How to Design Trials That Increase Patient Diversity Across Study Phases

Common barriers and solutions to move diversity forward seamlessly

Patient diversity in clinical trials is critical to ensuring that safe and effective therapies are brought to market. That said, it’s been historically difficult to achieve.

The United States accounts for more than 50% of global trial participants, of which 75% identify as Caucasian or of European descent, and only 5% as Black. In fact, more than 90% of the genetic material used for clinical trials in the U.S. is of European descent, leaving a significant gap of genetic variation in research.

To move patient diversity forward, our experts recommend a multi-dimensional lens to understand how the intersectionality of characteristics plays a role in diversifying clinical trials. Further, trial teams should be equipped to accommodate the multiple and shifting variables of diversity across patient populations.

Patient diversity in clinical research requires a multi-faceted approach.

While race and ethnicity are certainly driving factors behind diversifying clinical trials, they are not the only qualities drug developers should keep in mind.

Clinical trial diversity can — and should — consider characteristics and populations including:

• Race
• Ethnicity
• Age
• Sex and gender identity
• Sexual orientation
• Veteran status
• Socioeconomic status
• Education
• Religion
• Pregnancy/lactation status
• Physical abilities and disabilities
• Comorbidities
• Geography (urban vs. rural populations)
• Underserved and understudied populations

Incorporating multiple elements paves the way for a clinical trial to accurately reflect all the populations that could benefit from the treatment’s approval. A strong contract research organization (CRO) partner will consistently consider these characteristics as part of a comprehensive diversity plan.

Why does diversity matter?

For starters, regulatory agencies expect it, as evidenced by guidance published by the U.S. Food and Drug Administration (FDA) last year, which requires Phase III/pivotal trials to submit diversity plans. Looking beyond the recommendations of regulatory bodies, studies need to test medicines in real-world populations to ensure the solution that comes to market benefits all potential patients.

Research shows that therapeutic response, disease pattern and clinical presentation can vary across racial or ethnic groups. These differences were observed in approximately 20% of new molecular entities (NMEs) approved by the FDA, which resulted in different prescribing recommendations for specific populations.

A diverse clinical trial illuminates these differences before the therapy launches, enabling better outcomes for patients and health care providers.

Common barriers to achieving representative patient diversity in clinical trials and transformative solutions to overcome them

From planning and feasibility to execution and site support, all stages of a clinical trial are affected by the need to design and operationalize studies that meet diversity targets. These efforts are often met with common barriers that require innovative solutions.

Barrier: Historical lack of trust and cultural competency, including an unconscious bias toward patients and patient hesitancy to participate in clinical trials

• Results from a survey of Black breast cancer patients found that only 32% trust that people of all races and ethnicities get fair treatment in clinical trials. Despite that perception, 83% of patients surveyed were still somewhat or very likely to consider enrolling in a clinical trial.

Solution: Targeted minority patient plans and sustained community engagement

• Develop diversity plans at the program/molecule level that inform protocol and site-level recruitment targets.
• Engage underrepresented patient populations and patient advocacy groups early in the drug development process.
• Make connections with key diverse stakeholders around your sites to help educate and spread the word.
• Communicate your commitment to diversity to your partner CRO, sites and patients.

Barrier: Limited clinical trial awareness and health literacy

• In the same study of Black breast cancer patients, more than 60% reported never being offered a clinical trial or discussing clinical trials with their provider.
• According to the National Assessment of Adult Literacy, only 12% of Americans have proficient health literacy skills.

Solution: Enhanced educational materials and practices that facilitate understanding and participation

• Create patient-facing materials that are culturally appropriate and inclusive, so patients feel welcome to participate.
• Use easy-to-understand language on educational materials, taking care to simplify complex topics.
• Train investigators and staff to ask all potentially eligible patients about their interest in participating in the trial.

Barrier: Limited access to clinical trials due to insurmountable patient burden

• Studies show that less than 5% of adult cancer patients enroll in clinical trials.
• Distance to site, child/senior care, impact on work schedules and logistical cost all increase the difficulty patients face to participate in clinical trials, often limiting diverse enrollment.
• For neurodegenerative trials, recruitment must also extend to the caregiver.

Solution: Support and services that reduce key patient burdens

• Decrease the need for in-person visits by implementing digital and decentralized trial elements.
• Provide patient transportation, when possible.
• Offer reimbursement for expenses patients incur to participate in clinical trials, including:
  • Transportation to and from sites
  • Parking
  • Hotel accommodations
  • Child care costs
  • Lost wages
  • Meals while traveling
• Implement a patient concierge service to help patients manage the logistics of trial participation.

Barrier: Restrictive eligibility criteria

• Eligibility criteria can inadvertently exclude minorities due to comorbidities and lab value ranges.

Solution: Eligibility criteria that are clearly defined and not disproportionately restrictive

• Define study populations at the molecular level rather than by traditional and less-precise eligibility criteria.
• Avoid vague criteria and specify exclusionary characteristics.
• Document and track reasons for screen failure.
• Offer clear guidance on comorbidities that are exclusionary and follow for every patient.
• Consider the inclusion of adolescents (age 12-17) at all stages of development, when possible.

Partner with a CRO that is leading the way in ensuring life-changing therapies are available to all who need them.

It is estimated that by 2099, 80% of the global population will live in India or Africa, underpinning the need for drug developers to make a concerted effort now to increase diversity in clinical trials. Creating a patient population that reflects the real world is critical to ensure the creation of safe and effective drugs, and will only increase in regulatory significance.

The PPD™ clinical research business of Thermo Fisher Scientific is a patient diversity leader with innovative solutions to support sponsor diversity goals. Our dedicated diversity consulting team and extensive patient databases drive best practices in inclusive, representative clinical development, with patients at the center.