How do you pre-position assets around the IRB approval? These operational issues are solvable, Nelson said. Research in the preevent setting, where children are not at risk, is more challenging. There are some situations where neither pathway applies. In those cases, it was proposed that for studies that were scientifically sound and ethically appropriate, there could be a level of federal review. However, the decision whether to conduct the trial is a separate one from the parental decision whether to enroll their children in such a trial if there is no direct benefit to the child, Nelson noted.
Nelson added that although FDA does not have regulations governing research involving pregnant women, HHS human research regulations (45 CFR 46, Subpart B) provide for additional protections for pregnant women and fetuses. If an intervention is not for the direct benefit of the pregnant woman, then the risk to the fetus must be minimal. Again, according to Nelson, this regulatory framework constitutes a barrier to preevent studies of MCMs.
Participants discussed further the types of studies or data that would be needed for development of MCMs for children or pregnant women. Mathis said that “dose is everything.” A good deal of progress has been made for pediatrics because of the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act, but we need to commit more time and people to studying pediatrics, earlier on in the process. For pregnancy, it would be reasonable to assume that efficacy could be extrapolated, but PK data are most urgently needed. Nelson advocated for an open public deliberative process around both the science and ethics of conducting preevent trials.