Teaching Responsible Conduct
of Research
Michael J. Leibowitz, M.D., Ph.D.
Adjunct Professor, Medical Microbiology &
Immunology
University of California, Davis
Email: mjleibowitz@ucdavis.edu
October 10, 2011
Why Teach Responsible Conduct
of Research
• Scientists depend on prior data (not
conclusions)
• Public trust required
• Misconduct (even inadvertent) can end a
scientific career
• Biomedical research: Lives are at stake
• US Public Health Service requires RCR
training at every step of scientific
development
Training Is Effective
• 1,200 papers by 537 undergraduates in
social sciences and humanities
• Half of students received 15-min. webbased tutorial on avoiding plagiarism
• Plagiarism found in 3.3% of controls, 1.3%
of trained students
T.S. Dee & B.A. Jacob, National Bureau of Economic Research Working Paper
No. 15672, Feb. 2010 (http:www.nber.org/w15672)
Definition of Research
Research means a systematic investigation,
including research development, testing,
and evaluation, designed to develop or
contribute to generalizable knowledge.
• Not clinical practice, even if trying an
unproven treatment
• Not program or course evaluation (unless
plan to publish results)
• Not teaching a course (even if scientific)
Definition of Scientific Misconduct
•
•
•
•
Fabrication
Falsification
Plagiarism
Other definitions (not meeting the
standards of the scientific community) no
longer widely used
…in proposing, performing, or reviewing
research, or in reporting research results.
NIH Notice NOT-OD-10-019
• Suggested topics for instruction:
-conflict of interest: personal, professional, and financial
-human subjects, vertebrate animals, lab safety
-mentorship
-collaborative research
-peer review
-data acquisition and management
- policies for handling misconduct
-responsible authorship and publication
-contemporary ethical issues in research
-environmental/societal impacts of research
Other Topics to Consider
•
•
•
•
•
“Dual-Use” agents in the lab
Guide to academic survival
Students as research subjects
Ethical issues of genomics
Academic-Industrial collaborations
NIH Recommendations for RCR
• Face-to-face discussions need
• Faculty rotation ideal to get full faculty
participation
• At least 8 hours, preferably over semester
(1-2 credit semester-long class?)
• At each stage of career (including faculty),
and at least once every 4 years; faculty
participation in course can meet this
requirement
Cases for Discussion
• Detailed cases take longer, but may
appeal to experienced trainees
• Less detailed cases may be more
accessible to new trainees
• Role playing cases may encourage active
learning
• In some schools, students have written
their own cases
Detailed cases
• SG Korenman and AC Shipp, Teaching the
Responsible Conduct of Research through a
Case Study Approach, A Handbook for
Instructors, AAMC, Washington, DC, 1994
• Publisher requires permission and password
protection to post on-line
• Includes some role-playing
• Methods described may intimidate
inexperienced freshmen
Data Selection and Retention
CASE A2
Alan Yeager has completed a series of experiments characterizing the receptor
for a new class of hormones. During the course of his work, he studied binding
characteristics and hormonal responses in tissue culture and in vitro, utilizing
gels to characterize the molecular weights of receptor variants. This was
exciting work for a second-year graduate student doing his first project. One
day, Alan's laboratory chief asked him to prepare an abstract for an upcoming
meeting and a paper for publication, both to be based on the work Alan had
been doing. The abstract was due in one week.
As Alan examined his accumulated data, he noted that a number of cell culture
plates failed to respond to the hormonal stimulus and that there was
considerable variability in the dose-response relationship. His data are
represented in Figure 1.
Figure 1
Furthermore, on reexamination, he noted that a number of his gels were not very
aesthetic in appearance, yet he was sure that they demonstrated the molecular weight,
agonist binding, and subunit characteristics of the receptor.
Alan mentioned his distress to Pam Alden, a fifth-year graduate student, who said,
"Why don't you clean up your data? You'll never get the paper published unless you do.
