Research

Principal Investigator: Sandra Soo-Jin Lee, PhD
MPI: Janet Shim, PhD

A major challenge for precision medicine research is including historically under-represented groups in numbers sufficient to ensure statistically valid inferences of the influence of relevant risk factors, including genetic contributions to disease risk. Precision medicine researchers have recognized the critical need to enhance diversity and have implemented a wide variety of approaches to achieve this. All such approaches, however, are shaped by stakeholders’ understandings of what kinds of diversity matter, the local logistical constraints under which precision medicine research is actually being conducted, and the responses of communities to those approaches. Investigating these complex factors from the perspectives of multiple stakeholders in precision medicine research will be essential to effectively address longstanding inequities in genomic and related forms of precision medicine research.

Our study seeks to take advantage of the current proliferation of diversity and inclusion practices to study their heterogeneity, commonalities, and effects on diversifying participation in precision medicine research ("PMR"). We will determine through in-depth analyses of PMR studies how concepts such as definitions of diversity (e.g. genetic ancestry markers, self-reported race and ethnicity) impact practices such as retention, engagement, and return of results. Taking a life course perspective to research relationships, we aim to assess how approaches towards diversity and inclusion are managed in tandem with other research goals and the implications of specific trade-offs that result.

Our study aims are to:

1. Identify scientific and sociopolitical justifications for goals of inclusion and conceptual definitions of diversity in precision medicine research;
2. Determine how scientific, social, and technical factors influence the operationalization of diversity and implementation of inclusion in precision medicine research; and
3. Engage stakeholders to create data-informed guidance that describes the strengths and weaknesses of diversity and inclusion decisions and practices in precision medicine research.

Team Members

Sandra Soo-Jin Lee, PhD – PI, CUIMC

Janet Shim, PhD – MPI, University of California, San Francisco

Stephanie Malia Fullerton, DPhil – Co-I, University of Washington 

Aliya Saperstein, PhD – Co-I, Stanford University

Emily Vasquez, MPhil, MPH, ABD – Project Director, CUIMC

Mike Bentz, MPH - Research Coordinator, CUIMC

Mel Jeske, MA, ABD – Graduate Student Research Assistant, University of California, San Francisco

Nicole Foti, PhD(c) - Graduate Research Assistant, University of California, San Francisco

Principal Investigator: Sandra Soo-Jin Lee, PhD

In the emerging era of precision medicine, there have been increasing calls for diversity and the inclusion of historically under-represented racial and ethnic populations in biobanking and precision medicine research. Recent findings suggest that the lack of diversity in genetic repositories may pose serious challenges to identifying genetic variants that are clinically significant in certain populations. These concerns have been linked to ethical concerns over disparities in health and disease among racial and ethnic groups. Despite increasing scrutiny of diversity in recruitment efforts in genomics research, there are few studies that integrate scientific, social, and ethical concerns that are attached to discourse on diversity. This project aims to provide a conceptual framework of diversity that is multi-disciplinary and takes into account the historical and social context in which diversity is invoked in genomics.

The specific aims of this research are:

1. To investigate how discourse on human diversity and difference in population based genomics research has changed over time.
2. To identify the ethical implications for inclusion of diversity for researcher-participant relationships, including issues related but not limited to “recruitment,” “consent,” “group harm,” and “benefit-sharing."
3. To develop a conceptual framework for diversity in genomics research that addresses ethical values of respect, beneficence, and justice.

Principal Investigators: Mildred Cho, PhD and Sandra Soo-Jin Lee, PhD

ELSIhub is a collaboration between Stanford and Columbia Universities and partners at the Hastings Center and Harvard University, whose mission is to enhance the production and use of ELSI research by the ELSI community and other stakeholders. The goal of ELSIhub is to serve as a locus for resource sharing and community building to enhance the production, sharing, and use of research on the ethical, legal, and social implications of genetics and genomics ("ELSI research"), using the “knowledge to action” conceptual framework which highlights facilitators of and barriers to knowledge sharing and use. ELSIhub will be guided by the principles of responsiveness, inclusion, adaptability, rigor, transparency, and open access. It will build in responsiveness to community needs, focusing on ELSI researchers, and incorporating National Human Genome Research Institute and stakeholder input to prioritize services.

