In March, the Food and Drug Administration (FDA) issued a guidance, “Cancer Clinical Trial Eligibility Criteria: Minimum Age for Pediatric Patients.” The guidance is one of the latest moves by the agency to expand eligibility criteria, and hence the knowledge base for how drugs work in various populations, for the clinical trials they regulate. It makes recommendations not only for sponsors but also for IRBs. On May 13, PRIM&R submitted comments in response to the draft guidance.

In our comments, PRIM&R applauds the FDA for their latest work to improve clinical trial access for younger patients. Last year, we submitted comments on another FDA’s draft guidance document “Considerations for Inclusion of Adolescents in Adult Oncology Clinical Trials,” where we agreed with the need to design cancer clinical trials, where possible, to include pediatric patients, in the interest of learning more quickly about the dosing, safety, efficacy, and long-term effects of potential cancer treatments in these populations.

With respect to this draft guidance, PRIM&R thanks the FDA for the level of detail it provides regarding the types of evidence that could support including pediatric patients in adult clinical trials. We believe this is the first time the agency has provided such details, which will be invaluable to IRBs as they make the required determination whether enrollment in the study provides the prospect of direct clinical benefit to a pediatric subject. (The FDA’s language regarding what data they believe can be used to support the prospect of direct benefit is also consistent with recommendations made by the Secretary’s Advisory Committee on Human Research Protections in July 2005.)

PRIM&R goes on to request that the FDA clarify their suggestion that one reason to include pediatric patients in adult oncology trials is that separate pediatric trials may be “infeasible because the disease occurs so rarely in pediatric patients,” given the potential for different interpretations of “infeasible” in this context. “Infeasible” could be interpreted as meaning “operationally and/or logistically infeasible,” in which case inclusion of a small group of pediatric patients in an adult trial could address the infeasibility. Under this interpretation, inclusion of pediatric patients in an adult trial might be justified, so long as their inclusion resulted in pediatric data that could, by itself or in combination with other data, either from the same trial or other trials, support pediatric labeling regarding dosing, safety, and/or efficacy.

However, “infeasible” might instead be interpreted as meaning “scientifically infeasible.” If the pediatric population with the disease in question is too small to support a scientifically sound pediatric trial, it raises the question of how and in what conditions including a cohort of that very small pediatric population in an adult trial would allow for the collection of adequate data to draw conclusions about dosing, safety, and efficacy in that population, and would therefore be ethically justifiable. While PRIM&R thinks the FDA means “operationally and/or logistically infeasible,” this is not entirely clear from the text. PRIM&R encourages the agency to clarify which of these two senses of “infeasible” (or another) it means.  

Finally, PRIM&R suggests that the FDA encourage sponsors pursuing adult oncology clinical trials that include pediatric patients to describe in protocols how the pediatric data obtained will be used to support pediatric labeling, whether by itself or in combination with other data. This is particularly important given that the materials sponsors provide to IRBs often do not include information on modeling and simulation of pharmacokinetics and dosing, extrapolation of efficacy from one population to another, and other analyses that often involve data from more than one trial and/or from pediatric and adult patients. As a result, IRBs are frequently in the difficult position of trying to review and approve a protocol involving adults and pediatric patients without having the necessary information to do so.

What do you think of FDA’s draft guidance? Leave us a comment below.

PRIM&R has an upcoming webinar, Pediatric Risk Determination: IRB Considerations and Cases, on Thursday, September 19 that will review considerations for IRBs in assessing the risks and benefits of pediatric studies. Learn more and register on our website.