We always clean up the data around here. "She then suggested that the four culture
points failing to show a response (along the X-axis at the 0 nanomolar concentration)
be dropped because the cells were probably dead. She also pointed out that he might
eliminate the top data point at the 45 minute interval as an outlier. She examined the
gels and suggested retouching the negatives from which the prints were to be made,
including the duplication of one of the nicer gel lanes to replace another that turned out
poorly, but showed essentially the same result. "That will greatly improve your chances
of publication," she said. Alan replied, "Maybe I should repeat a few of the experiments
or try to improve the culture conditions?" “No,” said Pam, "if you're convinced of your
results, why go through the time, expense, and uncertainty of more repetitions? You'll
never complete an experiment in time for the abstract, anyhow.” Somewhat dismayed,
Alan thanked her and turned back to his work.
CASE A2 Questions
1. What do you think about Pam's comments on publication practices and her
suggestions for "cleaning up" the data?
2. How should Alan go about determining which points to include and which to
exclude?
3. What other course(s) of action would you recommend to Alan?
4. Pam's perception about improving the chances of publication by "cleaning up" the
data is not uncommon. How might journal editors and reviewers work toward
correcting this perception?
S.G. Korenman and A.C. Shipp, Teaching the Responsible Conduct of Research through a
Case Study Approach: A Handbook for Instructors, Association of American Medical Colleges,
Washington, DC, 1994.
Simplified Cases
• NH Steneck, Introduction to the
Responsible Conduct of Research, Office
of Research Integrity
• Very generalized, but no scientific
knowledge needed.
• Note: You can make up your own cases,
from scratch or from the literature/news
media
After many years using fish and frogs to study brain
function, Dr. Ruth Q. encountered some problems that can
be explored only using new animal models. For the near
future, she plans to turn to mice or rats, but eventually may
have to do some research using cats or dogs. To help
prepare the way for this new research, she decides to put a
note about her plans in the progress report for the current
research grant, which runs out next year.
The day after she gave a draft of the progress report to her
long-time research assistant, he came her with a troubled
look on his face. Although he never told her, the main
reason he applied for the job in her laboratory many years
ago was the fact that she did not use warm-blooded
animals in her research. If she changed her animal models
as planned, he would have to quit his job and had no
prospects for getting another position that paid as well and
was as rewarding.
Is Dr. Q. have any obligation to consider her research
assistant's views before she redirects his research?
What are objections raised to the use of some animals in
research and how can those objections be answered?
Why are there more objections to using some animals in
research compared to others?
N.H. Steneck, ORI: Introduction to the Responsible
Conduct of Research, Office of Research Integrity,
Rockville, MD
Data Management
• Bringing in an actual notebook can be very
effective
• Milliken, Pasteur and other famous
scientists can illustrate examples of
questionable data selection in high impact
publications; troubling but good to make
students realize that even great scientists
can have their ethics questioned!
Definition: Plagiarize
• “to steal or pass off as one’s own (the
ideas or words of another)”
• “to present as one’s own an idea or
product derived from an existing source.”
Webster’s Seventh New Collegiate Dictionary
Definition: Copyright
• “the exclusive legal right to reproduce, publish
and sell the matter and form of a literary, musical
or artistic work.”
• Note that this includes scientific publications.
Webster’s Seventh New Collegiate Dictionary
Why is plagiarism the most
widespread infraction despite being
the easiest to detect?
• Many authors may not know the rules!
• Computers make plagiarism easy!
• “Self-plagiarism” is still plagiarism!
– Are there exceptions? Controversial.
--Opportunity for discussion
Permission to Re-Publish is Not
Automatic
“The rightsholder did not grant rights to reproduce this item
in electronic media. For the missing item, see the original
print version of this publication.
Figure 3. cat-scratch disease showing inflammation of the
lymph node.
Division of Pediatric Surgery, Brown Medical School.
Accessed August 17, 2007, at
http://bms.brown.edu/pedisurg/Brown/IBImages/SkinST/
Catscratch.html.”
P.M. Rabinowitz et al., American Family Physician 76: 1318 (2007).
Plagiarism Checking Sites
Multiple sites and programs are listed at:
http://plagiarism.phys.virginia.edu/links.html
Also: http://www.turnitin.com for a program
designed for student papers and
applications.
