While members of the FDA Pediatric Advisory Committee (PAC) said much of the existing artificial womb technology (AWT) research is promising, they noted that the logistical and ethical concerns previously raised by the agency's staff members are complicated.
The committee did not vote during their 2-day meeting this week. Further discussion about first-in-human trials for AWT is ongoing, but is closed to press and the public.
AWT is meant to mimic the functions of a womb for extremely preterm infants, FDA reviewers explained in briefing documents released ahead of the meeting. While animal models of AWT appear promising, the technology hasn't been tested in people yet.
Looking at data from studies on animals including lambs and piglets, some PAC members were uncomfortable with the idea of making the jump to human trials.
Alan Flake, MD, director of the Center for Fetal Research at Children's Hospital of Philadelphia, presented his team's research on 300 lambs who were successfully treated with AWT, though he noted that "there is no perfect animal model."
Informed Consent and Ethical Considerations
PAC members emphasized the need for robust informed consent measures, with many highlighting the importance of culturally competent education about AWT. Focus groups for racially and culturally diverse women with high-risk pregnancies could help inform this education, some members suggested.
"We need to make sure that the parents are fully aware of the technology and understand what they're being asked to participate in," said PAC Chairperson Robert Dracker, MD, of SUNY Upstate Medical Center in Syracuse, New York, adding that they also need to "make sure that it is inclusive of all infants regardless of race, creed, color, and background and make sure the informed consent process is adequate for the parents of these infants."
Committee members also questioned whether AWT would put mothers at risk any more than the current standard of care or whether AWT could be weaponized to extend the fetal viability line.
Mark Mercurio, MD, MA, director of the biomedical ethics program at Yale School of Medicine in New Haven, Connecticut, suggested a meeting to discuss the ethics surrounding AWT, which several committee members supported.
Gwenyth Fischer, MD, of the University of Minnesota Medical School in Minneapolis, noted that patients should be involved in the process.
"I think that we have seen historically that highly invasive trials in pediatrics are very difficult to recruit for," Fischer said, adding that patient feedback could inform both trial design and the consent process.
Some members suggested having informational brochures about AWT available in ob/gyn offices where mothers could familiarize themselves with the option, should they deliver extremely preterm.
Gianna McMillan, DBe, the PAC patient-family representative, shared her own story of weighing the potential risks and benefits in her child's medical treatment. "I just don't want us to assume that because the issues are complex, and that the parents are distressed, that they cannot make a well-considered decision," McMillan said.
Clarity on Safety Monitoring
The FDA has stated that an AWT trial would likely begin one patient at a time, and PAC members wanted to know what metrics should be considered before enrolling more patients.
Robert Nelson, MD, PhD, senior director of pediatric drug development at Johnson & Johnson and the industry representative on the panel, noted that while long-term data on infant and maternal health are vital, waiting several years after the first AWT human trial to continue research would not be realistic. He said the FDA would "need to come up with some short-term measures, because otherwise this technology would be in development for the next 15 years before there's any meaningful data."
Other PAC members expressed concern over the long-term health effects that AWT could have on infants, with some noting that disability and quality of life may be equally as important as survival.
"The end point for measurement needs to clearly be defined based on the baby and the parents for quality of life," said Randi Oster, MBA, the PAC's consumer representative.
It would be useful to know what potential adverse events could affect infants in an artificial womb and how those events would be reported, members said. Clarity of financial liability -- including what entities would foot the bill for problems families may have down the line -- also is needed, they added.