Juliana Ison

The Michael J. Fox Foundation for Parkinson’s Research (MJFF) aims to speed clinical research by removing obstacles that stand in the way of drug development. In pursuit of this mission, the Foundation gathers insights from a wide range of stakeholders and uses these perspectives to enhance clinical trial processes from start to finish. In 

 Eye on Patient Advocacy series, we will share best practices and lessons learned from the field of Parkinson’s research that can be applied to clinical trials across disease states. In our latest column in this series, we discuss the dearth of research connecting social determinants to mistrust and distrust of clinical trials, and one study’s efforts to connect these dots.

Marginalized groups in the US, such as Black, Indigenous, Latinx, and transgender persons, have been historically neglected and systematically excluded in clinical trial participant recruitment. This exclusion is despite federal regulations that mandate the inclusion of women and other minorities in clinical trials.

 Recruitment strategies rarely prioritize the aforementioned marginalized groups in clinical trials despite evidence-based approaches such as sustained community education and engagement.

 Instead, researchers have continued to attribute the lack of diversity in clinical trials to the mistrust of marginalized communities.

 Mistrust is the belief that an individual from a marginalized group will not receive quality or fair treatment based on a history of maltreatment toward marginalized communities.

 However, interdisciplinary literature suggests social determinants—including poverty, segregation, food insecurity, and structural racism—not only produce poor experiences of health, but also a distrust of health research in general.

 Distrust refers to the suspicion that a specific provider, researcher, or institution can poorly treat or harm an individual from a marginalized group based on specific examples of discrimination or misconduct.

 Recent discussions on vaccine hesitancy have rightfully directed attention toward historic examples of misconduct toward Black communities. There are also historic reasons for distrust in Indigenous, Latinx, and transgender communities, which include imperialization, forced sterilization, and poor healthcare delivery.

 Hence, there is reason to believe that social determinants drive inclusion in clinical trials as well as trust.

Some literature suggests discriminatory experiences with other institutions—including law enforcement, housing, and schools—contribute to mistrust and distrust.

 For instance, as incarceration rates indicate, the burden of social injustice disproportionately impacts Black, Latinx, and transgender communities.

 Similarly, the recent forced sterilization of Latinx persons at the US/Mexico border presents another example of structural racism and institutional complicity.

 Interestingly, while there is strong evidence that mistrust and distrust contribute to lack of clinical trial participation for Black, Indigenous, Latinx, and transgender persons, there is also a dearth of research connecting mistrust, distrust, and clinical trial participation to social determinants. Additionally, there has not been an exploration of how Black, Indigenous, Latinx, and transgender persons, who have participated in clinical trials, have navigated barriers like social determinants and trust.

Trials and Trust/Investigación y Confianza 

study seeks to connect the dots from social determinants to clinical trial participation using narrative storytelling. 

Trials and Trust/Investigación y Confianza

 is a qualitative study collecting 40 narratives of Black, Indigenous, Latinx, and transgender persons currently living in the US and its territories who successfully completed clinical trials between 2010-2020. Participants are recruited through long-standing relationships the research team has with Black, Indigenous, Latinx, and transgender communities, as well as disease-specific research centers, community neurology centers, community health centers, foundations, support groups, adult day cares, nursing homes, and community-based organizations. The study is advertised in both English and Spanish using culturally-responsive content and media. Using semi-structured in-depth interviews, participants share the barriers to clinical trial participation that they faced and key facilitators that supported their completion. To explore the potential intersecting role of disease prognosis in motivation to participate in a clinical trial, the 

 study focuses on neurological conditions without effective treatments such as Parkinson’s disease, Alzheimer’s disease, and related dementias. The expected findings of this exploratory research include (1) a description of the impact of social determinants over the life course on mistrust, distrust, and clinical trial participation, (2) an understanding of the facilitators of clinical trial participation for individuals impacted by social determinants, and (3) a preliminary idea of how disease prognosis plays a role in the decision to participate in a clinical trial.

uniquely takes an emic approach to research by centering the voices of marginalized communities. 

 utilizes a novel approach to research by focusing on the successful completion of clinical trials by marginalized group members, further emphasizing the importance of diverse perspectives in clinical research. In addition, by engaging community stakeholders and returning the findings to communities, this study ensures the bidirectionality of research benefit for scientific and lay community alike. Lastly, by identifying barriers and key facilitators to clinical trial participation, The 

Trials and Trust/Investigación y Confianza Study

 will not only contribute to delineating the pathway to clinical trial participation for Black, Indigenous, Latinx, and transgender persons; findings from this study will also assist the research community with addressing social determinant barriers for future studies as this may increase diverse participation in health research.

, contact the study’s principal investigator, Dr. Paris Adkins-Jackson, at padkins-jackson@mgh.harvard.edu, and co-Investigator, Dr. Angie Sanchez, at asanchez27@mgh.harvard.edu.

Agarwal P, Ray S, Burdick D, Griffith A, Madan A. Optimizing Recruitment of Racial and Ethnic minority population in Clinical Trials in Parkinson’s Disease: Potential Barriers and Prospective Strategies. Neurology. 2017; 88(16 Suppl.): P4.010.