Plagiarism lasts forever!
Conflict of Interest
• Science should be unbiased
• Financial conflict of interest easiest to quantify
– $5K or 5% ownership often set as the limit, varies
• Funding sources as conflict of interest
• Conflict of commitment
• Professional advancement
• Expert reviewer may be conflicted
• Confidentiality; responsibility of grant and publication
reviewers
• Who should review?
• Data presentation can enhance teaching impact.
Does funding source matter?
• 603 consecutive papers and presentations on
leg orthopedic prostheses:
– Total hip replacement implants
• Commercially funded: 93% positive
• Independently funded: 37% positive
– Total knee replacements
• Commercial: 75% positive
• Independent: 20% positive
– Investigators receiving royalties reported no negative
outcomes
K.A. Ezzet, J. Arthroplasty 18(7 Suppl. 1):138-45 (2003)
How widespread is COI?
• Survey of medical school/teaching hospital
faculty (1663 at 50 schools, 2007)
– 52% had “any relationship” with industry
– 41% had relationship that contributed to most
important research
– 20% had industrial funding (48% clinical trials)
– Average industry funding per year: $33,417
– Average industry funding of clinical trial PI’s:
$110,869
DE Zinner, EG Campbell, JAMA 302:969-76 (Sept. 2, 2009)
Remedies for COI
• Self-regulation: Has not worked!
• Disclosure: “Sunshine as a disinfectant”
– May cause subject stress and anxiety
– Is it sufficient? Will subjects understand?
• Mediation/Management: blind trust,
proceeds to charity, outside supervisor for
research, etc.
• Prohibition: Some conflicts are prohibited
by journals or institutions, not manageable
COI Resources
• USPHS Conflict of Interest Page
http://grants.nih.gov/grants/policy/coi/index.htm
• NIH critique of Institutional Policies
http://grants.nih.gov/grants/policy/coi/nih_review.htm
• 42 CFR Part 50, Subpart F
http://grants.nih.gov/grants/compliance/42_CFR_50_Sub
part_F.htm
• AAMC site
http://www.aamc.org/research/coi/start.htm
Responsibility of Whistleblowers
• You should be vigilant and responsible.
False accusations may constitute
misconduct!
• Whistleblowers and accused have rights
• Think globally, act locally
• Seek advice before taking action
• Role of the Ombudsman
Special Topics
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•
•
•
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IACUC: Protection of animal subjects
IRB: Protection of human subjects
Chemical safety
Radiation safety
Containment of hazardous or infectious
agents
• Right to know laws
Introduction to Animal Research
• History and controversial political materials
can be a good way to start discussion; this
approach can be used for any topic.
History of Ethics of Animal
Experimentation
• Animal cruelty punished in ancient Greece
and India
• Descartes (1596-1650): Since animals
lack reason they can’t perceive pain
• Jeremy Bentham (1748-1832): “But they
can suffer!”
• Animal rights proposed by Peter Singer
(1975) and Tom Regan (1983)
Russell and Burch 3 R’s
• Replacement
– Substitution for living higher animals
– Use lower animals (insects), in vitro methods,
computer models
• Reduction
– Reduction in number of animals
– Power analysis, pilot studies
• Refinement
– Decrease in severity of procedures that cause pain
and distress
– Use painkillers, proper anesthetics, establish
experimental endpoints, limit restraining and fasting
Human Subjects Research
Human Subjects Presentation
• Even undergrads may use human subjects
(most likely in behavioral sciences)
• ALL human subjects research regulated
• Emotional impact greater for these cases;
ethical issues and conflicts may be more
apparent (even if harder to resolve)
• Prepares for future work
• For both humans and animals, good
science is required for RCR!
