FDA Releases Guidance to Encourage Clinical Trial Diversity

FDA recently issued final guidance to encourage clinical trial diversity from the design to execution of the tests. 

The guidance, Enhancing the Diversity of Clinical Trial Populations--Eligibility Criteria, Enrollment Practices, and Trial Designs, now addresses both demographic characteristics of study populations, including sex, race, ethnicity, age, and location of residency, as well as non-demographic characteristics, such as comorbid conditions or disabilities.

FDA first issued the guidance as a draft in 2019. Now, it provides the agency’s current thinking on steps to broaden eligibility criteria in clinical trials through inclusive trial practices, trial designs, and methodological approaches, the agency stated. 

Clinical trials exclude some patients to protect patient safety. 

Patient populations that are often excluded include pregnant women, older adults, medically complex patients who are more susceptible to adverse events, and those with kidney or liver impairment 

Clinical trial researchers generally exclude these populations from clinical trials because of a lack of information on how to adjust dosage level appropriately for the special needs of the populations. But this could change under the right circumstances, the FDA indicated.

“As data on excretory and metabolic pathways and drug-drug interactions become available during the drug development program, allowing appropriate dose adjustments, there should be fewer exclusions related to concomitant medications or comorbidities,” FDA said in the guidance.

“Similarly, as the safety experience with a product increases, eligibility criteria should be broadened to include more medically complex participants; any remaining exclusions should be justified,” the agency added.

The guidance also offers recommendations on how product sponsors can improve clinical trial diversity by accounting for logistical and other participant-related factors.

Overall, sponsors should consider trial design approaches that will include a broader population. For example,  characterizing drug metabolism across differing populations, establishing a broader pediatric development program, and including pharmacokinetic sampling to establish dosing in women who become pregnant during a trial. 

Other recommendations included eliminating patient burden by reducing visit frequency and boosting overall flexibility. This can be accomplished by implementing phone calls, emails, or other digital technology tools that can replace site visits. 

Sponsors should also adopt enrollment practices that enhance inclusiveness and expand overall access to patients who do not meet eligibility criteria for various reasons.  

For example, sponsors could offer ineligible patients who have serious or immediately life-threatening conditions treatment with an investigational drug. But specific criteria must be met, including that there is no alternative therapy option. 

Additionally, FDA stated that sponsors should consider conversations with patient advocacy groups to obtain suggestions for designing trials that participants would want to enroll in and support. 

“Clinical trials, and the people who volunteer to participate in them, are essential to help develop safe and effective medical products to fight diseases and illnesses,” FDA said. “The FDA remains committed to increasing enrollment of diverse populations in medical product development and will continue to engage with federal partners, medical product manufacturers, medical professionals, and health advocates to encourage this important goal.”

Addressing racial disparities is a top priority for the pharmaceutical industry, which is currently tasked with addressing unconscious bias, racism, and discrimination that impact drug development, distribution, and adherence.

For example, a September Health Affairs study showed that Black patients were five times more likely to be hospitalized for severe COVID-19 than White patients and six times more likely to die from the virus.

Additionally, 49 percent of Black Americans said they would not get a COVID-19 vaccine even if it was deemed safe by scientists and freely available, according to an October Kaiser Family Foundation (KFF) report. 

Safety concerns (39 percent) and distrust (35 percent) were cited as the top reasons. But a majority of Black adults also had little to no confidence that the vaccine development process was taking the needs of Black people into account.

Although CDC said that risk was a major factor for the coronavirus, early research on COVID-19 vaccine candidates mainly focused on white populations. 

FDA’s guidance to enhance clinical trial diversity is critical to get targeted treatments to underserved communities.