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

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

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

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

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

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

7. Protection of Research Subjects Right and welfare of the research subjects ought not be disregarded in favor of science 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 Researchers maintains a relationship of trust with the subjects Compromised Compromised Deception Deception Confidentiality not maintained Confidentiality not maintained

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

10. Sponsor Responsibilities Monitor the conduct of the research

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

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

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

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

15. Issues need Address Respect Respect Beneficence Beneficence Justice 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. Conflicts of Interest vs

18. 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. Baltimore Sun December 8, 2006 By Matthew Dolan

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 interest present a legitimate concern? Financial interests steer the Research activity to the point where it is compromised 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 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 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

24. Financial Disclosure Not meant to censor investigators from participation Not meant to censor investigators from participation May reduce likelihood of investigators biasing results of their clinical studies 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. Disclosure statements also apply to investigator/study staff spouse and dependent children.

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

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

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

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

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

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

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

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