Transcript Document 7323644

Responsible Conduct in Research
Katrina A. Bramstedt, PhD (CCF Bioethics Dept.)
Amir Darr, MA (CCF Gen. Clinical Research Center)
Course Outline
• 50-minute lecture (all students in one group)
– Principles of research ethics
– Study design, data collection, data storage
• Record-keeping, data selection, digital data (e.g. gels)
– Data and material sharing
• Who owns “your” data? “Your” materials?
– Authorship
• Criteria for authorship, timeliness
– Misconduct & whistleblowing
– Research with animals
• 60-minute small group case discussions
– Yeager case, Powell case, Gonzales case
Course Objectives**
• Recognize ethical obligations of basic science
research
• Identify elements essential to Appropriate
Laboratory Practice
• Articulate the 3 requirements for authorship
• Articulate 3 forms of research misconduct
• Identify ethical principles associated with animal
research
**This is a general course to satisfy RCR education
requirements.
Ethics is about…
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Minimizing harm
Maximizing benefit
Being fair
Being respectful of others
Principles of Research Ethics
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Honesty
Objectivity
Integrity (you, what you do, what you say)
Stewardship of resources (time, materials,
equipment, personnel)
• Collegiality (sharing)
• Justice (fairness in authorship, mentoring)
• Openness (disclosure)
People Often Ask Us…
• If there is no law against a particular behavior then
is the behavior ok? Can we be punished for a
behavior that is not “illegal”?
Our reply:
• Do you need a law to tell you what is ethically
inappropriate?
• Lack of a legal statute does not give you
permission to behave inappropriately.
Appropriate Laboratory Practice
• What is it?
– Following a written protocol
– Thorough and legible data documentation
(including reagent lot#, exp date, etc.)
– Appropriately storing data and specimens
– Appropriately storing reagents, chemicals
– Proper equipment maintenance and calibration
– Use of Standard Operating Procedures (SOPs)
Good Notekeeping
• Signed and dated lab books
• LEGIBLE writing
• No white-out
– Cross out with one line, initial and date.
• No “sticky” notes
• Have a blank page? Draw a line through it.
Data Selection & Retention
(aka Throwing out “bad” data)
• Be careful how you “pick and chose”
• Be consistent with regard to “high background”,
“artifact”, “low confidence values”, and “noise”
(versus signal)
• When reporting your data, disclose what you did:
– Two obese rats were excluded because…
– The first three data points were excluded because…
Dilemmas with Gels & Digital Data
(data enhancement)
Gels, X-Rays, photos are considered DATA
Digital Data Ethics
• Simple adjustments to the ENTIRE image are
usually acceptable.
• Selectively manipulating one area of the image is
questionable.
• Cropping an image is usually acceptable.
• If used, software filters must be noted in the figure
caption.
• The more processing you ‘have’ to do, the more
ethically problematic the manipulations become.
Who Owns “Your” Data & Materials?
• Per CCF policy, any invention made by CCF
employees & medical students that relate in any
way to his/her job/research responsibilities must
be assigned to the Clinic.
• Exchanges of research material with outside
researchers must be framed in written agreements,
since further discoveries may be made using the
material. CCF may be compensated for such
exchanges.
Conflict of Interest
• Financial
– Equity interest, consultant, paid speaker
• Non-financial
– Recognition, desire to advance one’s theory
• You might not be able to eliminate your
conflicts of interest, but there are other
options: reduce, avoid, disclose
http://www.dilbert.com/comics/dilbert/archive/dilbert-20051113.html
Authorship*
Acquisition of funding, collection of data,
or general supervision of the research
group, alone, does not justify authorship.
*Intl Comm of Medical Journal Editors. Uniform Requirements for
Manuscripts Submitted to Biomedical Journals: Writing and Editing for
Biomedical Publication. November 2006.
An Underlying Principle of the
Authorship Requirements
• Those credited with authorship
should be able to take public
responsibility for the research.
Author Requirements*
Authorship credit should be based on:
1) substantial contributions to conception and
design, or acquisition of data, or analysis and
interpretation of data; and
2) drafting the article or revising it critically for
important intellectual content; and
3) final approval of the version to be published.
Authors should meet conditions 1, 2, and 3.
*Intl Comm of Medical Journal Editors. Uniform Requirements for
Manuscripts Submitted to Biomedical Journals: Writing and Editing for
Biomedical Publication. November 2006.
DON’T GIVE HONORARY
AUTHORSHIP
DON’T TAKE HONORARY
AUTHORSHIP
Some Participating Journals
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Annals of Clinical and Laboratory Science
Journal of Laboratory and Clinical Medicine
NEJM
Lancet
JAMA
A Word of Advice
Decide up front who will work on the
manuscript and what the order of authors
will be.
(Not all people working on the project will
meet authorship requirements).
Authorship…one more thing
• Be timely with your publishing
– Out of respect for the funding agency
– Out of respect for society (it may benefit from
your research)
– Out of respect for the people you diligently
worked with
– Out of respect for the people you are writing
the manuscript with---don’t leave your coauthors hanging.
http://www.dilbert.com/comics/dilbert/archive/dilbert-20061010.html
Research Misconduct
• Fabrication (creating data)
• Falsification (changing data)
• Plagiarism (using another’s words or ideas
without giving them credit).
– This includes cutting and pasting from the
Internet.
