Why improving inclusion and diversity in clinical trials should be a research priority

By Karen Taylor, research director, UK Centre for Health Solutions, Deloitte Services LP

Several weeks ago, I participated in a panel discussion on inclusion and diversity in clinical trials. My research for the event and the discussion that ensued led me to conclude that while there have been some improvements, the pharma industry continues to struggle to recruit enough trial participants from important demographic groups, especially women, racial and ethnic minorities, and the elderly. As a result, the outcomes seen in clinical trials are likely to be unrepresentative of the patient outcomes in the real world.

The mismatch between population demographics and participants in clinical trials

The basic assumption of clinical research is that investigators take data from a relatively small but representative selection of subjects and generalize the results to the larger patient population. If the sample is too constrained or poorly selected, it hinders the broad applicability of the results. This is a statistical concern—and an ethical and medical one. Challenges include reluctance to conduct trials in “vulnerable populations,” namely children, cognitively impaired individuals, pregnant women, and the elderly, as concerns over the risk of doing more harm than good leads to “playing it safe” and excluding vulnerable populations from trials.¹

There is general acknowledgement that there has historically been a mismatch between the demographics of a population that a new therapy is expected to treat and the participants in the related clinical trials. Despite numerous initiatives to try and tackle this problem, increasing clinical trial diversity in an effective, sustainable, and scalable manner remains a challenge for the pharma industry, academic institutions, and clinical research in general.²

For example:

• Racial and ethnic minorities have historically been underrepresented—a situation that persists in modern trials. In the US, African Americans comprise 13 percent of the population but—until recently—five percent of clinical trial participants. Meanwhile, Caucasians account for 67 percent of the population but 83 percent of research participants.³
• Elderly people are often omitted from clinical trials. Consequently, clinicians have limited information on how a given treatment might affect their older patients—specifically, whether a prescribed medication will be effective (or safe) for an elderly person.⁴
• Researchers often struggle to enroll adequate numbers of women in studies—or, when they do, fail to report data by sex. This omission can prevent identification of differences that could influence treatment options. For example, two-thirds of the 5.1 million people worldwide who suffer from Alzheimer’s disease are women. Women are also twice as likely as men to develop the disease. Until recently, researchers assumed this was due to women having a longer lifespan. However, recent discoveries from female-centric studies suggest that hormonal and genetic differences in women could have a crucial part to play.⁵
• The major endocrine changes that women experience, particularly during puberty, pregnancy, and menopause, are known to increase the risk of depression. Yet, fewer than 45 percent of animal studies on anxiety and depression use female laboratory animals. These studies could result in treatments that are less effective for women than for men—or that have more debilitating side-effects for women.⁶

Today, fewer than five percent of adult cancer patients participate in clinical trials, with ethnic and racial minorities enrolling at even lower rates. Economic concerns play a role, as low-income patients might lack adequate resources to pay for travel, childcare and/or time away from work. Research also shows that symptoms of conditions such as heart disease, cancer, and diabetes vary by ethnicity as they do between the sexes. Consequently, if diverse groups aren’t part of research studies, it’s difficult to be sure of treatment equity—or potential side effects.⁷

Recent initiatives to improve diversity in clinical trials

In recent years, many organisations, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have launched initiatives to improve the diversity of clinical trials enrollment. For example:

• As part of the 2012 FDA Safety and Innovation Act (FDASIA 907), Congress required the FDA to report on the diversity of participants in clinical trials and the extent to which safety and effectiveness data is based on demographic factors such as sex, age, and race.
• Since 2014, the Center for Drug Evaluation and Research (CDER) has operated a transparency initiative called the Drug Trials Snapshots, which provides information about the demographic composition of the data collected in trials of newly approved medications. Its last three summary reports show an improvement in the trial demographics, with inclusion of more female (from 40 percent in 2015 to 56 percent in 2018) and black or African American participants (from five percent in 2015 to 10 percent in 2018). Latino or Hispanic patients, who account for 16 percent of the US population, were not recorded in the first two snapshots but accounted for 14 percent of trial participants in both 2017 and 2018.⁸

There is a wide body of research identifying the barriers impacting minority patients’ willingness to participate in trials. In November 2018, a comprehensive report identified key themes, solutions, and a communications message map to support a multi-stakeholder approach for overcoming five critical barriers to greater diversity in participation: mistrust, lack of comfort with the clinical trial process, lack of information about clinical trials, time and resource constraints associated with participation, and lack of awareness about the existence and importance of clinical trials.⁹ It also identified potential solutions to improve recruitment of racially and ethnically diverse patients to help industry and academic investigators to develop strategies for increasing diversity in clinical trials.

Financial incentives can promote participation, especially when linked to participant costs and effort. Use of financial incentives, without undue coercion of any population, can help equalize study participation.¹⁰

Research also suggests that providing transportation, flexible hours for patients, appropriate compensation, and mobile technology support such as apps for patients (and mobile phones for those who do not have one), together with increased transparency in reporting, could help increase diversity in clinical trials.

Importantly, the pace of digital transformation in pharma can also help address the above issues, especially the increasing use of mobile technology and social media platforms to improve communication between researchers and support of trial participants. Telemedicine is also a game changer when it comes to extending patient reach by giving patients access to mobile and video encounters with health care providers. Virtual clinical trials mean that any qualifying patient who wants to participate in clinical research might not be limited by location.¹¹

These technology solutions, together with actionable evidence on ways to improve recruitment, can provide opportunities to increase the diversity of trial participants and improve their satisfaction—and overall experience.

^{Endnotes
1. http://www.appliedclinicaltrialsonline.com/importance-age-diversity-clinical-trials
2. https://www.sciencedirect.com/science/article/pii/S0146280618301889
3. https://www.pharmavoice.com/article/2018-03-diversity/
4. http://www.appliedclinicaltrialsonline.com/importance-age-diversity-clinical-trials
5. https://mdgroup.com/en/news/the-importance-of-gender-diversity-in-clinical-trials/
6. https://mdgroup.com/en/news/the-importance-of-gender-diversity-in-clinical-trials/
7. https://www.kevinmd.com/blog/2019/03/how-telemedicine-is-increasing-diversity-in-clinical-trials.html
8. https://www.fdanews.com/articles/190190-cders-latest-clinical-trial-snapshot-reports-fewer-trial-participants
9. https://www.sciencedirect.com/science/article/pii/S0146280618301889
10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646546/
11. https://www.kevinmd.com/blog/2019/03/how-telemedicine-is-increasing-diversity-in-clinical-trials.html}

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