Abuses Led to Regulation
• Nuremburg Code (1947-1949)
• Tuskegee Syphilis Study, PR Birth Control
• Henry Beecher (NEJM, 1966): 22
examples of inadequate informed consent
in published studies in top journals
• Belmont Report (1978)
• Continued development of regulations
Belmont Report Principles
• Respect for persons; Autonomy
• Beneficence
• Justice
– Distributive justice:
• Fair subject selection; unjust to coerce to
participate or to unfairly exclude
• Equal sharing of risk and benefits
– Procedural justice
Three Principles for Treatment of
Human Subjects (Belmont Report)
• Respect for persons and their autonomy
• Beneficence (Risk vs. Benefits ratio must be
acceptable)
• Justice (Distributive and Procedural)
American Psychological Association adds
• Trust
• Fidelity and Scientific Integrity
The last 2 simply demand honesty, openness and
scientific validity, which are always required!
Current Controversies
• Pregnant subject, children, etc.: Does exclusion protect
or prevent development of needed treatments.
• Prisoners, students: Value of a “captive” population vs.
respect for persons not free to make choices.
• Fair compensation for human subjects vs. coercive
payment which clouds judgment
• Who should decide for the “impaired” patient?
Comatose? Young child? Depressed ambulatory
patient?
Mentorship
• This area is important to students and
faculty; formerly left to chance, but now
considered part of professional
development.
Mentorship
• There may be a conflict of interest
between a student/trainee and faculty
research supervisor
• Faculty member needs to advance funded
research and publish; student needs to
publish and complete degree in a timely
fashion with credentials for future
employment or education.
• Mentor role in professional development
Student Advisor Compact
Association of American Medical Colleges
Compact Between Biomedical Graduate
Students and Their Advisors:
https://services.aamc.org/publications/showfi
le.cfm?file=version127.pdf&prd_id=250&pr
v_id=308&pdf_id=127
Can be individualized like faculty Individual
Career Development Plan
Resources
• SG Korenman and AC Shipp, Teaching
the Responsible Conduct of Research
through a Case Study Approach, A
Handbook for Instructors, AAMC,
Washington, DC, 1994. Source of cases,
need permission to disseminate.
References
• NH Steneck, Introduction to the
Responsible Conduct of Research, Office
of Research Integrity. Short, simple
cases; OK to disseminate with reference
• K Barker, At the Bench, updated ed., Cold
Spring Harbor Lab. Press, NY, 2005
• K Barker, At the Helm, Cold Spring Harbor
Lab. Press, NY, 2002
Scientific Misconduct Policies SSU
See website:
http://linux.savannahstate.edu/osra/rcr.htm
Ethics Web Resources
• Office of Research Integrity
http://ori.dhhs.gov
• Poynter Institute, Indiana University
http://poynter.indiana.edu
• Lab management vignettes
http://learning.ucdavis.edu/LabAct/
• NIH on-line tutorial
http://phrp.nihtraining.com/users/login.php
Human Subjects Resources
• EJ Emanuel, RA Crouch, JD Arras, JD Moreno,
C Grady, Ethical and Regulatory Aspects of
Clinical Research, Johns Hopkins U. Press,
Baltimore, 2003. 86 source readings and
commentary
• BD Sales and S Folkman, Ethics in Research
with Human Participants, Amer. Psychol. Assn.,
Washington, DC, 2000. Focus on social
sciences
• RJ Amdur and EA Bankert, Institutional Review
Board Member Handbook, 2nd ed., Jones &
Bartlett, Sudbury, MA, 2007
References in Biomedical Ethics
• TL Beauchamp & JF Childress, Principles of
Biomedical Ethics, 5th ed., Oxford U. Press,
Oxford, UK, 2001
• Global Perspectives on Research Ethics and
Scholarly Integrity, Proceeding, Council of
Graduate Schools, 2008
• JV Lavery, C Grady, ER Wahl, EJ Emanuel,
Ethical Issues in International Biomedical
Research, A Casebook, Oxford U. Press,
Oxford, UK, 2007
Federal Laws on Scientific
Misconduct
• NSF, 45 C.F.R. Part 689:
http://www.nsf.gov/oig/resmisreg.pdf
• US PHS, 42 C.F.R. Part 93 and others:
http://ori.dhhs.gov/policies/statutes.shtml
• Update on the Requirement for Instruction
in the Responsible Conduct of Research
(Notice NOT-OD-10-019):
http://grants.nih.gov/grants/guide/noticefiles/NOT-OD-10-019.html