Why is Misconduct “Bad”?
• It affects the integrity of science as a
profession (which potentially adversely
affects research funding)
• It is not collegial
• It is an example of poor resource
stewardship
• Propels further generation of “bad” data as
the initial data foundation is “bad”
Misconduct Research
• Survey of 3247 researchers:
– 28% admitted to poor record keeping
– 16% admitted to changing the design, methodology, or
results of a study in response to pressure from their
funding source
– 15% admitted to dropping observations/data points
based on a gut feeling
– 10% admit to giving authorship to people who
didn't earn it
ref: Martinson et al. Nature 2005;435:737-738
What to do if you suspect
misconduct…
• Don’t assume you are “right”
• Don’t accuse
• Try to verify your suspicion (there may be
an acceptable reason for what is going on)
• Ask yourself, “what is my motive for
getting involved?”
• Ask the advice of someone you trust
Issues in Animal Research
Your Guides:
PHS Policy on Humane Care and Use of
Laboratory Animals – info about the role of
the IACUC
(http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf)
Guide for the Care and Use of Laboratory
Animals – info about vet care, housing, pain
control euthanasia, etc.
(http://www.nap.edu/readingroom/books/labrats/)
Issues in Animal Research
• Have you attempted to REPLACE animals with
another model?
• Have you REDUCED the number of animals to
the minimum needed for statistical purposes?
• Have you REFINED your lab techniques so that
animal pain and suffering are as low as possible?
• Is your protocol approved by the CCF Institutional
Animal Care and Use Committee?
Identification
• Make sure your animals are clearly
identifiable, whether singularly or in
groups.
• Options include cage labels, neck labels,
tattoo, microchip, etc.
Housing Your Animals
• Consider the animal species
• Housing should consider size of animal,
temperature, bedding needs, food, clean
water, light, noise, humidity, contact with
other animals, air exchange, vibration, etc.
• Keep the cages clean, and the animals free
from harm from other animals. (This
includes avoiding crowding within a cage).
Avoiding Animal Stress
If possible, before starting your project,
CONDITION your animals to their
environment, procedures, and research
personnel.
Pain/Suffering
• An animal with signs of pain or distress
not predicted in the protocol, must have
the pain or distress alleviated promptly.
• Alleviation of such pain or distress must
take precedence over completing a
project.
• If this is not possible the animal must be
euthanized without delay.
Pain/Suffering
Neuromuscular blocking drugs do not
provide relief from pain. They are used
to paralyze skeletal muscles while an
animal is fully anesthetized.
Pain/Suffering
• The use of local or general anesthetic,
analgesic or tranquillizing agents must be
appropriate to the species, and should at
least parallel their use in current medical or
veterinary practice.
• If the nature of the project precludes the use
of anesthetic or analgesic agents to alleviate
pain, the planned end-point of the project
must be as early as feasible to avoid or
minimize pain or distress in the animals.
Post-Op Care
• The comfort of animals must be promoted
throughout the post-operative period,
reflecting on warmth, hygiene, fluid and food
intake, surgical wound healing, and control of
infection, AND the use of analgesic,
tranquillizers and antibiotics.
• Ensure that animals recovering from
anesthesia do not injure themselves by
uncoordinated movements, and that
conditions are such that they are not
disturbed, attacked or killed by other animals
in the same enclosure.
Killing of Research Animals
• When it is necessary to kill a research
animal, humane procedures must be
used. These procedures must avoid pain
or distress, be reliable and produce rapid
loss of consciousness until death occurs.
• Other animals should not be present
when euthanasia is performed.
Red Face Test
Contact Information
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Compliance Hotline:
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Bioethics Consult Pager:
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(216) 791-4710 or (800) 826-9294.
(216) 464-8410 x22512
Office of General Counsel:
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(216) 444-2340
* Please note all reports/complaints can be
made anonymously to all groups listed.
Bibliography
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Korenman SG, Shipp AC. Teaching the Responsible Conduct of Research through a
Case Study Approach. New York: AAMC, 1994
National Academy of Sciences. On Being a Scientist: Responsible Conduct in
Research. Washington DC: Natl Academy Press, 1995.
University of Arizona Center for Toxicology. Digital Imaging: Ethics.
http://swehsc.pharmacy.arizona.edu/exppath/micro/digimage_ethics.html
Intl Comm Medical Journal Editors. Uniform Requirements for
Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical
Publication. November 2006. http://www.icmje.org/#author
Gunsalus CK. How to blow the whistle and still have a career afterwards. Sci Eng
Ethics 1998;4:51-64.
CCF Innovation. Available on-line at http://intranet.ccf.org/ccfi/
Medical Research Council. Good Research Practice. London: December 2000.
www.mrc.ac.uk/pdf-good_research_practice.pdf
National Health and Medical Research Council Animal Welfare Committee.
Australian code of practice for the care and use of animals for scientific
purposes, 7th Edition. 2004, Canberra, Australia.
Macrina FL. Scientific Integrity. ASM Press, Washington DC, 2000.
Cromey DW. Digital Imaging Ethics. September 2004.
http://swehsc.pharmacy.arizona.edu/expath/micro/gidimage_ethics.html
Institute of Laboratory Animal Resources. Guide for the Care and Use of Laboratory
Animals. 1996
PHS Policy on Humane Care and Use of Laboratory Animals. 2002