Despite concerted policy efforts in recent years, a new U.S. Food and Drug Administration (FDA) draft guidance says “challenges to participation in clinical trials remain, and certain groups continue to be underrepresented in many clinical trials.”
The draft guidance, “Enhancing the Diversity of Clinical Trial Populations–Eligibility Criteria, Enrollment Practices, and Trial Designs,” recommends new approaches for sponsors to consider to safely broaden eligibility criteria. At the same time, the guidance acknowledges there are often clear reasons for the existence of specific eligibility criteria.
For example, patients with decreased renal function or certain concomitant illnesses are often excluded because of concerns they may be more susceptible to adverse effects from investigational drugs that are metabolized by the kidney or that interact with other medications the patient takes, the agency notes in the guidance.
“Sponsors should adopt practices for determining eligibility criteria that will allow the clinical trial population to reflect the diversity of the patients who will be using the drug if the drug is approved,” FDA also says in the guidance.
Although there are many approaches a sponsor can take to broaden eligibility criteria in clinical trials, the FDA guidance provides several specific recommendations, including:
- Examine each exclusion criterion to determine if it is needed to help assure the safety of trial participants or to achieve the study objectives when developing clinical trial protocols. If not, consider eliminating or modifying the criteria to expand the study population as well as tailoring the exclusion criteria as narrowly as possible to avoid unnecessary limits to the study population. 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.
- Consider whether criteria from Phase II studies—which may be more restrictive and are often transferred to Phase III protocols—can be eliminated or modified to avoid unnecessary limits on the study population. Although excluding certain participants may be scientifically or clinically justified under specific circumstances (e.g., certain drug-drug or drug-disease interactions or concerns regarding a population’s vulnerability to a particular toxicity), such criteria may be removed or modified during study conduct based upon data available from the completion of other relevant studies (e.g., 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 (although in such a case, the consent form should identify this increased risk among certain participants).
- Base exclusions on an appropriate measure of organ dysfunction that does not lead to the unnecessary exclusion of certain populations when such exclusions are necessary because participants with impaired organ function would be placed at unreasonable risk.
Author: Michael Causey