A recent study published in the American Journal of Perinatology evaluated the use of ethical principles in clinical trials for conditions of pregnancy including fetal and neonatal alloimmune thrombocytopenia (FNAIT) and hemolytic disease of the fetus and newborn (HDFN).
Historically, pregnant individuals have not been included in clinical trials due to the potential risks to the individual and the fetus. Although this exclusion is meant to protect these potentially vulnerable populations, it has resulted in a lack of research on medication use during pregnancy.
The three major ethical principles of human subject research, as outlined by the Belmont Report, are: respect for persons, which includes obtaining informed consent; justice; and maximizing benefit (beneficence) while minimizing harm (non-maleficence). Each of these principles, the authors explained, should prioritize both the well-being of the fetus and the interests of the pregnant patient.
The question of whether paternal consent should be required for clinical trials, however, is complex in diseases such as FNAIT. If only the fetus is considered to benefit from the intervention, paternal consent would be required in the United States. However, paternal consent would not be required if the prevention of maternal complications is also considered. This subtlety highlights the difficulties of researching diseases of pregnancy.
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Currently, intravenous immunoglobulin (IVIG) is often used off-label in pregnancies at risk for FNAIT. Therefore, developing clinical trials is difficult due to the ethical concerns of assigning patients to a placebo and withholding IVIG. Study design is further complicated by the fact that IVIG regimens vary significantly between patients.
To address this issue, a placebo-controlled trial, FREESIA-1, is ongoing to evaluate the efficacy of nipocalimab in standard-risk FNAIT. If preliminary data show promising results, high-risk patients may enter an open-label study comparing nipocalimab with IVIG. This design helps ensure that patients receive access to care as soon as is safely possible.
“Knowledge of the clinical course and management of severe HDFN and FNAIT, the non-clinical and non-pregnant human clinical evidence, and input from physicians, patients, and health authorities permitted the design of clinical protocols that satisfy the principles of beneficence and non-maleficence in these rare and complex diseases,” the authors concluded.
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