Canadian experiences carrying out Genetic research with aboriginal communities

1. Canadian experiences carrying out Genetic research with aboriginal communities Training for researchers: How to conduct Research in AI/AN Communities Fort Yates, ND June 16th, 2005 Laura Arbour MD University of British Columbia

2. Where are we going? • Canadian Aboriginal Community Research Guidelines • Issues to consider when carrying out research • What is a research relationship? • Genetic research as an example • Primary Biliary Cirrhosis in the Pacific North West First Nations Peoples • Long QT Syndrome in Northern British Columbia • Folic acid and birth defects in children of Northern aboriginal women

3. Canadian Aboriginal Communities

4. Canadian guidelines defining ethical research in aboriginal communities • Dene tracking: A participatory research process for dene/metis communities (1993) • Inuit Tapirsat background paper on negotiating relationships in the north (1994) • Kahnawake Code of Research Ethics (1997) • Akwesasne Research Code of Ethics (1996) • Cree Board of Health and Social Services of James Bay Code of Research Ethics (2001) • Protocols and Principles For Conducting Research in an Indigenous Context (University of Victoria) • Tri-council policy (1998 with updates 2000 and 2002)\ • CIHR AEWG Guidelines in progress (expected completion November 2005)

5. Participatory Action Research Behaviour/attitudes Methods Sharing (OCAP) Community needs Respect for beliefs Education Capacity development

6. A research relationship that respects aboriginal individuals and communities within their culture, in keeping with values is essential to carry out a successful research program.

7. Principles • Research carried out in aboriginal populations must reflect the needs of the community • Community needs to be involved in all stages of research • The community will benefit from the research (capacity, equipment, health care programs, information, education) • Results will be returned to the community for their use in partnership with the researcher

8. Samples • How do biological research samples fit with all of this?

9. Arthritis Research in a West Coast Community • UBC researcher in the 1980’s was sought to carry out research on a problem affecting a large proportion of the community. • Consulted with community leaders • Community members were involved in the research • “action” was promised • Blood was drawn on more than 800 community members • Research intended could not be carried out

10. West Coast Study • Instead, individually non-identified samples were then used to carry out mitochondrial DNA studies to determine ancestral and migrational origins of the people of the community. • The blood and the information were used in subsequent studies • Awareness in the community came following a report on a documentary made of the work. • Community members wanted the blood back

11. Community approach to research gone wrong • Promise was not kept • Continue to want research carried out on their problem-But want the research carried out with their input and involvement • Committee struck to get the blood back (successful) • Research review committee now in place to review all research carried out in community

12. Biomedical Model of Research Vs Participatory Research • Basic Science research/ Clinical trials • Purpose is to add to body of scientific knowledge • Subjects are recruited (necessary to provide data) • Participants (subjects) little voice in the research process or results

13. Biomedical Research • Incentives are discouraged (reduce coercion) • Often waive rights of profit while participating • Data are ‘owned’ by the researcher and sometimes sponsor (rarely shared with subjects) • Results are published in peer reviewed journals, but not specifically directed to or shared with subject/community

14. Is this where the cultural problem lies? • Data and samples controlled by the researcher (property) • Research samples archived • (Until recently) identifiers removed secondary research done • Shared with other researchers (private and public) • (Now) move toward blanket consent • With the focus on scientific results individual and community interests may not have been appreciated • Expectations of community and researcher may be at a divide.

15. Canadian Discussions • National Council of Ethics in Human Research: Research involving individuals and communities: Genetics as a focus, Ottawa, November 1999. • 2) NCEHR, Canadian Commission for UNESCO, Health Canada: Continuing the dialogue: Genetic Research with Aboriginal Individuals and Communities , Vancouver January 2001. • 3) CIHR: IAPH Part 1 An exploratory workshop on a tribal controlled DNA bank, Vancouver, August 2001 • 4) CIHR: IAPH Part 2 An exploratory workshop on a tribal controlled DNA bank; Tofino BC, January 2002

16. “DNA on Loan” Emerging Principles for carrying out research in Canadian Aboriginal populations • Specimen collection, storage, uses and destruction should be in accordance with the wishes of the community • All blood and tissues accepted for research will be considered the property of the donor/community involved and thus will be considered on loan to the researcher

17. Principles for carrying out research in aboriginal communities • Research carried out in aboriginal populations must reflect the needs of the community • Community needs to be involved in all stages of research • The community will benefit from the research (capacity, equipment, health care programs, information, education) • Results will be returned to the community for their use in partnership with the researcher

