During the 2009 H1N1 influenza pandemic, pregnant women had higher complication rates. It is hypothesized that this might be because standard doses of oseltamivir, the recommended treatment for the prevention and treatment of H1N1, are inadequate during pregnancy because of changes in renal and hepatic function and drug volume of distribution. More generally, over 50% of pregnant women take prescription drugs. However, evidence of safety and efficacy of drugs in pregnancy is weak, placing pregnant women and the fetuses at risk.
Carrying out clinical trials of drugs administered to pregnant women who is carrying the fetus to term is ethically sensitive both because of concerns about birth defects in the developing fetus and also because the fetus cannot consent to be a research subject. The federal regulations for the protection of human subjects require for clinical trials involving pregnant women and fetuses that the risk to the fetus is caused solely by interventions or procedures that offer the prospect of direct benefit to the woman or fetus, that any risk is the least possible for achieving the objectives of the research, and that the woman be informed of the reasonably foreseeable impact of the research on the fetus. Many Institutional Review Boards (IRBs) are very conservative about approving clinical trials involving pregnant women who are carrying their fetus to term, even if the federal criteria are met.
In another example, clinical trials of HIV prevention -- including microbicide, vaccine, and pre-exposure prophylaxis trials -- commonly exclude pregnant women and withdraw women from the study if they become pregnant. That is, they discontinue the study intervention, but they continue to be followed for outcomes. Such exclusions result in a weaker evidence base regarding the benefits of risks of interventions in pregnant women.
What Would You Recommend? Suppose you are a member of an IRB reviewing a randomized controlled trial of standard vs. higher dose oseltamavir for pregnant women diagnosed with H1N1 influenza. First, to ensure that the benefit/risk ratio in the trial is acceptable, what protocol requirements and IRB procedures would you recommend? And second, what measures would you require to ensure that consent is informed and voluntary?