Health Equity and the Genomics Enabled Learning Health

Health Equity and the Genomics Enabled Learning Health System Ethical, Legal and Social Implications of Learning Health Care Systems University of Michigan Vence Bonham, J. D. Associate Investigator Social and Behavioral Research Branch Katherine Blizinsky, Ph. D. Research Fellow Social and Behavioral Research Branch

“Groups adversely affected by disparities could be among those that benefit most from a learning health care system” Genomics-Enabled Learning Health Care Systems, Workshop Summary , 2015, National Academies Press, Washington D. C.

How can genomic-enabled LHS enhance health equity? CDS Integration Tool Revision of Knowledge • • How does this new information change assumptions? What research is necessary to improve information utility? • • What does the current data suggest? How can that be used to improve care? Outcome Evaluation • • Does use of genomic information improve health outcomes? When and for whom? Blizinsky K, and Bonham VL, 2016

The Challenge

Challenges in use of genomic big data for health equity Popejoy, AB, and Fullerton, SM. Genomics is failing on diversity. Nature. 2016 Oct 12; 538(7624): 161 -164.

During the past seven years, the proportion of samples used in catalogued GWAS from participants who are not of European descent has increased fivefold. Yet nearly 78% of this growth is due to an increase in the number of samples from Japan, China, Korea, India and other populations from east Asia, south Asia and southeast Asia. Together, individuals of African and Latin American ancestry, Hispanic people and native or indigenous peoples represent less than 4% of all samples analyzed. Collectively, these are the most vulnerable and traditionally underserved populations in many of the world’s richest nations. Popejoy AB, Fullerton SM, Nature, 538: 161 -164, October 13, 2016

Why Does Representation Matter? “Disparities may result from errors that are related neither to access to care nor to posited “physiological differences” but, rather, to the historical dearth of control populations that include persons of diverse racial and ethnic backgrounds. ” Manrai AK et al. Genetic Misdiagnoses and the Potential for Health Disparities, New England Journal of Medicine, 375(7): 655 -665, (201^)

Challenges in use of genomic big data for health equity CYP 2 D 6 Atomoxetine Codeine CYP 3 A 5 Tacrolimus ABCB 1 Digoxin Cyclosporin Loperamide Quinidine ABCG 2 Topotecan Irinotecan Mitoxantrone Doxorubicin Rosuvastatin Metotrexate SCLCO 1 B Pravastatin Rosuvastatin UGT 1 A 1 Irinotecan UGT 2 B 7 Morphine Zidovudine VKORC 1 Warfarin Yasuda, SU, Zhang, L, and Huang, S-M. The Role of Ethnicity in Variability in Response to Drugs: Focus on Clinical Pharmacology Studies. Clin Pharmacol Ther. 2008 Sep; 84(3): 417 -23.

Case Study § Plavix (clopidogrel)

Plavix (clopidogrel) § Plavix is a prescription medicine used to treat people who have any of the § following: – Chest pain due to heart problems – Poor circulation in their legs (peripheral arterial disease) – a heart attack – a stroke

CYPC 219/Plavix; rs 4244285

a i s e yn > A % 50 ol P in

State of Hawaii Files Suit In March 2014, Hawaii’s Attorney General filed a lawsuit alleging on behalf of the state of Hawaii that the makers of Plavix have been deceptively marketing and unfairly labeling Plavix since its launch more than 15 years ago by failing to alert consumers that the drug has "a diminished or no effect on approximately 30 percent of the [Hawaiian] population because they metabolize the drug poorly due to their genetic traits. (Genome Web, April 16, 2014)

Vence L. Bonham, J. D. , Shawneequa L. Callier, J. D. , and Charmaine D. Royal, Ph. D. N Engl J Med 2016; 374: 2003 -2005 May 26, 2016 DOI: 10. 1056/NEJMp 1511294

“Eventually, precision medicine may revolutionize our understanding of race and its utility (or lack thereof) in clinical practice. ” Vence L. Bonham, J. D. , Shawneequa L. Callier, J. D. , and Charmaine D. Royal, Ph. D. N Engl J Med 2016; 374: 2003 -2005 May 26, 2016 DOI: 10. 1056/NEJMp 1511294

Hurdles to overcome: 1. Increase inclusion of patients of diverse ancestry in genomics and other biomedical research 2. Control of rising drug costs 3. Improve the ease and usefulness of implementing a precision medicine approach Vence L. Bonham, J. D. , Shawneequa L. Callier, J. D. , and Charmaine D. Royal, Ph. D. N Engl J Med 2016; 374: 2003 -2005 May 26, 2016 DOI: 10. 1056/NEJMp 1511294

Email: bonhamv@mail. nih. gov

Race and Ethnicity Are Important for the LHS

Social Domains § Education § Financial Resource Strain § Exposure to Violence – Safe at home § Social Identity – Race, and Ethnicity