Research Ethics & New Investigators

1. Research Ethics & New Investigators Melody Lin, Ph.D. Dec. 12, 2012

2. Objectives • Research Ethics & HSP • Pharmaceutical Incentives • Conflict of Interest • Tissue Issues

3. Research Ethics • Definition • A set of guidelines to assist the researcher conduct ethical research

4. Research Ethics • Ethical concerns • Relationship Between Society and Science • Professional Issues • Protection of Research Subjects

5. Relationship Between Society and Science • Society • Government funding research • Congressional influence on which studies are funded • Corporate funding research • Culture • Scientist’s own culturally based interests

6. Professional Issues • Scientific Misconduct • Fabricating, Falsifying or Plagiarizing (FFP) • proposing • performing • reviewing • reporting

7. Protection of Research Subjects • Right and welfare of the research subjects ought not be disregarded in favor of science

8. Trust • Researchers maintains a relationship of trust with the subjects • Compromised • Deception • Confidentiality not maintained

9. Monitoring Research • Sponsor • Regulatory agencies • IRB • DSMB • Public interest groups

10. Sponsor Responsibilities Monitor the conduct of the research

11. Monitors • Check the work of the EC or IRB • Make sure the protocol is followed • Verify data • Check safety issues

12. Regulatory Agencies • Government agencies have oversight responsibilities • FDA monitors clinical trials

13. Pharmaceutical Incentive $$$ • Recruit & retain subjects vs ss. Vulnerability • May stretch inclusive/exclusive criteria • Influence professional judgment • Finder’s fee

14. Physician Investigators • Prospects of Peer • Recognition • Publication • Financial gain • Economic incentives may create pressures • Compromise • Appearance of compromise • Integrity • Research • Researcher

15. Issues need Address • Respect • Beneficence • Justice

16. Conflict of Interest Situation in which the integrity of academic activity, especially research, may be, or may be perceived to be, compromised by financial or other interests.

17. Perceived Actual vs Conflicts of Interest

18. Baltimore Sun December 8, 2006 By Matthew Dolan Government Scientist Pleads Guilty Senior Alzheimer’s Researcher Admits Taking $285,000 In Fees, Expenses A senior government scientist working in Alzheimer’s disease research pleaded guilty today to accepting $285,000 in consulting fees and travel expenses from the world’s largest drug manufacturer without proper approval from his bosses. As part of his agreement with federal prosecutors, Pearson “Trey” Sunderland III, chief of the geriatric psychiatry branch of the National Institute of Mental Health, which is part of the National Institutes of Health, will be sentenced to two years of supervised probation and must forfeit $300,000.

19. Sources of Potential Conflict • Consultant • Speaker • Stock or Other Equity • Management Position • Income from Royalties or Licensing Fees • Board or Scientific Advisory Board Member • Gift • Relationship with Competitor • Loans (To or From) • Family Member has Relationship

20. Does conflict of interestpresent a legitimate concern? • Financial interests steer the Research activity to the point where it is compromised • Financial interest gives the appearance that the research activity may be compromised • Maintaining full research integrity would compromise the business plan and/or require excess resources

21. What’s the worst that could happen?

22. Jesse Gelsinger

23. Spectrum of Conflicts minor major $$$ or Equity Influence Complexity Sensitivity

24. Financial Disclosure • Not meant to censor investigators from participation • May reduce likelihood of investigators biasing results of their clinical studies

25. Financial Disclosure Questions of concern: • Does compensation to the investigator/study staff affect the value of the study outcome? • Is there proprietary interest by investigators/study staff in tested product? • Is there significant equity interest in sponsor of the study?

26. Financial Disclosure • Is there significant payments by sponsor of other sorts • Grant to fund ongoing research • Compensation in the form of equipment • Retainers for ongoing consultation or honoraria • Disclosure statements also apply to investigator/study staff spouse and dependent children.

27. Tissue Issues • Collection of new samples vs. use of existing samples • Plans for linking samples to medical records, identifiable information • Use/disclosure of research results • Informed consent • Adequate disclosure • Prospective • Existing, stored samples

28. Classification of samples • Not identified • No “human subject” if truly not identified • How much clinical and demographic data can be retained • Identified • Directly (name/ID) • Coded/linkable

29. Risks of using identified data Disclosure • To third parties • Potential for breach of privacy and confidentiality • To patients/subjects • Privacy intrusion from undesired contact • Harm from disclosure of results

30. Research design to reduce these risks • Maximize confidentiality • The “least necessary” or “least identifiable” dataset • Use of intermediary to hold link between code and identifiers • Obtain maximal legal and practical protections • e.g., data placed on computers not linked to the Internet • Develop approach for re-contacting subjects • Clinical relevance or value • Adequate counseling

31. Informed consent for research on human biological materials • If/when? • For prospective collection • Maybe for existing samples, depending on: • Identifiability • Adequacy of prior consent • Setting in which collected (research vs. clinical) • How? • Extent of detail • Frequency

32. Research • Conducted with unidentified samples is not human subjects research and is not regulated by the Common Rule.” • “Using coded or identified samples requires the consent, unless the criteria for a consent waiver have been satisfied.” NBAC (1999)

33. Waiver of informed consentfor use of existing samples (see 45 CFR 46.116) • Protocol must pose minimal risk • Determination of whether it might be desirable to communicate directly with patients • If yes, then > minimal risk, and consent should be obtained • Cannot adversely affect rights and welfare • Impracticability of obtaining consent • From some or all participants

34. New Physician Investigators • Ethical principles • Right, safety & welfare as paramount • Do no harm