Here’s a scenario anyone who has done clinical research will recognize: A 32-year-old woman participating in a Phase 1 healthy-volunteer crossover clinical trial tested negative for pregnancy when she enrolled and agreed to use contraception during the course of the trial, as specified in the protocol. After completing the first phase of the trial, she checked in for the second phase, at which time the required pregnancy test was positive.
For good reason, pregnancy tests are a standard part of screening for certain clinical trials. Participants with positive results are excluded from participating to protect them and their developing fetuses from potential harm. For clinical research that includes women of childbearing potential, pregnancy tests are performed at intervals during the trial. Protocols contain language to specify how to follow participants who inadvertently become pregnant during a study and procedures have been established to execute those protocols.
Balancing the need to have representative, diverse clinical trials with mitigating the risk of exposing a fetus to an experimental therapy requires thousands of pregnancy tests weekly in the U.S.
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Until recently, this was something I took for granted as established practice.
The U.S. Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization changed that.
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I trained in Ireland before that country legalized abortion (then known as “taking the boat to England”). I have practiced medicine in a hospital where it was not permitted to prescribe contraception (many women were prescribed combinations of estrogen and progesterone for “anemia due to heavy menstrual bleeding”). So I should be used to what is looming for women in states that have banned abortion or are planning to do that.
But now, as the CEO of a biotech company, the specter of criminalizing women for their reproductive health choices raises serious concerns for my company and others conducting clinical research in states that implement the most extreme restrictions. Many of these states host Phase 1 units and research centers.
I now find myself asking questions that need answers that aren’t easy to come by:
- How should trial sponsors think about site selection as they strive to enroll diverse participants and also protect female research participants?
- How should informed consent documents describe the risk of a pregnancy test result being recorded in the notes at the research site?
- Do trialists need to record the reason a healthy volunteer did not qualify for an early-phase, healthy volunteer trial?
- For participants who become pregnant during the course of a trial, will sponsors be able to collect accurate pregnancy outcome data in cases where a participant chooses to terminate? Will doing so create a paper trail that might expose the participant to potential criminal prosecution?
- And here’s the one that really worries me: Will sponsors and study sites be required to share clinical data, including pregnancy and outcome, with state officials?
In 1977, the FDA published a guideline that recommended excluding premenopausal women from participating in Phase 1 and Phase 2 studies. It has since been recognized that this guideline had important negative consequences for women’s health generally and was ethically questionable. In 1993, the FDA reversed that policy and now encourages including both genders in trials in the context of specific measures to mitigate risk of fetal exposure. Ensuring that data packages submitted to the FDA as part of the drug approval process are representative of the intended population from a demographic perspective is an increasingly important task for biopharma companies.
The Dobbs decision has the potential to slow the positive momentum in diversifying clinical trials and companies will need to carefully consider how to respond. I am not a research policy expert but, as a clinical developer, I have a toolkit for dealing with new risks in development programs: understand the risk, manage the risk, and communicate the risk to stakeholders. As the expected and unexpected implications of the Dobbs decision emerge, my colleagues and I plan to continue developing an understanding of the risks imposed by the legislation implemented on a state-by-state basis to study participants and to implement tactics to manage them while continuing to enroll diverse study populations.
To continue the story of the 32-year-old participant with which I opened the essay: She visited her obstetrician and was found to have had a miscarriage or spontaneous abortion, which was in line with her long history of irregular menstruation and recurrent miscarriage. Without any intervention, her pregnancy test returned to negative over a few weeks. If she had not been enrolled in the trial, she probably never would have known she was pregnant.
Miscarriage or spontaneous abortion is extremely common — and impossible to distinguish from medically induced abortion. This participant’s pregnancy disqualified her from continuing to be part of our trial. Post-Dobbs, and in a different state, she might now be suspected of a criminal act.
Aoife Brennan is the CEO of Synlogic, a Cambridge, Mass.-based company developing treatments for metabolic and immune-based diseases based on synthetic biology.
