Seven Strategies to Integrate Equity within Translational Research in Neurology

Abstract

The rapidly accelerating translation of biomedical advances is leading to revolutionary therapies that are often inaccessible to historically marginalized populations. We identified and synthesized recent guidelines and statements to propose seven strategies to integrate equity within translational research in neurology: 1) Learn history, 2) learn about upstream forces, 3) diversify and liberate, 4) change narratives and adopt best communication practices, 5) study social drivers of health and lived experiences, 6) leverage health technologies, and 7) build, sustain and lead culturally humble teams. We propose that equity should be a major goal of translational research, equally important as safety and efficacy.

Introduction

The pace of translational biomedical and technological advances to treat neurological conditions has been astonishing. Life-changing and curative therapies are now available for conditions previously considered incapacitating and lethal. Regrettably, the burden of neurological disease continues to increase as these therapies are often inaccessible to people historically marginalized due to their race, ethnicity, age, sex, gender, culture, or abilities.^1-3 Structural and systemic inequities that exist at upstream sociopolitical and economic levels have also shaped, infiltrated and compromised the scientific rigor and integrity prioritized by the translational research enterprise in neurology. Translational research grows from pre-clinical study design to clinical trials to therapy dissemination and implementation. In a similar fashion, avoidable research inequities begin at the design phase, and inadvertently grow to become healthcare disparities when reaching the dissemination and implementation phases (Figure 1). Inequitable research environments further facilitate this process, which could at least partially explain why healthcare disparities continue to grow despite significant efforts at the dissemination and implementation phases. In this manuscript, we synthesized recent guidelines and statements to propose seven actionable strategies to integrate equity within translational research in neurology (Table 1). We use race and ethnicity as the main examples, but these strategies could be applicable to other axes of diversity in an intersectional manner.

Figure 1. Schematic representation of equity, safety and efficacy during translational research and healthcare.

Equity is considered a major goal of healthcare, and it is usually addressed after implementation and dissemination of therapies developed during translational research. Safety and efficacy are considered major goals of translational research, and they are usually achieved through scientific rigor and integrity during earlier phases of translational research. Systemic and structural inequities affect all phases of translational research, and they could exacerbate existing healthcare disparities. Thus, equity could also be considered a major goal of translational research, equally important as safety and efficacy (Adapted from the National Center for Advancing Translational Sciences website: https://ncats.nih.gov/translation/spectrum).

Table 1.

Seven strategies to integrate equity within translational research in neurology.

Strategies	Recommendations
1. Learn history	- Learn about craniometry studies - Learn about “race corrections”
2. Learn about upstream forces	- Learn about the cost of translational research - Learn how research funding areas are prioritized in the U.S. and advocate for support for research to inform and drive health policies that reduce health disparities - Consider, validate and promote potentially less expensive research methods
3. Diversify and liberate	- Be inclusive, authentic, transparent, deliberate and accountable - Move from ethnographic authority to shared power and practices that prioritize science - Share roles of researcher and research participant - Include an “equity focus” or an “equity and implementation plan” during study design
4. Change narratives and adopt best communication practices	- Use a culturally humble communication style - Spell names correctly - Ask for correct name pronunciations - Ask for correct pronouns - Use language that promotes equity
5. Study social drivers of health and lived experiences	- Consider measuring and analyzing relevant social drivers of health - Consider using qualitative interviews or pre-defined scales to measure and analyze the lived experiences of racism, perceived discrimination and trust in research - Consider how social oppression has shaped our identities as researchers and research participants
6. Leverage health technologies	- Consider innovative and accessible health technologies - Monitor for and prevent unintended consequences of technology dissemination, including exacerbation of existing inequities
7. Build, sustain and lead culturally humble teams	- Welcome everyone as a potential team member - Measure and train yourself, and your team members, in implicit bias and shared leadership skills - Consider participating and contributing to programs that specifically address workforce diversity

Methods

The two first authors (KJL, TG) searched MEDLINE (PubMed) for statements and guidelines published by U.S.-based professional medical organizations to address equity in medicine between January 2019 and December 2022. The search strategy included the keywords “equity”, “diversity”, “inclusion”, and “guidelines”. The search was updated prior to manuscript submission (October 2023). They independently screened all titles and abstracts to select relevant articles for full text and reference list review, prioritizing data-driven and historically important work. After the initial article selection, they met twice with the two senior authors (RCG, RGH) and once with the rest of the co-authors to discuss initial results, and to add relevant work to substantiate the strategies proposed in this manuscript.