The specific aims of ELSIhub are to:

1. Create a platform to identify, collect, index, and share ELSI research products.

2. Provide analytic functions of curation and synthesis of ELSI research on key topics, and mapping the ELSI field.

3. Convene a broad base of stakeholders with relevant expertise to contribute to the development of ELSIhub resources and to address emerging ELSI questions on genomics research.

4. Engage in outreach, dissemination, and training to support the contribution to, and development and use of ELSIhub resources.

Principal Investigator:  Sandra Soo-Jin Lee, PhD

Summary:  Understanding the preferences and expectations of underrepresented communities for receiving genetic results in a research setting and navigating additional information and services in the clinical setting are critical to building and maintaining research relationships and engendering trust, particularly with groups who have historically not participated in biomedical research. The proposed supplement leverages a unique opportunity to investigate the preferences of African American and Hispanic/Latino communities, including the uninsured, who are being recruited into precision medicine research, for different types of genetic test results and their expectations and needs for information and resources to allow for informed, validated follow-up of research results and clinical care.

Narrative: This application builds on the R01 study the Ethics of Inclusion: Diversity in Precision Medicine Research and aims to investigate the preferences of African American and Hispanic/Latino communities, including the uninsured, who are being recruited into precision medicine research for different types of genetic test results and their expectations and needs for information and resources to allow for informed, validated follow-up of research results and clinical care.

Aims: Identify preferences of patients from underrepresented communities for the return of specific categories of genetic results and their expectations and needs to navigate follow-up care related to the return of research results.

Approach: Stakeholder-based investigation to include individual and group interviews of African American, Hispanic/Latino and/or uninsured individuals.

Longer-term:  Inform research guidance and policy.

Navigating Research Results Team:

• Louise Bier, MS, CGC
• Alejandra Aguirre, DrPH, MPH
• Sonia Mendoza-Grey, MPH 
• David Goldstein, PhD
• Stephanie M. Fullerton, DPhil
• Emily Vasquez, PhD, MPH
• Melanie Jeske, PhD, MS
• Michael Bentz, MPH
• Nicole Foti, PhD
• Aliya Saperstein, PhD
• Janet K. Shim, PhD, MPP
• Sandra Soo-Jin Lee, PhD

Principal Investigator: Maya Sabatello, PhD

Summary: People with disabilities comprise the largest health disparities group in the US. Their inclusion in precision medicine research is essential for health benefits to accrue to them and for upholding social justice by treating people with disabilities as equal members of society. Yet, people with disabilities are underrepresented in health research, including precision medicine research, though the reasons for this outcome are understudied. Research shows that trust is key for promoting ethical research and that distrust is a major barrier for participation of racial/ethnic minorities in precision medicine research. However, what constitutes trust and the factors affecting views on trustworthiness of precision medicine research among people with disabilities and translational genomic researchers are understudied, even as such views may be critical for disability inclusive precision medicine research. 

Our study engages with people with mobility, visual and hearing disabilities across racial/ethnic communities and with translational genomic researchers to close this gap. We will use a disability, community-based participatory research approach, and Concept Mapping, a multi-step process with mixed-methods design to develop a nuanced conceptual framework for understanding (dis)trust in PMR and an actionable, evidence-based roadmap for enhancing trustworthiness of precision medicine research among people with disabilities.

The study aims are to:

1.  Identify domains of (dis)trust in and trustworthiness of precision medicine research among people with mobility, vision and hearing disabilities
2. Compare sources of (dis)trust in and features of trustworthiness of precision medicine research among people with mobility, vision and hearing disabilities across racial/ethnic groups and between people with mobility, vision and hearing disabilities and translational genomic researchers
3. Develop evidence-based recommendations for building trust in precision medicine research among people with mobility, vision and hearing disabilities.

