The Ethical Treatment of Human and Non-Human Subjects in The

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The Ethical Treatment of Human and Non-Human Subjects in The Powered By Docstoc
					The Responsible Conduct of Research

      Paul Braunschweiger Ph.D.
         Professor of Radiation Oncology
         Chair, University of Miami IACUC
            Talking points

• What is RCR and why is it important
• New Guidelines, NSF, NIH.
• Intersection of RCR and Lab animal
• Resources for teaching the RCR
 NSF Mandate for RCR Education

• August 20, 2009 NSF implementation of Section 7009 of
  the America Creating Opportunities to Meaningfully
  Promote Excellence in Technology, Education, and
  Science (COMPETES) Act (42 U.S.C. 1862o–1).

• Requires that …..‘‘each institution that applies for financial
  assistance from the Foundation for science and
  engineering research or education describe in its grant
  proposal a plan to provide appropriate training and
  oversight in the responsible and ethical conduct of
  research to undergraduate students, graduate students,
  and postdoctoral researchers participating in the proposed
  research project.’’
  NSF Mandate for RCR Education

• January 4, 2010, NSF will require that, at the
  time of proposal submission to NSF, a proposing
  institution’s Authorized Organizational
  Representative certify that the institution has a
  plan to provide appropriate training and oversight
  in the responsible and ethical conduct of
  research to undergraduates, graduate students,
  and postdoctoral researchers who will be
  supported by NSF to conduct research.
               NSF Mandate for RCR Education

               • Content
                  – No specific recommendation.
                  – “Therefore, it is the responsibility of each institution to
                    determine both the content and the delivery method for the
                    training that will meet the institution’s particular needs for
                    RCR training in all areas at that institution for which NSF
                    provides support.”

               • Delivery method
                  – No specific recommendations
                  – “It will be up to each institution to determine how best
                    to ensure effective and appropriate education in
                    responsible research practices.”

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                   NIH Mandate

• Policy
  – NIH requires that all trainees, fellows, participants, and
    scholars receiving support through any NIH training, career
    development award (individual or institutional), research
    education grant, and dissertation research grant must
    receive instruction in responsible conduct of research. This
    policy will take effect with all new and renewal applications
    submitted on or after January 25, 2010, and for all
    continuation (Type 5) applications with deadlines on or after
    January 1, 2011.
• National Institutes of Health (NIH), NOT-OD-
  10-019, issued November 24, 2009.
                                   NIH Mandate
               • National Institutes of Health (NIH), NOT-
                 OD-10-019, November 24, 2009.
                 1. Develops principles on providing instruction in
                    responsible conduct of research.
                 2. Specific about who should participate, how often
                    instruction should occur, and the form that instruction
                    should take;
                 3. Addresses issues that have arisen as the practice of
                    biomedical, behavioral and clinical science has evolved
                 4. Provides guidance to applicants, peer reviewers and NIH
                    staff in determining how well specific plans for instruction
                    in responsible conduct of research compare with the best

RCR 12-29-07                                                NOT-OD-10-019, issued November 24, 2009.
               • This Notice applies to:
                 –   All NIH Institutional Research Training Grants,
                 –   Individual Fellowship Awards,
                 –   Career Development Awards (Institutional and Individual),
                 –   Research Education Grants,
                 –   Dissertation Research Grants,
                 –   Other grant programs with a training component that
                     requires instruction in responsible conduct of research as
                     noted in the Funding Opportunity Announcement.

RCR 12-29-07                                               NOT-OD-10-019, issued November 24, 2009.
                     Principles for the RCR
               1. Responsible conduct of research is an essential
                  component of research training. Instruction in RCR is an
                  integral part of all research training programs. Its
                  evaluation will impact funding decisions.

               2. Active involvement in the issues of responsible conduct of
                  research should occur throughout a scientist’s career.
                   – Instruction in responsible conduct of research should
                     therefore be appropriate to the career stage of the individuals
                     receiving training.

               3. Individuals supported by individual funding opportunities
                  such as fellowships and career development awards are
                  encouraged to assume individual and personal
                  responsibility for their instruction in responsible conduct of
RCR 12-29-07                                               NOT-OD-10-019, issued November 24, 2009.
                     Principles for the RCR
               4. Research faculty of the institution should participate in
                  instruction in RCR in ways that allow them to serve as
                  effective role models for their trainees, fellows, and

               5. Instruction should include face-to-face discussions by
                  course participants and faculty; i.e., on-line instruction may
                  be a component of instruction in responsible conduct of
                  research but is not sufficient to meet the NIH requirement
                  for such instruction, except in special or unusual

               6. Instruction in responsible conduct of research must be
                  carefully evaluated in all NIH grant applications for which it
                  is a required component.
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                5 Instructional Components

               1. Format
                 –   Face-to-face discussions among the participating
                 –   While on-line courses can be a valuable supplement
                     to instruction in responsible conduct of research,
                     online instruction is not considered adequate as the
                     sole means of instruction.

