Responsible Conduct of Research Involving Humans

1. Responsible Conduct of Research Involving Humans • Stan Korenman, M.D. • Professor of Medicine • Associate Dean, Ethics http://www.ctsi.ucla.edu/education/training/webcastsm261

2. What is Science? • Science is the systematic study of nature. • It involves all of nature and all the tools we useto study nature • Systematic study means the use of the scientific method

3. A Picture of the Corpus of Science An advance Bod y of Science

4. A Paradigm Shift An advance Bod y of Science

5. What Is the Scientific Method ? • Hypothesis directed ….or is it? • Experiments …. or observations • Conclusions tentative • Educated skepticism. “Prove it” • Each report contributes to the body • Each scientist is ethically responsible to preserve and enhance the body of science

6. Science As A Problem 1. Dangers Nuclear Energy Energy consumption Global warming Chemicals-CFCs, PCBs, Bisphenol A, Safety of transgenic plants and animals 2. Research Misconduct 3. Risks and Misuse of Human Research 4. Ever Changing Conclusions

7. Responsibilities Of Science 1. Reason is the instrument of societal development, and scientific investigation may be the ultimate expression of human reason. 2. The public supports science to better understand nature and help humanity. 3. Society’s increasing dependence on scientific inquiry for advances and for policymaking, conveys on science a great responsibility to maintain its integrity. 4. Thus, in carrying out its public trust, science operates in the realm of human duty i.e. in ethics.

8. Definition of Ethics • The science of morals; the department of study concerned with the principles of human duty. • EMERSONNature, Idealism Wks. (Bohn) II. 164 Ethics and religion differ herein; that the one is the system of human duties commencing from man; the other, from God Oxford Dictionary

9. Sources of Duties – What We Ought to Do • Not from: • Pressure groups • Professional organizations • Public opinion • The law • Religion • We derive our oughts from within. What does that mean?

10. Ethics: Study of Moral Behavior 1. CONSEQUENTIALIST ETHICS- Various forms of Utilitarianism; The act is unimportant – look for greatest good in the outcome Making the utilitarian judgment for each act is hard work – essentially impossible To make decisions easier, create rules. Rules comparing goods and greatest goods often lead to injustices as well as irreconcilable differences of opinion. What is a life really worth?

11. 2. DEONTOLOGICAL ETHICS We know instinctively what’s right- hard-wired Absolute rules like ten commandments, but values are cultural and change over time, so must rules (behaviors towards women, minorities, and sexual preference) Conflicting rules, legal and moral “Golden Rule” operates for every act TO MAKE THIS WORK OUT LOTS OF RIGHTS ARE DEFINED Life, liberty, property Autonomy, beneficence, justice, privacy Obligations to others. (fiduciary roles) You can’t put a value on a life.

12. 3. Virtue ethics Central concern is the life we live, to be a good person Choices influenced by what will develop us as good persons rather than be a slave to hard rules. Behavioral principles can have legitimate exceptions • Very susceptible to rationalization

13. Ethical Dilemma • Mary and Jody are conjoined twins. They, together have one heart and one pair of lungs. Surgery will permit Jody to survive and be reasonably normal while Mary must die. Without surgery, both will die in a month or so • CONSEQUENTIALISTS Operate • DEONTOLOGISTS - Let them both die because you must not violate the principle “Thou shall not kill” • Virtue – There can be exceptions to the biblical rule

14. Is It Wrong to Use Unneeded Frozen Embryos As Research Tools • Deontological argument: This is living human tissue with the potential to be a person- don’t mess with it. • Utilitarian argument: These blastocysts have zero chance of becoming a person and using them may result in a lot of good for a large number - use them. • These people are talking past each other.

15. Decisions Under Uncertainty • Expected Utility Theory • Rational decisions under uncertainty are made by estimating the value of the choices and picking the option with the greatest value. Prospect Theory

16. Prospect Theory Decisions are powerfully controlled by: • The initial condition. • Diminished sensitivity to changes. • Loss-aversion • When all the choices are bad, then risk taking David Hume

17. Framing the “Decision Architecture” Robert Cialdini: Influence; 6 Principles • Reciprocation Gifts • Consistency It’s Standard • Social Proof Kobe does it • Liking Really nice team • Authority MD won’t harm me • Scarcity Only a few places left

18. The End of Philosophy Plato • In an op-ed piece in the NY Times David Brooks pronounced the end of Philosophy because if our decisions are based on method of presentation and outside influences, then they can’t be called rational decisions at all. Do you agree with this? Is there a remedy?

19. Definition of Research Integrity • "Research integrity may be defined as active adherence to the ethical principles and professional standards essential for the responsible practice of research."

20. Active Adherence By active adherence we mean adoption of the principles and practices as a personal credo, not simply accepting them as impositions.

