Transcript Slide 1

Promoting Integrity in Your
Animal Research Program
Paul Braunschweiger Ph.D
Professor Radiation Oncology
Chair, University of Miami IACUC
Director, Office of the IACUC
Co-Founder, CITI Program.
www.citiprogram.org
Talking Points
• Why does integrity in the Research Enterprise matter?
• The Responsible Conduct of Research and the Public
Trust
– Consequences of violating the Public Trust.
• Understanding and managing the conflicts of interest
• Promoting Integrity and ethical behavior in your animal
research program.
– Post approval monitoring
– Foundation of ethical behavior is education.
Integrity
“A personal and steadfast
commitment to a set of moral or
ethical standards defined by
your religion, community or
professional discipline.”
Miriam Webster Dictionary www.Miriam-Webster.com
"Integrity" by Canneto, Columbus, OH
Integrity & Responsible Conduct of
Research
• Accepted practices for the RCR can vary from
discipline to discipline and even from
laboratory to laboratory.
• 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
Why Does Integrity Matter in
Research?
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Puts subjects at risk.
Injures careers
Wastes Resources
Wastes Time
Delays acceptance of other research
Delays development of affective therapies
or advanced technologies.
• Undermines the Public Trust.
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 public’s trust, brings Regulation.
• To preserve the Public’s Trust there must be:
– Accountability.
– Documentation of ethical conduct.
• Federal Regulations (AWA and PHS Policies) specifically require
documentation of ethical behavior.
• Regulatory requirements to document are designed to:
Help investigators conduct research responsibly
Preserve the Public Trust in research.
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Consequences of betrayal of the
Public Trust
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Puts subjects at risk
Federal inquiry / intervention
Institutional embarrassment
Fines
Wasted resources
Personal embarrassment
Loss of funding, Loss of livelihood
Jail
Justification and / or vindication for
groups with anti-research agenda.
A.L.F.
Ethical Basis for Responsible Conduct of
Animal Research
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Ethical basis for the Regulations
– 569 - 475 BC Pythagoras of Samos
– Greek philosopher - mathematics, astronomy, and
the theory of music.
– Believed in Reincarnation
– Should not be cruel to animals or eat them.
– Vegetarian
The Athens School by Raphael
Ethical Basis for Responsible Conduct of
Animal Research
• Aristotle
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Student of Plato, Teacher to Alexander the Great.
Research - Empirical observation and experience.
Scientific method.
Animals:
• Sensation, Passion, memory, understand
relationships.
• NOT Capable of Thought or reasoning
– Aristotle believed that creatures were arranged in a
graded scale of perfection.
Plato and Aristotle –
“The Athens School” by Raphael
– Man at a higher state of perfection because
Man can reason and reflect.
– Animals and plants exist for man’s use, but
not abuse.
Ethical Basis for Responsible Conduct of
Animal Research
• Ethical basis for the Regulations
– 2nd Century Galen "father of vivisection”
– 13th Century St T. Aquinas. Charity to animals.
– 17th Century - R. Descartes
• Animals are complex automata.
• Unconscious beings that can see, hear, touch, anger, fear
• Do not think or feel pain.
– 17th Century J. Rousseau.
• Animals are sensitive beings, devoid of intellect and
freedom
• Man has a duty towards animals to not uselessly mistreat
them.
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Ethical Basis for Responsible Conduct of
Animal Research
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Ethical basis for the Regulations
– 18th Century - Jeremy Bentham 1748 - 1832
• Utilitarianism
• The moral status of animals
• Animals had moral status and rights to be treated
humanely.
• “Cruelty towards animals is an incentive to cruelty towards
men.”
• In response to Descartes:
“The question is not, Can they reason? nor,
Can they talk? but, Can they suffer?”
Before his time
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Marshall Hall
by J Holl 1939
Marshall Hall (1790–1857), a physician and noted
physiologist, supported animal research but stated
‘Unhappily… the subjects of animal physiology are
sentient, and every experiment is attended by pain
and suffering.’
Hall set out five guiding principles of animal
research to stimulate debate in the scientific
community:
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i) the lack of an alternative
ii) a clear objective
iii) the avoidance of repetition of work
iv) the need to minimize suffering
v) full and detailed publication of the results.
In 1831, he outlined five principles to govern animal experimentation.
Of the Principles of Investigation in Physiology. Lancet 1 (1856), pp. 393–394.
Ethical Basis for Responsible Conduct of
Animal Research
• Ethical basis for the Regulations
– 20th Century – Organizations, Codes and
Legislation
• Nuremberg Code.
