Brief Chronology of the Havasupai Case & Settlement -- with Reminders & Possible Implications for HRPPs, IRBs, R

1. Brief Chronology of theHavasupai Case & Settlement -- withReminders & Possible Implicationsfor HRPPs, IRBs, Researchers, andthe Common Rule Secretary’s Advisory Committee on Human Research Protections (SACHRP) Wednesday, July 21, 2010 William L. Freeman

2. William L. Freeman, MD, MPH, CIP Program Director, Northwest Indian College Center for Health; and Human Protections Administrator Northwest Indian College 360-392-4284 wfreeman@nwic.edu WilliamLFreeman@att.net with material for this presentation adapted from: • Ron J. Whitener (Squaxin Island Tribe), School of Law, University of Washington • Wylie Burke, Chair, Dept. Bioethics & Humanities, University of Washington

3. Hy’shqe siam - Thank you, respected teachers • Community & non-community IHS IRB members • Sam Deloria, Lisa Preston, Dr. Francine (Romero) Gachupin, and others • Community & non-community NWIC IRB members • Juanita Jefferson, Dave Oreiro, and others • IRB staffs • Helen McGough, Moira Keane, and others • Participants • Kathleen Alexis, and others • Researchers • Wife - Carolyn Robbins

4. Chronology 1: Prelude • 7/89 Havasupai Tribe asked John Martin for help: diabetes (DM) • Arizona State University (ASU) anthropologist; long relationship, since 1963 • 9/89 Therese Markow applied for grant about schizophrenia in Havasupai • ASU genetic researcher (her focus had been genetics of drosophila) • 1/90 John Martin sent outline of DM study to Havasupai Tribe • recent research had showed an association of 1 gene with DM in Pima Indians • Therese Markow was Principal Investigator for DM-genetics study • 5/1/90 Therese Markow’s grant about schizophrenia funded • 5/8/90 Therese Markow & John Martin prepared grant proposal for DM-genetic study • “Biology, Behavior and Diabetes at Havasupai” • no other condition or research focus mentioned • 5/90 Tribal Chair wrote John Martin to support “diabetes project” • *6/90*for Therese Markow’s schizophrenia study: Kevin Zuerlein (med student) drew ~133 bloods (122 typed for HLA) with consent, and read Havasupai Clinic’s medical charts after hours, apparently without the Clinic’s or patients’ knowledge or permission

5. Chronology 2: the 2 studies & uses • 8/90 ASU News Bureau announced Havasupai Tribe + ASU joint education & research program on diabetes • *1/91* ASU IRB approved Therese Markow’s 1st study in Havasupai: “Schizophrenia: a genetic model” • (I have not found any record of Havasupai Tribal approval) • 3/91 ASU IRB approved Therese Markow’s DM-genetics study • closed 3/94; some interval after closure, ASU IRB routinely destroyed the file • ‘91-4 DM-genetics:Dan Benyshek, research staff, drew >200 bloods • used only oral script; it mentioned & discussed onlydiabetes • actual oral script is lost; Benyshek reconstructed script later • 11/92 ASU + OPRR sign Multiple Project Assurance of Compliance • Results: No association of putative gene Havasupai with type 2 DM • PI & Co-Is, & many other researchers, & pre- & post-doctoral researchers used DM study’s DNA for articles & theses: • migration, interbreeding, schizophrenia, etc. I assume Carletta Tilousi will report her & her tribe’s experiences

6. Chronology 3: before the law suits • Mid/2003 Tribe threatened ASU with lawsuit • ASU & HavasupaiTribe jointly selected Stephen Hart & Keith Sobraske: exhaustive investigation of facts, many interviews * • 12/2003 450+ page “Hart Report” issued • both ASU and Havasupai Tribe received the same report • (my Chronology 1 & 2 slides are abstracted from “Hart Report,” p. 23-31, “Condensed Chronology”) * 421 page report under ASU contract, Dec 23, 2003: Stephen Hart (Investigator, Burch & Crachiolo, P.A.) and Keith A. Sobraske (Investigator, Investigative Research, Inc.), "Investigative Report Concerning the Medical Genetics Project at Havasupai"

7. Chronology 4: “The Hart Report” 2003 “[T]he presentation made by Dr. Benyshek to the tribal members in 1991-1994,... the proposal as presented by Dr. Martin to the Tribal Council and other meetings,... and the documentation provided to the Havasupai (and documentation from the Havasupai), reflect that diabetes was the focus and that schizophrenia or other behavioral disorders were not even secondary considerations. It is our assessment that considering the totality of the circumstances it is most likely that the donors understood this to be a diabetes project only.” (63)

8. Chronology 5: the law suits • 7/04 Havasupai filed two lawsuits in Federal Court • 1 by Tribe, 1 by individuals • Court dismissed most claims (e.g., plaintiffs had no privacy interest because the specimens had been given voluntarily) • ‘05 plaintiffs withdrew from Federal Court & refiled in Arizona (AZ) Superior Court • 4/07 AZ Superior Court summarily dismissed case • for inadequate statement of facts • 11/08 AZ Court of Appeals reinstated case • found statement of facts was adequate, & that plaintiffs may have a privacy interest in specimens • therefore remanded the case back to AZ Superior Court • (AZ Court of Appeals is the final legal statement on the case)