Results

The initial search resulted in 71 articles. The updated search resulted in 105 articles. Title and abstract screen resulted in 32 relevant articles for full text and reference list review. After co-author meetings, the selection process resulted in the 68 articles, books, book chapters, policies and websites that are synthesized below as seven strategies to integrate equity within translational research in neurology (Table 1).

Strategy 1: Learn history

The historical roots of ongoing research inequities are complex and include unfair oppression based on differences in race, ethnicity, origin, culture, and other human traits.⁴ Historically, medicine has contributed to establishing race as a scientific, biological and hierarchical factor to distinguish individuals from diverse backgrounds. For example, craniometry studies that associated skull size with intelligence and morality created a flawed hierarchy that placed people from European ancestry at the top and people from African and Indigenous ancestry at the bottom.⁵ Differences in phenotypical traits (e.g. skull size and skin color), geographic ancestry, and cultural identity, have been used by different societies to create artificial categories that justify racism, slavery, colonialism, and other oppressive practices leading to ongoing marginalization, inequality, and structural racism.

In medicine, attributing phenotypical differences to biological factors has contributed to research inequities and healthcare disparities. For example, “race corrections” in pulmonary and renal function testing unfairly disadvantaged Black people, and these formulas are now being replaced by new systems.^6-9 A similar “biologically-dominant” approach has also been prevalent in neurology. For example, race-based differences in cerebral vessels and the pathophysiology of hypertension were posited as contributors to the disproportionately high incidence of stroke in Black people,^10,11 and they were used to potentially explain why hypertensive Black people have an adjusted relative risk of stroke that is more than twice as high as that of hypertensive White people.¹² However, subsequent research showed that differences in social drivers of health (SDoHs) are the major contributors to these disparities.^13,14

A “biologically-dominant” approach has also influenced treatment guidelines. For example, widely accepted algorithms for the treatment of hypertension in the U.S., based on evidence from clinical trials, include Black race as an important variable.^15,16 These guidelines recommend thiazide diuretics or dihydropyridine calcium channel blockers as first-line for Black people, instead of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. These recommendations were made with the well-intended goal of reducing racial disparities in hypertension control. However, the clinical trial data from which they emerge may have been misinterpreted.¹⁷ Recent studies suggest that providers are following these race-based recommendations; however, hypertension control remains worse for Black people.¹⁸ Tailoring therapies to each individual, regardless of race, could help everyone achieve better health outcomes.

Using pathophysiological explanations to justify inequitable health outcomes could distract research and treatment efforts while perpetuating structural racism and discrimination. Recently, the National Football League in the U.S. promoted the use of race-adjusted neuropsychological scores for the diagnosis of dementia in former players instead of considering social drivers that can impact brain health, which could unfairly disadvantage Black players seeking compensation.¹⁹ Deliberately studying and understanding the historical background that originated and may still contribute to research inequities and health disparities could help our research teams design studies for equity, which could lead to more equitable dissemination and implementation of novel therapies.

As researchers, we must acknowledge the critical impact that race identity and social differences have had in science. Justified by science, research has included colonizing practices, such as “codifying and discovering race in physical and social reality”,²⁰ and imposing the “scientific” method over “non-scientific” local practices. Research has also contributed to ongoing generational mistrust and social tension, as exemplified by the consequences of the “Tuskegee study”. We must also acknowledge that our subjective identities and life experiences inform how we seek, produce, interpret and use knowledge. Liberation will require historically-informed research teams that identify, question and change power relations, racist and colonial practices that could unfairly influence knowledge production and validation within their research efforts and within the research enterprise at large.

