Fostering Responsible Conduct of Research MedicReSConference May 5, 2017 Istanbul, Turkey Adil E. Shamoo, Ph.D., CIP University of Maryland School of Medicine

1. Fostering Responsible Conduct of Research
Presentation to:
MedicReS Conference
May 5, 2017
Istanbul, Turkey
By
Adil E. Shamoo, Ph.D., CIP
University of Maryland School of Medicine
108 N. Greene Street
Baltimore, MD 21201
Tel# 410-706-3327
Cell# 301-538-2599
E-mail: ashamoo@som.umaryland.edu
5/3/2017

2. US Research enterprise
> $450 Billion
Does size matter?
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3. Ethics and Law
Law
Law

4. Nobility
Vs
Pathology
Copyright, Shamoo Consulting 2005

5. 5/3/2017
• 1800s, Charles Babbage warned, lack of
ethics, honesty, and integrity in British
science.
• Nuremberg trials, 1946
• Oppenheimer and atomic weapons research
• 1961, Silent Spring by Rachel Carson,
Pesticide and Env.
• 1966, Henry Beecher
• Tuskegee Syphilis study (1932-1972)
• 1982, Broad and Wade, Betrayers of the
Truth
Brief History of Research Ethics # 1
Adil E. Shamoo, Ph.D.

6. Private Good
Vs
Public Good
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7. Survey of US College Students
(2,100)
 75 % admit to some cheating.
 41 % have Plagiarized through
the Internet.
 The Center for Academic Integrity, 2002.
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8. Nationwide Survey of Doctoral Students in Norway
(BMC Med Ethics, 2013: 14:3,)
189 respondents from 262 (72.1%)
 65% heard of researchers’ misconduct
 11% experience pressure for order of
authorship order
 10% thinks using dry lab is OK
 38% OK to change statistical method to
find significant results
 13% Ok to selectively omit data to
expedite publication
 10% Acceptable to falsify or fabricate
data to expedite publication
 79% Willing to report misconduct
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9. Misconduct Definition
“‘fabrication, falsification, or
plagiarism [FFP], in proposing,
performing, or reviewing research, or in
reporting research results”……Misconduct
does not include honest errors or
disagreement about methods, interpretations
of data, or scientific issues”
(Office of Science and Technology Policy 2000)
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10. Fabrication
Fabrication is making up data or results and
recording or reporting them.
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11. Falsification
Falsification is manipulating research
materials, equipment, or processes, or
changing or omitting data or results such that
the research is not accurately represented in
the research record.
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12. Plagiarism
Plagiarism is the appropriation of
another person’s ideas, processes, results, or
words without giving appropriate credit.
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13. Misconduct in Research
(From: RCR 3rd edition, 2015, p.38-39)
 Spectrum of behavior
 From: FFP to Questionable Research
Practices (QRP) such as:
o Enhancing digital images
o Excluding piece of data
o Poor record keeping
o Poor citation
o Not giving credit to others
o Self-plagiarism
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14. A Professor’s campaign against plagiarism
( Brien, K. M., 2014. The Baltimore Sun, May 4, p. 25.
Washington College in Chestertown, Md.)
 23 student papers.
 Discovered 2 blatant plagiarism.
 Ultimatum to student to come
forward or else.
 12 students came forward.
 5 were blatant plagiarism + 2
technically plagiarism.
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15. Scientific Misconduct Survey of Research
Coordinators
(Pryor, Habermann, and Broome, J. Med. Ethics, 2007, 33:365-369)
 Survey: 1645 of 5302 (31%) survey
 First Hand Knowledge: 18 %
 If CRC observe PI Misconduct:
 10 % would not report
 37 % Confront the PI but not report
 27 % ask PI to report and then if not, they report
 26 % would report it to authorities
 Perceived Prevalence of Misconduct:
 Plagiarism 67 % Never
 Falsifying data 71 % Never
 Intentional protocol Violations 65 % Never
(Related to human subjects)
 Findings: Overall, the perceived misconduct was low??????
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16. 5/3/2017
Case of Eric T. Poehlman, Ph.D. (49 years old)
# 1 ( Period affected,1987-2001)
 1987-1993, University of Vermont in
Burlington
 1993-1996, University of Maryland
School of Medicine
 1996-2001, University of Vermont in
Burlington
 2001, Canada Endowed Research Chair,
University of Montreal (worth = $
825,000)
 Resigned Jan, 2005.

17. 5/3/2017
Case of Eric T. Poehlman, Ph.D. # 2
( Areas of Research at UVM )
 Longitudinal Menopause Study
 The Longitudinal Study of Aging
 The Prospective Hormonal
Replacement Therapy

18. 5/3/2017
Case of Eric T. Poehlman, Ph.D. # 3
( Research Misconduct at UVM )
(Whistlblower, Research Assistant Walter F. DeNiro)
 Grants submissions and preliminary
studies
 $ 2.9 million in federal funding (out of $
11.6 million submissions)
 Falsification and fabrication
 Ten published papers (1992-2002)
retracted

19. 5/3/2017
Case of Eric T. Poehlman, Ph.D. # 4
( Types of Research Misconduct at UVM )
 The Longitudinal Menopause Study
Falsified and fabricated 33 women
subjects out of 35
 The Longitudinal Study of Aging
Increased number of subjects
Changed the data to create a trend
 The Prospective Hormone Replacement
Therapy. Fabricated data in preliminary
studies on 20 women