RCR 12-29-07                                          NOT-OD-10-019, issued November 24, 2009.
                  Instructional Components
               2. Subject Matter
               • While there are no specific curricular requirements for instruction
                  in responsible conduct of research, the following topics have
                  been incorporated into most acceptable plans for such
                   – Conflict of interest – personal, professional, and financial
                   – Human and non-human subjects welfare, and safe laboratory
                   – Mentor/mentee responsibilities and relationships
                   – Collaborative research including collaborations with industry
                   – Peer review.
                   – Data acquisition and management.
                   – Research misconduct and reporting misconduct .
                   – Responsible authorship and publication.
                   – The scientist as a responsible member of society, contemporary
                     ethical issues in biomedical research, and the environmental and
                     societal impacts of scientific research
RCR 12-29-07                                                   NOT-OD-10-019, issued November 24, 2009.
                   Instructional Components
               3. Faculty Participation
                   – Training faculty and sponsors/mentors are highly encouraged
                     to contribute both to formal and informal instruction in
                     responsible conduct of research. Full faculty participation.
               4. Duration of instruction
                   – “Substantive contact hours”. Acceptable programs generally involve
                     at least eight contact hours.
                   – Semester long program maybe better than a one day 8 hr workshop.
               5. Frequency of instruction.
                   – “…at the undergraduate, post-baccalaureate, pre-doctoral,
                     postdoctoral, and faculty levels.”
                   – …. Instruction must be undertaken at least once during each career
                     stage, and at a frequency of no less than once every four years.
               •   Grant applications must address all 5 components.

RCR 12-29-07                                                  NOT-OD-10-019, issued November 24, 2009.
                                 Peer review
               • Applications lacking a plan for instruction in responsible
                 conduct of research will be considered incomplete and
                 may be delayed in the review process or not reviewed.
               • Applications with a “Plan”
                  – Reviewers will specifically address the five Instructional
                    Components (Format, Subject Matter, Faculty
                    Participation, Duration and Frequency) .
                  – Review panel’s evaluation of the plan will not be a
                    factor in the determination of the impact/priority score.
                  – Plans and past record will be rated as ACCEPTABLE
                    or UNACCEPTABLE.
                  – Regardless of Priority Score, applications with
                    unacceptable plans will not be funded until the
                    applicant provides an acceptable, revised plan.

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               •   NIH policy requires participation in and successful completion of
                   instruction in responsible conduct of research by individuals
                   supported by any NIH training/research education/fellowship
                   /career award.
               •   It is expected that course attendance is monitored and that a
                   certificate or documentation of participation is available upon
                   course completion.
               •   NIH does not require certification of compliance or submission of
                   documentation, but expects institutions to maintain records
                   sufficient to demonstrate that NIH-supported trainees, fellows,
                   and scholars have received the required instruction.

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               •   The NIH Research Training website
                   ( includes additional
                   information on instruction in responsible conduct of research.
               •   Office of Research Integrity (, links to
                   instructional materials, and examples of programs that have been
                   regarded as good models for instruction in responsible conduct of
                   research (
               •   The National Academy Press has just published the 3rd. edition
                   of the classic, On Being a Scientist, and is available online at
               •   The CITI Program , On-line program in the
                   RCR. Text, case studies, video vignettes and quizzes in the nine
                   topic areas of RCR. Training data management.
               •   Responsible Conduct of Research Education Committee

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    What is the RCR

What is involved in RCR education
         Integrity & Responsible Conduct of

• Accepted practices for the RCR can vary from
  discipline to discipline and even from
  laboratory to laboratory.
• Some shared values for the RCR that bind all
  researchers together:
   – Honesty - conveying information truthfully and
     honoring commitments.
   – Accuracy- reporting findings precisely and
     taking care to avoid errors.
   – Efficiency -using resources wisely and avoiding
   – Objectivity - letting the facts speak for
     themselves and avoiding improper bias.
   – Compliance with regulatory requirements to        “Integrity” Fredric Terral 2007
     document ethical behavior.
• Integrity in the Research
     "Integrity Protecting the Works of Man." John Quincy Adams Ward, 1903