– Point 3. The experiment should be so designed
and based on the results of animal
experimentation and a knowledge of the natural
history of the disease or other problem under
study that the anticipated results will justify the
performance of the experiment.
• NIH, Russell WMS and Burch RL (1959);
– Reduction, Replacement and Refinement
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Ethical Basis for Responsible Conduct of
Animal Research
• Ethical basis for the Regulations
– 20th Century – Organizations, Codes and Legislation
• The Guide 1963, 1996
• AWA, 1966, amended 1970, 1976, 1985, 1989, 1991,
1993
• HREA 1985 -- IACUC
– 21st Century –
• Shift away from animal based models “Alternatives”
• Animal welfare vs. animal rights.
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"Integrity Protecting the Works of Man." John Quincy Adams Ward, 1903
Integrity in Your Animal Research Program
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Starts with Institutional Commitment
Promoted and nurtured by the IACUC
Embraced by the investigators, staff and students as
“The right thing to do”
Promoting Integrity and Ethical Behavioral
Shared Responsibility
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Veterinarians
Husbandry Technicians
Vet Technicians
Students
Lab technicians.
Grad students
Post docs
Collaborators
Principle Investigator
Institutional official
Animal Research Enterprise is a
Partnership?
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The Public
Investigators
Veterinarians
IACUC
Institutional official
Institutions
Animal subjects
Relationships with some common goals and
Interest among stakeholders, but, also
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Many Conflicting Interests
Conflicts of Interest in the Animal Use
Program.
• 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 potential conflict of interest involves a situation that may develop into
an actual conflict of interest.
Conflicts of Interest and Commitment
• A conflict of interest exists whether or not
decisions are affected by a personal interest.
• A conflict of interest implies only the potential for
bias, not a likelihood.
• A conflict of interest is not considered research
misconduct.
• A conflicts of interest could lead to misconduct,
questionable research practices and/or
noncompliance.
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Conflicts of Interest and
Commitment
• Tangible CoI
– An institution's researcher holds an executive position with a company
that stands to benefit from the animal research he is conducted at the
institution.
– An institutional official is faced with the suspension of a well funded PI’s
protocol for non-compliance.
– High profile, big $$ investigator expects preferential treatment from the
institution.
• Intangible CoI
– Intellectual Bias.
• Peer review
– Academic conflict of interest.
• IACUC reviews
• Conflicts of conscience
– Religious or Social beliefs might prevent an objective review of a
protocol or project (e.g., animal research; embryonic stem cell research
Conflicts of Commitment
• A researcher is overcommitted.
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Clinical duties
Academic committees
Lab animal research
Clinical research
Consulting activities
Graduate students and fellows
Family
• Leads to taking short cuts
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Promoting Integrity and Ethical Behavioral
Understanding and Managing the Conflict of Interest
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The Conflict
– Valuable medical advances with animals as test subjects.
– Society understands that animals:
• Can not understand the research.
• Can not consent to participate in what may cause them harm, pain or
death.
– Society demands that research animals only be used in ethically
designed and conducted projects.
– Investigators must get the data, publish the papers, get the grants
support their labs and get promoted.
– Institutions want the grants, patents and indirect costs.
– A conflict of interest with respect to institutional welfare, the
investigators welfare, the welfare of their animal subjects and the
Public Trust
Conflict Resolution
• Mismanagement of the conflict can lead to
noncompliance, questionable research practices,
sloppy science, and perhaps misconduct.
• The IACUC specifically empowered by the
federal regulations to manage the conflicts of
interest between:
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Investigators
Welfare of Animal Subjects
Institutions
Society
Promoting Integrity and Ethical Behavioral
Managing the conflict of interest
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Vast majority of investigators understand the conflicts
and the IACUC’s role in managing them.
Others require special help:
– Case 1. Ends justify the means;
• Busy investigator, juggling lab and clinical research
• Several big grants, $$$$$ to the institution
• Must get the data,
– Patients are waiting for new treatments
– The editor is waiting.
• Lip service to animal welfare.
• Follows most of the rules when convenient, but
• May take risks because:
– Doesn’t have time to submit the amendment.
– Chances of getting caught are slim and
– Consequences are minor or nonexistent
• Ultimately gets in trouble with the IACUC.
• Work is suspended
• Report to sponsor and regulators
Promoting Integrity and Ethical Behavioral
Managing the conflict of interest
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Others require special help:
– Case 2. Pushing the envelope
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Senior investigator
“I have been doing it this way for 20 years”
Wants to “do the right thing”.
“Knows the right” thing to do. But abhors any oversight,
Sees the IACUC as an impediment to academic
freedom.
