Outreach and Engagement Efforts in Research on Down Syndrome: An NIH INCLUDE Working Group Consensus Statement

Abstract

The National Institutes of Health formulated the Outreach and Engagement Working Group in Fall of 2019 to support the objectives of the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). This Working Group consisted of a multi-disciplinary team of stakeholders in research on Down syndrome that met to discuss best practices for outreach and engagement to Down syndrome communities, with an emphasis on representation and diversity. This review and consensus paper describes the importance of increasing representation in DS research for future cohort building and summarizes the priority issues identified by the Working Group members. An overview of Working Group activities is then presented, followed by consensus recommendations and a discussion of future opportunities and challenges.

In the United States (US), a recent renewed investment in research on Down syndrome (DS) has spurred tremendous innovation in both basic and clinical sciences. This effort is led by the US National Institutes of Health (NIH) through its initiation of the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) in 2018. The INCLUDE Project is a trans-NIH research initiative that aims to address critical health and quality-of-life needs for individuals with DS. Among the stated goals for the INCLUDE Project is the identification of predisposing risk and protective factors associated with DS through the “development of cohorts to perform deep phenotyping and study co-existing conditions” that will facilitate a comprehensive mapping of genomic, epigenomic, transcriptomic, and proteomic features in DS (https://www.nih.gov/include-project/include-project-research-plan). To reach these goals, the INCLUDE Project research plan specifies the need to recruit cohorts of people with DS at different ages of the lifespan and to capture the broadest array of phenotypes and ages of onset for coexisting conditions.

Though essential to the mission of INCLUDE, cohort building poses numerous challenges. Successful cohort building is contingent on the recruitment of large numbers of individuals with DS who are representative of the DS population. This representation must encompass different segments of the DS population in terms of race, ethnicity, phase of the lifespan, and many other identities. In appreciation of the importance of this undertaking, the NIH INCLUDE Outreach and Engagement Working Group was initiated in the Fall of 2019. This Working Group was tasked with generating recommendations for cohort building through outreach and engagement, with an emphasis on representation and diversity. The results of this 8-month effort involved recommendations for strengthening DS community outreach in a variety of ways. This consensus paper first describes the importance of increasing representation in DS research for future cohort building and summarizes the priority issues identified by the Working Group members. An overview of Working Group activities is then presented, followed by consensus recommendations and a discussion of future opportunities and challenges. We note that the issues presented originated in conversations about US-based research and recruitment efforts, however, many of the issues raised generalize cross-nationally, and it is our hope that this consensus paper will lead to broader conversations about representation in research on people with DS internationally.

Challenges and Goals for Promoting Research Participation

Advancing clinical research in DS and other neurogenetic conditions is contingent on adherence to sound methodological specifications, including participant recruitment. A truism in clinical research is that larger samples are better, but achieving large samples can be a challenge for studies focused on a neurogenetic condition like DS with varying cross-national prevalence rates, ranging from 1 in 444 live births to 1 in ~1,300 (De Graaf et al., 2017; Martin et al., 2018). Many studies characterizing phenotypic features associated with DS include samples below 50. Being statistically under-powered in this way places research studies at risk for Type II error, or the lack of detection of an effect that is truly present. Sample size limitations also place a greater emphasis on the need for replication work, as novel findings require converging results for scientific substantiation. Further, smaller samples make it more difficult to understand within-group heterogeneity and to identify factors associated with risk for co-occurring conditions in subgroups of individuals. With smaller samples of participants in research studies, there is likely to be an inaccurate representation of the full gamut of outcomes on a given dimension, thus skewing analyses and conclusions made from this work.

