Achieving representative enrollment – meaning diversity in race, age, gender and socioeconomic status – in clinical trials is essential to the development of cutting-edge therapies for the general population. Despite being recognized as a need within the industry, it has proven to be a longstanding challenge.
According to the 2019 ‘Drugs Trials Snapshots’ report released by the United States Food and Drug Administration (FDA), 72% of study participants were White, 18% Hispanic, 9% Black or African American and 9% Asian. Only 36% of participants were in the demographic subset of ‘Age 65 and older’. When comparing these figures to those of 2018, ethnic diversity in 2019 actually decreased.
That same year, the FDA released the draft guidance document, “Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs.” This document encourages sponsors to 1) broaden eligibility criteria, 2) use adaptive clinical trial models (start with a narrow population and expand to a broader population once interim data has been analyzed) and 3) consider other challenges to enrollment (e.g. number of study visits, financial costs, time commitment). While the release of this document represents a move in the right direction, more steps are needed to address unequal representation in clinical trial enrollment.
This need for representative enrollment has been further highlighted in the ongoing COVID crisis, where there is a disproportionate impact to people of color.
To learn more about the challenges with patient recruitment and gain insight on how sites can work towards increasing diversity in clinical trials, Clinical Research IO connected with Daniel Perez, Chief Operating Officer of MACRO Trials. MACRO trials is a multi-therapeutic Site Optimization Organization (SOO) in Beverly Hills, California. MACRO Trials has taken strides to prioritize representative patient enrollment by modifying internal site processes and collaborating with sponsors.
Why are people reluctant to participate in research?
According to Mr. Perez, information about ongoing clinical research studies is not always presented to participants in a way that engages them. The industry often uses technical terms that may be difficult for people to understand. As a result, people’s understanding of an ongoing trial may be superficial. In addition to this, there are varying levels of trust in the pharmaceutical industry. Without trust in research and nearby sites, people will be reluctant to participate. Other barriers to enrollment include time commitment, inability to take time off from work, financial burdens associated with transportation or missing work and the sheer number of study visits.
Why may sites struggle to achieve representative enrollment in their ongoing trials?
While some sites have attempted to make ongoing trials more accessible to a wider patient population, many others have not because they are unaware that they are able to initiate this effort. When sites do take steps to work with sponsors, the amount of work involved can be overwhelming and become easily discouraging. For example, if your site wants to enroll both English and non-English speaking patients, typically you must first notify your study monitor or clinical trial manager/lead. This individual will then initiate the approval process and must wait for the sponsor’s approval. Once approved, the site is still minimally responsible for coordinating translation of the informed consent documents. These translated documents must then be sent to the IRB for approval and additional standard operating procedures must be written for the non-English consenting process (i.e., quality assurance, time for question & answers, policies for having third-party witnesses, etc.). With all the structural intricacies built in, sites are not incentivized to pursue such opportunities given that sponsors/CROs historically do not volunteer additional financial resources to support this work. As a result, certain patient populations become excluded from participation.
Tangible actions that research sites can take to increase diversity
- Promote workplace diversity. When hiring new site staff, assess the candidate holistically by understanding both their life experiences and soft skills. “We hired individuals based on talent, life experiences and personableness. You can train people to learn many new skills, but you cannot train personableness and resilience. In addition to having diverse site staff, it is also critical to have a diverse set of investigators. Connect with community physicians of color so that you can have rapport and trust with the people around you,” said Mr. Perez.
- Customize studies within the constructs of the protocol to make participation more convenient and engaging for patients.
- Provide appropriate cultural competency and anti-racism training to all site staff. This training should not be fulfilled by a short video and quiz. Instead, training should involve the communities that your site wants to serve. Participants will pick up on whether site staff are knowledgeable and know how to interact with others.
- Be aware of ongoing social issues.
- Get involved in community-based work outside of clinical research. It is critical that site members build trust with the surrounding community. Consider creating roles within your company or organization that are dedicated to community outreach and building relationships.
- Utilize available technologies (e.g., eConsent, eSource, diary devices, site tablets) that are participant friendly, engaging and easily adaptable. This will enable your site to work with a wider patient population.
- Be adamant and persistent when requesting materials and support from your sponsors.
What can sponsors do to help?
- Offer patient recruitment services to help sites identify eligible participants.
- Offer translating and/or interpreter services.
- Widen eligibility criteria and focus on inclusion, rather than exclusion. When amending study protocols, identify ways to phrase criteria appropriately and sensitively. For example, in almost every protocol there is a criterion that says “Male or Female that…” and should be rewritten to include non-binary terminology.
- Ensure that there are true scientific grounds for every study procedure. Many secondary and tertiary endpoints may not be needed to determine safety and result in exclusion of many participants. By eliminating some of the additional endpoints, studies may become more inclusive.
- Empower sites to promote diversity and provide support, whether financial or structural (i.e. interpreter services).
In closing remarks, Mr. Perez offers the following advice to research sites…
“Take time to prioritize inclusion and diversity within your organization and for ongoing clinical trials. If you don’t invest the time and effort now to implement inclusive processes, the time will come when the industry has caught up and you may not be equipped to adapt.”