           Integrity in Research Enterprise

•   Starts with Institutional Commitment
•   Promoted and nurtured by the IACUC, IRB, IBC, CoIC, ESCRO
•   Promotes of scientifically valid data
•   Avoids or minimizes all COIs
•   Embraced by the investigators, staff and students as,
                               “The right thing to do”
Why Does Integrity Matter in

•   Puts subjects at risk.
•   Injures careers
•   Wastes Resources
•   Wastes Time
•   Undermines the Public Trust.
          The Public Trust
• The “Public” supports most of the research in the

• Sponsored research is a privilege and not an

• Society Trusts investigators to conduct research
  ethically and responsibly.

• Violation of the public’s trust, brings Regulation.
                  The Public Trust

• New Regulations are not the result of good or ethical
• Federal Regulations specifically require
   – Accountability
   – Documentation of ethical behavior

• Regulatory requirements to document are designed to:
   – Help investigators conduct research responsibly.
   – Preserve the Public Trust in research.

• Without the Public’s Trust there is no
               Betrayal of the Public Trust Brings

               • 1984 Univ. Penn. Head Trauma Study.
                  – PETA and ALF alleges inhumane research practices.
                  – Videos
                  – NIH investigated. Research activities not conducted
                    according the existing policies.
                     •   Lack of adequate anesthesia and analgesia.
                     •   Lack of sterile technique.
                     •   Lack of supervision by PI.
                     •   Lack of training of laboratory personnel.
                  – NIH Shut down the project.
               • Research Project permanently shut down.

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                   Consequences of betrayal of the
                           Public Trust

               •   Puts subjects at risk
               •   Federal inquiry / intervention
               •   Institutional embarrassment
               •   Fines
               •   Wasted resources
               •   Personal embarrassment
               •   Loss of funding, Loss of livelihood
               •   Fines
               •   Justification and / or vindication for
                   groups with anti-research agenda.

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The Foundation of Ethical
  Research Practices is
Research Ethics Education
                    Promoting integrity in the
                      Research Enterprise

               • Teaching the Responsible Conduct of
                 – Books, Journal articles
                 – Classroom experience
                 – Seminars and conferences
                    • Professional Societies
                 – Web based courses and tutorials.
                 – Mentoring

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               The Responsible Conduct of

               1.    Research Misconduct.
               2.    Data Acquisition and Management.
               3.    Responsible Authorship.
               4.    Conflicts of Interest.
               5.    Responsible Peer Review.
               6.    Human Subjects Protection.
               7.    Lab Animal Welfare.
               8.    Mentoring.
               9.    Responsible Collaborative Research.
               10.   Financial responsibility.
               11.   Environmental ethics.

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                  Data Acquisition and Management
                                      study design

               • Humane endpoints
                  – Minimizing Pain and distress
               • Statistically justified sample size determinations.
               • Data security –
                  – Photography and video in animal experimentation.
               • Data acquisition and usage,
                  – Data obtained from studies where unapproved
                    procedures have been used.
               • Pilot studies
                  – When does a pilot study cease being a pilot study.

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                  Responsible Authorship
               • Who on the research team deserves to be listed
                 in the byline of the paper and who should be an
               • According to the ICMJE
                  – Design of the experiments.
                  – Writing and/or editing the paper
                  – Approval of the manuscript before submission to the
               • Which can can be ethically published.
               • Publishing negative data

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    The social fabric of science
    Excellent approach to teaching
research ethics and lab animal welfare.
         The Ideal Mentor

 • “The truly complete mentor." This is "a
   single individual who is able to serve as an
   advisor/guide, developer of talent/coach,
   opener of doors/advocate, role model,
   interpreter of organizational or professional
   rules, protector, rule setter/boss - and
   carries on all of these functions on a long
   term basis."

Ideal mentoring may require input from more than one person!

Silen, "In Search of the Complete Mentor," in Mentations, Volume 5-Fall
               • Most mentors are not well trained.
               • Confusion, Res. Advisors vs. Mentors.
               • Trainees often learn unethical practices
                 and short cuts from the mentor / research
               • Taking short cuts can get the students
                 and fellows in trouble with the IACUC.

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Conflicts of Interest and
 Conflicts of Interest and Commitment
• A conflict of interest is a situation in which financial or other personal
  considerations have the potential to compromise or bias
  professional judgment and objectivity.