Yet, even when larger samples are obtained, additional standards must be in place that address the representativeness of that sample across a range of identities. First, there is a sociohistorical imperative, as persistent identity-based disparities within the DS population must be addressed. A particularly concerning example comes from a 2001 US Centers for Disease Control and Prevention report that demonstrated marked improvements in life expectancy for individuals with DS between 1967 and 1997. However, the median life expectancy for people with DS identifying as White was twice that of those identifying as Black (50 vs 25 years; Yang et al., 2002). Recently, investigators reported higher case fatality rates among Black infants with DS than among White infants with DS in a large US metropolitan area (Rasmussen et al., 2006; Shin et al., 2007). Racial and ethnic disparities in US-based studies can also be found in the incidence of various co-occurring conditions associated with DS; Latinx participants are more likely to demonstrate genetic vulnerability for leukemia and Moyamoya disease (Kainth et al., 2013; Pine et al., 2007), and Black participants are at elevated risk for atrioventricular septal defects (Freeman et al., 2008).

In addition to the sociohistorical imperative that is raised by these inequities, there is a broader argument that non-representative samples limit the generalizability of the research conducted, and therefore weaken the potential impact of the findings produced. For example, novel treatments that are designed for the population of individuals with DS must be tested on the full range of dimensions within the DS population, including diversity in race, ethnicity, primary language use, rurality, phase of lifespan, degree of developmental delay, and co-occurring biomedical conditions. These concerns are delineated below.

Race/ethnicity.

Racial and ethnic under-representation is widespread in US-based studies on individuals with DS. The implications of this challenge can be observed most readily in US-based research on treatment outcomes. Our review of the literature on clinical trials and evidence-based practices for people with DS revealed only a modest range of racial and ethnic diversity (Boada et al., 2012; Kishnani et al., 2010; Lott et al., 2011; Rafii et al., 2017; Rosenbloom et al., 2020; Sano et al., 2016; Spiridigliozzi et al., 2016). Across seven randomized controlled pharmaceutical trials with populations of individuals with DS published since 2010, five reported on race/ethnicity, and individuals from minority groups represented only 6.33% of the cumulative sample.

Broader evidence for under-representation is found in the “NIH Inclusion Data by Research, Condition, and Disease Category Report,” which indicates that the median percentage of African American participants enrolled in research projects associated with DS is ~3%, and for Hispanic participants, the median is ~4%. In addition, the NIH DS-Connect registry, which aims to recruit and facilitate increased participation of people with DS in research in the US, illustrates challenges in diverse representation, with the majority of enrolled participants (~88%) identifying as White. The paucity of diverse participation in DS research studies is particularly critical, given the cross-racial and ethnic health disparities associated with DS discussed above.

It is also critical to ensure that research efforts in DS communities address the intersectionality of DS and race/ethnicity. An intersectionality-based perspective acknowledges that various cooccurring challenges magnify all disparities, including health (Wilson et al., 2109). As such, an individual with DS from a historically disadvantaged background is at risk for additional challenges that must be understood and accounted for in study cohorts and model interpretation. Indeed, it has been suggested understanding racial and ethnic diversity in the US contributes to a more complete understanding of biomedical outcomes (Oh et al., 2015). Cohort building for research on people with DS, therefore, must represent this intersectionality to accurately inform scientific findings and future treatment and intervention work.

Phases of the Lifespan.

Representation across the lifespan is another priority emphasized in the INCLUDE Project research plan. There has been a notable increase in the number of studies focused on adulthood in DS over the past 20 years, which may be at least partially attributable to the risk for co-occurring Alzheimer’s Disease (AD) in people with DS. However, building a representative cohort that captures the full range of individuals with DS means involving participants throughout the entire lifespan, including characterizing the emergence of phenotypic characteristics from their earliest origins and presentations. A focus on adult participants in research, particularly in treatment studies, may contribute to specific limitations in our knowledge-base and jeopardize early identification and treatment progress. For example, it is possible that null findings in previous DS treatment studies may be attributed to the focus on adolescents and adults with DS who demonstrate reduced neuroplasticity relative to young children (Edgin et al., 2015). Recruitment of young children for both cohort and treatment studies is an important future direction, as early development provides a window of opportunity to capitalize on neuroplasticity.

