Protection of Human Subjects in Research

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Protection of Human Subjects in Research
Revised 10/12/04

• Bentley College
• Institutional Review Board (IRB)
• Principal Investigator Training

BENTLEY
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Composition of Bentley IRB

• Institutional Official Robert Galliers, Provost
  Academic Vice President
• IRB Administrator Mary Louise Pauli, Director of
  Sponsored Programs
• IRB Chair, Anthony F. Buono, Professor of
  Management Sociology, Coordinator, Bentley
  Alliance for Ethics Social Responsibility
• Federal regulations require a minimum of five
  members
• Bentleys IRB has 10 Members
• 7 senior full-time faculty from the various
  Business and AS Departments
• 2 Staff members
• One community member

BENTLEY
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Bentleys Mission

• We educate students to be leaders in business
  and related professions in ways that inspire
  students to be literate, articulate, ethical,
  creative and broad-minded with a rich campus
  life infused with intellectual, social and
  cultural diversity, community spirit, and a sense
  of civic responsibility valuing excellence in
  both scholarship and the classroom and
  achieving best practice in our respective
  fields.

BENTLEY
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The Beginning Nuremberg

• Nuremberg War Crimes Trials of Nazi doctors
• Medical experiments were performed on thousands
  of concentration camp prisoners
• In 1946, 23 physicians and administrators, many
  of whom were leading members of the German
  medical hierarchy, were indicted for crimes
  against humanity.
• 16 were found guilty and imprisoned, and 7 were
  sentenced to death
• A result was the Nuremberg Code (1947)
• Ten principles that form the basis for ethics
  codes internationally

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Nuremberg Code Key Tenets

• Voluntary consent of human subjects is absolutely
  essential.
• Animal experimentation should precede human
  experimentation.
• All unnecessary physical and mental suffering and
  injury should be avoided
• The degree of risk to participants should never
  exceed the "humanitarian importance of the
  problem."
• All risk should be minimized through "proper
  preparations.
• Participants should always be at liberty to
  withdraw from experiments.

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Controversial Studies

• Jewish Chronic Disease Hospital (1963)
• Patients with chronic debilitating diseases were
  injected with live cancer cells without their
  knowledge.
• The researchers were found guilty of fraud,
  deceit, and unprofessional conduct.
• U.S. Public Health Service Tuskegee Syphilis
  Study (1934-1972)
• Study began in 1934 as an examination of the
  natural history of untreated syphilis.
• 400 black males participated without informed
  consent and were misinformed about procedures in
  the interest of research.
• Although penicillin was found to be effective in
  treating syphilis in the 1940s, the study
  continued and the men were neither informed nor
  treated with the antibiotic.
• Publication of study results in 1972 prompted
  public outrage, leading to a mandate to regulate
  all federally supported research involving human
  subjects.

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Controversial Studies - 2

• Willowbrook State School Study (1963-66)
• At the NY State institution for mentally
  defective children, new entrants were
  deliberately injected with the hepatitis virus to
  examine the natural history of infectious
  hepatitis.
• Researchers defended the study arguing that is
  was likely the children would have contacted the
  disease anyway due to the crowded and unsanitary
  conditions at the school.
• Milgram Obedience to Authority Studies (1960s)
• Being told that they were volunteering for a
  study to test the effect of negative
  reinforcement (punishment) on learning behavior,
  the volunteer teachers were unknowingly the
  subjects of the experiment
• The teachers gave increasing electric shocks to
  learners who were confederates in the
  research study
• Study raised significant questions about the
  ethics of creating psychological stress and
  tension in human subjects and the extent to which
  the search for knowledge should justify such
  costs to the participants.

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Ethical Conduct of Research Background

• 1962 - FDA legislation required formal consent
• 1964 - Declaration of Helsinki focused on
  guidelines for medical research
• 1965/6 - NIH Advisory Committee developed
  guidelines for ethical review of all NIH-funded
  research protocols by peers plus others at
  institution before experiment could begin
• Included requirement for informed consent and
  assessment of risks and benefits
• Start of Institutional Review Boards (IRBs)

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Ethical Conduct of Research

• National Research Act (1974)
• Creation of National Commission for the
  Protection of Human Subjects of Biomedical and
  Behavioral Research
• Commission delivers the Belmont Report (1979)
• Recommendations implemented in the federal
  regulations known as the Common Rule (1981)

