verybody should benefit from the advancements in care and treatments made through research with no one, or no group, unfairly excluded. This can only happen if we understand how interventions work for different groups of people. To gather this evidence, research must be representative of the people who stand to benefit from it.

However, due to barriers that inhibit participation, many groups and communities in society are not benefiting from the findings of research. This in turn impacts their access to high-quality healthcare.

In the UK, the Health Research Authority (HRA) and Medicines & Healthcare products Regulatory Agency (MHRA) are well-placed to set expectations, and support researchers to meet expectations, for the design and planning of clinical trials and clinical investigations that support diversity of participants. This article illustrates the current work in this area.

The Importance of Diversity

Including a range of people in research, which is representative of the broader population, is crucial in providing an understanding of the safety and effectiveness of medicines and devices, as well as information about an illness or condition across different groups of people.

Research that is designed to include those who may be impacted by the findings helps to:

• Improve our understanding of a disease and the medicinal product or intervention under investigation;
• Ensure that the data generated reflects the diversity of the population expected to use the medicinal product or intervention; and
• Potentially identify effects on safety or efficacy outcomes that may be associated with or occur more or less frequently within these populations.

Health inequalities have a significant effect on individuals, communities, and society, impacting health outcomes and life expectancy, as well as costs to the health system and wider economy. Addressing health inequalities is a key priority as set out in the UK government’s 10 Year Health Plan. The UK can play an important role in reducing health inequalities by embedding a principle of inclusion in research.

There is strong public support for this. An online survey of more than 5,000 adults across the UK showed that 88% think it’s important to include a diverse mix of participants in research. The majority of people still hold this view, even if ensuring diversity means the research costs more money (70%) or takes more time (74%).

It is not only communities and/or societies who benefit from health professionals using the findings from representative research. This also benefits life science companies. Findings that apply to a larger proportion of the population are likely to support greater uptake of their products. Inclusive research can help patients and their healthcare providers discuss and make informed decisions on the most suitable treatment option available to them.

Current Barriers to Inclusive and Diverse Research

It is well-known that there are people and communities who, despite potentially having a higher disease burden for certain diseases compared to the general population, are frequently underrepresented or excluded from research. As a result, this lack of representation in research limits our knowledge of the safety and efficacy of treatments for certain populations.

There are many reasons, which are also well known, why individuals and groups are less represented in research. Barriers include:

• Unnecessary or restrictive inclusion and exclusion criteria
• Challenges and difficulties in accessing trials such as site location
• Lack of trust in research, medical institutions, or healthcare professionals
• Lack of knowledge or strategies among researchers for how to engage with certain communities or groups
• Communication or language barriers
• Lack of awareness of research including challenges in accessing information about research that is relevant to them.

Involving people and communities with relevant knowledge and experience is essential in designing inclusive trials. This ensures that studies are appropriate for the intended participants and reduces unnecessary burden from participation, making it easier to take part.

Consultation on New Clinical Trials Regulations

The consultation on legislative proposals to revise the UK regulations for clinical trials in 2022 asked whether legislative requirements to support diversity in clinical trials should be introduced. It found there was agreement that clinical trials should appropriately represent the wider population. However, there were mixed responses to the question of whether legislative requirements should be introduced to support diversity in clinical trial populations. These responses raised the issue that it may not be safe or ethical to include a fully diverse population in every trial, and that the unique risk, need, and benefit for different population groups in different trials should be considered.

The government response to the findings of the consultation on legislative changes was that explicit guidance would be better placed to address these issues and to ensure the flexibility needed to reflect the different types of clinical trials and participant populations.

HRA and MHRA Inclusion and Diversity Guidance

Including the right people in research needs to be considered from the start of the research process, from inception through to study design. To support this, HRA and MHRA have developed a set of draft questions and supporting guidance on how to develop an Inclusion and Diversity Plan (Plan) for sponsors and researchers to consider when designing clinical trials and clinical investigations.

Developing a Plan using the set of questions in the HRA and MHRA draft guidance will help researchers consider and demonstrate how their research is designed to include people who could be impacted by the findings, and that people underserved by research are not overlooked.

A Plan, submitted with an application, will help Research Ethics Committees (RECs) to understand the justification for decisions that researchers have made about who to recruit into their trials, inform their understanding of the overall application, and support discussions at the REC meeting.

Although underserved people and groups are generally considered to be people, communities, or groups who are less represented in health research, the communities that make up these groups may vary depending on the context or study. This is why the draft guidance asks researchers and sponsors to consider factors such as socioeconomic factors and geographic location, as well as age, sex, gender, and ethnicity, where they are relevant for their research. This will support them in considering how different characteristics interact and overlap to create greater disease burden and barriers to inclusion.

These questions prompt researchers to consider:

• Who is affected by the disease or condition being studied
• If the aims and design of the research mean that the findings will be generalizable to all identified and, if not, to explain why this is the case
• The recruitment goals for the study
• A plan to recruit and retain the proposed study population.

A pilot is currently underway in which sponsors and researchers have been asked to volunteer to develop a Plan and submit it as part of an application for review by a REC. The aim of the pilot is to assess the benefits of developing a Plan, with researchers and RECs providing feedback on their experience after the application has been reviewed. Five studies have now gone through the process under the pilot. After the pilot has been completed, the HRA and MHRA will review the feedback and use this to inform next steps.

For the purpose of this pilot, the MHRA Good Clinical Practice (GCP) inspectors will not be inspecting how the contents of the Plan were decided, how the Plan was written and approved, or adherence to the Plan. However, if aspects of the Plan are described in other documents included in the Clinical Trial Authorisation (CTA) such as the protocol, then that aspect may be reviewed on inspection by the MHRA.

Embedding a Culture of Inclusion

MHRA and HRA are working with sponsors and regulators, in the UK and globally, to support alignment of expectations in this area. The HRA and MHRA draft guidance complements the World Health Organization’s (WHO) guidance for best practice for clinical trials which identifies a lack of inclusivity and diversity as one of the issues contributing to the need to improve evidence generation. We are working with the National Institute for Health and Care Research (NIHR) to ensure that the information to be included in an Inclusion and Diversity Plan aligns with their requirement for applicants to demonstrate how inclusion is being built into all stages of the research lifecycle.

To support a consistent cross-sector approach to doing research in a more diverse way, we are also working with the research community to share knowledge within and across sectors. This continued work, alongside regulatory and funder expectations, will support embedding a culture of inclusion in clinical trials in the UK.

Conclusion

The UK government has signaled an ambitious intent to tackle health inequalities in both access and outcomes. Inclusive and diverse research will play a key role in this, helping to ensure the whole population has access to high-quality healthcare in the long term.

Embedding inclusion and diversity in research will further bolster the UK’s strong research infrastructure, making it easier to do high-quality research that the full diversity of the UK’s population can participate in and benefit from.

References available upon request.