In addition, to date, there have been no large-scale natural history studies of early development in individuals with DS from infancy through middle childhood. Given that this is the period when intellectual development is initially unfolding, and it is also the time when early manifestations of co-occurring conditions like autism tend to emerge, building a cohort of participants that addresses the large-scale questions posed by the INCLUDE project necessarily should include participants from the earliest phases of the lifespan. Additional emphasis on transformations that occur during adolescence are essential as well, given our growing understanding of the risk for Down Syndrome Disintegrative Disorder, or regression, during this phase of the lifespan. Effective outreach and engagement will likely involve building connections with families at different phases of family development and caregiving. Also, different outreach strategies may be needed to optimally recruit/involve families of infants and toddlers in research, compared to those used in outreach for families of adolescents or adults.

It is noted here that, in addition to the need for more representation from early childhood and adolescent participants, recruitment of older adults remains a necessity, because research to address the high AD co-occurrence rates in DS requires adequately powered research studies. This work also likely requires the inclusion of a broad age range of adults with DS, given the transition of many AD treatment trials to prevention, requiring younger, less cognitively impaired individuals. A lifespan approach to participant recruitment is necessary for generalizable and impactful future treatment work, particularly because there is a pressing need to understand the relative contributions of critical factors (e.g., genes, co-occurring illnesses) that overlap in influences within the neurotypical population, which will allow researchers to identify clinically useful biomarkers and targets for next generation clinical trials in DS.

Socioeconomic Status & Urban/Rural Residence.

Segments of the DS community may also be underrepresented in research because of geographic and socioeconomic factors. Although there is no comprehensive account examining these factors in DS research (e.g., the DS-Connect registry does not indicate rural vs. urban residence), rurality and high poverty density are known to provide barriers to access of diagnostic services for other neurodevelopmental conditions, such as autism spectrum disorder (Daniels et al., 2014; Mandell et al., 2010).

Despite the lack of a comprehensive account of SES influences on outcomes in individuals with DS, several recent studies outside of the US have begun to address this contextual influence on outcomes in children and families. For example, one study team reported differential developmental outcomes for children with DS from higher versus lower SES backgrounds in Latin America (Arango et al., 2018). When children with DS were compared to children without disabilities across measures of cognitive, language, motor, and social-emotional development, a larger differential between children with and without DS was observed among lower SES backgrounds, and less of a differential was observed between children with and without DS from higher SES backgrounds (Arango et al., 2018). Another recent study from the United Kingdom demonstrated a significant association between SES and intelligence scores throughout the lifespan in individuals with DS (Startin et al., 2020). SES is also known to interact with other factors in families of children with intellectual and developmental disabilities (IDD) in general, including subjective well-being and family stress (Gur et al., 2021). It may be the case, then, that families who experience lower SES are facing additional barriers to research participation, including more pronounced challenges in child developmental skills and increased levels of stress. Effective outreach and engagement that accounts for the intersection between SES, family stress, and overall child developmental skill acquisition is critical for improving representativeness in DS research.

Genetic and Phenotype Heterogeneity.

As noted above, one challenge for research on DS is to collect data that include the continuum of genetic and phenotypic outcomes associated with a trisomic imbalance for chromosome 21. For example, in the area of treatment work, some clinical trials for people with DS exclude people who have mosaicism for trisomy 21 or who have a trisomic (or partial trisomic) imbalance due to a structural chromosomal finding; yet, inclusion of these individuals is necessary to engage all interested stakeholders. Also, inclusion of people who represent the broad spectrum of phenotypic outcomes is important since studies that focus on the median or apex of the distribution of outcomes risk missing components of phenotypic consequences or responses to interventions/treatments. The concept of including individuals who represent extreme ends of the outcome spectrum is key to the successful practice of human-centered research design strategies followed in the private sector to solve problems and develop solutions/products, but this approach is less often utilized in academia (Chen, et al., 2020).

Primary Language.