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Principles of the Belmont Report

• Respect for persons
• obligation to treat individuals as autonomous
  agents able to chose for themselves
• obligation to protect those with diminished
  capacity
• Beneficence
• obligation to not harm
• obligation to maximize benefits and reduce harms
• Justice
• obligation to be fair and equitable
• obligation to distribute benefits and burdens
  fairly

BENTLEY
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Implementing the Principles of the Belmont
Report The Common Rule

• Respect for persons
• Informed consent
• Beneficence
• Minimization of possible risks, assessment of
  risks and benefits
• Justice
• Scrutiny of subject selection

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The Common Rule for Department of Health and
Human Services 45 CFR 46
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Bentley College
Institutional Review Board
Policies and Procedures (July 2001
Revised January 2003) Overview The
following policies and procedures are adopted by
Bentley College for oversight of research
by the Colleges Institutional Review
Board (IRB). They have been formulated in
response to consideration of 45 CFR 690,
the federal requirements known as the
Common Rule that may be examined in its
entirety at http//ohrp.osophs.dhhs.gov/hum
ansubjects/guidance/45cfr46.htm.
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Definitions Research

• Research means a systematic investigation,
  including research development, testing and
  evaluation, designed to develop or contribute to
  generalizable knowledge.
• 45 CFR 46.102d

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Definitions Human Subject
A 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 46.102f
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Definition Minimal Risk
means that the probability and magnitude of
harm or discomfort anticipated in the research
are not greater in and of themselves than those
ordinarily encountered in daily life or during
the performance of routine physical or
psychological examinations or tests. 45
CFR 46.102i
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General Considerations

• Know, understand, and follow the relevant
  principles, regulations, policies and guidelines
• Plan your research well before you start
• Keep your obligations to human subjects in mind
  during the research
• Anticipate and be empathic
• Anticipate possible problems and/or complications
• Try to put yourself in the participants place

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General Considerations -2

• Design your study to minimize risks and maximize
  benefits
• Consider psychological, financial, social,
  employment, and educational risks
• Dont ask more than you need to know
• Design for confidentiality
• Dont promise more than you can deliver
• Have plans to deal with possible participant
  distress or injury
• Maximize any direct benefits to the participants

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General Considerations -3

• Consider participant recruitment procedures
• Is the process free of coercion?
• Role conflicts? Power inequities?
• Have you selected the best population with which
  to investigate your question (vs. the most
  convenient)?
• Vulnerable population? Population that may
  benefit?
• Is the design inclusive? Equitable?
• Are inclusion and exclusion criteria clear and
  appropriate?

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General Considerations -4

• Consider informed consent procedures
• Have subjects been fully informed of all relevant
  information and planned procedures?
• Use of data? Who has access? Video or audio
  tapes?
• Has the information been understood?
• Presented appropriately? Ability to ask
  questions?
• Are subjects able to give consent?
• Cogently impaired? Underage? English-speaking?
• Who will inform and witness the consent?

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Remember Your Obligations

• Informed consent is a process
• Are there means to contact the researcher? Have
  you allowed for continuing exchange of
  information and questions?
• Monitor for problems, adverse events
• File with the IRB any necessary reports, requests
  for amendments, adverse events
• Above all, respect those who volunteer to
  participate in your research study

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Levels of IRB Review

• Exempt status
• Expedited review
• Full review

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Research that Qualifies for Exempt Status

• No more than minimal risk
• No identifiers Identities of subjects cannot be
  linked with the data or publicly available data
• No medical treatments are involved
• The research falls into one of the following
  categories
• Educational settings, involving normal
  educational practices
• Educational testing, surveys, interviews or
  observation of public behavior
• Research involving public officials
• Use of Existing data (no additional data to be
  gathered)
• Demonstration projects (public benefit or service
  projects)
• Taste and food quality evaluation and consumer
  acceptance

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Exempt Review Categories

• Detailed descriptions of exempt
• review categories are available at
• http//ohrp.osophs.dhhs.gov/humansubjects/guidance
  /45cfr46.htm46.101

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If Exempt Status Applies

• Request Exempt status on the Research Review
  Form, explaining why and citing appropriate
  regulatory details.
• Exempt status will be confirmed if research
  fulfills the exemption criteria
• While there is no further review for exempt
  status, the researcher should still follow the
  Belmont principles and Common Rule as appropriate

