By Maria João Cruz, PhD, Research Analyst, Centre for Health Solutions

Clinical trials provide the necessary evidence to prove safety and efficacy of new treatments and medical products. Given that the responses to a specific medication may differ among population subgroups depending on factors such as age, sex, genetic profile and ethnicity, clinical trials need to reflect the demographic diversity of the population that a pharma product is intended to serve.^1,2 Last August the Centre published a blog on the importance of inclusion and diversity in clinical trials and why it should be a research priority. At the time, we highlighted the initiatives being launched by regulatory bodies to improve diversity in clinical research but noted that, while there have been some improvements, pharma companies were still struggling to enrol participants from diverse demographic groups, particularly women, racial and ethnic minorities, and the elderly.³

Last week was National Inclusion Week and October marks Black History Month, so I thought this would be an appropriate time to explore whether there has been any progress in improving diversity and to understand better how to ensure that clinical trials represent the diverse populations they serve, especially ethnic minorities. Moreover, given we are currently living through the global COVID-19 pandemic, which has highlighted yet again the disproportionate effects of infectious diseases on people from racial and ethnic minorities, we explore how COVID-19-related clinical research is attempting to address the issue of diversity in clinical trials.

Why clinical trials need to be more diverse and inclusive

As we found in our first blog on this subject, racial and ethnic minorities continue to be under-represented in clinical trials and that, while barriers to diversity in trials are well recognised, sustainable solutions for overcoming them have proved elusive.^4,5 For example, in the US, 20 per cent of the people living with multiple myeloma are African Americans, yet they only account for six per cent of all patients in related clinical trials.⁶ Another example is the prevalence of type 2 diabetes in the UK, which disproportionately affects South Asians, whose mean involvement in clinical trials was found to be of 5.5 per cent, despite representing 11.2 per cent of the UK type 2 diabetes population.⁷

A comprehensive study of the barriers to participation in clinical trials that mainly impact racially and ethnically diverse patients found that the main barriers were: mistrust; lack of awareness/understanding of the value of research; fear; stigma of participating; poor engagement/communication from clinical researchers; and, importantly, general inaccessibility to clinical sites in more deprived areas, including time and resource constraints due to the financial burden and time commitment that participants might incur.^8,9

A report that studied a diabetes clinical trial, which compared non-African Americans to African Americans, found that the latter were more often ineligible due to existing comorbid conditions. The researchers recommended that monitoring trial eligibility criteria for differential impact, and modifying them when appropriate, may ensure greater enrolment yields.¹⁰

Prioritising inclusion of a diverse cohort of participants can result in a more robust and representative body of clinical knowledge that can also deepen our understanding of racial and ethnic differences in treatment responses.¹¹ Ensuring diversity in the clinical development of new drugs is not only a matter of scientific rigorousness and statistics, but also a matter of ethics and equitable access to healthcare. Every member of society should be able to contribute to and participate in clinical research of potentially life-saving and/or life-extending treatments. Overcoming the lack of diversity in clinical trials is a medical and moral imperative.

COVID-19 is having a bigger toll on ethnic minorities – being diverse and inclusive in the search for treatments and vaccines is vital

Mounting evidence is showing that the toll of COVID-19 is not equal, disproportionately affecting ethnic minorities.^12,13 A June 2020 report from Public Health England has found that, in the UK, people from Black ethnic groups were most likely to be diagnosed with COVID-19, and death rates from COVID-19 were highest among patients from Black and Asian ethnic groups.¹⁴ This report also found that, even when taking age into account (which was the largest disparity factor that was found), Black males were 4.2 times more likely to die from COVID-19 than White males.¹⁵ As research for COVID-19 treatments and vaccines continues to increase in pace and scale, it is imperative that clinical and observational research studies include representative and diverse groups of the whole population.

However, despite wide recognition of the importance of diversity in clinical research, such inclusion is not yet guaranteed. A systematic review published in June 2020 found that of 1,518 COVID-19 studies registered on ClinicalTrials.gov only six were collecting data on ethnicity.¹⁶ Meanwhile, in the UK, there is no obligation to record and report ethnicity in clinical research studies.¹⁷ However, in 2018 the UK’s National Institute for Health Research (NIHR) launched the INCLUDE projects, which provides a roadmap to steer development of initiatives to widen inclusion of under-served groups, including those from racial and ethnic minorities.¹⁸ The project is also intended to promote equality, diversity and inclusion in COVID-19-related trials, as research results must apply to everyone, particularly to those who are disproportionately affected. In late summer 2020, NIHR’s INCLUDE released guidance specifically designed to facilitate best practice in the design, funding, approval, regulation and delivery of research on COVID-19.¹⁹

Indeed, some initiatives are underway to try and address this issue. For example, the Centre for BAME Health, which is supported by the NIHR Applied Research Collaboration East Midlands and the NIHR Leicester Biomedical Research Centre, has partnered with the NIHR to ensure people from BAME groups are included in COVID-19 research.²⁰ Meanwhile, in May, the US Food and Drug Administration (FDA) released guidelines calling for minorities to be adequately represented in drug trials related to COVID-19; and, during a U.S. congressional hearing on July 21, four of the five major pharmaceutical companies in attendance pledged to have more inclusive clinical trials.²¹ It is too early, as yet, to know the extent to which these pledges are actually realised.

