In post-Roe US, clinical trials may be too risky during pregnancy

A year after the fall of Roe v. Wade, clinical researchers are still grappling with how to ethically adjust to the new reality—which at this point involves abortion bans and restrictions in roughly half of US states. In a policy forum piece published Thursday in Science, a group of health experts and bioethicists led by Jeremy Sugarman at Johns Hopkins University lays out the ethical, legal, and practical challenges researchers face in the new era. Bans and restrictions lead to "increased maternal morbidity and mortality and deepening socioeconomic and racial inequities," they wrote, but also "pose risks to clinical research participants and potentially compromise the scientific and social value of some research." Clinical trials of experimental treatments inherently pose unknown risks to participants' health—and even their lives. For pregnant participants, those risks can extend to their fetuses. As such, it's standard for trials to include periodic pregnancy testing for all participants capable of getting pregnant and for participants to agree to use contraception. But, with nearly half of all pregnancies in the world being unintended, it's no surprise that unexpected pregnancies can and do arise in the course of clinical research. When that happens, a pregnant participant may feel termination is the best option for them, given the risks of the trial. But abortion restrictions and bans could make that option difficult to obtain, if not entirely out of reach, depending on the trial's location. Moreover, trial protocols that require in-clinic pregnancy testing could create paper trails, which may pose legal risks for both participants and clinical research staff. This could be the case even if a participant doesn't pursue termination. There are high rates of miscarriages early in pregnancies, and clinical trial protocols that involve periodic testing can pick up pregnancies that would have otherwise come and gone without notice. Miscarriages (aka spontaneous abortions) are indistinguishable from medically induced abortions.

Real risks

This isn't a hypothetical scenario. In an op-ed last year in Stat, Aoife Brennan, the CEO of a Massachusetts-based company developing treatments for metabolic and immune-based diseases, described the situation of a 32-year-old woman who was participating in a Phase 1 trial. She tested negative for pregnancy at enrollment and agreed to use contraception. Still, when she checked in for the second phase of the trial, she tested positive. A visit to her OB-GYN revealed that she had a spontaneous abortion, in line with her history of recurrent miscarriages and irregular menstrual cycles. At the time, the only consequence was that she was disqualified from the rest of the trial. But, "Post-Dobbs, and in a different state, she might now be suspected of a criminal act," Brennan wrote. One suspicion raised by such a case is a self-managed abortion, which is a medication-based abortion done without medical supervision (usually at home) using pills that people are able to order online from a variety of places. So far, none of the new restrictions and bans since Roe v. Wade fell have directly criminalized self-managed abortion, though three states had such laws on the books prior to that (Oklahoma, Nevada, and South Carolina). Still, according to an analysis last year by If/When/How, a legal organization that supports abortion rights, states don't have to have those laws to try to prosecute people. The organization identified 61 cases in 26 states of people being criminally investigated or arrested for allegedly self-managing their own abortions or helping someone else do so. "So what this means is that overzealous prosecutors and police misapplied criminal laws to arrest people," Laura Huss, lead author of the report, told NPR last August. And there are certainly anti-abortion groups who hope to see more criminal punishments for people who terminate pregnancies. But, rather than going after pregnant people directly, the new restrictions and bans over the past year focus on people and health care providers who provide or aid abortion. The rules threaten penalties, fines, and even jail time. In Alabama, providing abortions of viable fetuses can be punishable by life in prison (Title 26). A Texas law encourages private citizens to sue anyone suspected of providing or aiding someone in obtaining an abortion, with statutory judgments no less than $10,000, plus legal fees. A poorly written law in North Carolina, set to come into effect July 1, suggests it may be unlawful for providers to even "advise" patients on seeking abortion after the state's 12-week ban, even for lawful procedures in other states. (The law is facing a federal lawsuit, which, among other things, argues that this provision violates the First Amendment rights of providers.)

Effects on clinical research

Altogether, the current landscape stands to chill good clinical research. People capable of being pregnant may not be willing to participate. Researchers may be wary of collecting much-needed pregnancy-related data. And it could cause researchers to lose ground in efforts to boost diversity in clinical trials, compromising "the scientific and social value of research" and "reinforcing longstanding gender disparities, which are due in part to long-standing underrepresentation of people who can become pregnant in research." In the policy forum in Science, Sugarman and colleagues outline important points researchers should consider when running clinical research amid all of this. Clinicians should be well informed of current laws and upcoming changes regarding abortion access, as well as how laws are enforced in the area around the research, to gauge true risks, they write. That may require engaging with local health care providers and abortion advocates to understand the local landscape. If it appears that the risks from reproductive health care restrictions are not "reasonable in relation to the potential scientific and social value" of the research, trial runners should "consider not pursuing research at that particular site." If the trial goes forward, the researchers should make specific provisions in their protocols for safe, legal abortion access for participants, ensure confidentiality on this point, and take additional measures to mitigate risks for participants, such as altering pregnancy testing frequency or having participants test at home. Additionally, Sugarman and colleagues recommend that researchers obtain informed consent from participants about pregnancy risks and abortion access during the research and monitor participants for harms related to reproductive health care. Institutional Review Boards (IRBs) should also offer additional oversight, taking the factors into consideration. "In especially restrictive environments, stopping rules regarding these issues may be indicated," Sugarman and his colleagues write. Last, the lessons learned should be "described and disseminated widely" as a means to generate best practices, the experts write.

Harms

In the meantime, harms from the new restrictions and bans are becoming more apparent. In a national survey of hundreds of OB-GYNs published this week by KFF, 64 percent of doctors said they believe the new laws have led to more deaths among pregnant people. Sixty-eight percent said the new restrictions and bans have worsened their ability to manage pregnancy-related emergencies. Thirty-six percent of doctors nationally, 55 percent in states where abortion is banned, and 47 percent in states with gestational limits, all said their ability to practice within the standard of care has become worse. More than half of OB-GYNs practicing in states with gestational limits (59 percent) and abortion bans (61 percent) said they are very or somewhat concerned about their own legal risks when making patient care decisions about the necessity of an abortion. International data suggests that restrictions to abortion access do not reduce the overall number of abortions; they merely reduce the number of safe abortions. Each year, between 5 percent and 13 percent of maternal deaths globally are due to unsafe abortions. And pregnancy itself is estimated to be 14 times deadlier for pregnant people compared with safe, legal medication abortion.