HUMAN SUBJECTS RESEARCH

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HUMAN SUBJECTS RESEARCH
Old Dominion University
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Overview

• Definitions
• Historical Framework
• Federal Guidelines
• Human Subjects Research at ODU

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What is Research?

• Research means a systematic investigation,
• including research development, testing and
• evaluation, designed to develop or contribute to
• generalizable knowledge. Activities which meet
• this definition constitute research for purposes
  of
• this policy, whether or not they are conducted or
• supported under a program which is considered
• research for other purposes. For example, some
• demonstration and service programs may include
• research activities
• 45 CFR 46.102(d)

• http//www.hhs.gov/ohrp/humansubjects/guidance/45c
  fr46.htm46.102

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What is a Human Subject?

• Living individual about whom an investigator
• (whether professional or student) conducting
• research obtains
• 1)data through intervention or interaction with
  the
• individual
• -or-
• 2) identifiable private information
• 45 CFR 46.102(f)

http//www.hhs.gov/ohrp/humansubjects/guidance/45c
fr46.htm46.102
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History
Those who cannot remember the past are
condemned to repeat it ." - George Santayana
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Tuskegee Syphilis Study (1932-72)

• Initiated by the US Public Health Service
• Studied the natural history of syphilis by
  denying treatment to the 399 poor black
  sharecroppers who were enrolled in the study
• Participants were told that they were being
  treated for bad blood
• Individuals were deceived by the officials that
  conducted the study
• In 1997, President Clinton apologized on behalf
  of the United States Government to living
  survivors of the study

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Nazi War Crimes World War II

• "Medical experiments" were performed on thousands
  of concentration camp prisoners
• Examples of tortures
• Forced killings
• Injecting people with gasoline
• Mutilation
• Immersing people in ice water
• Forcing people to ingest poisons
• 23 physicians and administrators were indicted
  before the War Crimes Tribunal at Nuremberg

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Nuremberg Code (1947)

• The voluntary consent of the human subject is
  absolutely essential.
• The experiment should be so conducted as to
  avoid all unnecessary physical and mental
  suffering and injury.
• The degree of risk to be taken should never
  exceed that determined by the humanitarian
  importance of the problem to be solved by the
  experiment.

http//www.hhs.gov/ohrp/references/nurcode.htm
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Willowbrook (1963-1966)

• Institution for "mentally defective" children 
• Parents were told that there were no openings for
  admission unless they agreed to enter their child
  in the study
• Children were deliberately infected with the
  hepatitis virus in order to study natural
  history
• Raised questions about the consent process
  including
• Adequacy and freedom of consent
• Disclosure of risks
• Treatment options

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The Belmont Report (1979)

• The National Commission for the Protection of
  Human Subjects of Biomedical and Behavioral
  Research issued a report Ethical Principles and
  Guidelines for the Protection of Human Subjects
• Three principles
• Respect for Persons
• Beneficence
• Justice

• http//www.hhs.gov/ohrp/humansubjects/guidance/bel
  mont.htm

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Respect for Persons

• Respect individual autonomy
• Subjects must
• Be informed of the nature and risks of the study
• Not be coerced to participate
• Be able to withdraw at any time
• Be given special protection if they have
  diminished autonomy (children, incapacitated,
  prisoners)

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Beneficence

• Subjects well-being must be secured
• Researchers must maximize benefits and minimize
  possible harms

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Justice

• Subjects must be selected so that the risks of
  the study are distributed among the population
  fairly and without bias
• Subjects must be selected so that the benefits of
  the study are distributed among the population
  fairly and without bias

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Federal Regulations DHHS

• 45CFR46 (Common Rule)
• Federal Policy for the Protection of Human
  Subjects
• Applies to research supported by or subject to
  regulation by Federal Departments or Agencies

http//www.hhs.gov/ohrp/humansubjects/guidance/45c
fr46.htm
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Federal Regulations FDA

• 21CFR50 (Protection of Human Subjects)
• Regulations about FDA-regulated clinical
  investigations
• http//www.access.gpo.gov/nara/cfr/waisidx_98/21cf
  r50_98.html
• 21CFR56 (Institutional Review Boards)
• Regulations about IRB composition, operation,
  responsibility
• http//www.access.gpo.gov/nara/cfr/waisidx_98/21cf
  r56_98.html

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What are the differences?

• Common Rule is based on funding
• FDA regulations are based primarily on use of
• FDA regulated products drugs, devices, or
• biologics

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Office for Human Research Protections (OHRP)

• Regulates
• Federally-supported research
• Institutional Review Boards (IRB)
• All research if a university chooses to apply
  45CFR46 to research (ODU does)

http//www.hhs.gov/ohrp/
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OHRP
http//www.hhs.gov/ohrp/humansubjects/guidance/dec
isioncharts.htm
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ODU Human Subjects Review

• All human subjects research must be reviewed and
  approved prior to the collection of data
• 1 Institutional Review Board (IRB)
• Reviews non-exempt and Federally-funded projects
• 5 Human Subjects Review Committees (College
  Committees)
• Review exempt protocols

• http//www.odu.edu/ao/research/policy-procedures/h
  uman-subjects.html

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ODU Human Subjects Review All human subjects
research must be reviewed approved prior to
data collection
Is the study federally-supported?
yes
no
no
Does the study meet exemption criteria?
Submit to IRB
yes
Submit to College Committee
http//www.odu.edu/ao/research/Policy-procedures/h
uman-subjects.html
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OHRP
http//www.hhs.gov/ohrp/humansubjects/guidance/dec
isioncharts.htm
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Types of exempt research(see 45CFR46)

• Research on normal educational practices
• Research using educational tests, surveys,
  interviews or observations of public behavior
  must be anonymous if questions carry risk or are
  sensitive
• Surveys, interviews or observations of public
  officials
• Collection of anonymous or publicly available
  existing data
• Taste and food quality surveys

http//www.hhs.gov/ohrp/humansubjects/guidance/45c
fr46.htm46.101
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College CommitteeApplication Process

• Application Form for Exempt Research
• Identify exemption and provide rationale
• Include methodology, survey forms, etc.
• Submit 5 copies of application committee (check
  with College Deans office for procedure)

http//www.odu.edu/ao/research/irbforms2004/exempt
20appl20ication.doc
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What is anonymous?