Strategy 2: Learn about upstream forces

European empires were capitalist systems that generated the conditions for structural racism while colonizing and extracting resources globally.²⁰ The use of the term race evolved when the “biological distinctiveness” of humans became economically important for the slave trade.²¹ As evidenced during the COVID-19 pandemic, similar sociopolitical and economic forces continue to shape inequitable structures and systems that are at the root of health inequities and healthcare disparities. In neurology, one of the main upstream drivers of treatment inaccessibility is the high cost of translational research.²² This high cost could generate inequities within the translational research cycle directly (e.g. by making certain research efforts financially unattainable) and indirectly (e.g. by creating inequities within research funding and healthcare paying mechanisms). From the research funding perspective, animal and pre-clinical studies that define mechanisms of novel molecules and devices with treatment potential are more frequently funded by governmental entities. Funding at this stage requires going through a rigorous competitive process based on scientific merit. Through this process, governmental entities are able to influence research efforts based on public health and scientific priorities. Since researchers from historically marginalized groups may be at a disadvantage when competing for government funding,²³ their efforts are less likely to influence public health and science. Completing subsequent phase 1, 2 and 3 trials is costlier but it could lead to approval for commercialization. These trials are more frequently funded by industry, whose primary motivation of profit/gains for shareholders could be driving higher costs for healthcare payers.²⁴ The prioritization of biological and mechanistic research by major funding bodies, leaving implementation science to be mainly influenced by unpredictable market forces, could shape all downstream efforts to achieve equity.

We need to deliberately study and understand how social, economic and political forces influence our research endeavors,²⁵ as well as who is funded to conduct work and what work is funded. This could help our research teams design and advocate for equitable studies and policy changes to allow healthcare payers to negotiate drug pricing (e.g. the Centers for Medicare and Medicaid Services in the U.S.).²⁶ We also need to consider, validate and promote potentially less expensive and more cost-effective research methods, including “non-scientific” local practices that could have a larger impact in promoting wellbeing and preventing disease (see strategy 1). Engaging in structural competency training could facilitate learning how upstream drivers shape healthcare disparities and health inequities that may have begun during the earliest phases of study design, during the priority setting process. Our research teams must have space and time to analyze the social, economic and political factors that may be influencing our scientific efforts. Decision-makers who allocate funds should also be incentivized to re-assess the prioritization process to align with the goal of reducing inequities.

Strategy 3: Diversify and liberate

Considering historical, sociopolitical and economic factors, diverse researchers, research participants and their communities should be at the center of any model trying to achieve equity in research, clinical implementation and public health. Diversity of research participants is essential to ensure that research findings are generalizable. In the U.S., the National Institutes of Health (NIH) is mandated by law to ensure the inclusion of women and historically marginalized groups in all NIH-funded clinical research in a manner that is appropriate to the scientific question under study.²⁷ Additionally, the statute requires clinical trials to provide information about differences by sex, race and ethnicity. High-impact journals have recently implemented similar policies.^28,29 Despite these efforts, minimal enrollment of subjects from historically marginalized populations continues to limit generalizability, equitable implementation and dissemination of resulting therapies.³⁰ Reporting requirements could also perpetuate inequities by enforcing the choice of certain categories while excluding others (e.g. requiring binary sex reporting).

Contemporary research is moving beyond inclusion to transparency and accountability. Researchers are taking responsibility for what they do or fail to do, while ensuring that research participants and communities are continually informed about the research process.

Traditionally, research has been designed and conducted by researchers who play significant decision-making roles but tend to exclude themselves as research participants.³¹ However, our personal histories, lived experiences, education and training can shape the way we interpret reality and produce knowledge. For example, research legitimacy in conventional academic practice implies power and privilege, as it is usually conferred by members of dominant groups when produced by members of those groups. In this context, the research enterprise could benefit from adopting shared, liberating practices that prioritize scientific integrity. Sharing this common vision could re-establish trust as we work together in an authentic spirit of collaboration, while acknowledging the privilege that comes with certain positions and identities.³² Liberating research requires shared scrutiny and consensus modification of dominant, self-perpetuating practices that reproduce historical power relationships contributing to health inequities and disparities.

