Mifepristone study highlights need for more transparency, data collection in FDA’s REMS program
Patients who reviewed and signed a patient agreement form (PAF) for mifepristone and misoprostol under the US Food and Drug Administration’s (FDA) risk evaluation and mitigation strategy (REMS) program were equally knowledgeable about medication abortion compared to patients who completed a knowledge survey before reviewing and signing the PAF, according to the results of a recent randomized controlled trial published in JAMA Internal Medicine.
The findings “suggest that the PAF provides little additional educational benefit in the context of routine clinical care,” M. Antonia Biggs, of the Advancing New Standards in Reproductive Health program at the University of California, San Francisco, and colleagues wrote in their study.
“Patients already have high levels of medication abortion knowledge without the PAF, and requiring them to review and sign it does not meaningfully improve their understanding,” they explained. “The FDA should consider removing the PAF requirement to streamline medication abortion provision.”
Biggs and colleagues evaluated 292 patients who received mifepristone and misoprostol medications between January and October 2025 who received the PAF and compared their knowledge of medication abortion to 301 patients who completed a knowledge survey before receiving the PAF. The survey consisted of 12 items asking patients about care, effectiveness, and administration as well as the potential serious risks and side effects surrounding medication abortion.
The results showed no significant difference in the number of mean items answered correctly between the group that received the PAF first compared to those receiving the knowledge survey first (10.44 vs 10.26), with nearly all patients answering items correctly about the need for contacting a provider for infections and heavily bleeding. Patients in both groups were least likely to answer questions correctly that asked how often treatment is not effective (54%) and when to take misoprostol after mifepristone (77%).
The researchers said knowledge of medication abortion in both groups could be potentially due to counseling received before the PAF. They noted their findings could be useful to policymakers “as they consider whether the current level of regulatory oversight for mifepristone is appropriate.”
Improving REMS program transparency, data collection
In a related commentary, Eric P. Sun; and Reshma Ramachandran, of the section of general internal medicine at Yale School of Medicine, said the surveys conducted by manufacturers on whether PAFs increase patient and prescriber knowledge of products subject to the REMS program tend to lack elements such as pre-post testing and adequate controls while relying on convenience sampling.
“These surveys do little to evaluate whether the elements of the REMS improve knowledge or change behavior,” Sun and Ramachandran wrote.
They noted that in 2016, FDA’s internal staff recommended removal of the PAF for mifepristone, but were overridden by the FDA commissioner because of the “additional assurance provided by the patient agreement form.”
The current study contains “robust evidence to support the conclusion previously drawn by the FDA’s staff scientists in 2016 that the patient agreement form is duplicative of standard counseling provided to patients,” Sun and Ramachandran wrote.
Moreover, the lack of data collection surrounding REMS programs makes it difficult to determine whether they are effective. “Without rigorous and transparent evaluations of the REMS, patients risk losing access to medications with unnecessary regulations or risk harm from medications with ineffective ones,” they wrote.
Sun and Ramachandran proposed new REMS have prespecified evaluation plans that contain rigorous study designs and data collection plans, while evaluation plans of existing REMS be redesigned for methodological rigor. The agency could also create a mandate for better data collection and design of assessments of REMS programs and could also partner with other institutions for these evaluations rather than relying on manufacturers alone.
FDA has the potential to have a more effective REMS program by pursuing better data collection and improved transparency, Sun told Focus in an interview.
“We hope this study is a first step towards better science and subsequent decision-making for the program,” he said.
However, he said it is “hard to say for sure” whether FDA would undertake these suggestions. While FDA internal staff are likely to reference the current study and consider it as strong evidence for removing the PAF, “the FDA commissioner has the final say, and we have a candidate who has expressed strong views in the past on mifepristone,” he said.
“Additionally, there is significant political pressure on the agency right now around mifepristone, which has led to the agency undertaking a safety review,” he noted.
Sun said the agency “should ensure the independence of their staff scientists to make the best decisions based on the highest quality evidence and be transparent about what evidence was used.”
The current safety review of mifepristone is something he and Ramachandran are watching closely. “However, given the over 25 years of literature, over 100 published studies confirming the safety of mifepristone, and FDA’s extensive, multiple reviews of the REMS requirements for mifepristone where they took an exceptionally cautious approach, it seems unlikely that anything new will be found,” Sun said.
FDA should be more transparent about how they are conducting the safety review, including publishing protocols for the medical and scientific community to evaluate. “Making a change to the REMS absent that would be potentially misleading for patients and clinicians in understanding the safety profile for mifepristone,” he said.