Principal Investigator: Alexis Walker, PhD

Summary: This R00 Award investigates approaches to social and ethical issues within the private sector genomics industry in the US, examining stakeholder perspectives on pathways towards equitable and just outcomes for the field. It does so through methods for both descriptive and normative ethics as well as stakeholder engagement. This includes an investigation of how members of the private sector genomics industry think and talk about the ethical and social dynamics of their work, using interview, survey, and observational methods. 

Members of the private sector genomics industry make daily decisions that shape the distribution of the benefits of biomedicine -- from decisions about product pricing to companies’ very understandings of their target customers and markets. With the industry’s central role in shaping how genomic innovations reach the public, perspectives from members of this industry are especially important to possibilities for ethical futures. This study leverages its descriptive examination of stakeholder perspectives to then inform normative analyses and participatory policy and governance planning. In addition to a broad scoping of ethical and social issues as seen from across the industry, the project addresses issues of responsibility, profit, and models of innovation in private sector genomics. 

The study aims to:

1. Describe the perspectives of individuals working in genomics in the private sector regarding the social and ethical challenges faced in the industry, as well as individuals’ and companies’ responses to these challenges.
2. Normatively evaluate the ethics of private profit and social obligation in the genomics industry, based on systematic application of key normative theories in bioethics and business ethics.
3. Identify strategic priorities for ethics intervention in private sector genomics, based on a deliberative engagement process with industry stakeholders.

PI: Ali Gharavi, MD; MPI: Maya Sabatello, LLB, PhD

Summary: The return of individual genetic results in nephrology is key for translational genomic efforts to promote patients’ clinical care, but its success hinges largely on the ability of nephrologists and nephrology researchers to implement and facilitate the process. However, no clear policies currently exist about return of genetic results in nephrology research, and no study to date has explored the ethical and practical challenges nephrologists experience in this process. The supplement collaborates with CureGN, a 70-sites consortium dedicated to the return of genetic results for rare renal disorders, and national organizations devoted to cure heritable renal diseases, to investigate the experiences of nephrology healthcare providers in returning genetic results from research. 

• Aim 1: Identify overarching ethical and practical challenges in return of genetic results in nephrology research and possible remedies for these challenges by surveying adult and pediatric nephrologists and other nephrology providers
• Aim 2: conduct an iterative process to develop recommendations for return of genetic results from nephrology research. 

Research Team:

• Hila Milo Rasouly, PhD
• Maddalena Marasa, MD
• Olivia A. Balderes, MA
• Victoria Kolupaeva, PhD
• Maya Sabatello, LLB, PhD
• Ali Gharavi, MD

PI: Jessica Ezzell Hunter, PhD; Site PI, Sandra Soo-Jin Lee, PhD  (NCI)

Summary: An estimated 1 in 190 women carry a pathogenic variant in BRCA1/2, which is associated with a 46-57% risk of breast cancer and 20-40% risk of ovarian cancer by age 70. Carriers account for 10% and 15% of breast and ovarian cancer cases, respectively, and up to 20% of high-grade serous ovarian cancer cases, the most aggressive subtype. Despite recommendations that all ovarian cancer cases should receive genetic counseling and testing, irrespective of family history and age at onset, a recent national study indicated that only 10% of cases underwent genetic testing. This represents a missed opportunity to inform these women and their at-risk family members about their future cancer risk. Our multidisciplinary team marshals expertise in bioethics, genetic epidemiology, genomic medicine, biostatistics, health communication, and medical genetics to address the ethical, regulatory, and scientific challenges to address challenges in applying a traceback testing approach to retrospectively identify women who have a prior diagnosis of ovarian cancer. This study generates evidence on the feasibility of traceback testing using tumor registries and archived pathology samples that are critically important to guide the future implementation of such programs beyond ovarian cancer. 