Research participants are conventionally thought of as objects of study, and researchers as “objective” data collectors and interpreters who can theorize and create “valid” knowledge apart from subjects. This practice carries the risk of de-legitimizing research participants and their communities as “objective” and “valid” knowers. It could also create an authoritarian and artificial division between the “objective” knowledge created by the researcher and the “subjective” knowledge that resides within research participants and their communities.

The appropriation of experiences and voices of people from historically marginalized groups is another practice at the root of generational mistrust in research. Liberating research requires questioning the practice of ethnographic authority. Our challenge and responsibility is to promote and uphold spaces for all constituents to be able to equally produce, interpret and disseminate knowledge. This is different from the authoritarian position of just enrolling and following research participants in order to validate research findings. Research participants should be thought of as theorists and creators of their own everyday lives, their own knowledge and practices, instead of purely subjects of study. We need to challenge the notion that knowledge has a unidirectional flow from the source (i.e. research participants) to “the expert” (i.e. researcher) to the academic community.²⁸

A continuous partnership with research participants and communities is required to originate, discuss and enhance shared research ideas. We should be authentic, transparent, clear, and intentional as shared ideas develop into co-created studies. Between January 2016 and December 2020, the National Institute of Neurological Disorders and Stroke (NINDS) funded over 9100 grants, subprojects and supplements. Double-blinded screening and coding revealed that 58 of these applications were related to health disparities. Out of these 58, only 16 describe a community engagement process (e.g. community advisory boards, community health workers, neighborhood clinics). As privileged members of academia, we have the responsibility to: 1) offer opportunities for community members to participate in study design, conduct, data collection, analysis, interpretation and publication, 2) facilitate participation as research participants for all, 3) share study data individually and with participating communities, 4) ensure study results benefit all, and 5) share and enhance future directions with participation of all. Including an “equity focus” or an “equity and implementation plan” during the phase of study design could help fulfill some of those responsibilities. Research teams also have the moral obligation to help research participants navigate the additional layers of complexity added to our already complex healthcare system. This level of collaboration could result in long-lasting mutual benefits for study participation, recruitment, retention and implementation of study findings.^33-35

Strategy 4: Change narratives and adopt best communication practices

Narratives are collections of stories and messages that represent an idea or belief.³⁶ Using dominant narratives could perpetuate inequities in research. For example, in a recent lecture the speaker said: “We should include more minorities with Alzheimer’s in our trials”. An alternative could have been: “We should include more people from historically marginalized communities who live with Alzheimer’s disease in our trials”. Another example is to use the term “social drivers of health” instead of “social determinants of health”, as the latter could imply that nothing can be done to change. Long-lasting changes in dominant narratives and scripts will require a culture change facilitated by diversification of the research workforce at all levels, including high-level leadership. In the meantime, we need to make a deliberate effort to use a culturally humble communication style when approaching our colleagues, trainees, research participants and communities. For example, spelling written names correctly, and asking for correct name pronunciations and pronouns could help re-establish trust. We need to understand and use appropriate language to communicate about discrimination and racism.^37,38 Ideally, terms and definitions will be universally agreed upon in the future. We need to deliberately educate ourselves, our research teams, and the communities we are liberating, on the use of language that promotes equity.^29,39,40 More examples and recommendations can be found in “Advancing Health Equity: A Guide to Language, Narrative and Concepts” by the American Medical Association and the Center for Health Justice of the American Association of Medical Colleges.³⁶

Strategy 5: Study SDoHs and lived experiences

The creation of the Patient-Centered Outcomes Research Institute (PCORI) in the U.S. in 2010 is a positive example of how the extension of “patient-centeredness” from healthcare to research is publically recognized and supported.⁴¹ Similarly, the importance of SDoHs and lived experiences in research could be understood as being “patient-centered”.

