Responsible Conduct in Research

1. SSCI E-100a: Proseminar in Research Methods and Scholarly Writing Responsible Conduct in Research David Penetar, PhD Assistant Professor, Harvard Medical School

2. Major Ethical Issues in Research Personal Behavior: - Plagiarism - Falsification - Fraud/Fabrication - Conflicts of Interest Collaborative Behavior: - Authorship - Conduct of Experiment

3. Percentage of scientists who say that they engage in the behavior listed within the previous three years Falsifying or ‘cooking’ research data Ignoring major aspects of human-subject requirement Not properly disclosing involvement in firms whose products are based on one’s own research Relationships with students, research subjects or clients that may be interpreted as questionable Using another’s ideas without obtaining permission or giving due credit Unauthorized use of confidential information in connection with one’s own research Failing to present data that contradict one’s own previous research Circumventing certain minor aspects of human-subject requirements Overlooking others’ use of flawed data or questionable interpretation of data Changing the design, methodology or results of a study in response to pressure from a funding source 0.3 % 0.3 % 0.3 % 1.4 % 1.4 % 1.7 % 6.0 % 7.6 % 12.5 % 15.5 % (n = 3,247)

4. Major Ethical Issues in Research What are our obligations when conducting research?

5. Major Ethical Issues in Research: Plagiarism Plagiarism: - Passing off a source’s information, ideas, or words as your own by omitting to acknowledge that source - An act of Writing with Sources: A Guide for Students, G. Harvey

6. Major Ethical Issues in Research: Plagiarism • Copying text without proper recognition • Not giving credit for genesis of study

7. Major Ethical Issues in Research: Fraud Fraud - serious misconduct with intent to deceive - Must be able to replicate the results - Have confidence in the data/conclusions - Detection is most likely when replication cannot be confirmed Causes:

8. Major Ethical Issues in Research: Fraud ? Sir Cyril Burt’s study of IQ of twins who were reared apart. Suggested that genetic factors are extremely important in developing intelligence Other scientists noticed some irregularities in the data and could not locate his two research assistants

9. Major Ethical Issues in Research: Fraud Fraud--January 11, 2006 Korean scientist Hwang Woo-Suk resigned after two seminal papers on stem cell research that were published in Science were found to be based on fabricated data. He claims that he was deceived by younger colleagues at another institute.

10. Major Ethical Issues in Research: Fraud How to deal with it:

11. Major Ethical Issues in Research: Fraud? • Identifying “aberrant” data • - What defines an “outlying” data point? • - When can a data point be removed--if ever? • - How should this be described?

12. Major Ethical Issues in Research: Collaborations • Authorship • Often is decided before study is conducted, but can change dramatically during study conduct • Must be decided before paper is written • First author is main contributor to this particular study (rationale, conduct, analysis and writing) • Last author is usually lab chief

13. Major Ethical Issues in Research Conduct of Research - Sound Science - Risk/Benefit Ratio - Privacy and Confidentiality - Protection of Special Populations - Stress and Psychological Harm - Deception (& Alternatives to Deception)

14. Foundations of Protections of Human Volunteers Hippocrates (~400 B.C.) physicians should “abstain from whatever is deleterious and mischievous.” Thomas Percival (1803) “…new methods of …treatment should be devised but … should be … governed by sound reason, .. or well-authenticated facts … previous consultation of the physicians … to the nature of the case.” William Beaumont (1833): Experimentation is needed; information cannot be otherwise obtained. Investigator must be conscientious and responsible; methodological approach; no random studies. Voluntary consent is necessary. Discontinuation of experiment when it causes distress to the subject or the subject objects or becomes dissatisfied.

15. Foundations of Protections of Human Volunteers • Claude Bernard (1865): “Those [experiments] that can only harm are forbidden. Those that are innocent are permissible, and those that may do good are obligatory.” • The Prussian Directive (1900): • Prompted by Neisser’s studies with immunizations against syphilis • - Prohibited experiments in minors and those not fully competent. Unequivocal consent required after explanation of the experiment and possible adverse consequences. Only certain people were allowed to do the research and they must keep written records.

16. Foundations of Protections of Human Volunteers

17. The Nuremberg Trials: 1946-1947 23 defendants; 3 non-physicians - 16 found guilty 7 were hanged (4 physicians) 5 sentenced to life in prison 4 sentenced to 10-20 yrs - 7 were acquitted and freed Separate Trial - 31 “underlings” were also found guilty; 22 of them were hanged

18. Foundations of Protections of Human Volunteers The Nuremberg Code (1947) • True informed consent prior to experimental procedures; allowed to discontinue at any time • Research based on prior work with animals • Truly necessary with benefits justifying risks and no unnecessary physical or mental suffering or injury • The person performing the task is qualified • No experiment shall be undertaken where death or injury will likely occur • Proper preparation and adequate facilities to protect subjects • Terminate study upon observing the likely risk of injury, disability or death