Pushes the administration for less oversight.
Reluctantly compliant, but doesn’t buy into the process.
Provides poor example to trainees lab staff.
Ultimately he or the trainee / staff member gets in
trouble with the IACUC.
Work may be suspended
Report to sponsors and the regulators
Promoting Integrity and Ethical Behavioral
Managing the conflict of interest
• Others require special help:
– Case 3. Ignorance is bliss
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Big $$ program,
Corporate and Public funding
Thousands of animals.
Really wants to do the right thing, but:
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Poorly organized lab.
Personnel Overwhelmed
Understaffed, Poorly trained staff
Under funded or
Too cheap to invest in lab manager.
• Inevitably will have problems with the
IACUC.
• Work will ultimately be suspended.
• Report to sponsors and the regulators
Promoting Integrity and Ethical Behavioral
Managing the conflict of interest
• Common elements are:
– Inevitably will have problems with the
IACUC.
– Work will ultimately be suspended.
– Report to sponsors and the regulators
• Investigators are busy, high
achievers who are under
considerable professional pressures
to:
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Get the data.
Get the data in print.
Get the next grant funded.
Keep staff employed
Start the company
Get promoted.
Get the raise
Promoting Integrity and Ethical Behavioral
Managing the conflict of interest
• How can the institution help all it’s investigators
conduct their work to the highest ethical
standards?
Promoting Integrity.
Institutional level
• Institutional Official
– Clear understanding of the IO’s role and responsibility
• Ethics Education and training
• Reporting to the Regulators
– Infrastructure & Resources for veterinary staff.
– Infrastructure & Resources for the IACUC
• Staffing
• Training
• Oversight Programs
– Conflicts of Interest
• Institution vs. IACUC vs. Faculty
– Commitment to AAALAC accreditation
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Promoting Integrity
The IACUC
Active and rigorous promotion of the “3R”
• Reduction.
– Science Review for experimental design
• Controls
• Sample size determination.
• Pilot studies
• Replacement
– Literature review for models with less ethical cost.
• Refinement
– New approaches to mitigate against pain and distress.
• Analgesia strategies
• Enrichment
• Better documentation for waivers of analgesia.
– Technical refinement to reduce model failure.
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Promoting Integrity
The IACUC Membership
• IACUC membership
– Member education and training.
• New member training.
• Continuing education, refresher courses.
• IACUC Members need to understand the expectations of the
regulators.
• Include educational sessions at meetings.
• Participation in national meeting and OLAW, USDA
sponsored events.
– Enhance the role of the Community Member
• Insure Community Member understands the process and
his/her role.
• Encourage questions.
• Multiple Community Members.
– Non Science members
• Statistician
• Librarian
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Promoting Integrity
The IACUC Membership
• IACUC membership
– Science members
• Anesthesiologist or pain researcher
– Evaluate your IACUC member performance.
• Attendance
• Protocol Review
• Participation in Subcommittee Activities
– Excuse non-participatory members.
– Retain responsible members.
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Promoting Integrity
IACUC Procedures and Process
• Protocol Review
– Designated Review vs. Full Committee Review
• Clear written policies.
• Choice of Reviewers
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Science Review
Literature Search Review
Statistical Review
Analgesia review
• Efficient communication between the “3 I’s”
– IACUC, IBC, and IRB.
• Confidentiality
• Manage conflicts of interest.
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Promoting Integrity
The IACUC
Issues of non-compliance
• Dealing with non-compliance.
– Provide a easy way for the reporting of concerns.
– Clear policies and SOPs for reviewing allegations of noncompliance.
• Communicate those polices to investigators.
• Follow the policies.
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Get the IO involved early.
Confidentiality.
Protection of whistleblowers.
Reporting promptly to the regulators, AAALAC, sponsors.
Promoting Integrity
Investigators
• Education and Communication.
– Simple and effective means of communication between
the IACUC and investigators.
• When policies change alert the investigators.
• Have a mechanism in place.
– Training and education
• Basic Animal Welfare Instruction
• Refresher or continuing education.
• Wet labs.
– Documentation of training.
– Enforcement of the training mandates.
• Monitor Adherence to the protocols
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Promoting Integrity in Your Animal
Research Program.
The Post Approval Monitor (PAM)
Integrity in the research program requires oversight.
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Post Approval Monitor (PAM)
“We are the IACUC and we are here to help you.”
• PAM - lab science training and customer service
demeanor.
– Arranges meeting with PI & the research team. (annually)
– Reviews all active protocols.
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Unreported changes to the protocol.
New personnel, training issues.
Record keeping procedures.
Provides Information.
