US reproductive laws could limit women’s participation in clinical trials

The open language of US abortion laws could have unintended consequences and might discourage the participation of women in clinical trials altogether. Credit: Rena Schild / Shutterstock

It has been over two years since the US Supreme Court’s decision in Dobbs versus Jackson Women’s Health to overturn the constitutional protection for abortion that had previously been established as a result of the 1973 Roe versus Wade decision.

While most of the focus has been on the direct consequences of the abortion restrictions, namely maternal morbidity, and mortality, these restrictions have ethical, legal, and practical implications for everyone involved in clinical trials.

The recent US elections and the upcoming Donald Trump administration have only increased the topic’s uncertainty. Allison Whelan, assistant professor at the Georgia State University College of Law, notes that President-elect Trump’s position on abortion has been inconsistent. Adding that, on the one hand, he has boasted about making the overturn of Roe versus Wade possible, while on the other hand, he has also said he would veto a federal abortion ban and leave it to the states.

Experts have raised concerns over various aspects of clinical research involving people who can become pregnant. A 2023 research paper, noted multiple points that could affect the participation of women in a clinical trial, regardless of disease indication. The researchers noted that “research interventions, by definition, expose participants to unknown risks. When research participants become pregnant, those risks can include threats to the health or life of the pregnant person, as well as potential harm to their foetus”.

Before enrolling in a clinical trial, research participants must give informed consent. Trial sponsors will need to consider whether and how to inform participants of potential or hypothetical risks revolving around the issue of abortion.

Whelan was clear that while “there aren’t any states that have gone so far as to explicitly criminalise the pregnant person who receives an abortion, there are ways that states can, and have, prosecuted people for actions during pregnancy that harm a foetus or end a pregnancy. Many of these laws are not even specific to abortion or mention abortion at all.”

These include child neglect and abuse laws or “chemical endangerment” laws, which have been used to prosecute pregnant persons for using drugs or alcohol during pregnancy, among other things. The risks of these laws being applied increase if a state recognises a fetus as a person under the law.

Whelan, in a law review, gave the example of how a state may seek to prosecute a pregnant person for their involvement in a clinical trial. “For a pregnant person in a clinical trial, the state could argue that the person intended to expose, or at least knowingly exposed, the foetus to the investigational (i.e., unapproved) drug by enrolling in the trial. If the potential risks of an investigational drug are known (e.g., as indicated in informed consent documents), a court may dismiss any argument that the pregnant person “lacked fair notice that [their] conduct constituted child abuse.”

Whelan notes that informed consent documents may need to not only cover these medical risks of the trial but also think about “non-health-related” hypothetical risks, including privacy risks. This includes informing the participants about the legal uncertainties.

For example, pregnancy is often an exclusion criterion for enrolling in a clinical trial. To participate, pregnancy-capable women may need to take contraception and be required to undergo pregnancy tests that they may not have taken outside the research context.

Whelan says: “If a person becomes pregnant during this trial, and they want to remain in this trial, the only real way for them to do so is to terminate their pregnancy. If that participant is a resident of Texas, a state with restrictive abortion laws – how do you accurately portray to them that if they get pregnant during this trial, and if you want to terminate the pregnancy so they can remain in the trial, really the only way they are going to be able to is to leave the state to get an abortion. 

“But just by informing that participant that they would have to terminate their pregnancy to remain in the trial, the clinical trial sponsor is putting themselves at risk for informing them about the fact that they would need to get an abortion.

“Texas, for example, has a law that allows private individuals to sue anyone who performs or facilitates (i.e., aids and abets) an illegal abortion. It’s possible that simply informing somebody that they would need to get an abortion to remain in a clinical trial could be broadly construed as aiding and abetting an abortion.”

This potentially exposes the trial sponsor to litigation. Whelan notes that whilst “some of these risks just seem ridiculous to think about, this is the reality we now live in. We have to think about these things because I do think that there are prosecutors like Ken Paxton, Attorney General of Texas, who is willing to at the very least, threaten to go to extreme lengths to crack down on abortion.”