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Research that Qualifies for Expedited Review

• If no more than minimal risk is involved
• If research activity falls solely within one or
  more of the following categories
• Voice, video, digital or image recordings
• Group of behavior characteristics
• Previously approved research (continuing review)
• Certain medical studies, including clinical
  studies of drugs and medical devices, blood
  samples, routine noninvasive procedures and
  prospective specimen collections (which are
  unlikely at Bentley) .
• If there are minor changes (amendments) in
  previously approved research (during period
  approved)

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Expedited Review Categories

• Detailed descriptions of expedited review
• categories are available at
• http//ohrp.osophs.dhhs.gov/humansubjects/guidance
  /expedited98.htm

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Criteria for IRB Full Review Approval of
Research (45 CFR 46.111)

• Risks to subjects are minimized
• Risks to subjects are reasonable relative to
  anticipated benefits
• Selection of subjects is equitable
• Informed consent will be sought and documented
• Provisions for data monitoring for subjects
  safety
• Provisions to protect privacy and maintain
  confidentiality
• Additional safeguards are provided as
  appropriate if vulnerable
• subjects are involved
• The Bentley IRB Application asks that the
  information outlined above be provided by the
  Principal Investigator.

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Valid Informed Consent

• Fully informed
• Information understood
• Voluntary, free of coercion
• Given by competent adult

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For children and others not legally able to
consent

• Permission from parent, guardian, or legal
  representative, and
• Assent from the individual

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Basic Elements of Informed Consent (45 CFR 46.116)

• The subject is competent and can fully comprehend
  the information
• Statement of the research - purpose, duration,
  procedures
• Reasonably foreseeable risks or discomforts
• Reasonably expected benefits to subject or others
• Extent to which confidentiality will be
  maintained
• Whom to contact if subject has questions
• Statement that participation is voluntary no
  penalty or loss of benefits if decline to
  participate can withdraw at any time

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Possible additional elements of informed consent

• Risks not currently foreseeable
• Circumstances under which subjects participation
  may be terminated by researcher
• Any additional costs to subjects
• Consequences of early withdrawal
• Statement that researcher will tell subject of
  significant new findings discovered during course
  of study
• Approximate number of subjects

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Vulnerable Populations

• Subjects likely to be vulnerable to coercion or
  undue influence
• Children
• Prisoners
• Pregnant women
• Mentally disabled persons
• Economically or educationally disadvantaged
  persons
• Employees? Students? Clients?

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Research with Children

• Subpart D 45 CFR 46.401-409 applies to research
  with children
• "Assent" means a child's affirmative agreement to
  participate in research. Failure to object should
  not, absent affirmative agreement, be construed
  as assent. (45 CFR46.402b)
• Risk/benefit determination

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Risk/Benefit Categories for Research with
Children

• Research not involving greater than minimal risk.
• Research involving greater than minimal risk but
  presenting the prospect of direct benefit to the
  individual subjects.
• Research involving greater than minimal risk and
  no prospect of direct benefit to individual
  subjects, but likely to yield generalizable
  knowledge about the subject's disorder or
  condition.
• Research not otherwise approvable which presents
  an opportunity to understand, prevent, or
  alleviate a serious problem affecting the health
  or welfare of children.

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Dual Role Issues

• Individual as researcher and teacher/principal
• Important to reduce potential for coercion of
  participants who are students or employees
• Consider who will recruit students/employees
• Will they be given an opportunity to decline?
• If they choose not to participate, will their
  peers know? (e.g., If students do not
  participate, will they be given other tasks to
  complete while their peers are participating in
  the research?)

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HIPAA Information(Health Insurance Portability
and Accountability Act)

• Bentley is not a covered entity under HIPAA
• Bentley researchers, however, may work with
  covered entities
• PIs who work with health information need to
  complete the Statement on HIPAA PHI Use form
  see Mary Louise Pauli, IRB Administrator, for
  further information

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For Additional IRB Information

• Tony Buono, IRB Chair
• AAC315 781-891-2529
• abuono_at_bentley.edu
• Mary Louise Pauli, IRB Administrator
• LCC 270 781-891-2660
• mpauli_at_bentley.edu