    – The appearance of a conflict of interest is one in which a reasonable
      person would think that the professional's judgment is likely to be
    – A CoI exists whether or not decisions are affected by a personal
    – A potential CoI involves a situation that may develop into an actual
      conflict of interest.
    – A CoI is not considered misconduct in research, since the definition for
      misconduct is currently limited to F.F&P.
    – A CoI could lead to misconduct.
      Conflicts of Interest and

• Tangible conflicts of Interest
   – Investigator has a financial stake in the
     outcome of an experiment or trial.
• CoIs require management strategies
   – Disclosure by the investigator,
   – CoIs managed by the institution,
   – Reported to the Feds.

Emory University                Harvard University
Took >$500K in unreported      $4 million in unreported
consulting income from Glaxo.   consulting revenues from
Gov. Funded research on        Pharmaceutical Industry.
Glaxo drugs                     Promoted antipsychotic drugs
                                in children

                                GOV. GRANTS
      Conflicts of Interest and
• Conflicts of commitment.
   – Using institutional time for consulting.
   – Using institutional resources for personal gain.
   – Using graduate students/fellows for work on company
• Other intangible conflicts of interest.
   – Personnel and professional.
       • IACUC, IRB, ESCRO.
       • Personal relationships. Good and Bad.
   – Conflicts of conscience
       • Religious beliefs.
       • Philosophical differences (e.g., status of animals.)
CoI in Animal Research
Understanding and Managing the Conflict of Interest

• The Public’s Interests
    – Society demands medical advances.
    – Society understands that animals as subjects:
       • Can not understand the research.
       • Can not consent to participate in what may cause them
         harm, pain or death.
    – Society demands documentation that animal research is
      ethically designed and conducted.
      Understanding and Managing the Conflict of Interest


      • The investigator Interests
           – Get the data, publish the papers, get the grants, support their
             labs, get promoted, get a raise, buy the new boat.

      • The Interests of the Veterinarians
           – Animal welfare Vs. Helping investigators get their work done.
           – Veterinarians as co-investigators, coauthor.

      • Institutional interests
           – Institutions want the grants, patents and indirect costs.
           – IOs need to be willing to deal with problematic faculty
             regardless of the grant suppport.

The IACUC specifically empowered by the Federal Regulations and UM Policy to manage the
                                tensions and conflicts.
The IACUC and Conflict Management
• IACUC has the oversight responsibility for all
  animal use at the Organization.
   – Manages interests of the “Public” vs other competing
   – Makes sure the investigators consider the interests of the
   – Reviews animal activities for sound experimental design
     and the 3Rs.
   – Insures the veterinary program is not unduly influenced by
     the organization.
   – Insures that institutions commit appropriate funding to
     support the mission of the Animal Use Program.
   – Independently investigates non-compliance.
       • Can suspend activities that are not being conducted ethically
         and put animals at risk.
                The IACUC and Conflict

• IACUC Reports the good, the bad and ugly to:
   – Institutional Official
   – OLAW and USDA
   – Follow - up
• IACUC appointed by highest institutional authority.
   – Protect the University’s interests
   – Manage the CoI
   – Maintain the Public’s trust
Research Ethics Education
     CITI Program

•   Human Subjects Protection
•   Good Clinical Practice.
•   Lab Animal Welfare.
•   Responsible Conduct of Research.
•   Bio-safety and Bio-security
    – 305 243-7970
CITI Laboratory Animal
   Welfare Program
     IACUC Members
Lab Animal Welfare Course
       Site Usage

        sites    CRs     CR per month % increase
 2009   311     49,566       4,506       32%
 2008   271     40,908       3,409
              LAW Courses 2009

Basic Courses
  Working with the IACUC
  Working with the VA IACUC
  Essentials for IACUC Members

  Working With Animals In Biomedical Research - Refresher
        LAW Courses Completed

Model Specific Courses
  Working with Mice in Research
  Working with Rats in Research Settings
  Reducing Pain and Distress in Laboratory Mice and Rats
  Aseptic surgery
  Working with Swine in Research Settings
  Working with Rabbits in Research Settings
  Working with Amphibians in Research Settings
  Working with Nonhuman Primates in Research Settings
  Working with Dogs in Research
  Working with Guinea Pigs in Research Settings
  Working with Hamsters in Research Settings
  Working with Cats in Research Settings
  Working with Gerbils in Research Settings
       Joseph Wright (September 3, by Joseph Wright (1734-1797)
“An Experiment on a Bird in The Air Pump “ 1734 - August 29, 1797),
                   British National Gallery- London

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