ABSTRACT
Racial and ethnic minorities and residents of rural communities (rural residents) experience the
greatest health disparities. Health disparities, as defined by the World Health Organization, are
plausibly avoidable differences in health outcomes closely linked with social, economic, and
environmental disadvantages. Health disparities, which cost the U.S. economy more $1 trillion
annually, are worsened by underrepresentation in biomedical research (UBR). The National
Academy of Medicine, the Food and Drug Administration (FDA), and other authoritative bodies
have issued reports and are promoting strategies to increase the participation of racial/ethnic
minorities, rural residents, and other UBR populations in biomedical research as a necessary step
to mitigate health disparities. To wit, this proposal aims to increase the participation of racial/ethnic
minorities and rural residents in the largest precision medicine initiative in history by incorporating
the All of Us Research Program Heartland Consortium (AoURP-HC) as a Healthcare Provider
Organization (HPO) into the National Institutes of Health's (NIH) All of Us Research Program
(AoURP). The AoURP-HC is a partnership of academic medical centers, hospitals, and community
organizations in the central United States that will work together to enroll Kansas, Missouri,
Nebraska, and Iowa residents into the most ambitious precision medicine initiative in history. The
AoURP-HC will engage with the NIH's AoURP to further the goal of enrolling one million
individuals who reflect the diversity of the United States, focusing on racial/ethnic minority
groups and rural residents who are historically among the most UBR. The disproportionate and
calamitous impact of COVID-19 on racial/ethnic minority groups and rural residents lends urgency
to efforts to enrich the AoURP with UBR populations. Our team, while on the pandemic frontlines,
observed the geographic and race/ethnicity-based disparities in the impact of COVID-19. For
example, Gove County, Kansas, had the highest COVID-19 death rate in the US, and the rural
town of Quinter, Iowa, lost 1 in 132 residents to COVID-19, compared to the national average of
1 in 10,000 deaths.1 Race/ethnicity emerged as a significant determinant of COVID-19-related
deaths in the US (after age 75 years³), with more than three-fold differences in adjusted mortality
rates (per 100,000) among different racial/ethnic groups. This disproportionate COVID-19
morbidity and mortality in UBR populations, underpinned by genetic, physiologic, environmental,
occupational, and lifestyle factors, will be better elucidated by the AoURP.
The AoURP-HC aims to address the underrepresentation of the central U.S. in the AoURP by
establishing a formal partnership among four academic medical centers, along with their affiliated
hospitals and clinics. The proposed collaboration will pursue four objectives: (1) we deploy a
metrics-driven campaign will aim to enroll >30,000 full participants in five years of whom 50%
will be racial ethnic/minority groups and rural residents; (2) we will send electronic health
records periodically by means of secured and standardized AoURP IT processes and procedures to
the Data and Research Center; (3) we will work collaboratively with the national AoURP
infrastructure, including HPOs, the Biobank, and the Consortium Steering Committee, to develop
and implement AoURP research protocols; and (4) we will abide by AoURP policies, maintain
fidelity to the AoURP core values, and actively participate in AoURP ancillary studies, task forces,
and working groups. Pursuant to these objectives, we will implement a comprehensive participant
engagement and retention plan that values the participants as partners and convene a Participant
Advisory Board to design and implement program activities. Our targeted enrollment of UBR
populations into the AoURP will enhance the geographic and ethnic diversity of the All of Us
cohort, enhance public participation in precision medicine research, and help to ensure the benefits
of targeted therapies and personalized preventative strategies reach rural populations.