• Data collected in a manner so that subjects
  cannot be identified, directly or through
  identifiers linked to the subject
• Do not use name/SS lines on survey forms
• Consent not needed if used (and allowed) collect
  it separately

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Examples of when survey research requires IRB
approval

• Federally Funded projects
• Research involves vulnerable populations
• prisoners
• fetuses
• children
• pregnant women
• human in vitro fertilization
• Sensitive topics are used and results are not
  anonymous

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IRB Application Process

• ODU Human Subject Research Review Application
  Form (Appendix C)
• Informed consent document
• Supplemental forms (if applicable)
• Request for waiver of consent (Appendix F)
• Drugs, agents, and devices form (Appendix G)
• Biological Materials Form (Appendix H)
• Submit at least 10 copies of application to the
  Office of Research, one week prior to IRB meeting

http//www.odu.edu/ao/research/services/forms-proc
edures-compliance.html
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Responsible Project Investigator (RPI)

• Faculty or full-time staff member who assumes
• the following responsibilities
• Submission of all required forms to the IRB
• Conduct of the research
• Compliance with IRB decisions
• Submitting proposed changes to previously
  approved research

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Appendix C Overview

• Study purpose
• Sample size
• Study population
• Vulnerable subjects
• Recruitment
• Inclusion/exclusion criteria
• Experimental procedures

• Compensation
• Informed Consent
• Risks
• Benefits
• Protection of anonymity
• Training

http//www.odu.edu/ao/research/irbforms2004/irbapp
lication.doc
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What is Informed Consent (IC)?

• A person's voluntary agreement, based upon
• adequate knowledge and understanding of
• relevant information, to participate in research
  or to
• undergo a diagnostic, therapeutic, or preventive
• procedure.
• OHRP IRB Guidebook

http//www.hhs.gov/ohrp/irb/irb_glossary.htm
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OHRP
http//www.hhs.gov/ohrp/humansubjects/guidance/dec
isioncharts.htm
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OHRP
http//www.hhs.gov/ohrp/humansubjects/guidance/dec
isioncharts.htm
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Informed Consent(based on OHRP checklist)

• Statement that the study involves research
• Explanation of the purposes of research
• Expected duration of participation
• Description of procedures
• Description of any experimental procedures
• Description of risks or discomforts
• Description of benefits
• Disclosure of appropriate alternative procedures
  or courses of treatment
• Investigators should follow the ODU template for
  IC

http//www.hhs.gov/ohrp/humansubjects/assurance/co
nsentckls.htm
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Informed Consent Continued

• Statement describing the extent to which
  confidentiality of records identifying the
  subject will be maintained
• Explanation about whom to contact for answers to
  pertinent questions about 1) the research, 2)
  research subjects' rights, and 3) in event of a
  research-related injury to the subject
• Statement that participation is voluntary,
  refusal to participate will involve no penalty or
  loss of benefits to which the subject is
  otherwise entitled, and the subject may
  discontinue participation at any time without
  penalty or loss of benefits, to which the subject
  is otherwise entitled

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RPI Education

• All RPIs, proposing non-exempt research must
  document on-line training within the past 12
  months from http//cme.cancer.gov/clinicaltrials/
  learning/humanparticipant-protections.asp
• A copy of the certificate must accompany proposal
  applications to the IRB (and NIH)
• RPIs must ensure training of all personnel

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Training required for all RPIs!
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Study Approval

• Studies may be approved for up to 1 year
• Study is complete when data analysis and data
  collection are complete

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Progress Report

• Submit a progress report if the project is to
  last longer than approval period, which is
  typically 1 year
• Progress reports must be submitted 2 months prior
  to approval expiration
• Submit report to the Office of Research
• (2035 Hughes Hall)

http//www.odu.edu/ao/research/irbforms2004/progre
ss20report.doc
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Close Out Report

• Submit a Close Out Report when data collection
  and data analysis are complete
• Close Out Report should be submitted 1 month
  after the project expiration date
• Submit report to the Office of Research
• (2035 Hughes Hall)

http//www.odu.edu/ao/research/irbforms2004/closeo
utreport.doc
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Adverse Events

• An adverse event (AE) is any illness, injury,
  trauma experienced by a subject during the course
  of a study that required medical or psychological
  treatment. Such events may occur during data
  collection or outside of data collection, at the
  research site, or away from the research site.
• A serious AE is one that resulted in death, life
  threatening situation, inpatient hospitalization,
  significant disability, or a birth defect.
• An unexpected AE is an adverse event that is not
  currently listed in informed consent.

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Reporting Adverse Events

• Report all Adverse Events, even if not related
• to the study
• Serious or Unexpected Report to IRB within 5
  days AE form (If serious, physician comment
  required)
• Neither Serious nor Unexpected Report to IRB
  within 1 month AE form

http//www.odu.edu/ao/research/irbforms2004/advers
e20events.doc
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Contact Information

• David Swain, IRB Chairperson
• [phone]
• dswain_at_odu.edu
• Susan Metosky, Human Protections Administrator
• [phone]
• smetosky_at_odu.edu

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Conclusions

• Treat human subjects ethically
• Be aware of Federal, State, and Institutional
  regulations and guidelines
• Ask questions