The US Food and Drug Administration (FDA) on Thursday issued a draft guidance aimed at increasing diversity in clinical trial populations as part of its efforts to encourage drugmakers to enroll populations that more closely reflect the populations that will take the drugs in the real world.
“This guidance recommends approaches that sponsors of clinical trials to support a new drug application [NDA] or a biologics license application [BLA] can take to broaden eligibility criteria, when scientifically and clinically appropriate, and increase enrollment of underrepresented populations in their clinical trials,” FDA writes.
The guidance, which was required under section 610 of the Food and Drug Administration Reauthorization Act of 2017
(FDARA), builds on past efforts by FDA and Congress to broaden clinical trial eligibility criteria to historically underserved populations, including women, the elderly and minorities.
While inclusion and exclusion criteria play an important role in protecting patients and ensuring trial results are interpretable, FDA says that many patients are “excluded from trials without strong clinical or scientific justification.”
However, by excluding patients, such as the elderly, pregnant women, children, patients with comorbidities or patients who are taking other drugs, without clinical or scientific justification, FDA says drugmakers may miss important safety signals and end up with less generalizable results.
Within the 18-page draft guidance, FDA provides recommendations on a range of topics aimed at increasing diversity in clinical trials, including enrichment, inclusive trial practices and trial design and methodological approaches that could result in a wider range of populations being eligible for a study.
To promote greater inclusion, FDA recommends sponsors review each exclusion criterion and eliminate or alter any that are not necessary for assuring patient safety or achieving the study objectives. FDA also suggests sponsors review exclusion criteria between Phase II and III studies, as some exclusion criteria may no longer be needed based on the results of other studies such as drug-drug or drug-disease interaction studies.
“It may be possible in some cases to have the development program include specific studies in higher risk populations conducted at sites with expertise in working with such participants,” FDA states, noting that consent forms should explicitly state if there is an increased risk for those participants.
The guidance also discusses expanded access as an option to increase patient access to investigational drugs. While FDA points out that the primary purpose of expanded access is to treat, monitor or diagnose a patient’s disease or condition, the agency acknowledges that, “In certain limited circumstances, data from expanded access use may inform clinical development.”
For rare disease clinical trials, the guidance provides a separate set of recommendations for broadening eligibility criteria and enhancing recruitment.
“Because rare diseases often affect small, geographically dispersed patient populations with disease-related travel limitations, special efforts may be necessary to enroll and retain these participants to ensure that a broad spectrum of the patient population is represented,” FDA writes.
As such, FDA recommends drugmakers engage with patient advocacy groups early on to gather input on their trial designs and protocols.
In limited circumstances, FDA also suggests that drugmakers should consider plans to re-enroll patients from early studies in later phases. “Traditionally, participants are often ineligible for a phase 3 trial if they had been previously exposed to the drug in an earlier-phase trial; however, with so few participants in rare disease trials, re-enrolling participants may facilitate the analysis of safety and efficacy in the broadest possible population,” FDA writes.
Lastly, FDA says drugmakers should consider offering an open-label extension study following early-phase studies “to encourage participation by ensuring that all study participants, including those who received placebo, will ultimately have access to the investigational treatment.”
, Federal Register Notice