Another factor that contributes to underrepresentation in treatment studies relates to language barriers. In US-based research on other neurodevelopmental conditions, like autism, children whose parents do not have English as their primary language are less likely to receive an early diagnosis (Schieve et al., 2012). US-based studies have also demonstrated that language barriers can also pose challenges to families as they navigate services and treatments for their child (Sakai et al., 2019). Recent work suggests that the use of interpreters in treatment settings has benefits beyond the ability to straightforwardly exchange information for families of children with autism spectrum disorder (Sakai et al., 2019). Qualitative studies conducted in the US that involve parents who have navigated this language barrier report that the use of interpreters also facilitates the building of trust between families and providers (Sakai et al., 2019).

Extrapolating from these insights, a similar set of processes could be recommended to ensure representation of participants with DS whose primary language is not English in US-based research studies. Interpreters would ideally be not only bilingual and bicultural, but they should also have background and training in the field of developmental disabilities and supporting outcomes for families (Sakai et al,. 2019). Efforts to bridge the language divide in DS outreach extend back several decades in the US, including a well-documented effort in the early 2000s by the Down Syndrome Association of Atlanta (in the state of Georgia; Martorell & Martorell, 2006). In an effort to meet the needs of a growing number of Spanish-speaking families of children with DS in the Atlanta region, an outreach effort was organized by the region’s DS association. Lessons learned are described in a narrative account of this effort, and they include the need to move beyond the simple translation of materials and conference brochures to address a range of family concerns (Martorell & Martorell, 2006). An active effort to build ongoing relationships was described as an essential aspect of this process (Martorell & Martorell, 2006), and prior outreach efforts such as that described in the Atlanta case study should inform best practices for increasing diverse primary language representation in research studies.

Degree of Developmental Delay.

Another critical challenge that must be addressed in outreach efforts involves the inclusion of those individuals with DS who demonstrate more pronounced levels of developmental delay. Though this subgroup of individuals with DS may be poised to demonstrate the greatest degree of response to treatments, they may often be excluded from basic science and treatment studies because of study design and inclusion criteria established by researchers, such as the ability to be evaluated on the selected outcome measure for a particular treatment trial (see Esbensen, Schworer, Fidler & Thurman, 2022 for a discussion of this issue). If measures are selected to capture treatment effects that do not include the developmental range of individuals with more pronounced delays, their response to treatment will not be captured. To date, however, when considering commonly used outcome measures for current treatment studies, the use of fully scalable measures that capture a wide range of developmental performances has not been widespread. Relatedly, when considering the inclusion of individuals with more pronounced levels of intellectual disability, challenges arise regarding the ability to obtain fully informed consent or assent, especially in the case of adults with DS. This issue is discussed further in the section below on “Ethical Considerations: The Critical Role of Informed Consent/Assent.”

Co-occurring conditions: medical information and documentation.

As the INCLUDE Project name indicates, a critical outreach goal is to represent individuals with a range of co-occurring conditions that are often associated with a DS diagnosis. These conditions are not only important for the identification of critical targets and the evaluation of treatments and therapies in people with DS, but they are also important for understanding how different conditions may impact individuals in varying ways throughout the lifespan. Understanding the impact of infantile spasms or congenital heart defects, both of which are more common in people with DS than in the general population, is vital to the characterization of development during the neonatal period in DS. It is also critical, however, to characterize the downstream impact of conditions like infantile spasms or congenital heart defects on outcomes during childhood, adolescence, and adulthood. Thus, effective outreach for cohort building in DS will necessarily involve the recruitment of participants who can represent both the proximal and distal outcomes linked to a wide range of co-occurring conditions.

A particular challenge in achieving representation across co-occurring conditions is that an accurate understanding of co-occurring conditions and their manifestation in people with DS can only be accomplished with meticulous collection of medical record information and documentation of those reports. Challenges arise from lack of medical records as families change healthcare providers and records are only kept on file for a limited period of time. Often researchers only have access to caregiver report, which can introduce a reporter perspective to data collection. As such, there is a critical need for guidelines for collection of medical information both from medical records and from caregiver report.

