1427–1430.

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Goodman K. W. , Ethics and Evidence-Based Medicine (Cambridge: Cambridge University Press, 2003).

By this is meant systematic reviews of the literature, aka metaanalysis.

Adams M. S. and Conrad D. A. , “Annual Review: Observed Deficiencies and Suggested Corrections”, IRB: A Review of Human Subjects Research 18, no. 5 (1996): 1–6.

Available at <www.hhs.gov/ohrp/humansubjects/guidance/contrev0107.htm> (last visited July 7, 2009).

Meinert C. L. , “Masked Monitoring in Clinical Trials – Blind Stupidity?” New England Journal of Medicine 338, no. 16 (1998): 1381–1382.

Meinert C. L. , “IRBs and Randomized Clinical Trials”, IRB: A Review of Human Subjects Research 20, no. 1 (1998): 9–12.

See Wells , supra note 5.

To be fair, this is based on the pvalues 0.169 that by study's end A would be favored, and 0.00002 that B would be favored. The chance that neither would be favored is 0.8309.

Royall R. M. , “Ethics and Statistics in Randomized Clinical Trials”, (with discussion), Statistical Science 6, no. 1 (1991): 52–88.

Veatch R. M. , “Comment”, Controlled Clinical Trials 19, no. 6 (1997): 532–533.

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Kadane J. B. , ed., Bayesian Methods and Ethics in a Clinical Trial Design (New York: Wiley, 1996).

Hellman D. , “Evidence, Belief and Action: The Failure of Equipoise to Resolve the Ethical Tension in the Randomized Clinical Trial”, Journal of Law, Medicine & Ethics 30, no. 2 (2002): 375–380.

Gifford F. , “Freedman's ‘Clinical Equipoise’ and ‘Sliding-Scale All-Dimensions-Considered Equipoise,’” Journal of Medicine & Philosophy 25, no. 4 (2000): 399–426.

Chiong W. , “The Real Problem with Equipoise”, American Journal of Bioethics 6, no. 4 (2006): 37–47.

Chiong suggested a rough-and-ready test for the universalizability of some practice: whether we would be willing to imagine ourselves, our loved ones, or our peers on the receiving end of some treatment. What would it be like if everybody did that?

Meier P. , “Statistics and Medical Experimentation”, Biometrics 31, no. 2 (1975): 511–529.

Amdur R. J. , “Provisions for Data Monitoring”, in Amdur R. J. and Bankert E. A. , eds., Institutional Review Board: Management and Function (Sudbury, MA: Jones and Bartlett, 2002): 191–196.

Wendler D. and Rackoff J. , “Consent for Continuing Research Participation: What Is It and When Should It Be Obtained?” IRB: Ethics & Human Research 24, no. 2 (2002): 1–6.

Miller F. G. and Wendler D. , “Is It Ethical to Keep Interim Findings of Randomized Controlled Trials Confidential?” Journal of Medical Ethics 34, no. 4 (2008): 198–201.

Beauchamp T. L. and Childress J. F. , Principles of Biomedical Ethics, 5th ed. (New York: Oxford University Press, 2001).

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Menikoff J. , What the Doctor Didn't Say: The Hidden Truth about Medical Research (New York: Oxford University Press, 2006).

The consent form also failed to mention that that the patient could get the chemotherapy from a doctor, outside of the study, and thus be sure of getting this, instead of the 50% chance in the study. See id., at 130.

Veatch R. M. , “The Right of Subjects to See the Protocol”, IRB: Ethics & Human Research 24, no. 4 (2002): 6–8.

Levine R. J. , Ethics and Regulation of Clinical Research, 2nd ed. (New Haven: Yale University Press, 1986).

This differs from the “reasonable person” standard, as described by Menikoff (supra note 42, at 92), who suggests that “…the appropriate standard for determining disclosure in the research setting should always be the reasonable person standard.” Beauchamp and Childress (supra note 2, at 327) thought DSMBs should “supply physicians and patients with significant safety and therapeutic information that is relevant to a reasonable person's decision to remain in or withdraw from the trial.” Reasonable people need not insist on statistical significance before they are willing to act.

Buchanan D. and Miller F. G. , “Principles of Early Stopping of Randomized Trials for Efficacy: A Critique of Equipoise and an Alternative Nonexploitation Ethical Framework”, Kennedy Institute of Ethics Journal 2, no. 2 (2005): 161–178.