Fostering diversity in clinical trials: need for evidence and implementation to improve representation

An implementation science approach to diverse trial recruitment is needed

As well as pharmaceutical companies, the focus of the work by Miller and colleagues,6 diversity commitments have been adopted by many funding bodies, regulatory agencies, and journals. Also, numerous toolkits7 are available to guide trial teams to build equity, diversity, and inclusion into their research programmes. Subsequent evaluations, however, suggest that this work has had limited effectiveness.

For example, some funding agencies require an approach to sex and gender based analyses8 9 as part of the grant process. Although this approach has increased the proportion of applications that claim to consider sex and gender, observational evidence suggests that these requirements have not resulted in a more thoughtful approach to recruitment, collection of data, or reporting of results for female participants, women, and under-represented sex and gender minority groups.10 Similarly, efforts by the National Institutes for Health to increase the number of racial and ethnic minority participants in funded trials have not meaningfully dealt with this under-representation,11 and race and ethnic group of participants was not reported in about 50% of contemporary clinical trials published in high impact medical journals.3

The reasons that these well intentioned commitments have not resulted in real world improvements in diversity in clinical trials are not known. This problem highlights a need for implementation science, an approach to understanding why and how interventions, such as diversity commitments, do or do not work in some settings. This discipline offers a much needed, evidence based roadmap to fulfil diversity commitments, particularly in complex systems, such as health and medical research. Implementation science directs teams to describe the state of the local context, understand barriers and facilitators of current behaviour, and develop strategies informed by theory to enable success.

Trial teams should proactively identify and manage barriers to representative trial recruitment and retention

Applying an implementation science approach starts with understanding the local context, as emphasised by Miller et al, who reported that describing barriers to inclusive recruitment and retention are an essential diversity commitment. Many studies have described barriers to participation from the perspective of under-represented groups12 and proposed interventions for research teams to deal with these barriers.13 Investigators should note that these barriers and solutions likely vary by the topic, population, intervention, and setting of the trial, however, emphasising the need for a local approach rather than one-size-fits-all practices. For example, female participants are typically under-represented in cardiology trials14 but adequately represented in geriatric trials,15 which under-recruit participants with medical comorbidities, disabilities, and cognitive impairment.16

Emerging reseach has examined systems level16 and research team drivers17 18 of under-representation in clinical trials. Although many barriers are related to perceived resource constraints to recruit and retain under-represented groups,18 attitudes of researchers might be an overlooked barrier. For example, a qualitative study suggested that many trialists perceived barriers to more diverse trial participation as insurmountable rather than modifiable, despite generally agreeing that diversity was an important goal.17 Without dealing with this perception, other interventions to improve inclusion in clinical trials are likely to be under supported and unsuccessful.

Pilot and feasibility studies could incorporate an assessment of specific barriers to inclusive trial recruitment and retention for individual trials and settings. Numerous validated instruments and tools to describe barriers to implementation exist that can be administered through field notes, surveys, or interviews, depending on the skills and resources of the trial team.19 20 For example, surveys of acceptability and feasibility21 of inclusive trial recruitment strategies among trial team members, before implementation, can identify if attitudes of researcher are a key barrier. All assessments should be informed by implementation frameworks and relevant critical approaches, such as critical race theory or critical race feminism.

After describing contextual barriers to selected diversity commitments, approaches of implementation science confirm the findings of Miller et al, suggesting that trial teams proactively work with relevant community members and other stakeholders to deal with barriers before enrolment. This work can use implementation theory22 or mapping methods.23 Investigators could test the effectiveness of these targeted strategies to improve representation of clinical trials with study-within-a trial methods,24 thus contributing to the evidence base for inclusive trial design and improving the scientific productivity of the parent trial.

Diversity commitments are a shared responsibility between sponsors and institutions

Diversity commitments require coordinated, systems level support and accountability for both industry and investigators. Diversity in recruitment requires additional resources, time, and skills from trial teams, and this requirement for diversity needs to be balanced with the feasibility and generalisability of the trial. With decades of literature showing under-representation of trial participants for numerous acute and chronic diseases, new systems level approaches are necessary.

Firstly, the clinical trials community needs specific evidence on how to improve recruitment and retention across a diverse group of participants to match the epidemiology of the target disease, with input from patients, caregivers, and communities. Clinical trial networks are well placed to lead large study-within-a trial projects to generate this evidence, and funding agencies can incentivise this work with more resources for teams who include these protocols in their applications.

Secondly, this work should be mandated, monitored, and incentivised by an infrastructure for research and health services. For example, regulatory bodies could require protocol sections for each trial's specific diversity commitments. Guideline bodies, such as the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, should look at improving outdated recommendations for different ethnic group and geriatric participants, based on work on the eligibility criteria of pregnant and breastfeeding individuals as a precedent.25 Research ethics boards could incorporate an assessment of risks to diverse recruitment as well as to existing assessments of participant risks. Funding bodies should require trial teams to define prespecified goals for diverse recruitment and allow budgetary items to support these goals, such as transportation for study participants or hiring experts in equity, diversity, and inclusion.

Most importantly, patients and their healthcare providers should be empowered to hold sponsors and investigators accountable. Through professional and patient organisations, these stakeholders should use their platforms to celebrate patient centred, inclusive trials by prioritising participation, committing to all study procedures, and ensuring adherence and follow-up.