9. Chronology 6: Settlement • 4/21/10 Settlement announced (in my understanding of possible priority) 1.A. AZ issued formal apology 1.B. ASU returned bloods to Tribe 3. ASU & Tribe will collaborate in major programs for health, education, & economic development - the Tribe still believes health research CAN be helpful 4. Havasupai Tribe recognized ASU’s efforts to improve oversight & conduct of research 5. $700,00 to 41 people in lawsuit • original suits had asked for $75 M

10. Reminders to us from Havasupai - 1 Different people have different values and concerns • “The decrease in the settlement’s monetary award shows that the Havasupai Tribe did not get what it wanted (& thus had a weak legal case).” VS. • “The Tribe achieved its highest priorities.” (I do not, and will not, speak for the Havasupai Tribe.) • ASU returned bloods to Tribe • in my experience with 2 other Tribes in similar circumstances, returning the specimens to the Tribe was a HIGH priority, to give them proper respect and care. • similar to importance to US of return of M.I.A. remains

11. Reminders to us from Havasupai - 2 Those differences of values are a major justification for truly informed consent • A research project’s impact on a person--a net positive or negative--depends in part on those values • To enable each individual to make an informed decision, the researcher must give information that is “understandable” (45 CFR § 46.116, General Requirements for Informed Consent) • one approach to “consent” in the commercial world – caveat emptor – “you gotta read the fine print, buddy” – is not acceptable to most IRBs and to OHRP.

12. Possible implications of Havasupai –1a People MAY have a “privacy interest” in their specimens • AZ Court of Appeals mentioned plaintiffs’ “privacy interest” repeatedly, to justify decision to remand • (did NOT rule that plaintiffs’ privacy interest was sufficient to award damages) • directly countered Federal Court’s dismissal of “privacy interest” due to the specimens being voluntarily given • AZ Court cited 2 cases (1 from 9th Federal Circuit Court) • “[I]t goes without saying that the most basic violation possible involves the performance of unauthorized tests – that is, the non-consensual retrieval of previously unrevealed medical information that may be unknown even to plaintiffs.” (p. 32, quoting from 9th Circuit Court)

13. Possible implications of Havasupai –1b People MAY have a “privacy interest” in their specimens (continued) • AZ Appeals Court cited 2 cases, both • were from medical care • were secondary use of specimens volunteered for other purposes • were decided for plaintiff • AZ Court did not mention anonymized specimens Do participants have a continuing “privacy interest” in what research is done on their specimens? • vs. 45 CFR § 46.101(b)(4) – exempts anonymized specimens

14. Possible implications of Havasupai –1c • What information do actual participants in genetic research want? (from Abstract by EJ Ludman et al) • In a large study, 88% of 1,311 consented to send their DNA to a national genetic database; 12% refused -> • interviewed a random sample (365) of those who consented • Reconsent (=be asked first): • “very important” = 69%; “somewhat important” = 21% • Being notified only (= no Reconsent, no Opt Out) • “completely unacceptable” = 67%; “somewhat” = 20% • Their information added to national databank without notification or permission: • “completely unacceptable” = 54%; “somewhat” = 16%

15. Possible implications of Havasupai –2 Tribes AS TRIBES have “privacy interests” and can suffer “dignitary harm.” Do other communities as well? • AZ Court of Appeals joined and considered together the suits by Havasupai individuals and Tribe • did not mention Tribal Sovereignty, or legal powers of Tribal Governments • “We do not cite these authorities as proof of the Tribe’s claims or to establish any particular damage amount due the Tribe. We offer them instead to demonstrate the validity of the Tribe’s contention that the privacy invasions it alleged naturally may give rise to deeply personal and subjective injury of the sort on which the Tribe based its settlement demand.” (p. 35) • Do “disease communities” (e.g., pseudoxantha elasticum [PXE, a genetic disease]; lymphangioleiomyomatosis [LAM, a disease possibly genetic and/or other]) also have “privacy interests” in specimens collected by & from them?

16. Sources • Harmon, Amy. “Tribe wins fight to limit its use of DNA.” New York Times 2010; Apr 22. • Harmon, Amy. “Havasupai case highlights risks in DNA research.” New York Times 2010; Apr 23. • Hart S, Sobraske K. “Investigative report concerning the medical genetics study at Havasupai” (“Hart Report”). 2003; Dec 23. • Rubin P. Indian givers. Phoenix New Times 2004; May 27. (http://www.phoenixnewtimes.com/content/printVersion/174475) • Whitener RJ. Research in Native American communities in the genetics age: can the federal data sharing statute of general applicability and tribal control of research be reconciled? (to be published in a law journal in December)