20. Fiddes Case Background
 Dr. Fiddes president of a clinical
research company in Whittier
California
 Conducted over 200 studies for as many as 47
drug companies beginning in the early 1990’s
 Engaged in extensive fabrication and
falsification of data
 Aug. 1997 plead guilty to felony charge of
conspiracy to make false statements to the FDA
in connection with the Drug approval process

21. Fiddes Case Background
 Examples of misconduct
 Made up fictitious study subjects
 Fabricated lab results by substituting
clinical specimens and manipulating lab
instrumentation
 Prescribed prohibited medications to
manipulate data

22. Fiddes Case Background
 Sept. 1998 sentenced to 15 months in
federal prison
 Ordered to pay $800,000 in restitution
 June 1999 Disqualified as a clinical
investigator by Commissioner of FDA

24.  Under-reporting of adverse
events in many clinical trials that
have a direct impact on the
integrity of data. (Past and On-going)
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History of Research Ethics

25. 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
0
20
40
60
80
100
120
140
160
180
#ofInst.IncidentReports
Year
# of Institutional Incident Reports
Shamoo, A. E.(2001), Accountability in Research 8:197-218
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26. Meta analysis of 21
Surveys on Misconduct
 1.97 % of Scientists admitted to have
fabricated, falsified or modified data or results
at least once.
 33.7 % admitted other questionable
practices.
 14.2 % for falsification for other colleagues.
 72 % of questionable practice for other
colleagues.
(Faneli, 2009, PLoS ONE, 4:e5738)
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27. Example of Potential Outcome of
Misconduct in Scientific Research
 In clinical trial (Phase III)
 1000 Subjects (Volunteers) as exp. Arm
 1000 subjects as Control arm.
 Adverse-events were not reported by:
 1 death, 2 hospitalizations
 Later Drug Used in 10 million people
 Adverse events would be
 10,000 +/- ? deaths,
 20,000 +/-? hospitalizations
The making of a scandal
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28. 5/3/2017

29. Is it
Irreproducibility
Or
Misconduct ?

30. • Irreproducibility may be due to
misconduct (Shamoo and Resnik, 2013, 2016, Kornfeldt
and Titus, 2016)
• 2/3 of retractions are due to
misconduct
 (Fang et al, 2012, Retraction Watch, 2016)
• 2% of researchers admits to
misconduct (Fanelli, 2009)
Is it Irreproducibility
Or
Misconduct # ?

31. • Comparing 121 rodent carcinogenicity
studies – reproducibility was 57 % (Gotman et al,
2001)
• Analysis of 67 in-house validation studies
found only 20-25% reproducible (Prinz et al,
2012)
• A Group of 270 researchers attempted to
reproduce 100 experiments published in 3
top psychology journals – 36% replicated
(Open Science Collaboration, 2015)
Examples of
Irreproducibility

32. Gender of Researchers affect
Mice and Rat responses (Sorge et al,
2014, Nature Methods)
• Using rodent pain as indicator
• Adult male researchers reduced rodent
pain by 36% (analgesic)
• Both gender rodents had the same effect.
• The agent of pain analgesic is male
Olfactory
• Replicated by using bedding, clothing,
swipe of odor,…)

33. Predatory Journals
Exacerbate irreproducibility:
(Clark and Smith, 2015)
• Open access journals with high
fees
• Rapid publication
• Negligible peer review

34. General Factors leading to
misconduct in Science
• Bad apple vs. systemic
• Individual virtues vs. Institutional ethics
• Social control (Rewards and Sanctions)
(Emile Durkheim, Robert K. Merton, and Harriet Zuckermann)
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35. Special Factors contributing
to Misconduct in Science
• Reputation
• Fame (Nobel Prize Syndrome)
• Conflict of Interest (i.e. Financial)
• Promotion
• Pressure to produce
• Poor Training
• Complex research environment
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36. Lessons So Far From Misconduct
Data
 Misconduct May be a Low Probability
Event with a Potential for High Impact.
 Researchers at Any Type of Institution
and Academic Rank May Be Accused
and Found Guilty of Misconduct.
 Clinical research represents 25-30 % of
misconduct investigations and findings

37. Current Methods To Prevent/Contain
Misconduct
(From: Shamoo, 2013, Accountability in Research:20:369-379, 2015)
1. Voluntary Compliance with Ethical
Norms.
2. Regulations and Standards.
3. Education and Training.
4. Whistleblowers.
5. Data Audit (Data Validation).
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38. Education and Training
 Formal training in RCR ineffective in reducing
unethical behavior(Anderson et. al., 2007). And it does not
improve skills in research ethics (Kalichman group, 1992,1996,
1998).
 Reviewing ORI Misconduct files found ¾ of mentors
did not review source data and 2/3 did not set
standards for their trainees (Wright et. Al., 2008).
 Only 8.2% of faculty/staff in 144 top NIH/NSF
funded research with human subjects receive
training in RCR (Resnik and Dinse, 2012)
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39. Suggested Means for Data Validation
(Data Audit)
 Article in Nature on “Data Audit”
(Shamoo and Annau, 1987)
 Article in AAAS Observer “We Need
Data Audit” (Shamoo, 1988).
 Other Efforts 1987 - Present
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40. 5/3/2017
In Summary:
1. Research Integrity
a. Honesty
b. Objectivity
c. Openness
d. Carefulness
2. Respect for Person
a. Protection of human subjects
b. Fairness
c. Respect for subordinates and
Collaborators
d. Loyalty
e. Respect for IP
3. Social Responsibility
a. Public responsibility
b. Lawfulness
c. Efficiency

41. The
END
Questions?
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