ETHICS IN HUMAN SUBJECT RESEARCH

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• ETHICS IN HUMAN SUBJECT RESEARCH
• AND
• RESEARCH INVESTIGATOR RESPONSIBILITY
• Abdul S. Rao, MD, MA, D Phil
• Professor of Biology
• Vice Provost for Research and Sponsored Programs
• Dean, College of Graduate Studies
• Middle Tennessee State University

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• It is the mission of the physician to safeguard
  the health of the people. His or her knowledge
  and conscience are dedicated to the fulfillment
  of this mission
• Adopted from the Declaration of Helsinki

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• Much of early medicine involved experimentation,
  most of which was un-regulated
• For years, society depended on the integrity of
  the researcher for the conduct of ethical
  research since the law(s) that governed this
  activity were sparse
• However, today, ethical issues involving human
  subject research are perhaps the most codified of
  all scientific endeavors
• Interestingly, for the most part, the regulations
  that govern human subject research were, and
  continue to be, developed in response to ethical
  violations

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The Nuremberg Trial

• In 1947, twenty-six Nazi physicians were tried in
  Nuremberg, Germany for research atrocities
  performed on POW
• Exposure to extremes of temperature
• Performance of mutilating surgeries
• Deliberate infection with a variety of lethal
  pathogens

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The Nuremberg Code

• Provided the foundation for the Declaration of
  Helsinki
• Set forth TEN conditions that must be met to
  justify research involving human subjects
• Voluntary informed consent of subjects
• Experimental design based on previous animal
  studies
• Careful risk-to-benefit analysis in the context
  of the importance of the problem being
  investigated
• Performance of experiments ONLY by scientifically
  qualified persons
• Subject-initiated withdrawal from the study at
  any stage
• Investigator-initiated cessation of the
  experiments in the face of possible injury,
  disability, or death

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The Declaration of Helsinki

• The need for more restricted guidelines for
  conduct of research involving human subjects was
  recognized by WHO and other such organizations
• In 1964 the World Medical Association sponsored a
  conference in Helsinki, Finland to formalize the
  guidelines
• Recommended written informed consent
• Required review and prior approval of protocol by
  the IRB
• Distinguished between therapeutic and
  non-therapeutic research

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The Tuskegee Study

• Conducted at the Tuskegee Institute, Alabama from
  1932-1972
• Funded by US Public Health Services
• Involved 412 African-American male
• ALL were infected with Syphilis
• Widely believed to be a distinct disease from
  that in whites
• No patient consent was obtained
• Spinal taps were disguised as free treatment
• Largely designed to study the NATURAL course of
  the disease
• In 1940s when penicillin, known to be effective
  in the treatment of syphilis became available,
  these men were neither informed nor treated with
  this antibiotic
• It was not until 1973, that the government
  finally took steps to ensure treatment of few
  surviving infected patients

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The National Research Act

• The Tuskegee Study prompted in 1974 for the
  enactment of the National Research Act which
  resulted in the establishment of the National
  Commission for the Protection of Human Subjects
  in Biomedical and behavioral Research
• In 1979, the Belmont Report was published which
  is considered as the cornerstone of the ethical
  principles
• Three ethical principles
• Respect for persons
• Beneficence
• justice

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The Belmont Report - I

• Respect for persons
• Acknowledges the dignity and autonomy of
  individuals and requires that people with
  diminished autonomy be provided with protection
• Requires that subjects give informed consent to
  participate in research
• Provides for additional protection to subjects
  felt to be vulnerable such as
• Live human fetuses
• Children
• Prisoners
• Mentally disabled
• People with severe, chronic illnesses

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The Belmont Report - II

• Beneficence
• Requires that the study be carefully designed so
  that benefits are maximized and any potential
  harm is minimized
• Justice
• Requires that all subjects be treated fairly
• Requires that there must be equity in subject
  selection to insure that certain individuals or
  classes of individuals such as prisoners,
  elderly, or financially impoverished are not
  systematically selected or excluded (unless there
  are scientifically or ethically valid reasons for
  doing so)

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The Issue of Informed Consent

• The subject must first be competent to consent
• Understand the consequences and be able to make
  decisions
• The consent must be voluntary and free from any
  coercion
• The consent must be informed
• Participants must have adequate information to
  make informed decision
• Merely presenting the information to the subject
  is not enoughthey must be able to fully
  comprehend the risks and the benefits
• Investigator must verify that the subject indeed
  understands the various options and risks and
  potential benefits of the study
• To obtain informed consent is the responsibility
  of ALL involved in the study not just the
  principal investigator

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Case 1 - I

• You have been attending a meeting and are
  listening to Dr. Smith give his keynote address
• His overview involves clinical studies, and he
  shows slides of patients undergoing a procedure
  as part of an IRB-approved clinical trial
• In all instances
• The faces of ALL the patients are clearly visible
• Some slides also has patients name and other
  identifiers clearly visibleone patient tag read
  Mrs. McDonald
• After the lecture, one of your colleague (who
  also attended the talk) walks up to you and
  confides that Mrs. McDonald was her step-mother

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Case 1 - II

• She believes that this is a violation of her
  step-mothers privacy and that of the accepted
  standards of conducting clinical research
• She claims that Dr. Smiths presentation was an
  egregious violation of human subject research
  practices and thinks that he should be punished
• She asks you what she should do about this
  situation?

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Case 2 - I

• Professor Prozac is a course director of a
  physiology lab taught to medical students
• One of the lab exercises involves students
  drawing blood from one another (under
  supervision) and using the serum to perform a
  variety of chemical and cellular analysis
• At the conclusion of this lab exercise, Professor
  Prozac announces to the class of 100 students
  that he would like to retain their left-over
  blood sera

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Case 2 - II

• He informs them that some of the sera will be
  used individually while some will be pooled
• In all cases these sera will be used to gather
  baseline control data in a number of research
  projects
• Professor Prozac asks if anyone wants to refuse
  having his or her sera used for research but no
  one objects

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Case 2 - III

• Are Professor Prozacs actions appropriate?
• Is an IRB-approved protocol required?
• Do the students need to give informed consent?