The need for diversity in clinical trial populations has been a topic of discussion across regulators and the industry in general for decades.
Despite the introduction of US policies, beginning with the 1993 National Institutes of Health (NIH) Revitalization Act which called for the inclusion of more women and communities of colour in clinical trials, clinical trial data has remained largely based on healthier Caucasian subjects with minimal representation from minorities (African American, Latinx, Asian, Native Americans), the elderly, young, and those with co-morbidities.
To encourage more of a focus on clinically relevant populations, the US Food and Drug Administration (FDA) recently released “Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry” to increase participant access to clinical trials and the enrolment of underrepresented populations to ensure clinical trial data reflect the population most likely to use the drug if approved1. The guidance encourages sponsors to remove overly restrictive and legacy exclusions, broaden protocol eligibility criteria, and improve trial recruitment practices so trial data is clinically relevant for the end-user.
Historical performance data, like that provided in FDA Drug Trials Snapshots, has shown that using traditional recruitment practices by themselves does not enhance the diversity of clinical trial populations. Fundamental barriers and deeply rooted mistrust of medical research motives among communities of colour require a more thoughtful and deliberate approach to participant outreach. PPD has seen recent successes in the recruitment of more clinically relevant trial populations through the implementation of patient-centred trial solutions designed to address the most common barriers to clinical trial participation among these diverse patient populations – mainly trust, understanding, awareness, access, time, and cost, especially when delivered in collaboration with organizations focused on communities of colour and community leaders to ensure optimal receptivity.
The issue of diversity in clinical trials spans all indications and geographies, though it is a bigger concern in the US due to the variability in healthcare, and health status, as a result of race, ethnicity, age, and social determinants. This has been further exacerbated by the COVID-19 crisis, which has forced many of these topics into the public spotlight with the development of vaccines and treatments providing hope of a return to normalcy. As the US moves closer to having approved vaccines and treatments for COVID-19, there is consensus that the data supporting regulatory approval must demonstrate safety and efficacy for representative populations that would receive the vaccine or treatment when approved. The disproportionate impact the pandemic has had on African Americans, Latinx, the elderly, and those with co-morbidities underscores the need for sufficient representation of these populations in the development of COVID-19 vaccines and treatments to ensure the data collected is relevant for the larger US population when approved.
To put this in perspective, US Census Bureau data from 2019 and the Centers for Disease Control (CDC) data through October 2020 show that African Americans make up 13.4% of the US population but represent 17.4% of COVID-19 cases and 21.0% of COVID-19 related deaths. Similarly, the Latinx population represents 18.5% of the US population but 29.4% of the COVID-19 cases and 17.4% of the COVID-19 related deaths2. With African Americans and Latinx populations experiencing higher incidences of COVID-19 positive cases and deaths, one might expect higher representation from these groups in current COVID-19 trials, which was not initially the case. Clearly, in order to ensure a clinical trial population represents the population of interest, a more thoughtful and deliberate approach to recruiting a truly representative sample is required to ensure optimal clinically relevant safety and efficacy data.
Effective implementation of diversity and inclusion in clinical trial populations requires a collaborative and holistic approach, as well as a willingness to learn from past experiences. Leveraging patient-centric solutions combined with data and technology collaborations is critical.
Leveraging data and technology
Building an effective and diverse recruitment strategy starts with understanding the profile and demographics of the target population. Who are the end users of the drug if approved?
Using a combination of data sources and subject engagement practices can help understand the nuances of the participants being sought for enrolment. Again, referring back to the COVID-19 example where there is a disproportionate impact on African Americans, Latinx, and elderly populations, recruitment strategies need to include a higher percentage of volunteers from these groups.
Data needs to be leveraged to support site and patient recruitment strategies and identify the right sites or intentionally place sites in areas ideally suited to support the enrolment of the target population. Protocol optimization and/or virtualizing clinical trial design can significantly broaden eligibility and access for participants leading to faster recruitment with greater diversity in clinical trial populations. Experience has shown that incorporating a decentralized trial design can deliver 30-60% of participants from underserved communities versus the 2-10% seen in traditional trials.
Building trust while increasing awareness and understanding
Traditional social determinants of health equity are wrought with bias and a historical lack of applied ethics. In order to successfully bolster more diverse participation in clinical trials, we must first acknowledge the role history plays in the mistrust – if not outright distrust – of those populations when approached about participating in a clinical trial.
Certain communities of colour remain skeptical about promoting participation within their communities when social contracts such as the Tuskegee Syphilis Experiment and Havasupai Diabetes Project are still top of mind. Thus, any meaningful collaboration within the African American, Native American, and Latinx communities must balance this history with the need for diverse representation in clinical trials. This balance will require age-relevant and culturally competent educational materials to reverse the lack of health literacy that exists, an effort to engage with community leaders to foster greater awareness and to build trust, and openness to study design. Over one-third of the adult population in the US is unable to understand and navigate the healthcare system adequately to make educated healthcare decisions or act upon a physician’s instructions5. Half the population cannot read above 8th-grade level, yet most health resources are written at an 11th-grade level, often with little regard for readability scoring metrics or the importance of visual design6. These statistics, and others, have led to delays in recruitment, trial leakage, and underrepresentation among key segments of the population.
Improving access and removing barriers
Lack of awareness of clinical trial options, as well as insufficient access to clinical trial sites, are major barriers contributing to the under-representation of communities of colour in clinical trials. It has been shown that individuals are more willing to participate in clinical trials if suggested by their physician. However, a large percentage of Americans have insufficient access to healthcare which means their clinical trial options are limited to what they see or hear in the public domain. Recruitment efforts often rely on social media and paid search engines which work well in some indications and with certain patient groups; however, a large segment of the population does not engage with social media or utilize search engines to gather health information. Recognizing the differences in the way individuals access information and who they view as trusted sources is critical; who is sharing the message is often more important than the message itself.
References
1 US Food and Drug Administration. Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry. Available at: https://www.fda.gov/media/127712/download. Accessed November 20, 2020.
2 CDC COVID Data Tracker. Demographic Trends of COVID-19 Cases and Deaths in the US Reported to CDC. Available at: https://covid.cdc.gov/covid-data-tracker/#demographics. Accessed October 30, 2020.
3 PPD and partner data
4 Anderson D, Fox J, Elsner N. Digital R&D. Transforming the Future of Clinical Development. Deloitte Insights. Available at: https://www2.deloitte.com/us/en/insights/industry/life-sciences/digital-research-and-development-clinical-strategy.html
5 Hersh L, Salzman B, Snyderman D. Health Literacy in Primary Care Practice. Am Fam Physician 2015 Jul 15;92(2):118-124. Available at: https://www.aafp.org/afp/2015/0715/p118.html. Accessed November 19, 2020.
6 Strauss V. Hiding in Plain Sight: The Adult Literacy Crisis. Washington Post, Nov. 1, 2016. Available at: https://www.washingtonpost.com/news/answer-sheet/wp/2016/11/01/hiding-in-plain-sight-the-adult-literacy-crisis/?noredirect=on. Accessed on November 20, 2020.