18. Implementation • Community consultation/consent process • Depending on type of governing body can take many forms • On-going research relationship • frequent discussions, reports, feedback, evolving results, plans for presenting information at conferences, publications • As long as research samples exist, on-going consultation about how the samples will be used (DNA or other samples are “on loan”) • Built in governance is part of this model

19. Primary Biliary Cirrhosis • progressive autoimmune liver disease predominantly affecting young women • leads to portal inflammation, scarring, cirrhosis, liver failure, transplantation, death • uncommon in most populations (1/50,000)

21. Indications for liver transplant in BC over 10 year period. 25% of those referred for transplant for PBC were First Nations Leading indication (8 times) for liver transplant in First Nations People of BC British Columbia: population 3.9 million 171,000 are aboriginal (about 4%)

22. PBC Research Process • Potlatch (invited) • Discussion with Family Elders • First Nations Chief’s Health Committee consultation • Local newsletters, newspapers directed towards First Nations in BC • Education brochures developed with participants • Community discussions • Community research review (when community has review process) • First Nation student involvement • Regular research updates (each participant, each governing committee) • Regular research updates to participants • Pre-publication review • Publication updates sent to participants

23. Folate and birth defects

24. Folic acid and birth defects • Conclusive evidence that 50-75% of spina bifida, can be prevented with supplemental vitamins containing folic acid. Estimated that 20% of all birth defects, in addition to SB, could also be prevented with the use of vitamins supplements (Botto et al AJMG, Part C (Semin.Med Genet) 125C:12-21, 2004) • Public health efforts to encourage all women of childbearing years to take a multivite containing 400µg of folic acid • But only 15-30% of women adhere to this • Mandatory fortification of grain products (flour, cereals) commenced in Canada, US in 1998 (increasing intake by about 100 mcgs/day).

26. Spina Bifida, folate metabolism and dietary folate intake in a Northern Aboriginal population • Clinical observation that there was a disproportionate number of spina bifida patients who were FN • Rate of spina bifida was increased in FN of James Bay region (1/260). All cases were non-syndromic, most cases were lumbar sacral, low lesions • Study was commenced 1996, (partly funded and fully supported by the Cree health committee) to determine the nutrient/genetic basis • All mothers of children with spina bifida in the region were invited to participate. • Active community participation, “wellness committee” campaign to take a vitamin a day, “healthy babies”

27. Results • No evidence of altered folate metabolism • No evidence that genes important in folate metabolism conferred risk for altered metabolism • However, evidence that red blood cell folate was significantly lower than comparison groups (pre-fortification:484 nmol/L Vs 527-694 nmol/L) • Consistent with dietary assessments in the region (for women of childbearing years: 129 µg/day of folate) and other studies of northern dietary intake of folic acid. • Arbour L, Delormier T et al 2002 Int Journal Circump Health 61:341-351

28. Birth defects in Nunavut and Nunavik

29. Estimated RR for birth defects in Inuit children from Baffin Island and Arctic Quebec –the baseline Arbour et al, 2004 International Journal of Circumpolar Health 63(3) 251-265 Based on chart review of 2567 live births 1989-1994

30. The Genetic, nutrient, and environmental determinants of congenital heart malformations in Inuit children and their mothers (1Arbour L, 1Field L, Egeland G, 3Rozen R); • commenced July 2004 1UBC, Medical Genetics; 2CINE McGill University; 3Departments of pediatrics and Human Genetics, McGill University

31. Process • RFA announced • Visit to Iqaluit • Meeting with numerous stake-holders, community, health care providers (GPs, MOH, nurses, dieticians, CHRs) Nunavut research institute, NTI, ITK “Is this important to you? Would you support the work being done?” • Advisory board struck • Grant written, • Awarded, • Nunavut Research Institute licensing, Hamlet offices • Regular updates (participants), visits, discussions about research and any other topic Brochures “Healthy hearts: happy babies” Students are involved • Every community, we talk to CHRs, nurses, doctors, Inuit nursing students..we listen to them…what ideas do they have. Research is always being updated.

32. Consent form/research agreement • Ideally research agreement should be developed with aboriginal community • Consent forms should include all important aspects of research agreement • Aims, risks, (stigma), handling of research samples, data, expected presentations, use of tribal affiliation, confidentiality, publications, when to expect research results.

33. Challenges

34. Benefits