A new ethical framework to determine acceptable risks in fetal therapy trials

Abstract

Objective Fetal therapy trials pose complex ethical challenges because risks and benefits to both fetuses and pregnant persons must be considered. Existing regulatory guidance is limited and many proposed ethical frameworks have unnecessarily restrictive criteria that would block the development and implementation of important new fetal therapies. We aimed to develop a new ethical framework for assessing the risks and benefits of fetal therapy trials. Methods We reviewed existing regulatory and ethical guidance on fetal therapy trials. We used conceptual analysis to design a new ethical framework, which is grounded in general ethical principles for clinical research. Results We propose a new framework for assessing the risks and benefits of fetal therapy trials. We suggest that the potential benefits of a fetal therapy trial – for the fetus, the pregnant person, and society – should outweigh the risks for the fetus and the pregnant person. Furthermore, the risk‐benefit profile for just the fetus and the risk‐benefit profile for just the pregnant person should be appropriate. Conclusions We hope that this new framework will permit important studies while protecting pregnant persons and fetuses from disproportionate harms.

Precarious hope: Ethical considerations for offering experimental fetal therapies outside of research after initial studies in humans

“…Risks should be considered in relation to anticipated benefits, taking into account the likelihood and magnitude of both, and of available alternatives. 16,17,19 Higher risks may be justifiable in attempting to ameliorate severe conditions, particularly when no alternative treatment exists. For example, while a 60% risk of preterm prelabor rupture of membranes may be acceptable 8 to attempt enhanced survival in BRA, the same risk would not justify using experimental fetal therapy to reduce the incidence of childhood eczema.…”

“…If non-pregnant adults can accept uncompensated risks to advance science or help a stranger, then pregnant individuals should be allowed to do the same to benefit their fetuses. 16,17 However, even for consenting adults, there are limits to how much risk clinicians can ethically expose patients to; for example, a 50% mortality rate, akin to deliberate Ebola infection 39 is too high. 40 Fetal therapies that expose pregnant individuals to too much risk should not be offered.…”

“…Assuming proper informed consent, competent adults are permitted to accept risks not compensated by benefits to themselves in other settings such as research (e.g., healthy volunteer studies) 15,38 or living organ transplants. If non‐pregnant adults can accept uncompensated risks to advance science or help a stranger, then pregnant individuals should be allowed to do the same to benefit their fetuses 16,17 . However, even for consenting adults, there are limits to how much risk clinicians can ethically expose patients to; for example, a 50% mortality rate, akin to deliberate Ebola infection 39 is too high 40 .…”

“…We previously proposed an ethical framework for assessing fetal therapy trials. 16,17 (We proposed that the potential benefits of a fetal therapy trial -for the fetus, the pregnant individual, and society -should outweigh the risks for the fetus and the pregnant individual. Furthermore, we argued for proportional risk limits for both the fetus and the pregnant individual such that benefits for others cannot be used to justify inappropriate risks to them).…”

“…Research is essential to develop high‐quality evidence to advance the interests of future patients. We previously proposed an ethical framework for assessing fetal therapy trials 16 ,. 17 (We proposed that the potential benefits of a fetal therapy trial – for the fetus, the pregnant individual, and society – should outweigh the risks for the fetus and the pregnant individual.…”