We note that both sources of medical information (caregiver report and medical records) are valuable and necessary to fully understand conditions that may be occurring. For example, medical records for an individual with DS may document that a diagnosis of sleep apnea is currently treated via positive airway pressure. However, supplemental information from caregivers can provide more nuance regarding the adherence to this treatment, and whether sleep apnea continues to pose challenges. Similarly, medication prescriptions may be listed in medical records, but caregiver reports may indicate that additional over the counter or holistic treatments may be used that are not documented in healthcare records. The effort to harmonize medical data collection and tracking is currently being addressed by the INCLUDE Data Coordinating Center (DCC). Establishing consistency across research studies will allow merging of smaller datasets to build those larger cohorts needed to reduce the data analysis issues related to small sample size.

Summary.

Adequate representation of people with DS is critical for cohort building, one of the key goals of the INCLUDE Project. To do so, recruiting large samples is necessary, but not sufficient. Innovative outreach and engagement efforts are necessary to ensure that individuals with DS are well-represented across racial and ethnic identities, at various levels of SES, across rural and urban settings, in linguistically-diverse populations, throughout the various phases of the lifespan, along the varying dimensions of developmental delay, and across co-occurring conditions. To achieve these important cohort characteristics, innovation is needed in relationship-building between researchers and stakeholders in the DS community.

Formulation of the INCLUDE Outreach and Engagement Working Group

In the fall of 2019, as a part of the effort to meet the research plan goals of the NIH INCLUDE Project, a working group was assembled that consisted of researchers, advocacy group members, clinicians, and other stakeholders in the DS community. This working group grew from the Fall 2019 INCLUDE NIH-sponsored workshop entitled “Planning a Virtual Down Syndrome Cohort Across the Lifespan,” which included a breakout session on “Outreach Activities and Participant Engagement.” The focus of the original workshop was to address the INCLUDE Project Component 2, which (as noted above) aims to develop a cohort of people with DS across the lifespan that will enable comprehensive phenotyping and pan-omics research at a scale that has not been conducted before (https://www.nih.gov/include-project/include-project-research-plan). The ultimate goal of Component 2 of the INCLUDE Project is to identify risk and protective factors associated with co-occurring conditions in DS. As a part of this workshop, participants discussed technical issues related to data harmonization and data sharing, but additional conversations were focused on how best to build relationships with stakeholders in the DS community through more effective outreach and engagement. Those initial discussions regarding improving outreach approaches led to the formulation of the Outreach and Engagement working group.

The working group met approximately monthly from Fall 2019 through to Spring 2020 via video-conference. The overarching questions posed to the group by NIH officials were: 1. “What are the best strategies to reach out to the community, including clinicians, researchers, and advocacy groups?;” 2. How can minority populations be encouraged to participate?; and 3. What feedback (e.g., results reporting, surveys, newsletters) do families find worthwhile to maintain engagement?” Participants included US-based national DS advocacy group leaders, representatives from a DS research organization in the US, a self-advocate, and a family member of an individual with DS, researchers who study DS, and a prevention scientist with expertise in outreach and engagement in prevention/intervention research. NIH officials also attended each meeting.

Initial discussions focused on outreach to specific stakeholders in the DS community, which were identified as self-advocates, parents and family members, therapists, allied health care providers, educators, and advocacy groups. Sessions involved discussions with leading health care providers for people with DS regarding what strategies have worked and what has not worked in terms of outreach regarding their involvement in research. In other sessions, family members of young children and older individuals with DS were invited to attend meetings and answer questions about their attitudes towards and experiences with research participation. These conversations grew into an effort to incorporate Community Based Participatory Research (CBPR) approaches to outreach, with an emphasis on building partnerships that are mutually beneficial for community members, practitioners, and researchers. The emphasis of understanding the CBPR approach involved an appreciation of the lived experiences of community stakeholders throughout the research engagement process (Riggs et al., 2021).

