Jonathan D' Moreno, Ph'D' Center for Biomedical Ethics University of Virginia

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Jonathan D. Moreno, Ph.D.Center for Biomedical
EthicsUniversity of Virginia
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Ethics of Clinical Investigation

• Pre- WWII
• Nuremberg Code and aftermath
• 1962-1972-Scandals and Tragedies
• National rules and international codes
• Current issues

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The Nuremberg Code, 1947

• The voluntary consent of the human subject is
  absolutely essential.

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Army Inspector General, 1975

• Following revelations of Army LSD experiments in
  the 1960s
• ...a startling lack of consistency in the
  interpretation of the regulations.

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The American Pantheon

• Thalidomide, 1962
• Henry Beechers NEJM paper, 1966
• Brooklyn Jewish Chronic Disease Hospital
• Willowbrook State Hospital
• Tuskegee Syphilis Study, 1932-72

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THE BELMONT REPORTNational Commission for the
Protection of Human Subjects of Biomedical and
Behavioral Research 1979

• A. Boundaries between research and practice
• B. Ethical principles underlying the conduct of
  research
• Respect for persons
• Beneficence
• Justice

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45CFR.46 Protection of Human Subjects

• PHS policy (1966)
• National Research Act (1974)
• DHEW regulations (1981)
• Part A is the Common Rule for 17 Federal
  agencies (1991)
• Parts B,C,D for vulnerable populations
• B Fetuses, pregnant women, infants of uncertain
  viability
• C Prisoners
• D Children

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Central concepts of common rule

• IRB reviewneed not be local IRB
• Exempt researche.g., educational tests, unlinked
  biomaterials from public sources
• Expedited reviewe.g., minimal risk
• Informed consent
• Parent or legal guardian

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Renewed concerns about clinical trials

• UCLA suicide, 1994
• Normal volunteers deaths (Rochester, Hopkins,
  Case Western), 1996-2002
• Gelsinger death at Penn, 1999
• Kennedy-Krieger lead study, 2001

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Declaration of Helsinki (2000)

• The benefits, risks, burdens and effectiveness of
  a new method should be tested against those of
  the best current prophylactic, diagnostic, and
  therapeutic methods. This does not exclude the
  use of placebo, or no treatment, in studies where
  no proven prophylactic, diagnostic, and
  therapeutic method exists.

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Declaration of Helsinki (October 2002 statement)

• ... a placebo-controlled trial may be ethically
  acceptable, even if proven therapy is available,
  under the following circumstances- Where for
  compelling and scientifically sound
  methodological reasons its use is necessary to
  determine the efficacy or safety of a
  prophylactic, diagnostic or therapeutic method,
  or - Where a prophylactic, diagnostic or
  therapeutic method is being investigated for a
  minor condition and the patients who receive
  placebo will not be subject to any additional
  risk of serious or irreversible harm.

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Current Issues in the Ethics of Clinical Trials

• International research
• Pediatric research
• Persons lacking decision making capacity
• Human biomaterials
• Innovative surgery
• National security

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Institute of Medicine report, October 2002

• IRBs should focus on ethics, not science or
  conflict of interest
• Non-partisan congressional advisory body
• No-fault compensation system for harms
• Informed consent should not focus on protecting
  institutions, but on protecting subjects

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• For here we are not afraid to follow the truth
  wherever it may lead.