Inclusionary Trials: A Review of Lessons Not Learned

"Bench scientists, translational investigators, clinical and public health researchers and practitioners, and others must adopt a community-centered approach to research to ensure the translation of our work and to achieve health equity."

A longstanding body of literature describes the value of community-based participatory research (CBPR) in increasing marginalised community participation in research. Shared leadership between academic and industry with marginalised communities can foster inclusive participation in vaccine trials and increase public trust in the development of the vaccines and other therapies used during public emergencies. This article outlines practices that contribute to a lack of inclusive participation and suggests steps that trialists and other researchers can take. In addition, it discusses how research institutions can reexamine their policies to increase participation in clinical trials and instil institutional trustworthiness.

The authors begin by arguing that a lack of diverse representation in vaccine, pharmaceutical, and other trials is largely due to barriers built into the infrastructure of scientific research. These practices include: failing to appreciate how certain eligibility criteria may unjustly and disproportionately exclude certain groups; placing trial sites in settings convenient to researchers yet often inaccessible to marginalised groups; having monolingual English-speaking staff and materials; providing rigid and complex consent and documentation to groups with challenges to health literacy; failing to acknowledge or mininally addressing barriers to participation (e.g., transportation, childcare); and, in the case of COVID-19 vaccine trials, lacking quarantine support for those who may contract the virus. Exclusionary practices are reinforced when researchers who work within research institutions fail to seek, be aware of, and/or devalue community input.

Furthermore, educational curricula often fail to fully incorporate content that would help scientists gain competencies in community engagement and community partnerships to improve science. In addition, many scientists may assume that community inclusion is important further down the research road, after phase 2 trials. However, as argued here, if diversity in participation is not achieved in the development of the science, then the translation and applicability of clinical research may be undermined. Researchers who do engage marginalised communities may wrongly take the position that their contributions are of lesser value, which is evident when they fail to partner with communities during the research design stages.

The article examines various institutional policies that contribute to the exclusion of marginalised populations. For example, during the COVID-19 pandemic, grassroots community partners, including promotoras or community health workers, undertook education, testing, and vaccination and served as trusted messengers in the community. Yet promotoras, who may not be United States (US) citizens, often face barriers to salaried payments for their services and delays in reimbursement for their labour. The widespread experience of COVID-19 could have inspired the use of pragmatic vaccine trials instead of traditional clinical studies where participants traveled to research institutions. This exclusionary practice and others described here "rely heavily on traditional top-down research procedures, institutional restrictions, and a lack of innovation in envisioning a more inclusive research paradigm."

Per the authors: "Going forward, it is possible to conduct clinical trials differently." Specifically, they describe CBPR as an inclusionary approach that integrates community as an elemental part of the research process. "Through shared decision-making and collaboration, a CBPR study decenters the needs of an institution and its researchers and centers the needs of the community in an equitable way...." CBPR is characterised by 4 parts:

1. Community engagement: "continuous and bidirectional sharing of information and resources between scientific and community partners throughout the process of research development (e.g., identifying appropriate research questions and designs) and implementation (e.g., instrument development, methods selection, recruitment strategies)....It is a process that thrives on localization of efforts, ideas, and relationships....Mutual recognition of expertise supports the coproduction of ideas, the selection of appropriate methods and approaches, and the identification of research questions valued by all parties....[E]stablishing the foundation of trust upon which such sharing becomes possible is a multistage process in which both parties evaluate each other."
2. Partnership: prolonged engagement and participation that "demonstrate[s] that the scientific partner is committed to the well-being of the community....Partnership is necessary to ensure the proposed intervention addresses community needs, that the intervention or pharmaceutical will be useful to the community of focus, and that those committing time and effort will benefit from the research endeavor. Partnership is not a barrier to the creativity and innovation inherent in clinical trial research."
3. Action: "the codesigning of research that will contribute to change for communities in prioritized areas....Therefore, it is critically important to understand the experiences and concerns of communities to eliminate injustices inside and outside the research arena and to reduce health inequities."
4. Change: "a gradual process....Consequently, scientific partners should consider building interdisciplinary teams with clinical scientists, public health researchers, social scientists, community organizers, policy analysts, social workers, and others to ensure the span of priorities of communities can be served alongside the science. There is a grave need for the investment of research institutions in community partnership and engagement to sustain social change."

Good CBPR practices include planning for community engagement during the planning and recruitment phases, having regular dialogues with communities about their priorities, supporting them throughout a study, and navigating complex structural determinants of health.

The paper concludes with recommendations for promoting inclusionary clinical trials, including:

• Provide community benefit - e.g., increasing knowledge and access to trustworthy information, building trust in research, strengthening community access to resources, and building community capacity by including community members on the research team whenever possible to draw on their lived experiences.
• Reexamine policies and procedures so as to challenge norms - e.g., mold our research institutions to meet the needs of communities. To do so, we must relinquish power, centre communities, and make way for community agency. "We must shift our focus from seeing how funders and scientific researchers benefit above others to acknowledging how we can use our scientific privilege to benefit communities."

The authors suggest that these approaches "will have the ripple effect of increasing awareness, research participation, trust, and efficacy, thus enhancing our ability to conduct rigorous inclusionary research that can improve scientific outcomes."