The human genome project found that our genomes are 99.9% identical in every person around the globe.⁴² Thus, it may not be possible for any of us to be assigned to biologically distinct subcategories. Moreover, differences in racial and ethnic categories defined by society may be better explained by environmental rather than biological differences. Since racism originated racial categories in a society-specific manner (see strategy 1), racial categories could have historical and societal value in a place-specific manner but they may not be appropriate as research variables (as the goal of science is the generalization of knowledge). Nonetheless, racially-based categories remain prominent variables in translational research and they are often used to extrapolate research findings to diverse populations. Analyzing research findings by racial categories, hypothesizing and attributing differences to racially-based pathophysiological differences could lead to race being misconstrued as a risk factor. For example, multiple sclerosis was called the “white man’s burden spread from western Europe” in the 1970s.⁴³ Rather than exploring social factors (such as differences in the access to diagnosis), initial explanations focused on biological factors (such as potential genetic and geographical differences). Recent studies have shown increasing rates of multiple sclerosis in historically marginalized populations,⁴⁴ who also bear a larger burden of progression and disability when compared to White people.^45,46 Rather than a risk factor that predicts disease or disability, race might be better conceptualized as a risk marker of vulnerability to the effects of structural and systemic bias, disadvantage and racism in society. SDoHs and the lived experiences of racism might exert a powerful influence on the risk of disease. For instance, there is evidence that discrimination, a key driver of SDoHs, is associated with alpha-adrenergic hyper-reactivity and peripheral vasoconstriction, which could lead to hypertension.^47,48 Thus, discrimination and racism could contribute to the higher risk of hypertension and stroke in Black compared to White patients.

The isolated collection, analysis and reporting of research data based on pre-defined racial and ethnic categories could perpetuate certain inequities (see strategy 3). Since racial categories may not be adequate research variables in isolation, research teams should also consider measuring and analyzing the potential influence of SDoHs and diverse lived experiences. For example, if diet is important for the research question being addressed, then food insecurity and access to healthy food could also be measured. In 2021, the American Stroke Association published recommendations to achieve health equity.¹⁴ These recommendations include evaluating SDoHs when managing stroke risk factors and integrating health literacy into secondary prevention.

Research teams could also use qualitative interviews and pre-defined scales to measure the lived experiences of discrimination and racism at all levels, including structural (e.g. generational trauma), institutional, interpersonal and internalized.³⁷ Some examples include the “Index of race-related stress” and its brief version,^49,50 the “Everyday Discrimination Scale” (a 9-item scale that includes race-related discrimination and general stress),⁵¹ the PhenX data collection worksheet on major experiences of discrimination,⁵² among others.⁵³ Trust in biomedical research can also be measured using validated tools, such as the “Perceptions of Research Trustworthiness Scale”.⁵⁴ When analyzing and reporting research findings, we should remember that races and ethnicities are social constructs that go deeper than the skin. Research seeking to liberate historically marginalized populations must include the study of their lived experiences of oppression.

Strategy 6: Leverage health technologies

Health technologies are one of the main drivers of the high cost of healthcare in the U.S. Research advancing the development, validation, feasibility, and effectiveness of innovative and accessible digital health as interventions to address health inequities technologies (e.g. mobile health, telemedicine and telehealth, health information technology, remote monitoring devices, etc.) has the potential to reduce barriers related to access. Due to income inequality and structural racism, historically marginalized communities and individuals living in rural areas and urban silos have limited access to neurological specialists and therapies. Digital health technologies could increase access to these specialists and decrease time to access care for populations burdened by structural disadvantage.⁵⁵ When applying technological advances to the care of people living with Parkinson’s disease, we have learned that the use of technology could also exacerbate inequities given that access to technology is unevenly distributed.⁵⁶ For example, approximately 75% of adults in the U.S. had access to high-speed internet at home in 2021. However, only 55% of adults making $30,000 or less per year had access to this service.⁵⁷ Having learned from history, we must avoid colonizing practices when attempting to disseminate technology widely. Some recommendations to consider include partnering with community-based organizations to provide asynchronous access to computers and high-speed internet, partnering with internet companies to provide low-cost access, and geo-targeted recruitment efforts.⁵⁸ We should prioritize studying accessible technologies that address access, reach, delivery, effectiveness, scalability or sustainability of interventions that target health inequities experienced by historically marginalized populations.

