Broaden Criteria to Maximize Trial Results, FDA Says

June 10, 2019

Sponsors should think about loosening their exclusion criteria to allow more diverse patient populations—especially when recruiting for later stage trials, the FDA says in new draft guidance published last week.

The agency says that part of the low recruitment problem may be that sponsors are stuck on finding patients who only suffer from a given disease and no others. Perhaps worse, they exclude populations such as elders, kids, obese (or overly thin) patients, and HIV-positive patients.

“For example, if there are unreasonable risks to participants with advanced heart failure, but enrollment of those with a milder disease would be appropriate, the exclusion criteria should specifically define the population of heart failure participants that should be excluded,” the agency said in the 18-page document.

This is especially true of Phase II trials as they tend to be more restrictive. Sponsors should consider eliminating or modifying certain criteria when they move to Phase III.

For trials focused on rare diseases or conditions, the FDA advises sponsors to consider engaging with patient advocacy groups early in the process, planning to re-enroll participants from early-phase trials into later-phase trials and conducting open-label extension studies to ensure that all study participants will have access to the investigational treatment.

The agency offers several examples of trial design and methodologies to broaden inclusion, including adaptive clinical trials, expansion cohorts that allow for dose modification in specific populations, the creation of pediatric development programs that stagger enrollment based on age and the inclusion of a broader participant group as part of the secondary efficacy and safety analyses.

The document also offers several recommendations for enrollment and retention practices that enhance inclusiveness, including working with communities to address participant needs and gather valuable insights for trial design, and holding frequent recruitment events in nonclinical settings.

The draft guidance also urges drug sponsors to think carefully about the logistical and financial obstacles to bringing people into clinical trials. It reiterates that regulators allow sponsors to reimburse recruits for “reasonable travel expenses” that include airline tickets, parking and hotels. It even suggests that it might be okay to pay patients to join a trial but “recognizes that payment for participation may raise difficult questions” that institutional review boards should examine carefully.

Read the draft guidance here:


-By Leslie Ramsey