The Responsible Conduct of Research

1
The Responsible Conduct of Research

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

2
Talking points

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

3
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.
  1862o1). http//edocket.access.gpo.gov/2009/pdf/E
  9-19930.pdf
• 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.

4
NSF Mandate for RCR Education

• January 4, 2010, NSF will require that, at the
  time of proposal submission to NSF, a proposing
  institutions 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.

5
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 institutions 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.

6
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.

7
NIH Mandate

• National Institutes of Health (NIH),
  NOT-OD-10-019, November 24, 2009.
• Develops principles on providing instruction in
  responsible conduct of research.
• Specific about who should participate, how often
  instruction should occur, and the form that
  instruction should take
• Addresses issues that have arisen as the practice
  of biomedical, behavioral and clinical science
  has evolved
• 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 practices.

NOT-OD-10-019, issued November 24, 2009.
8
Applicability

• 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.

NOT-OD-10-019, issued November 24, 2009.
9
Principles for the RCR

• 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.
• Active involvement in the issues of responsible
  conduct of research should occur throughout a
  scientists career. 
• Instruction in responsible conduct of research
  should therefore be appropriate to the career
  stage of the individuals receiving training.
• 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 research.

NOT-OD-10-019, issued November 24, 2009.
10
Principles for the RCR

• 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 scholars.
• 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 circumstances.
• Instruction in responsible conduct of research
  must be carefully evaluated in all NIH grant
  applications for which it is a required
  component. 

11
5 Instructional Components

• Format
• Face-to-face discussions among the participating
  trainees/fellows/scholars/participant.
• 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.

NOT-OD-10-019, issued November 24, 2009.
12
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 instruction
• Conflict of interest personal, professional,
  and financial
• Human and non-human subjects welfare, and safe
  laboratory practices
• 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

NOT-OD-10-019, issued November 24, 2009.
13
Instructional Components

• 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.
• 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.
• 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.

NOT-OD-10-019, issued November 24, 2009.
14
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 panels 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. 

15
Compliance

• 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.

16
Resources

• The NIH Research Training website
  (http//grants.nih.gov/training/extramural.htm)
  includes additional information on instruction in
  responsible conduct of research.
• Office of Research Integrity (http//ori.hhs.gov/)
  , links to instructional materials, and examples
  of programs that have been regarded as good
  models for instruction in responsible conduct of
  research (http//bioethics.od.nih.gov/researchethi
  cs.html).  
• The National Academy Press has just published the
  3rd. edition of the classic, On Being a
  Scientist, and is available online at
  http//books.nap.edu/catalog.php?record_id12192.
• The CITI Program www.citiprogram.org , 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 (RCREC) http//rcrec.org

17
What is the RCR

• What is involved in RCR education

18
Integrity Responsible Conduct of Research

• 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
  waste.
• Objectivity - letting the facts speak for
  themselves and avoiding improper bias.
• Compliance with regulatory requirements to
  document ethical behavior.
• Integrity in the Research

Integrity Fredric Terral 2007
19
Integrity in Research Enterprise
"Integrity Protecting the Works of Man." John
Quincy Adams Ward, 1903 

• 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

20
Why Does Integrity Matter in Research?

• Puts subjects at risk.
• Injures careers
• Wastes Resources
• Wastes Time
• Undermines the Public Trust.

21
The Public Trust

• The Public supports most of the research in the
  US.
• Sponsored research is a privilege and not an
  entitlement.
• Society Trusts investigators to conduct research
  ethically and responsibly.
• Violation of the publics trust, brings
  Regulation.

22
The Public Trust

• New Regulations are not the result of good or
  ethical behavior.
• 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 Publics Trust there is no research

23
Betrayal of the Public Trust Brings Regulation

• 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.

24
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.

A.L.F.
25
The Foundation of Ethical Research Practices is
Research Ethics Education
26
Promoting integrity in the Research Enterprise

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

27
The Responsible Conduct of Research

• Research Misconduct.
• Data Acquisition and Management.
• Responsible Authorship.
• Conflicts of Interest.
• Responsible Peer Review.
• Human Subjects Protection.
• Lab Animal Welfare.
• Mentoring.
• Responsible Collaborative Research.
• Financial responsibility.
• Environmental ethics.

28
Data Acquisition and Managementstudy 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.

29
Responsible Authorship

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

30
Mentoring

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

31
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 1998,at
http//www.hms.harvard.edu/dcp/mentations/fall_98/
searchofmentor.html
32
Mentoring

• Most mentors are not well trained.
• Confusion, Res. Advisors vs. Mentors.
• Trainees often learn unethical practices and
  short cuts from the mentor / research advisor.
• Taking short cuts can get the students and
  fellows in trouble with the IACUC.

33
Conflicts of Interest and Commitment
34
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
  compromised.
• A CoI exists whether or not decisions are
  affected by a personal interest.
• 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.FP.
• A CoI could lead to misconduct.

35
Conflicts of Interest and Commitment.

• 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.

36
WHAT DO THESE 4 PHYSICIANS HAVE IN COMMON
Dr. CharlesNemeroff

• Harvard University
• 4 million in unreported consulting revenues from
  Pharmaceutical Industry.
• Promoted antipsychotic drugs in children
• GOV. GRANTS

• Emory University
• Took gt500K in unreported consulting income from
  Glaxo.
• Gov. Funded research on Glaxo drugs

37
Conflicts of Interest and Commitment.

• Conflicts of commitment.
• Using institutional time for consulting.
• Using institutional resources for personal gain.
• Using graduate students/fellows for work on
  company projects.
• 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.)

38
CoI in Animal Research Program
39
Understanding and Managing the Conflict of
Interest

• The Publics 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.
  

40
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.
41
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 interests.
• Makes sure the investigators consider the
  interests of the animals.
• 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.

42
The IACUC and Conflict Management

• IACUC Reports the good, the bad and ugly to
• Institutional Official
• OLAW and USDA
• Follow - up
• IACUC appointed by highest institutional
  authority.
• Protect the Universitys interests
• Manage the CoI
• Maintain the Publics trust

43
Research Ethics EducationCITI Program

• Human Subjects Protection
• Good Clinical Practice.
• Lab Animal Welfare.
• Responsible Conduct of Research.
• Bio-safety and Bio-security
• citisupport_at_med.miami.edu
• 305 243-7970

• Human Subjects Protection
• Good Clinical Practice.
• Lab Animal Welfare.
• Responsible Conduct of Research.
• Bio-safety and Bio-security

44
CITI Laboratory Animal Welfare Program

• Investigators
• IACUC Members

45
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  

46
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 Course

47
LAW Courses Completed2009
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

48
www.citiprogram.org
49
Joseph Wright (September 3, 1734 - August 29,
1797),
An Experiment on a Bird in The Air Pump by
Joseph Wright (1734-1797) British National
Gallery- London