FDA has released guidance on how sponsors of clinical trials can increase the diversity of participating populations.
FDA has issued draft guidance discussing how sponsors can enhance the diversity of populations in clinical trials.
While the agency noted that it has made progress in increasing enrollment diversity, there are still significant obstacles to overcome.
“Over the past few decades, FDA policy initiatives have focused on promoting enrollment practices that lead to clinical trials better reflecting the population most likely to use the drug if the drug is approved, primarily through broadening eligibility criteria,” FDA said.
“Despite these efforts, challenges to participation in clinical trials remain, and certain groups continue to be unnecessarily underrepresented in many clinical trials.”
FDA noted that broadening eligibility criteria would help to increase enrollment of underrepresented populations in clinical trials. While eligibility criteria are often designed to protect patients from any potential adverse events, these restrictions can also limit the generalizability of trial results.
“Failure to include complex participants in a development program may lead to a failure to discover important safety information about use of the investigational drug in patients who will take the drug after approval,” FDA said.
“Broadening eligibility criteria, when appropriate, maximizes the generalizability of trial results and the ability to understand the therapy’s benefit-risk profile across the patient population likely to use the drug in clinical practice, without jeopardizing patient safety.”
To broaden eligibility criteria, sponsors can examine each exclusion criterion, and determine whether it is needed to help protect people’s safety or to achieve the study objectives. If not, sponsors should consider eliminating the criteria or tailoring the exclusion criteria as narrowly as possible, FDA said.
“For example, if there are unreasonable risks to participants with advanced heart failure, but enrollment of those with milder disease would be appropriate, the exclusion criteria should specifically define the population of heart failure participants that should be excluded,” the agency wrote.
Sponsors could also consider using an adaptive clinical trial method, which allows for pre-specified trial design changes during the trial, including altering the trial population.
“An adaptive design can start with a narrow population if there are concerns about safety and can expand to a broader population based on interim data from the trial as well as external data,” FDA said.
“Adaptive trials may also provide for broader enrollment when there is uncertainty regarding whether the drug will be effective in certain populations, with an interim analysis that will enable adjustment of future enrollment based on pre-specified criteria regarding response.”
Additionally, sponsors could improve diversity in clinical trials by accounting for logistical and other factors that could limit participation. For example, FDA suggested that when designing the study, sponsors could consider recruitment challenges that may occur because of the study’s schedule.
“Reduce the frequency of study visits to those needed to appropriately monitor safety and efficacy and consider whether flexibility in visit windows is possible and whether electronic communication (e.g., telephone/mobile telephone, secured electronic mail, social media platforms) or mobile technology tools can be used to replace site visits and provide investigators with real-time data,” FDA said.
Sponsors could also offer financial reimbursements for travel and other costs associated with clinical trial participation. To further broaden enrollment, sponsors should work directly with communities to address participants’ needs, and to involve patients, patient advocates, and caregivers in designing clinical trial protocols.
“Patients may provide valuable insight into challenges and burdens and may be more willing to accept risk for a potential benefit as long as the risks are clearly communicated in the informed consent and the research team explains the risks,” FDA said.
“Community-based participatory research promotes the design of clinical research with the assistance of community members and leaders to more effectively meet the needs of potential participants.”
Recruiting clinical trial participants in diverse locations can help boost diversity as well, FDA said.
“Make recruitment events accessible by holding them often, as well as offering them during evening and weekend hours,” the agency wrote. “Consider holding the events in non-clinical but trusted locations (such as houses of worship) and social commercial venues (such as barbershops and beauty salons) as a means of connecting with diverse populations.”
FDA will accept comments on this draft guidance until August 6, 2019.
With these new recommendations, FDA aims to increase the diversity of populations in clinical trials and improve patient safety.
“Broadening eligibility criteria and adopting more inclusive enrollment practices will open clinical trials to a diverse participant population reflective of the population that will use the drug if the drug is approved,” FDA concluded.
“To avoid unnecessary exclusions and obtain critical safety and effectiveness data applicable to a more representative patient population, sponsors should consider the recommendations in this guidance when designing and conducting clinical trials.”
Date: June 11, 2019
Source: Health IT Analytics