Responsible Conduct in Research

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Responsible Conduct in Research

• Katrina A. Bramstedt, PhD (CCF Bioethics Dept.)
• Amir Darr, MA (CCF Gen. Clinical Research Center)

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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

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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.

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Ethics is about

• Minimizing harm
• Maximizing benefit
• Being fair
• Being respectful of others

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Principles of Research Ethics

• 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)

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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.

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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)

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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.

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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

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Dilemmas with Gels Digital Data(data
enhancement)

Gels, X-Rays, photos are considered DATA
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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.

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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.

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Conflict of Interest

• Financial
• Equity interest, consultant, paid speaker
• Non-financial
• Recognition, desire to advance ones theory
• You might not be able to eliminate your conflicts
  of interest, but there are other options reduce,
  avoid, disclose

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http//www.dilbert.com/comics/dilbert/archive/dilb
ert-20051113.html
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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.
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An Underlying Principle of the Authorship
Requirements

• Those credited with authorship should be able to
  take public responsibility for the research.

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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.
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• DONT GIVE HONORARY AUTHORSHIP
• DONT TAKE HONORARY AUTHORSHIP

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Some Participating Journals

• Annals of Clinical and Laboratory Science
• Journal of Laboratory and Clinical Medicine
• NEJM
• Lancet
• JAMA

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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).

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Authorshipone 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---dont leave your co-authors
  hanging.

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http//www.dilbert.com/comics/dilbert/archive/dilb
ert-20061010.html
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Research Misconduct

• Fabrication (creating data)
• Falsification (changing data)
• Plagiarism (using anothers words or ideas
  without giving them credit).
• This includes cutting and pasting from the
  Internet.

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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

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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 2005435737-738

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What to do if you suspect misconduct

• Dont assume you are right
• Dont 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

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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/reference
  s/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/)

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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?

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Identification

• Make sure your animals are clearly identifiable,
  whether singularly or in groups.
• Options include cage labels, neck labels, tattoo,
  microchip, etc.

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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).

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Avoiding Animal Stress

• If possible, before starting your project,
  CONDITION your animals to their environment,
  procedures, and research personnel.

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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.

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Pain/Suffering

• Neuromuscular blocking drugs do not provide
  relief from pain. They are used to paralyze
  skeletal muscles while an animal is fully
  anesthetized.

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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.

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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.

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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.

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Red Face Test
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Contact Information

• Compliance Hotline
• [phone] or [phone].
• Bioethics Consult Pager
• [phone] x22512
• Office of General Counsel
• [phone]
• Please note all reports/complaints can be made
  anonymously to all groups listed.

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Bibliography

• 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.ar
  izona.edu/exppath/micro/digimage_ethics.html
• 4. 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
  1998451-64.
• 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