21. Principles • Honesty, • The golden rule, • Trustworthiness, • High regard for the scientific record. “While we encourage vigorous defense of one’s ideas and work, ultimately research integrity means examining the data with objectivity and being guided by the results rather than by preconceived notions.” NAS Res Integrity

22. Practices Honesty, fairness and proficiency in 1. proposing, performing, and reporting research 2. representing contributions to research proposals and reports 3. peer review Collegiality in scientific interactions, communications and sharing of resources Avoidance and disclosure of conflicts of interest Protection of human subjects Humane care of animals Adherence to the mutual responsibilities of mentors and trainees

24. Social responsibility Performance Reporting Mentoring Communication Conflicts of interest Responsible Conduct of Research

25. Pope John Paul II, The preeminence of the profit motive in conducting scientific research ultimately means that science is deprived of its epistemological character, according to which its primary goal is discovery of the truth. The risk is that when research takes a utilitarian turn, its speculative dimension, which is the inner dynamic of man’s intellectual journey, will be diminished or stifled. 3/25/02

26. Social Responsibility • Do science and scientists have ethical responsibilities to society beyond discovering truths and problem-solving? • Do they have a responsibility to report results, however negative the predictable consequences. • Do they have an ethical responsibility to defend science (intelligent design)

27. Social Responsibility • “We make it possible and others use it for good or evil.” • Scientists must be involved in the consequences of their work. • Nuclear fission, Internet, Cloning, Medicine, Ecology, Sociology • Can’t predict the consequences of discoveries and inventions (invention of the computer)

28. Responsible Performance A. Experimental design is most critical 1. Openness 2. Adequate controls 3. Objective end points 4. Proper analytic tools used properly We now have (brute force biology), a different design B. Complete and accessible records Privacy and security (think huge databases) C. Play by the rules Human and animal subjects, OSHA, Radiation Safety, HIPAA, etc.

29. Ownership of Data Data include any information obtained during the process of research, no matter in what form it is produced, or in what form it is stored. Medical information - belongs to the research participant and must be protected for privacy Research – University owns it and shares with PI Drug studies- by the sponsor and the institution Trainees own no data, not even what they worked on

30. NIH Rules on Sharing • NIH reaffirms its support for data sharing, believing that it is essential for expedited exploitation of research results. • Timely release and sharing of the final research data from NIH-supported studies for use by other researchers. • Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are required to include a plan for data-sharing or state why data sharing is not possible. • “The timely release of information” must be no later than the acceptance for publication of the main findings from the final data set.

31. Responsible Reporting A. Full attribution and citation of sources B. Relevant data included or absence explained C. Technical information for replication included or available online. D. Authors all contributing and responsible (in their own domain). E. Data reported only once as original work

32. GOOD STUFF Initial idea Research plan Regular review Doing the work Analyzing results Writing it up LESS IMPORTANT Provides funding Provides probes, cells, transgenics, clones Occasional advice Does an assay Paper once-over Authors All Contributing And Responsible First authorship requires both major work and major writing

33. Rules for Publishing Clinical Trials in Major Journals • Registration at inception • Disclosure of all author conflicts of interest to institution, participants, editors • Roles of sponsor and investigators in the experimental design, collection, analysis, and interpretation of data, and of writing of the report Grassley • Determination that the authors had full access to the data

34. Review of: Grants Publications Appointments Promotions IRB submissions ESCRO proposals RAC submissions Data monitoring They require: Objective review Expert assessment Openness to innovation Withdrawal if possible conflict of interest Absolute confidentiality Your Other Job, Peer Review

35. Responsible Communication • The most difficult situations between scientists are due to failure to communicate, sometimes accidental, sometimes deliberate. The rupture of trust usually cannot be repaired, to everyone’s disadvantage. • Terms of collaboration • Sharing of resources • Patent and licensure • Authorship • Interpretation and reporting of results Collaboration is almost universal in human research.

36. Mentoring • The job of the mentor is to facilitate the success of the trainee. If you don’t believe that, then don’t take on trainees. • (Trainees, try to find a mentor who cares about your success.) • Explicit moral climate. We do science right! • The research team needs ethical guidance from its leaders • Enthusiasm for innovation and failures. What can we learn? rather than, you made a mistake! Openness. You can talk about your work. • Explicit guidelines for records, data management, authorship

37. Academic Mentoring • Three years ago UCLA developed a mentoring program that has been very successful in moving the youngest faculty up the ladder. • They help with going through the promotion process, negotiations, and general career advice. • Advisors are from different departments than the faculty and can be objective. • www.faculty.diversity.ucla.edu

38. Social responsibility Performance Reporting Mentoring Communication Conflicts of interest Proposing research to degrade others Fabrication, falsification Plagiarism Exploiting, abusing trainees Secrecy Failure to disclose Irresponsible Conduct of Research

39. Unethical Research? When Southam began injecting people with HeLa cells in 1954 there was no formal research oversight in the US. Since the turn of the century, politicians had been introducing state and federal laws with hopes of regulating human experimentation, but physicians and researchers always protested. The bills were repeatedly voted down for fear of interfering with the progress of science, even though other countries –had enacted regulations as early as 1891. What would have happened with Henrietta’s cells if informed consent were required?