Throughout the coronavirus disease 2019 (COVID-19) pandemic, pregnant women have been excluded from clinical trials on new therapeutics and vaccines. This exclusion has led to an immense void in knowledge regarding the most effective approach for the treatment of pregnant women diagnosed with COVID-19.
Although the United States Food and Drug Administration (FDA) has recently promoted the inclusion of pregnant women in clinical trials, clarifications on its associated challenges are needed.
Study: Scientific, Ethical,and Legal Considerations for the Inclusion of Pregnant People in Clinical Trials. Image Credit: Africa Studio / Shutterstock.com
In a recent American Journal of Obstetrics and Gynecology study, researchers summarize the scientific, legal, and ethical considerations related to research associated with pregnancy. They have further recommended strategies that scientists can overcome the challenges associated with including pregnant women in clinical trials.
The exclusion of pregnant women from COVID-19 trials was consistent with the historical exclusion of this group from most clinical trials. Although 90% of pregnant women take at least one medication during pregnancy, very few medical products are developed for pregnancy-related conditions.
Both medical professionals and patients have very little information available on the risks associated with most medications for pregnant women and the growing fetus.
Most of the medical products that are prescribed to pregnant women are only approved for adult use. Unfortunately, these medications are prescribed to these women, despite the lack of data related to the specific dose or safety profile of a particular drug during pregnancy. To address this gap in research, it is important to enroll pregnant women in clinical trials, as well as clinical pharmacology and reproductive toxicity studies.
In February 2021, the Duke-Margolis Center for Health Policy, under a cooperative agreement with the FDA, conducted a public meeting that discussed the ethical and scientific considerations for including pregnant women in clinical trials. This meeting was attended by academics, government agencies, industries, and patient advocacy groups.
The current study reports some of the scientific, ethical, and legal considerations that will support the inclusion of pregnant women in future research and clinical trials.
The convention clearly stated that non-clinical and clinical data are essential components of the drug development process. Non-clinical studies provide safety information that is essential to determining dosage, eligibility criteria, and drug labeling.
Typically, these studies support enrolling pregnant women in clinical studies. However, the clinical data collection process would assist in informed regulatory decision-making processes and evidence-based care delivery.
The participants at the convention discussed two types of non-clinical studies including those regarding developmental toxicity and reproductive toxicity. Reproductive toxicity assesses the reproductive competence of sexually mature females and males. Comparatively, developmental toxicity studies evaluate the adverse effects of a specific drug when the fetus is exposed during the pre-conception, prenatal, or postnatal stages.
Typically, non-clinical studies utilize various animal models to assess the efficacy and safety profile of a new drug. The primary goal of clinical trials including pregnant women is to develop therapeutics for pregnancy-related conditions, such as preeclampsia, as well as intrahepatic cholestasis of pregnancy and preterm birth.
During the convention, bioethicists indicated that clinical studies in which pregnant women are included had been guided by a protectionist ethic, which had long-term harmful consequences. This protectionist ethic failed to acknowledge that all research might not have direct befit to participants; however, it would have a positive impact on other current and future pregnant women.
Often, individuals have been reluctant to participate in studies that require the unnecessary use of contraception. This raises the ethical concern of imposing needless requirements that prevent participation.
It is imperative to develop a framework or guidelines with common criteria that justify the inclusion or exclusion of pregnant women in clinical trials. The convention participants emphasized that the ethical framework must be focused on recruiting participants based on protecting pregnant women through their inclusion in research.
At the Duke-Margolis Center for Health Policy convention, participants discussed how legal considerations, such as misperceptions of liability, dissuade research institutions from enrolling pregnant people in clinical trials.
Legal experts highlighted some of the considerations that influence the stakeholders’ decision about the inclusion or exclusion of pregnant women. To this end, it is a myth that the inclusion of pregnant women in studies is legally impermissible.
The participants stated that the exclusion of pregnant women from clinical studies, guided by a misperception of legal status, significantly increases their risk once drugs reach markets and are prescribed to them. Thus, legal experts must be engaged in the drug development process to ensure that strong risk mitigation strategies are available to prevent adverse effects.
The inclusion of pregnant women in clinical studies will not happen immediately; however, a proper framework will accelerate the process. The clinical research community can raise awareness among various stakeholders to initiate this change.
The participants of the Duke-Margolis Center for Health Policy also mentioned that the utilization of existing data including electronic health records and trial infrastructure could help leverage the generation of supportive evidence.
- Sewell, C. A., Sheehan, S. M., Gill, M. S., et al. (2022) Scientific, Ethical,and Legal Considerations for the Inclusion of Pregnant People in Clinical Trials. American Journal of Obstetrics and Gynecology. doi:10.1016/j.ajog.2022.07.037.