Recommendations of the INCLUDE Outreach and Engagement Working Group

Community-Based Participatory Approaches to Outreach and Engagement.

To increase representativeness in DS research across a range of dimensions, a primary recommendation from the Outreach and Engagement Working Group was the implementation of evidence-based public health strategies guided by an overarching community-based participatory research (CBPR) approach. Successful implementation of this research framework will improve the impact of DS research and serve as a template for inclusive recruitment in IDD research more broadly. In this section, we provide an overview of the CBPR framework and issues related to implementation. We then describe specific CBPR-related recommendations generated by the working group to promote diverse representation in future INCLUDE cohorts.

The CBPR framework involves a partnership between researchers and stakeholders in the scientific process (Israel et al., 2010), and recognizes the important role of community priorities, insights, and preferences. The advantages of a CBPR approach to study design is that researchers and community members can work together to select the issues, challenges, and concerns that are meaningful to the community of interest (Minkler, 2004). These priorities may not be readily identifiable by those outside of the community, including researchers (Minkler, 2004). This framework also prioritizes the dissemination of knowledge to the community to inform decision making within a community regarding their preferred programming and practice-related decisions (Israel et al., 2010; McDonald & Stack, 2016).

Though researchers play a critical role in the scientific process with their training, knowledge base, and methodological skills, CBPR approaches complement these skills with real world insights of community members (Israel et al., 2005), leading to research with greater ecological validity and potential impact. It has also been suggested that the design of research studies can benefit from the insights and opinions of community members (Riggs et al., 2021), who can provide feedback regarding their experience in the research process and what changes to procedures could remove additional barriers to research participation. In this way, the bidirectional nature of CBPR research means that research and study designs can be strengthened, and more relevant and impactful science can be generated to ultimately benefit community members.

The use of CBPR approaches for populations of individuals with IDD has grown in popularity over the past decade (Riggs et al., 2021) and implementing such approaches has great promise for strengthening research on people with DS. Though the implementation of CBPR principles may vary across study discipline and researcher-community partnerships, they are considered foundational to the generation of informed, impactful science. Application of these principles in future DS research will ensure that the knowledge that is generated, and the treatments that are developed, are truly well-aligned with the goals and the interests of stakeholders in the DS community.

Additional Working Group Recommendations.

Beyond the broader application of CBPR approaches to outreach and engagement with stakeholders in the DS community, the Working Group also identified specific strategies that can be readily implemented for INCLUDE cohort building:

1. A Focus on Deliverables.

As described in the section above, the concept of individuals providing information or biological specimens as a single “one-way” interaction with researchers is evolving. Increasingly, researchers are adopting models wherein participants are viewed as stakeholders in the research process, with the expectation that they will receive “deliverables” as a result of their contributions. The form of the deliverables will vary among projects, but could include group research result summaries, individualized result summaries, access to updates in the field, educational or volunteer services provided to support groups by the research team, and/or access to research-related scientific and social networks. Thus, one practical recommendation for improving engagement with a wide range of stakeholders in the DS community involves identifying deliverables of value, and to incorporate those elements as a part of the bi-directional research process.

2. Improved Outreach through Social Marketing.

The results of a survey conducted by LuMind showed that 98% of their membership indicated a wish to contribute to research, yet only 36% of the respondents had actually participated (White et al., 2021). This finding inspired the members of the INCLUDE Outreach and Engagement Working Group to explore using marketing strategies to enhance community involvement in research. For example, one could apply the 4 “Ps” of the marketing mix technique to identify: (1) the “product” desired/needed; (2) the “price” for acquiring that product; (3) the “place” to best market or deliver the product; and (4) “promotion” methods for optimally communicating the availability of the product (Grier & Bryant, 2005). In Working Group discussions, “Products” desired by both community stakeholders and researchers included helping others, obtaining results, and/or gaining resources that could improve the quality of life for people with DS and their family members. “Price” items identified as potential deterrents for self-advocate/family member participation included (but are not limited to): risk or anxiety as to the activities and outcomes of the research, time constraints, and costs (i.e. travel; time off work). Examples of “Price” components denoted as potential deterrents for researchers included long timelines to meet study recruitment needs, time/frustration related to completing human research regulatory compliance requirements, as well as high effort/low outcome risks.

