"Biospecimen exceptionalism revisited: uses of genetic and EHR data in the LHS"

1. "Biospecimen exceptionalism revisited: uses of genetic and EHR data in the LHS" David Magnus, PhD Thomas A. Raffin Professor of Medicine and Biomedical Ethics and Professor of Pediatrics Director, Center for Biomedical Ethics Stanford University

2. No COI • Vice-Chair of the NIH Precision Medicine Initiative “All of US Research Program” IRB

5. Two Primary Sources of Data • Electronic Health Records (EHR) • Biospecimen samples • Genomic information derived from them • Can include samples collected for research • Excess samples collected as part of clinical care • Under common rule these were considered to be similar in terms of the regulations that govern them • Secondary uses of de-identified data (regardless of source) where researcher would be unable to re-identify was not considered human subjects research

6. NPRM to Common Rule: Biospecimen Exceptionalism • Secondary Uses of Data • No consent required for secondary uses of data as long as investigator does not contact subject and “will not re-identify subjects or otherwise conduct an analysis that could lead to creating individually identifiable private information” • Biospecimens • But secondary uses of biospecimens would now be considered human subjects research and require informed consent (even if source could not be re-identified) • Broad consent including 12-15 required elements required before storing or using samples for research

8. Final Version of the Common Rule • Abandoned the hard biospecimen exceptionalism of the NPRM • But created option for broad consent • Left open possibility that all future genetic information will be deemed “idenfiable”

9. Biospecimen exceptionalism explored • Need data for how patients and potential research participants view differences between data and biospecimens • Explore whether there are significant differences across groups (especially under-represented groups) • Especially important because the resources at financially stressed, minority serving institutions may lack resources to fully implement more robust requirements

10. The VALUES Study Patient Values and Attitudes about a Library of Knowledge: Uses of EHRs and Samples in Research Aim 1: Assess and compare patient attitudes towards use and governance of clinical data and samples in a racially and ethnically diverse patient population. Aim 2: Identify factors associated with attitudes and preferences towards clinical data and sample use, sharing and governance.

11. Multi-disciplinary, Multi-institutional Collaboration Research Team Stanford University School of Medicine Sandra Soo-Jin Lee, PhD (PI) Mildred Cho, PhD David Magnus PhD Steve Goodman, MD, MHS, PhD Kelly Ormond, MS Nina Varsava, JD Palo Alto Medical Foundation Research Institute Hal Luft, Ph.D. Meghan Halley, PhD, MPH Katie Gillespie, MA, MPH Yasmin Hernandez Lu Wah Hung Seattle Children’s Hospital Benjamin Wilfond, MD Stephanie Alessi Kraft, JD Consultants BoosterShot, Inc. Gary Ashwal Alex Thomas, MD Supported by the National Library of Medicine (1R01LM012180-01)

12. Focus Groups and Analysis • 20 focus groups of Palo Alto Medical Foundation patients • African-American • Chinese (2 English, 2 Mandarin) • Hispanic/Latino (2 English, 2 Spanish) • Non-Hispanic White • South Asian • N = 122 participants (56 male, 66 female) • Codebook developed from a priori codes and initial review of transcripts; code applications iteratively piloted and refined • Each transcript coded by one team member • All coders achieved inter-rater reliability ≥0.8 • Team-based thematic analysis

13. The Library of Medical Information

14. Putting EHRs and Samples in the Library

16. Probed for differences • Asked participants how they would feel about their EHR data being used for the research explained in videos that explained the creation of the “Library of Medical Information” • Then asked how they would feel about their biological samples being used for the same research

17. No difference in risks between biospecimens and EHR data • “I have no problem with the tissue samples or the blood…To me it's the same as the data.” (Hispanic Focus Group Participant) • Expressed in 19 of 20 focus groups: • 3 AA • 4 Chinese • 4 Hispanic • 4 South Asian • 4 Non-Hispanic White

18. Biospecimens are an extension of the “self” and require special care and respect • “I feel more uncomfortable with giving a biological specimen because it feels like an attachment or extension of myself… a blood sample or a tissue sample feels connected to me and that makes me feel more vulnerable. ‘Cause that was a direct piece of me versus a reaction to me. And then I think of the example of Henrietta Lacks, and I’m like, I don’t want to be Henrietta Lacks.” (South Asian Focus Group Participant) • Expressed in 9 of 20 focus groups: • 2 AA • 1 Chinese • 2 Hispanic • 4 South Asian • 0 Non-Hispanic White

19. Biospecimens are sources of unjust profitability • “If they’re going to pick fifty samples and yours happens to be one of them and they discover some world-saving drug and they make a trillion dollars, where’s your share of that? Because you helped do that.” (Non-Hispanic White Focus Group Participant) • Expressed in 8 of 20 focus groups: • 1 AA • 2 Chinese • 1 Hispanic • 0 South Asian • 4 Non-Hispanic White

20. Biospecimens contain DNA, which creates the possibility of identifiability and risks to privacy • “I don't tend to be really concerned about privacy, but when it's your biological samples, I think my kind of privacy alert went up - just as far as DNA analysis and Big Brother. That seems a little scarier for some reason.” (South Asian Focus Group Participant) • Expressed in 20 of 20 focus groups: • 4 AA • 4 Chinese • 4 Hispanic • 4 South Asian • 4 Non-Hispanic White

21. Biospecimens create the potential for human cloning • “Can you make another “me” out of that, right? I don’t want that to happen…A clone, right? I don’t want that to happen.” (African American Focus Group Participant) • Expressed in 8 of 20 focus groups: • 3 AA • 1 Chinese • 2 Hispanic • 2 South Asian • 0 Non-Hispanic White

22. Biospecimen use in research may warrant separate consent from EHR’s • “I would say yes. I'd like to separate [the consent processes]. If I couldn't separate bio from just electronic health record, I don’t think I would [participate].” (Hispanic Focus Group Participant) • Expressed in 12 of 20 focus groups: • 1 AA • 3 Chinese • 3 Hispanic • 3 South Asian • 2 Non-Hispanic White

23. Biospecimen Exceptionalism • More data needed—quantitative studies • Challenge of going from opinion to normative policy development • Most prevalent concerns (privacy, confidentiality) suggest education rather than exceptionalism • Suggestive pattern of other concerns suggest that there might be differences that could matter for recruitment of under-represented groups in research • Metaphors used in describing research uses sometimes emphasize data, sometimes emphasize samples (e.g., database vs biobank vs library) which could unintentionally impact recruitment