Student Presentation - Savannah State University

Responsible Conduct of
Research: How to Succeed and
Avoid Scandal in Science
Michael J. Leibowitz, M.D., Ph.D.
Adjunct Professor, Medical Microbiology &
University of California, Davis
October 11, 2011
Why Responsible Conduct of
• Scientists depend on prior data (not
• 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
Definition of Scientific Misconduct
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.
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)
Experimental Data
Who owns them?
Dated and signed
Not removable or erasable
How keep computerized data?
Data are needed for publications, patents
and to defend against charges of
misconduct, and most importantly, in order
to repeat or trouble-shoot experiments
Publishing a Paper
Why publish?
When you ready to publish?
Who should be an author?
What is your responsibility?
How do you avoid plagiarizing?
Where to submit?
Who reviews?
What to expect from peer review?
How to respond to reviewer critiques?
What are your responsibilities as a reviewer?
Publishing a Paper
• Authorship is the “coin of the realm”
• When you ready to publish? Tell a complete
story, reproducible data, significant contribution
• Author/contributor: significant contribution to the
design, experimentation, and reporting of the
• Rewards and responsibilities of authorship:
credit and blame
• New initiative to identify contribution of each
contributor (not exactly same as author) of a
paper (Rennie et al., JAMA 278:579, 1997)
Fabrication and Falsification
• Unlike plagiarism, obviously wrong and
requires conscious action by the wrongdoer
• How can this be prevented?
-Other researchers
Falsification and Fabrication
• Is it ever possible to omit data from
• Must all data be published?
Data Selection and Retention
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
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.
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
Who owns a publication?
All authors?
Senior (first) author?
Submitting (PI) author?
Employer(s) of authors?
Funding agencies?
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.
How to use the work of others
Quotation with attribution
When is permission needed? From
Permission to Re-Publish is Not
“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
P.M. Rabinowitz et al., American Family Physician 76: 1318 (2007).
Training Prevents Plagiarism
• 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 (
Plagiarism Checking Sites
Multiple sites and programs are listed at:
Also: for a program
designed for student papers and
Plagiarism lasts forever!
Patents Protect Intellectual
Property (IP)
• Protection of IP: Patent vs. Proprietary (issue for
• Patent priority formerly based on date of invention in US,
changing to date of patent application
• Invention must be new, not “prior art”
• Must be reduced to practice in patent application
• No prior disclosure: Patent before publish. Remember:
Public disclosure makes IP public.
• Protecting trainees’ right to publish
• US laws changing
• Foreign patents require separate application; date from
• Inventor may not be “owner” of patent (usually employer)
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
– Results of Industry vs. Government funded research
• Professional advancement
• Expert reviewer may be conflicted
• Confidentiality; responsibility of grant and
publication reviewers
• Who should review?
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
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:
DE Zinner, EG Campbell, JAMA 302:969-76 (Sept. 2, 2009)
• May not be sufficient, but is required by many
funding agencies and journals
• Early disclosure can prevent later
• Includes all payments (received or planned),
equity interest, fiduciary responsibility, personal
financial interest including relatives (spouse,
parent, child, siblings, domestic partner,
including “step,” “half,” “in-law,” etc.)
• Size and nature of a financial conflict of interest
affects how it should be managed
Who Needs to Disclose?
• Investigator = principal investigator and any
other person who is responsible for the design,
conduct, analysis or reporting of research.
• Not just PI, it can be anyone (key personnel,
even tech) who is involved in design, conduct, or
reporting of sponsored research
• Term also includes investigator’s spouse and
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
• NIH critique of Institutional Policies
• 42 CFR Part 50, Subpart F
• AAMC site
Responsibility of Whistleblowers
• You should be vigilant and responsible.
False accusations may constitute
• Whistleblowers and accused have rights
• Think globally, act locally
• Seek advice before taking action
• Role of the Ombudsman
Special Topics
IACUC: Protection of animal subjects
IRB: Protection of human subjects
Chemical safety
Radiation safety
Containment of hazardous or infectious
• Right to know laws
History of Ethics of Animal
• 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)
Development of Laws
•Mid-1800 Regulation of animal research in UK
•1966 laboratory Animal Welfare Act –Pet
nabbing Public concern (2-4-66 Life magazine)
•1985 Animal Welfare Act (protocol review)
•1985 Health Research Extension Act (PHS
•1998 CHIMP Act ,The Chimpanzee Health
Improvement, Maintenance, and Protection,–
sanctuaries for some 1,600 retired research
Animal Welfare Act
• Warm-blooded animals except mice, rats,
Health Research Extension Act
• All vertebrate animals used in PHS
funded activities
• Guide for the Care and Use of
Laboratory Animals, National Research
Council, National Academy Press,
Washington, DC 1996
IACUC: Institutional Animal Care
and Utilization Committee
• Must approve all studies before initiate
• Exemption must be determined by IACUC
• Includes veterinarian, scientists, nonscientists
IACUC Functions
• Review and approve proposed protocols
related to the care and use of animals
• Inspect animal facilities and evaluate the
animal care program every six months
• Handle concerns about animal care and use
• Suspend an activity in violation of the Guide,
PHS and/or institutional use policies
• Maintenance of IACUC records
• Develop reports to the Institutional Official
• Cannot be overruled by Institutional Official
IACUC Approval
• Ethical use of animals requires valid
experimental protocol: Good science!
• Requires experimental protocol including
Justification for species used and numbers
Methods to reduce pain and suffering
Appropriate end point
Literature search
• Required for publication of results and for grant
• Changes cannot be made without prior IACUC
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
History of Clinical Trials Ethics
• Comparison of 6 interventions to prevent scurvy
on 12 sailors (Lind, 1747)
• Trial of cowpox as vaccine for smallpox (1767);
used controls
• Bacillus reported cause of Yellow Fever, no
informed consent, condemned (1897)
• Walter Reed, Yellow Fever caused by virus;
informed consent (indicated in pubs.), payment,
only adults, self experimentation (1900)
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
• 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!
The Institutional Review Board
• Includes scientists, physicians, community members
• Must approve all human experimentation prior to
• If human experimentation (including surveys) is to yield
generalizable knowledge (publishable), it is research
• Not required for program assessment that is not
• Exemption and accelerated approval options are up to
the IRB
• IRB approval required for publication and funding
Informed Consent
• Consent documents must be part of IRB
application and require approval
• Must include objective and methods of
• Assent documents for children, impaired
Informed Consent
• Voluntary: problems with prisoners,
students, employees, children, etc.
• No undue inducements
• Must be understandable to subject, may
need multiple versions, all need approval
• Risks and potential benefits must be
presented accurately
• Right to withdraw at any time
• Deception generally not allowed
• 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:
• 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
• NH Steneck, Introduction to the
Responsible Conduct of Research, Office
of Research Integrity. Short, simple cases
• 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:
Ethics Web Resources
• Office of Research Integrity, includes
interactive movie
• Poynter Institute, Indiana University
• Lab management vignettes
• NIH on-line tutorial
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
• BD Sales and S Folkman, Ethics in Research
with Human Participants, Amer. Psychol. Assn.,
Washington, DC, 2000. Focus on social
• 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
• NSF, 45 C.F.R. Part 689:
• US PHS, 42 C.F.R. Part 93 and others:
• Update on the Requirement for Instruction
in the Responsible Conduct of Research
(Notice NOT-OD-10-019):