Officials at the Food and Drug Administration have issued draft guidance aimed at increasing the diversity of clinical trial populations, including adding children and adolescents earlier in drug development and making trial participation less burdensome for patients.
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Despite efforts to enroll clinical trial participants who better reflect a real-world population, “challenges to participation in clinical trials remain, and certain groups continue to be unnecessarily underrepresented in many clinical trials,” the FDA noted in the document’s introduction.
The FDA noted that these challenges could have a significant impact on trial outcomes.
For example, the failure to include complex patients in a clinical trial “may lead to a failure to discover important safety information about the use of the investigational drug in patients who will take the drug after approval.”
In its draft recommendations, the FDA calls on trial sponsors to conduct a closer examination of exclusion criteria and to make it as narrow as possible; consider whether criteria from phase 2 studies, which are restrictive but often transferred to phase 3 protocols, can be eliminated or modified; and consider including children and adolescents when appropriate.
Recommendations related to trial design include characterizing early on the drug metabolism and clearance across populations that may metabolize or clear the drug differently, such as elderly or patients with liver or kidney dysfunction. The agency also called on trial sponsors to use “adaptive clinical trials,” which allow for prespecified trial design changes during the trial, and an early pediatric development program.
Another set of draft recommendations relates to ensuring trial participation is less burdensome for patients by reducing the frequency of study visits and making participants more aware of reimbursement for travel and lodging associated with the trial.
Additionally, the agency is recommending that trial sponsors adopt enrollment and retention practices that enhance inclusiveness, such as ensuring that trial sites include geographic locations with a higher concentration of racial and ethnic minority patients, and holding recruitment events on nights and weekends and in nonclinical locations.
Finally, the FDA issued a set of recommendations to trial sponsors aimed at broadening eligibility criteria when evaluating drugs intended for the treatment of rare diseases. In those trials, the FDA recommended reenrolling participants from early-phase trials in later-phase trials if it can be done safely.
“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,” the agency stated.
At first blush, the draft recommendations are being greeted with a positive response.
Dr. Richard Schilsky
“We certainly need more diversity in clinical trial populations, so I think anything that FDA can say that will help encourage that is a good thing,” Richard Schilsky, MD, senior vice president and chief medical officer at the American Society of Clinical Oncology, said in an interview, noting that this new guidance builds off the work that ASCO and Friends of Cancer Research did with the FDA on previous efforts to expand clinical trial populations.
“I think that this new guidance, as best as I can tell, builds off of that, generalizes it across all therapeutic areas and goes a little bit beyond eligibility criteria to other features of clinical trials that may be impediments to patient participation and thereby limit the diversity of the populations in the studies,” he added.
That said, Dr. Schilsky said he welcomed the draft document as a step toward getting broader participation from patients who are more representative of the ultimate users of these treatments.
“All people who could potentially benefit from the trial should have the opportunity to participate as long as it’s safe for them to do so, and they should not be excluded based upon some of these arbitrary structural things,” he said.
“More importantly, we need data on how these new interventions perform in the patients who are seen and treated by doctors every day. We don’t want data just on patients who have no comorbid illnesses, patients who are otherwise perfectly well, patients who could run a marathon before they go to the doctor’s office. Those are generally not the patients that most doctors are seeing. If they are not represented in the trial population, then we are left with having to extrapolate from the trial data to a population for whom there is no information on how to use the treatment,” he added.
Public comments on the draft document are due on Aug. 6.