1. 1 Ethical issues in genomics research Bernard Lo, M.D. March 3, 2009

2. 2 Study of predisposition to prostate cancer  Carry out genome-wide analyses  Use as controls men who were subjects of study on diabetes

3. 3 Additional research questions  Do controls develop disease?  Do those with SNPs have higher risk of developing disease?  What genes predict better prognosis or response to treatment?

4. 4 Ethical concerns 1. Can you share genome-wide data with other researchers? 2. Are de-identified samples and sequences rendered identifiable by whole genome sequencing? 3. Can you use existing data for additional research without consent?

5. 5 Ethical concerns 4. Can you follow participants as prospective cohort using medical records without consent?  Need identifiers  Link to cancer regsitry, Medicare claims databases

6. 6 Review of ethical issues 1. Risk/ benefit balance must be acceptable  Risks must be minimized  Confidentiality is main concern 2. Informed consent  Exception for de-identified data or waiver

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8. 8 Confidentiality

9. 9 Special concerns about genetic confidentiality  Information considered particularly sensitive  About relatives and groups  Highly predictive of future illness “Future diaries”

10. 10 Special concerns about genetic confidentiality  Sensitive research projects  Genetics of antisocial behavior  Human evolution  Beliefs about group ancestry  Some participants may object

11. 11 Breaches of confidentiality  Stolen or lost laptops with identifiable data  Bankruptcy  Although low probability, large impact

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13. 13 Genetic Information Nondiscrimination Act (2008)  Remove barriers to genetic testing  Health insurers may not  Use genetic information to set eligibility or premiums  Require or request genetic testing

14. 14 Genetic Information Nondiscrimination Act (2008)  Employers may not  Use genetic information in employment or promotion decisions  Require or request genetic testing

15. 15 Limitations of GINA  After job offer, employer may request medical records  Impractical to delete genetic information  Not apply to disability, life, long-term care insurance  Adverse selection if individual rating

16. 16 HIPAA and research  Must get authorization to use identifiable health information  For each specific research study No future authorization  May waive authorization  Limited data set  De-identified data exempt

17. 17 What are de-identified data?  18 specific identifiers  Overt identifiers  Geographic data more precise than first 3 digits of zip code  Dates except for year  Biometric identifiers  Any other unique identifying characteristic

18. 18 Impact of HIPAA on research  More difficult to recruit participants  Increased selection bias  Made use of existing specimens more difficult

19. 19 HIPAA fails to protect privacy  Poor oversight of research  Weak security protections  Applies only to covered entities

21. 21 HIPAA fails to protect privacy  Protection does not follow information

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23. 23 Privacy concerns about sharing sequencing data  Identify individual from pooled specimens  Re-identification of de-identified specimens  Use in objectionable studies  Cannot withdraw from research once data are released

25. 25 Re-identification of genome-wide association subjects  Reference samples in forensic databases  DOJ has 6.2 million profiles  STRs at 13 locations  Full genome sequence can be matched  Although low probability, high impact

26. 26 Re-identification of genome-wide association subjects  What additional protections might make risk of re-identification minimal?  Explicit ban  Strengthen protections for databases that contain identifiers

27. 27 Sharing genomic sequence data  Data use agreement  Restrict future uses  Restrict access to whole-genome data  Access only at certain sites  Not download data from site  NIH biostatistician to do analyses

28. 28 Sharing of genomic sequence data  Tradeoffs between research efficiency and privacy

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30. 30 Use of existing samples in research  Value for research  No consent required if anonymized (de- identified)  General consent for unspecified future research or genetic research suffices

31. 31 Ethical rationale for waiver or general consent  Very low risk  No participant would object  May not be appropriate for sensitive genomic studies

32. 32 Problems with general consent if not understand  Whole genome sequencing  Dissemination of data  Not feasible to withdraw from research  Possibility of re-identification

33. 33 Problems with general consent if not understand  Intention to patent discoveries  Income from licensing and royalties  Future studies that might be considered objectionable

34. 34 Recommendations for consent  Explicit consent for  Whole genomic sequencing  Dissemination of sequencing data

35. 35 Recommendations for consent  Explicit consent for  Patents arising from discoveries Specify financial arrangements Sharing with individual donors not feasible May need to negotiate with advocacy groups who recruited donors

36. 36 Recommendations for consent  Explicit consent for  Future studies Consent for all studies approved by IRB or oversight committee Require specific consent for highly sensitive studies Permission to recontact for sensitive studies

37. 37 Recommendations for consent  Tradeoff between research efficiency and respect for donors  Researchers may exclude those who do not accept these conditions

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39. 39 Reforming HIPAA  IOM report “Beyond the HIPAA Privacy Rule: Enhancing Privacy, Improving Health through Research http://www.iom.edu/CMS/3740/43729/61796.aspx

40. 40 Conclusion  Privacy Rule does not protect privacy and impedes important research

41. 41 New Framework  Congress should authorize new approach to ensuring privacy that would apply to all health research  Enhance privacy through improved security, transparency, accountability

42. 42 Recommendations  Revise provisions of Privacy Rule that hinder research but do not provide meaningful protections

43. 43 Recommendations  Encourage use of limited data sets  Make data use agreements more efficient and effective

44. 44 Recommendations  Facilitate use of existing data  Allow future research with IRB oversight  Allow linking data from multiple sources Certify trusted intermediaries, who then give researchers de-identified data sets

45. 45 Recommendations  Clarify if DNA sequences are considered identifiable

46. 46 Recommendations  Stronger security protections  Encryption  IRB to include security expert  Penalties for attempted re-identification  Notify participants of breaches

47. 47 Recommendations  Inform participants and public of research results and their importance

48. 48 Take home points  Resolving ethical issues is crucial for genomics research to proceed  Scientists need to be involved in addressing ethical issues

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