New Guidance on Diversity in Clinical Trials Planning. Monitoring. Compliance

Clinical trials have long suffered from a lack of racial and ethnic diversity. There are many reasons—geographic, socio-economic, historic, and educational. Yet the safety and efficacy data which drives them is only helpful if it accurately reflects outcomes in the entire population for whom the product will be prescribed.

The recent spotlight on matters of diversity and inclusion has helped focus attention on the need for change.

Now five government agencies—the Oncology Center of Excellence (OCE) in collaboration with the Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), the Center for Devices and Radiological Health (CDRH), and the Office of Minority Health and Health Equity (OMHHE) at the Food and Drug Administration—have joined to issue draft guidance designed to help bolster clinical trial enrollment of participants from underrepresented racial and ethnic populations.

While this guidance is still under review and consists of recommendations rather than requirements, it provides a useful framework for the industry as people consider how to make trials truly inclusive. Still, following these recommendations adds another layer of complexity for contract research organizations (CROs) and sponsors to manage. Fortunately, technology can simplify the implementation of many of these recommendations.

The ongoing quest for health equity

Quite simply, race and ethnicity both play a role in human health. It is widely recognized that some populations face a genetic predisposition to specific diseases, such as sickle-cell anemia and Gaucher Disease, passed on when children inherit a mutated gene from each of their parents. It is equally true that therapies metabolize differently across ethnicities. Even considering all people of a specific ethnicity as a single group can be misleading. For instance, although in the American public health system it is common practice to combine data linked to all Asian American communities, this practice can mask critical differences between various Asian groups; there are distinct medical variances among Americans of Filipino, Vietnamese, Chinese, Japanese, and Korean heritage. Skin pigmentation is also a factor many trials should consider; it can make a difference in the efficacy of dermatologic treatments, topicals, and some devices, such as pulse oximeters.

All this underscores the imperative to broaden representation in clinical trials, including Black or African American, Hispanic/Latino, Indigenous and Native American, Asian, Native Hawaiian and Other Pacific Islanders, and other persons of color.

As the guidance states:

Adequate representation of these populations in clinical trials and studies supporting regulatory submissions helps ensure that the data generated in the development program reflect the racial and ethnic diversity of the population expected to use the medical product if approved and may potentially identify effects on safety or efficacy outcomes that may be associated with or occur more frequently within these populations.

Further, the guidance does not stop at racial and ethnic diversity. The FDA advises sponsors to include a broad representation of all demographic attributes, including sex, gender identity, age, socioeconomic status, disability, pregnancy status, lactation status, and co-morbidity. They conclude that this is most likely to happen if there is a clear plan both to ensure participation of these historically underrepresented populations and to analyze the resulting data appropriately. You can read the full draft guidance here.

Establishing a plan for racial and ethnic diversity in a clinical trial

The FDA already requires that some demographic information be tracked. For instance, IND holders must report the number of participants in a study, tabulated by age group, race, and gender. Similarly, new drug applications must present efficacy and safety data by gender, age, and race, noting any dose modifications needed for a specific subgroup. This new guidance goes one step further, asking sponsors to detail in advance how racial and ethnic data will be collected and analyzed. The guidance recommends that a Race and Ethnic Diversity Plan:

  • Outlines the precise operational measures that will be implemented to ensure that study subjects reflect the entire population
  • Defines the enrollment goals for underrepresented racial and ethnic participants as early in clinical development as is practical
  • Should begin with an assessment of any data that may indicate the potential for the medical product to have differential safety or effectiveness due to race or ethnicity
  • Describes the planned assessment of race and ethnicity in addition to other covariates with known potential to affect the safety and effectiveness of the medical product
  • Details the sponsor’s plan to collect data to explore the potential for race- or ethnic-related differential safety and efficacy throughout the entire development lifecycle, not just during pivotal studies

This plan itself should be developed early in the process. Specifically, the guidance suggests that companies developing new drugs should submit their plan as soon as possible—and no later than when the sponsor is seeking feedback regarding the applicable trial, often at the EOP2 meeting. For devices, sponsors should submit their Plan as part of their investigational plan included in the IDE application.

Harnessing technology to simplify the implementation of a diversity plan

While it is clearly important for clinical development to ensure that new products are both safe and effective in all populations, following this new guidance places yet another burden on clinical operations teams. Once a plan is put in place, CROs and sponsors are obliged not only to follow it but to be able to demonstrate compliance with that plan. Utilizing the Remarque Systems platform is a simple, streamlined way to do both.

This centralized operating platform brings all clinical trial data together in real time, then displays it in a way that allows the clinical operations team to confirm they are following their diversity plan:

  • Track enrollment in real time across specified racial and ethnic groups
  • Document actions taken to course-correct when necessary, automatically building a clear audit trail 
  • Create dashboards that cross-reference race and ethnicity with other relevant covariates, both known and potential
  • Easily review the data to determine if there are differences in safety and effectiveness across populations, with no manual analysis needed
  • Consistently evaluate the data in all phases and then roll up data to deliver cross-study reports demonstrating ongoing safety and efficacy monitoring

In short, by establishing dashboards that display specific data—for instance, PK and PD data—broken down by pre-defined ethnicities or other demographic information, researchers can immediately identify areas where performance may vary, areas that bear deeper investigation. This ability to quickly identify and interrogate the data in platform, co-incidentally creating a clear record of patient results and actions taken, alleviates much of the potential burden of this important new guidance.

Embracing diversity: Clear guidance and technological support set the course for truly diverse clinical trials

There is no question that CROs and sponsors need to consciously ensure that clinical trials include a broadly diverse patient population, a group that reflects the racial, ethnic, and general demographic make-up of their intended patient groups. Such diversity is the only way to confirm safety and efficacy for all. The new government guidance simply begins to codify an approach that many experts agree is long overdue.

Yet, monitoring enrollment can prove tricky—and adding another layer of analysis to track disparate results may seem daunting, especially when compliance will be scrutinized. After all, once there is a written plan in place, auditors will demand proof of adherence.

Questions abound: How will clinical operations teams create and manage a plan? How are they collecting and analyzing the data? How are they documenting compliance?

Remarque Systems can greatly simplify this task, collecting and analyzing racial, ethnic, and other demographic data within the platform, supporting the operational measurement oversight to ensure much-needed trial diversity.