Human Subjects Research Procedures

1
Human Subjects Research Procedures Protections

• Gayle Simon, M.P.H.
• Division of Research Administration
• Graduate Research Affairs
• San Diego State University

2
Past and PresentResearch Controversy

• 1932 -72-Tuskegee Syphilis Study
• 1946 - Nazi Experiments/Nuremberg Doctors Trial
• 1972 - Willowbrook/Hepatitis Study
• 1998 - Inveresk Research Laboratories Pesticide
  Study (Scotland)
• 1999 - Gene Therapy Study (U of Penn)
• 2001- Asthma Study (Johns Hopkins)
• 2001 - Lead Study (Johns Hopkins)
• 2001 - Melanoma Vaccine Study (U of Oklahoma)
• Y2K3 Beyond??

3
U.S. Federal Regulations 45 CFR 46

• Protect rights of human research participants
• Establishes procedures for reviewing ethics and
  appropriateness of human research
• Provides requirements for obtaining informed
  consent
• Includes special protections for vulnerable
  groups
• Requires IRBs to review all research at
  institutions receiving federal funds

4
What is an IRB?

• An IRB is a committee that determines that
  research studies conform to the ethical
  principles and federal regulations regarding the
  health, welfare, safety, rights, and privileges
  of human subjects.
• IRBs are composed of individuals with the
  expertise and background needed to conduct a
  complete and adequate review of the research
  planned by an institution
• The IRB at SDSU reviews all research with human
  subjects conducted by SDSU-affiliated researchers

5
What is research?

• Defined by 45 CFR 46.102(d) as
• A systematic investigation, including research
  development, testing and evaluation designed to
  develop or contribute to generalizable knowledge.
• Generalizable knowledge
• publication (article, thesis or dissertation)
• professional presentation

6
What is a human subject?

• Human subject is defined by 45 CFR 46.102(f) as
• A living individual about whom an investigator
  (whether professional or student) conducting
  research obtains data through intervention/interac
  tion or identifiable private information

7
Ethical principles

• The federal regulations are based on the ethical
  principles outlined in the historical document
  called The Belmont Report
• Respect for Persons
• Beneficence
• Justice

8
Information Reviewed by the IRB

• Background literature
• Subject groups (e.g. vulnerable vs. healthy)
• Subject recruitment
• Informed consent
• Privacy confidentiality of records
• Conflict of interest
• Risks Benefits
• Research design

9
Why review research design?

• But if a research study is so methodologically
  flawed that little or no reliable information
  will result, it is unethical to put subjects at
  risk or even to inconvenience them through
  participation in such a study.
• - OHRP IRB Guidebook

10
Controversial Research Design

• Non-medical research
• Use of deception/falsifying information
• Medical research
• Placebo controlled trials
• Are placebo studies deceptive?

11
Arguments for and against use of placebo controls

• For
• Protects society from availability of ineffective
  treatments
• Against
• Other designs exist that are less risky to
  individuals with equivalent societal value
• (Rothman, K. Michels, K., NEJM, vol. 331, Aug.,
  1994)

12
When are placebo controls ethical?

• There is no standard treatment
• There is standard treatment but known high
  placebo effect or bad side effects of the std.
  treatment
• Standard therapy is not effective (difficult to
  determine drug may have different effect in
  each individual)
• When a placebo is used with standard therapy
• Patients refuse standard therapy (b/c of toxicity
  or not well tolerated - also difficult to
  determine)
• Risks limited to temporary, minor discomfort
  (like headache, nausea)
• (Ref. Amdur Biddle, 2000 Emanuel Miller,
  2001)

13
Discussion Ethical or Unethical?
14
Learn More

• SDSU IRB (CPHS) gra.sdsu.edu/irb
• OHRP Office for Human Research Protections
  http//ohrp.osophs.dhhs.gov
• Department of Health and Human Services Title 45
  Part 46, Protection of Human Subjects
  http//www.access.gpo.gov/nara/cfr/waisidx_00/45cf
  r46_00.html
• IRB Forum (home page has articles about recent
  controversial studies) www.mcwirb.org