By Karen Taylor, Director, Centre for Health Solutions
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 sufficient 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 demographic and demographics of 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 generalise 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 both a statistical concern, and an ethical and medical one. Challenges include a reluctance to conduct trials in ‘vulnerable populations’, namely children, cognitively impaired, pregnant women, and the elderly, where 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 in the past there has often 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
- Racial and ethnic minorities have historically been underrepresented, a situation that persists in modern trials. In the US, African Americans comprise 13 per cent of the population but, until recently, five per cent of clinical trial participants. Meanwhile, Caucasians account for 67 per cent of the population but 83 per cent of research participants.3
- Elderly people are often omitted from clinical trials. Consequently, clinicians actually have limited information on how a given treatment may affect their older patients. Specifically, whether a prescribed medication will be effective for the elderly, or even safe.4
- Researchers often struggle to enrol adequate numbers of women or, when they do, fail to report data by sex. As every cell is impacted by the genetic code relating to sex, this omission prevents 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 much at risk of developing the disease as men. 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
- Likewise, studies into treatments for anxiety and depression. 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 per cent of animal studies on anxiety and depression use female laboratory animals. The risk is that these studies will 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 per cent 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 may lack adequate resources to pay for travel, childcare and/or time away from work. Research also shows that the symptoms of conditions such as heart disease, cancer, and diabetes vary across lines of ethnicity, as they do between the sexes. Consequently, if diverse groups aren’t part of research studies, it’s difficult to be sure on treatment equity or potential side effects.7
Recent initiatives to improve diversity in clinical trials
In recent years, many organisations, including the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have launched initiatives to improve the diversity of clinical trials enrolment. For example:
- As part of the 2012 FDA Safety and Innovation Act (FDASIA 907), the US 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 per cent in 2015 to 56 per cent in 2018) and black or African American participants (from 5 per cent in 2015 to 10 per cent in 2018). Hispanics, who account for 16 per cent of the population, were not recorded in the first two snapshots, but accounted for 14 per cent of trial participants in both 2017 and 2018.
There is a wide body of research that identifies the barriers impacting minority patients’ willingness to participate in trials. In November 2018 a comprehensive report identified key themes and solutions and a communications message map to support a multi-stakeholder approach for overcoming five critical barriers to participation of racially and ethnically diverse patients: 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 alike to develop strategies for increasing diversity in clinical trials.
Financial incentives are a valuable option that can promote participation, especially when linked to the cost and effort expended by the participant and seen as just reward for participation. Use of financial incentives, without undue coercion of any particular population, can serve as a means to equalise study participation.10
Research findings also suggest that providing transportation, flexible hours for patients, appropriate compensation, and mobile technology support such as an ‘app’ for patients and mobile phones for those who do not have one, together with the increase in transparency of reporting, should start to improve still further the diversity and representativeness of clinical trials.
Importantly, the pace of digital transformation that is now evident across the pharma value chain should 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 nurses and doctors. Virtual clinical trials mean that any qualifying patient who wants to participate in clinical research regardless of where they live, and which doctor they see regularly, can participate in ground-breaking research.11
These technology solutions, together with increasing actionable evidence of what helps improve recruitment, provide important opportunities to not only increase the diversity of trial participants but also increase satisfaction and improve the overall experience of research participants.