The “Place” for joining in research was also identified as an important factor in the individuals’ desire to participate, with decision-driving factors including (but not limited to) convenience of the location, as well as the ability for a sibling(s) to attend and be occupied during the research session (thereby eliminating the need to find childcare). Participating in research as part of an advocacy meeting or educational event was also noted as an asset; along with the research being offered by a trusted allied health provider. “Promotion” aspects identified as important included sharing success stories of gains realized from the research. Other attributes identified as important for research success included developing a trust relationship, willingness of the researcher to contribute to the community (could be via educational activities, volunteering, joining in activities), and the researcher(s) demonstrating respect for people with DS and their family members.

3. Outreach to Newer Investigators.

The INCLUDE Project has successfully grown the number of investigators conducting research related to DS. With this growth comes the need to train new investigators on practices that will increase their success in conducting research with people with DS. The Working Group recommended that this type of training may focus on the design of successful study visits and study expectations, identifying behavioral support strategies to incorporate into study visits when needed, understanding participant and family needs and priorities, and creating a supportive and empathic research experience. Educating newer investigators in the research community is necessary to continue to provide individuals with DS and their families with a positive research experience, which can support increased research participation and engagement from families.

4. Broader dissemination of research findings.

The traditional format for disseminating research findings is through peer-reviewed research publications. Yet to increase research participation and engagement from individuals with DS and their families, the Working Group identified the need for connection with the general community to disseminate findings in lay terms. By presenting research findings to the community through national and regional DS meetings, researchers can build rapport with individuals with DS and their families. By disseminating information through social media outlets, DS research is shown to be a valued part of the public discourse.

Research engagement is further facilitated when potential participants understand the need for research in general and/or for a specific research study. Providing education to individuals with DS and their families on what research advances are being made in the field of DS is helpful for engaging the community. There is also the need for the research community to understand what types of questions are important to families. Building a culture of collaboration, where individuals with DS and their families are appreciated not just for their participation, but also for their input on how to improve study visits or modify research questions is essential for advancing research in DS.

The Working Group conversations made salient the importance of considering a wide array of dimensions when conducting outreach activities to promote research participation. Consensus was built around the long-term need for CBPR-focused study designs in DS research. More proximally, recommendations were made that included deliverables for the research experience, and the importance of considering the benefits, barriers, and preferences of varying subgroups of stakeholders in the DS community. Implementing these near-term and long-term strategies will likely be effective for improving representation in future DS cohorts.

Future Directions & Challenges

The core recommendations from the Outreach and Engagement Working Group involve the broader implementation of CBPR approaches, and each of the specific recommendations offered in this consensus paper is rooted in a CBPR framework. In building toward the future, increased effort to expand engagement in DS research is warranted. In addition to the recommendations identified above, the Working Group identified potential challenges to enhancing community-engaged research that may arise, including: (a) increasing funder and institutional appreciation of the value (as well as time investment) of conducting community-engaged research; (b) the need for training opportunities for researchers and community leaders to enhance their skills for team-building; (c) the need for institutional support to sustain relationships when funding ends; (d) increased flexibility of Institutional Review Boards to embrace the nuances of strategies that are optimal for community-engaged research; and (e) avoiding “burn out” related to the strain that can arise for both community leaders (who are often volunteers) and researchers (Irby, et al., 2021). One approach suggested by Stallings, et al. (2019) to enhance recognizing the value of community-stakeholder engaged research is to develop a taxonomy to aid in identifying community-stakeholder research and facilitate extracting metrics related to these projects. This approach may prove useful for the implementation of CBPR approaches in future DS research.