19. Additional Reading Lopez-Munoz F, et al. (2007) Psychiatry and political-institutional abuse from the historical perspective: The ethical lessons of the Nuremberg Trial on their 60th anniversary. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 31: 791-806

20. Beneficence Justice Respect for Persons Foundations of Protections of Human Volunteers Kefauver-Harris Amendments & Declaration of Helsinki The Belmont Report (1974/9)

21. Foundations of Protections of Human Volunteers CFR Title 45 Part 46: Protection of Human Subjects Referred to as the “Common Rule” - IRB Review of Research - Requirements for Informed Consent - Institutional Assurances of Compliance

22. Foundations of Protections of Human Volunteers Additional Protections: - Office for the Protection from Research Risks - National Bioethics Advisory Commission - President’s Council on Bioethics

23. Major Ethical Issues in Research Institutional Review Board (IRB) • Local panel review • Composition: • Evaluate study and proposed conduct • Compares protocol with informed consent • Insures compliance with all governmental mandates

24. Major Ethical Issues in Research Criteria for IRB Approval • Risks to subjects are minimized • Risks are reasonable in relation • Selection of subjects is equitable • Informed consent is sought from each individual • Informed consent is appropriately documented • When appropriate: • Data collection is monitored to ensure subject safety • Privacy and confidentiality of subjects is protected • Additional safeguards are included for vulnerable populations

25. Major Ethical Issues in Research Other IRB Determinations • Investigator Conflict of Interest • Serious or Continuing Noncompliance • Unanticipated Problems • Multi-site/Collaborative Research

26. Major Ethical Issues in Research Informed Consent - Providing a participant with all of the details associated with the rationale, methods, expected results and outcome of an experiment - Allows the subject to decide for him/herself whether they wish to participate

27. Major Ethical Issues in Research Informed Consent Must fully inform “...acute doses of cocaine have been associated with fatal or near fatal effects on the heart...” “...the procedure may result in infection...” “...is not designed to be of benefit to you...”

28. Major Ethical Issues in Research • Risk/Benefit Ratio • The relative weight given to the actual risk experienced by the participant versus the actual, perceived or potential benefit to the subject or to society as a whole • Actual benefits to the participants are rare; more commonly, the benefits are for the population as a whole

29. Major Ethical Issues in Research • Privacy and Confidentiality • - Experimenters must assure privacy and confidentiality of their participants • - Important when studies on sexual behavior, divorce, family violence, drug abuse, etc. are involved • HIPAA compliance • Exceptions: • When a participant reveals “danger to self or others”, especially child abuse to a clinician • Reporting of communicable diseases

30. Major Ethical Issues in Research Special Populations - Ensure voluntary participation because not all populations are equal - Children, psychiatric patients, elderly and prisoners all need special attention - Guardians and minor’s assent deal with these limitations

31. Major Ethical Issues in Research Stress and Psychological Harm - Physical harm— possible when administer drugs (experimental) surgical procedures medical devices - Psychological harm--more frequently definition of harm--actual or perceived

32. Major Ethical Issues in Research Deception - Rationale: participant’s complete knowledge of the study will alter their responses leading to bias and invalid results - Action: lead a participant to believe something about the study that is untrue - Expectations: do participants expect to be deceived?

33. Major Ethical Issues in Research: Deception - Advertised as a test of learning and memory - Told it was a study on effects of punishment on learning Procedure: Participant and “learner” who was confederate Required to learn word pairs When error was made, participant instructed to deliver increasing levels of electrical shocks Milgram’s Obedience Experiment

34. Major Ethical Issues in Research: Deception Milgram’s Obedience Experiment - Shock lever labeled from 15 to 450 (XXX) volts - Used a mock shock machine - “Learner” pretended to receive shocks and pleaded to be able to end study - Experimenter “coerced” learner into remaining in study

35. Major Ethical Issues in Research: Deception • Milgram’s Obedience Experiment • Results: • - 65% of participants continued to deliver shocks all the way up to the highest level! • The study, while controversial, revealed many insights to beliefs about human’s ability to resist authority

36. Would People Still Obey Today? Conducted a ‘partial replication’ of original experiment Results: Burger JM (2009) Replicating Milgram, American Psychologist, 64, 1-11.

37. Major Ethical Issues in Research: Deception • Ways to Handle Deception: Debriefing • - The traditional solution to the problem of using deception • Even used when there is no stress • - Explain the tests and results, rationale and subject’s responses; alleviate tension and stress

38. Foundations of Protections of Human Volunteers Research Ethics Milestones Decade Trigger Events 1930 The Syphilis Study (begins) 1940 The Nazi Experiments Human Radiation Experiments (begins) 1950 Nuremberg Code Willowbrook Hepatitis Study 1960 Thalidomide Tragedy Kefauver-Harris Amendments Milgram’s Study Declaration of Helsinki 1970 The Syphilis Study (Exposed) 1980 The ‘Common Rule’ 1990 OPRR/National Bioethics Advisory Commission Gene Transfer Subject Death 2000 President’s Council on Bioethics