– Training opportunities,
– Reporting concerns
– Amendments
• We are the IACUC and we are here to help you.
– Report at the monthly IACUC meeting.
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Promoting Integrity in Your Animal
Research Program.
Investigator Training
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Promoting Integrity
Investigator Training
• PHS Policy and USDA Regulation
– Basic Training Lab Animal Welfare
– Continuing Education
• Investigators, staff, students
• IACUC members
– Procedure or model specific training
• Training vehicles
• 1 on 1 instruction
• Classroom sessions
• Web based instruction
– “Home Built”
– AALAS Learning Library, IACUC.org
– CITI Program.
• Combination of approaches.
• Evaluation of the training program
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CITI Program
Lab Animal Welfare Educational Program
opened 5-15-07
Anonymous Voluntary User Satisfaction Survey Data
8-27-07 to 4-2-08
Training Program Evaluation
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Age, gender, course completed, years conducting L.A.
Research
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About how many hrs did it take you to complete your Lab
Animal Welfare Course requirements?
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The quiz questions addressed the relevant issues in the
modules?
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I think that the Internet is an appropriate tool to deliver basic
instruction in the ethical conduct of research with animal
subjects.
Training Program Evaluation
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After completing this instruction, I now have a better
understanding of how to apply the "3Rs" to insure that my lab
animal studies are conducted to the highest ethical standards?
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Now that I have completed the course, I am more confident in
my ability to advise a student or a colleague on how to apply the
"3Rs" to insure that their lab animal studies are conducted to
the highest ethical standards?
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Now that I have completed this course on the ethical conduct of
studies with laboratory animals, I intend to take a more active
role in assuring that lab animal research at my institution is
conducted to the highest ethical standards by pursuing
professional certification, an ethics committee or by joining an
Institutional Animal Care and Use Committee (IACUC)
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How do you rate the Course?
Assuming a similar time commitment, would you prefer another vehicle for this
mandated instruction?
80%
70%
% Responders (1352)
60%
50%
40%
30%
20%
10%
0%
No, this
approach is
best.
8-27-07 to 4-1-08
Book or
workbook
tutorial
Traditional
classroom
presentation.
Video
presentation
Audio
presentation.
After completing this instruction, I now have a better understanding of how to
apply the "3Rs" to insure that my lab animal studies are conducted to the
highest ethical standards?
30%
9%
68%
% Responders (n=1311)
25%
20%
15%
10%
5%
0%
1
2
3
Strongly disagree
4
5
6
7
8
Strongly agree
9
Now that I have completed the course, I am more confident in my ability
to advise a student or a colleague on how to apply the "3Rs" to insure
that their lab animal studies are conducted to the highest ethical
standards
% Responders (n=1315)
30%
25%
9%
69%
20%
15%
10%
5%
0%
1
2
3
Strongly disagree
4
5
6
7
8
9
Strongly agree
I intend to take a more active role in assuring that lab animal research at my
institution is conducted to the highest ethical standards by pursuing professional
certification, or by joining an ethics committee or Institutional Animal Care and Use
Committee (IACUC).
30%
14%
58%
% Responders (n=1297)
25%
20%
15%
10%
5%
0%
1
2
3
Strongly disagree
4
5
6
7
8
9
Strongly agree
Summary
• The active promotion of integrity in the
research enterprise is essential to maintain
the Public Trust.
– Without the Public Trust there can be now
research
• Institutional Support provides the backbone
for the Animal Research Program.
– Educate the IO
– AAALAC accreditation
• Management of conflicts of interest
between
– Investigators, the institution and the animal
subjects is crucial to well run animal care
program.
“Integrity” by Joris Plu 2005
Summary
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Institution and the IACUC should make it easy for
investigators to be compliant.
– Take a look at your process. Reduce the time between
submission and approval.
– Institute Post Approval Protocol Monitor system
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“We are the IACUC, yes we are the cops, but we are here to help
you.”
• Marked reduction in non-compliance.
– The foundation of research integrity is education
• Early, often, multiple formats
• Evaluate your Animal use training program. Is it working
for you?
• Listen to the feedback from your learners.
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Promoting Integrity is everyone’s responsibility.
– Leads to good animal care
– Leads to good science.
– Compliance
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The Responsible Conduct of Research is beyond simply
being compliant with Federal regulations.
It is just The “right thing to do”.
“New Integrity” by Artibella Avanti
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
Promoting Integrity in Your
Animal Research Program
Paul Braunschweiger Ph.D
Professor Radiation Oncology
Chair, University of Miami IACUC
Director, Office of the IACUC
Co-Founder, CITI Program.