Jackson JD, Sanchez A, Ison J, Hemley H, Siddiqi B. Importance of Diversity in Parkinson’s Research. 

https://www.appliedclinicaltrialsonline.com/view/importance-of-diversity-in-parkinson-s-research

Freedman LS, Simon R, Foulkes MA, et al. Inclusion of women and minorities in clinical trials and the NIH Revitalization Act of 1993—the perspective of NIH clinical trialists. Control Clin Trials. 1995;16(5):277–285.

Jackson JD, Moy B, Evans MK. The Elimination of Cancer Health Disparities: Are We Ready to Do the Heavy Lifting? 

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Griffith DM, Bergner EM, Fair AS, Wilkins CH. Using Mistrust, Distrust, and Low Trust Precisely in Medical Care and Medical Research Advances Health Equity. 

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Curry L (Ed.), Jackson J (Ed.). Science of Inclusion: 

Recruiting and Retaining Racial and Ethnic Elders in Health Research

https://onlinedb.geron.org/cvweb/gsa_live/cgi-bin/msascartdll.dll/ProductInfo?productcd=GSA_Inclusion

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Loeb TB, Adkins-Jackson PB, Brown AF. No internet, no vaccine: How lack of internet access has limited vaccine availability for racial and ethnic minorities. 

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. Published February 8, 2021. Accessed Feb. 13, 2021.

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; all with CARE Research Center-Massachusetts General Hospital; and 

This study is supported by The Michael J. Fox Foundation, Genentech, a member of the Roche group, and Boston University’s Alzheimer’s Disease Research Center.

The MJFF Research Engagement Team includes 

, Research Partnerships Officer at The Michael J. Fox Foundation in New York, NY. To contact the MJFF Research Engagement Team, email: 

The Systemic Synuclein Sampling Study (S4) was a multicenter, cross-sectional, observational study sponsored by MJFF. The primary objective of this study was to better understand the progression of Parkinson’s disease (PD) by identifying the optimal biofluids and tissues for measuring the protein alpha-synuclein outside of the brain as a potential biomarker in individuals with PD. The secondary objective of the study was to create standard operating procedures for the collection and assessment of multiple tissues and biofluids to better understand alpha-synuclein’s potential as a biomarker for PD.

In January 2017, MJFF launched a survey to assess the need for transportation infrastructure at clinical trial sites. Data from the survey was used to inform the design of a transportation intervention that was tested via the Parkinson’s Disease Trial Recruitment Innovation (PD-TRI) project, an MJFF-funded pilot study aimed at reducing barriers and enhancing facilitators to clinical trial recruitment.

Patient retention is an important element of the Parkinson’s Progression Markers Initiative (PPMI), a landmark, longitudinal, observational study sponsored by MJFF. PPMI aims to find reliable and consistent biomarkers for PD progression by studying cohorts of Parkinson’s patients, populations at risk for PD, and controls without PD.

Although the barriers to PD clinical research among underrepresented groups (URGs) have been well identified, it remains unclear whether suggested interventions will improve engagement of traditionally underrepresented populations in PD research. For these reasons, MJFF sponsored the Fostering Inclusivity in Research Engagement for Underrepresented Populations in Parkinson’s Disease (FIRE-UP PD) Study to 1) explore whether it is possible to identify best practices to engage URGs in PD clinical research, 2) to assess knowledge and attitudes toward clinical research designs, and 3) to increase participation of URGs to Fox Insight.

Articles

Understanding the role of social determinants on clinical trial participation and trust.

Clinical Trials and Trust

 Eye on Patient Advocacy series, we will share best practices and lessons learned from the field of Parkinson’s research that can be applied to clinical trials across disease states. In our latest column in this series, we explore the importance of addressing barriers to participation for historically underrepresented and marginalized groups.

Despite growing emphasis on increasing diversity in clinical research, the proportion of underrepresented groups (URGs; defined in this study as women and gender minorities, racial and ethnic minorities, individuals earning below a median household income of $57,000, a high-school education or less, and/or rural residents) in Parkinson’s disease (PD) research remains low, with as many as 91% of participants identifying as non-Hispanic Caucasian in various studies.1–3 Although some studies, such as the MJFF online PD research platform Fox Insight (FI), have been designed to reduce or eliminate research barriers for URGs, equitable representation in PD research remains elusive.4 Without diverse inclusion in these trials, estimates of PD disparities in underrepresented populations, which remain poorly understood, may widen.5–7

Although the barriers to PD clinical research among underrepresented populations have been well identified, it remains unclear whether suggested interventions from the existing literature will improve engagement of traditionally underrepresented populations in PD research. For these reasons, MJFF sponsored the Fostering Inclusivity in Research Engagement for Underrepresented Populations in Parkinson’s Disease (FIRE-UP PD) Study to 1) explore whether it is possible to identify best practices to engage URGs in PD clinical research, 2) to assess knowledge and attitudes toward clinical research designs, and 3) to increase participation of URGs to FI.