Ethical Considerations: The Critical Role of Informed Consent/Assent.

In the context of these recommendations for enhanced outreach, the Working Group also identified a critical ethical dimension that researchers and stakeholders in the DS community should continue to discuss. With greater representation across different ability levels and co-occurring conditions, important concerns may arise regarding informed consent and assent procedures for participants with DS. The end-goal of establishing large, representative cohorts of participants in research on DS must be accompanied by ethical practices and careful consideration of human subject protections.

The informed consent process includes two-way (or more) conversations and documentation of that communication via consent forms or e-consent forms. The consent/assent process is accomplished by the investigative team describing the project in language (both verbal and written) that can be readily understood by individuals from a wide range of educational backgrounds. Components of the informed consent process include descriptions of the study activities, risks associated with those activities, and the “deliverables” they can expect to gain from their participation.

To meet the needs of participants with DS with varying degrees of developmental delay, the consent and assent processes should be customizable to the individual. For study participants who are children, consent is typically first obtained from the parent/legally authorized representative (LAR) before obtaining assent from the minor with DS. Navigating consent processes with adults who have DS involves additional degrees of complexity. Some adults with DS may have the receptive understanding to provide informed consent, while others may require the option to provide assent, with their caregiver/LAR providing informed consent. Confirmation that a participant with DS understands their role as a study participant can be attained via a variety of approaches, including the use of developmentally appropriate language, encouraging participants to ask questions, and gauging their response to developmentally appropriate study-related questions. Given that many people with (or without) DS benefit from visual information, pictures can often help potential study members understand the research expectations more fully and aid in the consent/assent process. Novel approaches to informed consent from other fields, for example to ensure that participants understand invasive medical procedures, include the presentation of accessible videos of treatment procedures, in addition to a traditional consenting process (Bowers et al., 2017). Adult participants with DS who do not have decisional capacity may be asked for their assent before obtaining consent from their caregiver/LAR. Also, many adults with DS who are decisionally competent may opt to have their caregiver/LAR join in the consent discussion.

There are numerous issues to consider in establishing best practices for obtaining consent; particularly for adults with DS who show a range of intellectual disability. The Alzheimer’s Biomarker Consortium in Down Syndrome (ABC-DS) describes challenges in navigating the varying approaches to this process that differ by state within the US, with approaches that range from the use of an LAR to the assumption of an adult’s ability to provide consent unless it is demonstrated otherwise (Handen et al., 2020). The ABC-DS consortium describes that in some cases, protections are in place to reduce the risk of exploitation of people with intellectual disability, which is a response to historically unethical behavior from a time when such issues were not in consideration. This motivation to protect individuals from procedures that involve risk must be preserved, but also balanced against the risk of excluding many people with DS from potentially informative research studies and beneficial treatments. A continued conversation regarding best practices for navigating the ethical complexity of informed consent for individuals with DS will be critical for continued innovation in this field.

Concluding Thoughts

Throughout the course of the Working Group activities, a final key point of consensus was that we are embarking on a truly exciting moment in research involving individuals with DS in the US and throughout the world, with great promise of impactful and innovative treatments and scientific discoveries. The NIH INCLUDE Project has catalyzed researchers from a wide range of disciplines in the US to pose new research questions and conceptualize the best ways to answer larger scale questions that have remained unaddressed across decades of research for this population. The success of these research activities will be contingent upon the recruitment of representative samples of participants and ultimately, large comprehensive cohorts of people with DS throughout the lifespan. Though there are important challenges that researchers will face in working toward these goals, strengthening the relationships between research teams and DS communities is a cornerstone of future success in our field. Implementation of research approaches that emphasize mutuality, collaboration, and partnership across all stakeholders in DS research will lay the path toward ground-breaking and potentially life-changing scientific work.