Pharmaceutical companies spend billions to develop new therapies. The uncertainties in the statewide abortion laws, along with the fear of actual and perceived risk may make it harder to enrol pregnancy-capable people, which encompasses almost every woman between the ages of 18 to 49 years for the clinical trial.

Research studies often require participants to undergo pregnancy tests at regular intervals. Experts have noted in some instances “these tests can potentially detect and document early pregnancies that otherwise would have gone unnoticed given high rates of miscarriage in the first trimester, which in turn might raise concerns in some jurisdictions that the participant obtained an illegal abortion”.

Whelan states that although some laws and policies protect clinical trial data, “a state prosecutor may make an informal request, which can be very intimidating. Even if there is no legal requirement to hand over the information sought, fear and intimidation can be very persuasive. That fear might cause trial staff to hand over the requested information, thinking that that person is legally entitled to it, when, in fact, they are not”.

Whelan adds: “But again, once it’s out there, it’s out there. We also have to think about if states become aware that this information might exist in clinical trial data, they might try to amend some of their state law clinical trial protections so that they could provide some carve-outs that would allow them to get access to this information if it involves potential pregnancies. If no federal abortion ban gets enacted, which I think would be difficult to get in place, then anti-abortion states may try to get more creative with ways to crack down on abortion, says Whelan.

The fear of prosecution can be a very effective deterrent and have a massive impact. In February, the Alabama Supreme Court ruled that embryos used by in vitro fertilisation (IVF) facilities constitute living children, and IVF facility staff can be held liable for destroying them.

Immediately following this, all the IVF facilities in the state halted business. While the Alabama lawmakers did not intend for this outcome and tried to change course by passing an amendment to the law on 6 March to exempt IVF clinics and staff from all criminal and civil prosecution, the law proved the terrifying impact open language in the US state laws can have.

In most instances, the trial sponsors can set up sites in states which are broadly protective of reproductive rights. This may not be feasible in all cases, especially in rare disease studies where the participant pool is limited.

Whelan says that in these cases you may be able to set up a trial site in California, but you may need to call participants from states such as Texas and Missouri, which have more restrictive abortion laws. In these cases, it is unclear how far could states go, or at least threaten to go if a state citizen becomes pregnant within that trial, they might need to get an abortion.

In the wake of the anti-abortion movement, certain therapies, especially those used in medical-assisted abortion have been scrutinised and seen their access limited. Whelan notes that one such example is mifepristone, which has many potential uses beyond abortion. Adding that many people she talks to, do not realise or know that it’s already approved for a different indication in the US.

In 2012, the US Food and Drug Administration (FDA) approved mifepristone as a maintenance treatment for endogenous Cushing’s syndrome. Studies are also investigating mifepristone as a treatment for post-traumatic stress disorder (PTSD). In high doses, the therapy has central effects and blocks the cortisol’s feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis dysregulation in PTSD.

Whelan notes that mifepristone and misoprostol, another drug often associated with abortion, can be quite versatile and have broader use. However, the stigma associated with these drugs can restrict or make it harder to obtain funding to investigate these therapies in other disease indications.

Whelan says that although seeking federal protections for women’s reproductive rights may be harder under the Trump administration, there are some steps that sponsors can take to mitigate the potential impact of the state abortion laws on clinical trials.

“I do think that certificates of confidentiality are still going to remain very important. The clinical trial sponsors need to be sure to get certificates of confidentiality whenever possible, but also realise that their protections are not absolute,” says Whelan.

Additionally, pharmaceutical companies should not only let the hypothetical risks completely scare them away but also leverage their economic and political power to make the US lawmakers consider the broader impact of these abortion laws.

In September, the World Health Organization released guidance to include pregnant and lactating women in clinical trials. Other global health organisations have also made multiple calls for increased trial diversity and inclusion of pregnant women. It is high time to consider the wide-reaching impacts of US abortion laws and how they might discourage the participation of women in clinical trials, thereby, erasing all the positive strides made to promote the inclusion of women.