A request for proposals (RFP) was released for academic medical centers within the Parkinson Study Group research network to participate in FIRE-UP PD. Sites were instructed to identify a specific URG or geographical region to focus on, a specific barrier to PD research participation experienced by this group as categorized by the Picillo PD research barrier framework8, and a specified intervention as categorized by the Picillo et al. framework. Eight participating sites were selected, and were paired based on their proposed interventions and randomly assigned to either intervention or control conditions. Sites in Chicago, Boston, Denver, and Southern Florida were assigned to the intervention condition and were given $45,500 to execute their proposed design, whereas a second site in Chicago, the rural northern Midwest, the greater Seattle metropolitan area, and San Francisco were given $10,000 to serve as passive controls, maintaining their current recruitment workflow. Interventions included developing educational tools and surveys to engage community health centers in PD diagnosis (Boston), partnerships with local PD support groups to discuss PD research (Southern Florida), developing multi-stakeholder alliances and focus groups to create community-specific educational toolkits (Chicago), and recruiting community stakeholders to reimagine medical and research information for the community through a collaborative method called Boot Camp Translation (Denver).

The study was divided into three temporal phases for all sites: pre-intervention, to establish a recruitment baseline; intervention, to deliver a specified intervention or in the case of control sites, to continue passive recruitment activities, and post-intervention, to determine change from baseline. In addition to recruitment measures to FI, the FIRE-UP PD study was designed to collect survey responses from participants with regard to awareness and trust of PD research. Sites collected the Trust in Medical Research Scale (TIMRS), the Patient Engagement in Research Scale (PEIRS) and PD Research Participation Surveys, which assessed specific PD research designs and their impact on participation willingness. All sites also collected barriers to PD research participation, capturing reasons why URG individuals, who would otherwise participate in FIRE-UP PD, could not do so. All sites displayed FI recruitment materials as designed by MJFF and had a dedicated tablet device for FIRE-UP PD surveys and FI registration.

The FIRE-UP PD study enrolled 488 individuals across the eight sites (intervention n=295), while 230 individuals (intervention barrier n=101) faced insurmountable barriers to participation, outlined in 

Changes in trust, measured via TIMRS did not significantly improve for intervention sites relative to control sites, although a trend towards improvement emerged, t(382)=1.80, p=.073.There was no disproportionate change in patient engagement or in overall research participation willingness for intervention relative to control, all ts < 1. However, participant characteristics indicated that intervention site participants were significantly more diverse at both pre- and post-intervention with respect to race, ethnicity, income, and educational attainment.

Diverse accrual to FI (n=181) improved across all sites over the study period relative to sites’ own baselines, although intervention sites significantly improved diversity with respect to race, ethnicity, income, and educational attainment, while control sites improved race and ethnic diversity alone, as seen in 

The FIRE-UP PD study was designed to measure barriers, attitudes, and FI accrual for URG populations accessing PD clinical research. The study suggests that URG recruitment could have increased by as much as 50% if common participation barriers such as language, time, and the digital divide were addressed. Although sampling and selection factors obscured trends in the attitudinal surveys, intervention sites recruited a broadly diverse sample of participants to complete surveys as well as enroll in FI, despite intervention sites’ focus on a single URG. Notably, although control sites were instructed to continue their baseline recruitment activities, nevertheless these sites yielded increased racial and ethnic diversity in FI. This suggests that while targeted interventions may yield substantial benefits to improved diversity of PD research participation, merely orienting to the problem of lack of study representativeness may alter even passive recruitment practices in subtle ways to promote more inclusive research participant cohorts. Developing detailed recruitment protocols that focus on particular URG populations as well as barriers faced by these groups may be a promising addition to PD research, although future studies will need to better understand specific mechanisms of efficacy and comparative effectiveness given similar site and study characteristics.

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, all with CARE Research Center-Massachusetts General Hospital; and 

MJFF and Dr. Jackson would like to acknowledge the following individuals for their contribution to the research presented in this case study: Dr. Michael Schwarzchild (Co-I), Dr. Angie Sanchez (Research Fellow), Ms. Helen Hemley (Project Manager), and the site principal investigators: Dr. Mitra Afshari, Dr. Pinky Agarwal, Dr. Michael Aminoff, Dr. Meagan Bailey, Dr. Katelyn Bird, Dr. Stephanie Bissonnette, Dr. Michelle Fullard, Dr. Tarannum Khan, Dr. Danielle Larson, Catherine Wielinski, MPH, and Karen Williams, MS.

, Research Partnerships Officer at The Michael J. Fox Foundation in New York, NY. To contact the MJFF Research Engagement Team email: 

Building a Physician Referral Network: A Case Study

General practitioners often are not involved in the recruitment strategy for clinical trials. Historical barriers have made engagement with physicians challenging. They may fear losing care of patients to clinical trial site providers, be unfamiliar with the trial and principal investigator (PI), or have concerns about jeopardizing the doctor-patient relationship. One approach to building trust and overcoming these obstacles is for research institutions and PIs to actively engage with community physicians.

Eliminating barriers to engage underrepresented populations.