Using advanced technologies to overcome barriers and improve diversity in clinical research

In order for the pharma industry to serve a diverse community of patients, all key stakeholders involved in the clinical trial process need to take steps to make sustained changes to become more inclusive. Implementing technological innovations has an immense potential to help the industry improving inclusion and diversity in clinical trials, particularly by leveraging the use of home-based mobile and wearable technologies, together with social media platforms, to remotely monitor and support patients. This enables improved communication between clinicians, researchers and participants, while allowing for more flexibility. Such technologies have the potential to enable trials to reach remote and under-represented areas by overcoming the challenges and barriers to participation related to distance, costs and availability.²²

As we highlighted in our Intelligent clinical trials report, advanced technologies, particularly those with artificial intelligence (AI) capabilities, have a real potential to transform various aspects of clinical trials, including helping to reduce the burden of recruitment and enrolment through the use of trial-patient matching algorithms, ensuring a more efficient and faster identification of patients with adequate criteria. These technological innovations can not only help improving diversity and inclusion in clinical trials, but also help increase the overall experience and satisfaction of participants throughout the study, thereby improving retention and trial success rates.

Conclusion

Ultimately, all patients want access to the best treatment for their medical condition and pharma companies want to improve health outcomes for all patients. Consequently, representative diversity in clinical trials is vital to ensure all new medicines that reach the market are applicable to all population subgroups they are intended to serve. As all stakeholders involved in the clinical trial process seek to align more closely to patients’ needs, the evidence is clear that targeted initiatives are needed to ensure that no groups are excluded from participation.

Importantly, the COVID-19 pandemic has shone a spotlight on the need for any result generated from COVID-19-related clinical research to be representative of the whole community that will be in receipt of the treatment and/or vaccine. We believe that embracing digital health technologies and patient support platforms can revolutionise clinical research with improved success in attracting and engaging diverse patient populations and help the industry achieve the patient-centricity it strives for. For the industry, the time is ripe to improve collaboration and work together to diversify the pool of patients involved in clinical research and ensure all demographics are accurately and fairly represented in the years to come. As a minimum, it needs to be mandated that ethnicity and other population data should be collected as part of every clinical trial.

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¹ https://pubmed.ncbi.nlm.nih.gov/25669658/
² https://www.sciencedirect.com/science/article/pii/S0146280618301889
³ https://blogs.deloitte.co.uk/health/2019/08/why-improving-inclusion-and-diversity-in-clinical-trials-should-be-a-research-priority.html
⁴ Ibid.
⁵ https://www.sciencedirect.com/science/article/pii/S0146280618301889
⁶ https://www.myeloma.org/diversity/how-myeloma-different-african-americans
⁷ https://onlinelibrary.wiley.com/doi/abs/10.1111/dme.13103
⁸ https://www.sciencedirect.com/science/article/pii/S0146280618301889
⁹ https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2931380-5
¹⁰ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843916/
¹¹ https://www.sciencedirect.com/science/article/pii/S0146280618301889
¹² https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30228-9/fulltext
¹³ https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2931380-5
¹⁴ https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/908434/Disparities_in_the_risk_and_outcomes_of_COVID_August_2020_update.pdf
¹⁵ https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/908434/Disparities_in_the_risk_and_outcomes_of_COVID_August_2020_update.pdf
¹⁶ https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30148-6/fulltext
¹⁷ https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2931380-5
¹⁸ https://www.nihr.ac.uk/documents/improving-inclusion-of-under-served-groups-in-clinical-research-guidance-from-include-project/25435
¹⁹ https://www.nihr.ac.uk/documents/ensuring-that-covid-19-research-is-inclusive-guidance-from-the-nihr-crn-include-project/25441
²⁰ https://www.nihr.ac.uk/blog/ensuring-ethnic-diversity-in-covid-19-research/25160
²¹ https://www.verywellhealth.com/covid-19-vaccine-trial-diversity-5075500
²² https://www.clinicalleader.com/doc/practical-ways-to-increase-diversity-in-clinical-trials-0001