In comments submitted on behalf of its members about new draft guidance from the U.S. Food and Drug Administration (FDA) in December, the Association of Clinical Research Professionals (ACRP) urges the agency to, among other things, pay close attention to the intersection of parents’ and children’s rights when seeking consent or assent to participate in a clinical investigation.
In response to FDA’s request for public input on its forthcoming guidance, the comments from ACRP were submitted to https://www.regulations.gov regarding “Ethical Considerations for Clinical Investigations of Medical Products Involving Children: Guidance for Industry, Sponsors, and IRBs” (Docket No. FDA-2022-D-0738).
In reference to the draft guidance’s “Ethical Framework,” ACRP notes that, “There seems to be a disconnect between parent consent and a child who does not want to assent. This is addressed to some degree in the first full paragraph of page 10, but if a child is blatantly refusing a study that a parent is consenting to, perhaps there should be an age where lack of assent should be deemed refusal to participate. In different states there are different considerations that need to be made. In some states children of a certain age have more medical autonomy. State and local considerations should be reflected in the guidance. The guidance should speak more to the intersection of consent and assent in situations where there might be disagreement, especially with respect to the age of the child (example age 5 versus age 17).”
ACRP also requested clarification that, while all clinical studies should be well-designed in order to collect useful data and not to expose participants to unnecessary risks, the status of children as a vulnerable population means they are due additional considerations in terms of design. “It should be clearly stated that this is scientifically necessary for all clinical investigations to be ethical,” ACRP advises.
Further, ACRP suggests, “Additional detail on component analysis and determination of what constitutes minor increase over minimal risk could be beneficial.” In the draft guidance, some examples are given of what is minor increase over minimal risk versus exceeding that level, but not necessarily a clear rubric for how that might be extended to other interventions.
Statements in the guidance also “speak to the necessity of inclusion of pediatric patients in clinical trials and product development, presumably in hopes of increasing the number of indications that might be approved in pediatric populations—absolutely true statements,” ACRP comments. “On the other hand, there is limited provision for how sponsors and investigators might accomplish that in scenarios where adult studies may not be feasible or ethical. Considering FDA’s threshold for evidence in support of marketing applications, what is the likelihood of approval of applications for such indications? It would be helpful to have more guidance from the agency on how one would address some of the typical requirements for [early-phase trials] in the scenario where you wouldn’t be able to do adult studies,” for example in dose-finding, pharmacokinetic, and pharmacodynamic studies.
For the full set of comments from ACRP and others, visit the guidance on the FDA site.
Edited by Gary Cramer