Strategy 7: Build, sustain and lead culturally humble teams

According to the latest U.S. census, the population of the U.S. continues to diversify: ~18.5% people self-identify as Hispanic or Latino (the fastest growing group) and ~13.4% as Black or African American. Yet, only 5.5% of medical school faculty self-identify as Hispanic or Latino and 3.6% as Black or African American. Diversification is occurring in all age groups, including the group over age 65, which is most affected by neurodegenerative diseases. Adapting and implementing the previously-suggested strategies will require diverse and culturally humble teams that have a sense of belonging to their increasingly diverse communities.

For the last 20 years, the Northern Manhattan Stroke Study (NOMASS) has followed over 250 thousand individuals of diverse racial and ethnic groups (63% Hispanic or Latino, 20% Black and 15% White). Findings from this study suggest that if everybody could achieve ideal cardiovascular health, the incidence of cardiovascular death would become less disparate.^13,34,59 This study also suggests that differentiated prevention campaigns targeting the different risk factors found in each group (as opposed to giving the same recommendations to all), could help achieve equity. Furthermore, just reducing differences is not be enough, if all groups worsen.⁶⁰ We believe that diverse and culturally humble teams would be able to partner with their communities to design, conduct, analyze, report and implement findings from similar studies. Teamwork and shared leadership are essential to prevent, navigate and address health inequities affecting our growingly diverse population. A multi-sectorial, collaborative, evidence-based approach that includes all constituents is needed to address health inequities within research. A teamwork approach that distributes leadership amongst diverse members of our communities in a culturally sensitive manner is critical. Reduced participation of trainees, researchers and clinicians from historically marginalized populations during translational research is an ongoing problem that might further accentuate existing inequities and disparities.^61-64

Despite recent progress in the diversification of the research workforce, the racial gap in funding rates for principal investigators on NIH R01 awards has continued.^23,65 Persistent structural racism and stereotyping may be creating barriers for people from historically marginalized groups to pursue research careers in medicine.⁶⁶ Training that emphasizes group level information (e.g. population risk factors) could reinforce racially-based stereotypes. In a study published in 2016, approximately 50% of trainees self-identified as White held false beliefs about biological differences between Black and White people.⁶⁷ Similar implicit biases could undermine research integrity. We should consider regular measurement and education on implicit bias, cultural humility and leadership skills for us and all members of our research teams.⁶⁸

The NINDS has established the Office of Programs to Enhance Neuroscience Workforce Diversity,⁶⁹ which coordinates diversity activities with the goals to increase applications from historically marginalized groups, to identify and root out bias in peer review and all other aspects of funding decisions, and to develop and track metrics openly. The NINDS funds several extramural training programs to increase recruitment of talented researchers from all groups, balance perspectives in setting research priorities, improve capacity to recruit subjects from diverse backgrounds, and improve capacity to address healthcare disparities. The NIH has also developed the National Research Mentoring Network for biomedical researchers from diverse backgrounds, which includes grant writing programs that have yielded promising results.⁶⁵ In 2020, the NINDS began a health equity strategic planning process that has recently culminated in 18 high-level recommendations, including for the training of scientists from historically underrepresented backgrounds.⁷⁰ Academic institutions are also developing exchange programs to deliberately enhance the cross-cultural skills of their faculty and trainees.⁷¹ Since transformative education is key for liberation, similar efforts could be considered by all constituents of the translational research cycle.

Conclusion

Equitable research that begins at the earliest phases of the translational research cycle could improve outcomes for all. However, structural and systemic inequities have shaped, infiltrated and compromised the translational research enterprise in neurology. Here, we have presented seven strategies to integrate equity within translational research. We propose that equity should be considered one of the goals of translational research, equally important as safety and efficacy.