Principal Investigators: Katherine McDonald, PhD, and Maya Sabatello, LLB, PhD

Summary: Adults with intellectual disability experience significant health disparities and may benefit from precision medicine research advances. However, they are underrepresented in research and understanding of solutions to the ethical, legal, and social consent-related challenges that present barriers to their inclusion in this research is limited. Gaps in knowledge about the views of adults with intellectual disability on key issues in precision medicine research such as genomic privacy and empowerment as well as absence of practical tools for precision medicine researchers perpetuate their exclusion and create barriers to generating new knowledge to address the health needs of this underserved population. Our multidisciplinary team and academic-community partnership will explore these challenges and address them by developing a disability accessible and protocol-adaptable precision medicine research consent toolkit. This research is the first-time multiple stakeholders including adults with intellectual disability will collaborate to use empirical ethics inquiry to address consent and other challenges to inclusion in precision medicine research. The Project ENGAGE toolkit will help precision medicine researchers avoid the pitfalls of bias and upholds principles of human agency valued by community members and yield critical theoretical and practical insights to precision medicine research inclusive of adults with intellectual disability.

Principal Investigator: Maya Sabatello, LLB, PhD

Summary: The use of Artificial Intelligence and Machine Learning (AI/ML) analytical tools to predict disease risk, onset and progression, and treatment outcomes is growing and holds promise for improving health outcomes for marginalized health disparities population. Blind people experience significant health disparities and could benefit from AI/ML advances but disability bias in clinical settings—independently and compounded by racial and gender biases—may preclude the potential benefits from accruing to them. This study emerged from, and continues to employ, community-based participatory research. It builds on an intersectionality framework to explore disability and racial and gender biases in electronical medical records (EHRs) of blind and nonblind diabetes patients, and to develop reproduceable, publicly available phenotype definitions and a list of disability biasing language. Our multidisciplinary team comprises expertise in ELSI research, disability studies, medicine, computer science and biomedical informatics. This project has the potential to inform equitable AI/ML models in clinical care, improve health outcomes of an often invisible but large and growing health disparity population, and build a dialogue on disability ethics and equity of AI/ML among clinicians, data scientists, blind adults, and ELSI researchers.

Principal Investigator: Jennifer Reardon

Co-Principal Investigators: Sara Goering and Sandra Lee

Summary: Science, technology, engineering, and mathematics (STEM) research raises issues of ethics and justice. Reviewers and funders of STEM research now often ask for integration of ethical, legal, and social implications and diversity, equity, and inclusion issues in the design of proposed research. This shift in expectation means that bioethicists, social scientists, and scholars in the arts and humanities are now asked to join science and engineering research teams. Their inclusion in the scientific process from the ground up is important; however, it is not clear how to integrate these scholars into the process. For instance, it is not clear who has the relevant expertise or what counts as successful integration. The investigators of this project are conducting a thorough review of past integration efforts and case studies in the fields of genomics, neuroscience, and artificial intelligence to build an evidence base that will facilitate more ethical and just STEM research. As such, the project will pave the way for the development of new guidelines for forming collaborative teams in science and facilitating sustained institutional changes that promote equitable and ethically robust research in science and engineering. The created guidelines will be a valuable resource for researchers, administrators, review boards, funders, and other stakeholders in STEM research. The project also offers training opportunities for graduate students and postdoctoral researchers.

Increasingly public and private institutions and funders recognize the critical importance of incorporating ethical and societal analysis into the design of science, technology, engineering, and mathematics (STEM) research. This research initiative evaluates previous efforts to integrate or embed initiatives focused on ethical, legal, and social implications (ELSI) and diversity, equity, and inclusion (DEI) issues into science and engineering research projects. The evidence base is being built up in two ways: (1) a content analysis of documents and literature that describe “integrated” and “embedded” ELSI research and DEI objectives within it; and (2) a case study comparison of the meaning of “integrated” and “embedded” ELSI and DEI in the fields of genomics, neuroscience, and artificial intelligence. Through this analysis, the project team identifies best practices that will inform the creation of practical, conceptually engaged, and ethically robust guidelines for ELSI and DEI in STEM research. This research supports the future development of Leadership in the Equitable and Ethical Design for STEM research guidelines. The goal of these guidelines will be to specify the role, points of engagement, timeline, and possible outcomes of DEI and ELSI collaborations in a manner that supports a more robust integration of DEI and ELSI into STEM research. Ultimately, the research will support the creation of a cross-sectors effort to reformulate the meaning of ethical and equitable science in a manner that creates sustained organizational culture and policy changes that center DEI, ELSI, and the goals of advancing equity and justice.