榴莲视频

There has long been a belief that pregnant and lactating women are excluded from clinical research due to potential legal liability. However, until now, there has never been a systematic examination of legal liability in the US for the inclusion of pregnant and lactating women in clinical research and whether this fear of liability is supported by evidence. A new report from the National Academies of Sciences, Engineering, and Medicine asserts that while fear of legal liability is pervasive, actual legal liability is not, and is often conflated with other concerns, such as reputational risk, increased costs, and trial complexity.¹ The report uses the word 鈥渨omen鈥� to highlight the complex and highly pertinent history of discrimination against women and the impact this continues to have on their health and well-being. However, the findings and recommendations in this report apply to all individuals who can become pregnant or lactate, regardless of their gender identification.

An original analysis of the case law commissioned by the committee that authored the report found little evidence of liability associated with clinical research involving pregnant women and found virtually no evidence of liability for research involving lactating women since the US Food and Drug Administration (FDA) modernized its drug approval process in 1962.² However, in postmarket settings, the authoring committee did find evidence of harms that resulted in legal liability for FDA-approved products used during pregnancy, suggesting that some of this postmarket liability may have been mitigated had pregnant women been included in clinical studies. By excluding pregnant and lactating women from clinical studies due to perceived liability risks, these populations, as well as their fetuses and breastfeeding children, are harmed.

In an ideal world, pregnant and lactating women would have the ability to make informed decisions that optimize their perinatal and postpartum health and the health of their children. Just like everyone else, pregnant and lactating women get sick and may need to take medication. But because clinical trials routinely and systematically exclude pregnant and lactating women from participation, these women and the clinicians caring for them do not have sufficient evidence to make informed decisions on the dosage, safety, and efficacy of therapeutics.³ This presents women and health care professionals with 2 flawed options: to use a treatment that puts the woman and her child at an uncertain risk of harm for an uncertain benefit vs forgo treatment that may result in harm from the untreated condition. There is an urgent need to ethically and responsibly include pregnant and lactating women in clinical research to provide evidence to guide these clinical decisions.

Pregnant and lactating populations have distinct physiologic characteristics and very different risk profiles that should also be acknowledged. For example, risk of harm is minimal in research involving lactating women, where it is estimated that 90% of medications pass through human milk at low enough levels to be safe for ingestion by breastfeeding children.⁴ Further, clinical studies with lactating women can be conducted without exposing breastfeeding children to any medical product because lactating women can pump and not feed their babies that expressed milk. Despite this minimal risk of harm, lactating women are rarely included in clinical studies. The National Academies鈥� report outlines distinct strategies that can be taken to minimize harm for research involving pregnant and lactating populations, including stronger federal guidance and research design.

Historical tragedies involving medication use during pregnancy causing harm to the fetus in utero, such as with thalidomide, cast a long shadow on the willingness to include these populations in clinical research. In response to the thalidomide tragedy, Congress passed legislation to strengthen the licensure system for new drugs and expanded FDA鈥檚 authority to refuse approval of medications that do not meet safety, effectiveness, and labeling requirements, essentially modernizing the US drug development system. Ironically, however, in the 60-plus years that have passed since the dangers of thalidomide became widely known, pregnant and lactating women have not received the full benefits of that legislation. They and their clinicians are still forced to make treatment decisions in the kind of information vacuum that allowed thalidomide to cause such widespread harm. As a society, it is time to acknowledge the harm this dearth of information causes and take action to ensure clinical studies involve these populations moving forward.

The effects of persistent mistaken perceptions of liability will continue unless action is taken. The recommendations in this report focus on 3 interconnected approaches to reduce potential liability risks associated with including pregnant and lactating women in clinical research and better align the perceptions of liability with the evidence base for conducting research with these populations. The first approach includes strategies that directly mitigate liability; the second seeks to minimize potential harm to research participants, thereby reducing the grounds for liability; and the third aims to allay the concerns that discourage researchers and sponsors from including pregnant and lactating women in clinical research. Due to the interconnected and self-reinforcing nature of these 3 approaches, some of the recommendations encompass actions in multiple approaches. For example, any action that minimizes potential harm to research participants will also mitigate the potential for liability.

The specific recommendations included in the National Academies鈥� report fall under several central themes:

• Greater Regulatory Clarity: Clear and specific guidance from FDA on conducting clinical studies with pregnant and lactating women can both minimize harm to research participants, as well as mitigate potential liability associated with that harm. The report鈥檚 recommendations include a call for FDA to revise guidance to make clear its expectation that pregnant and lactating women be included as early as possible in clinical studies, as well as increased clarity on study designs, safeguards, and product-specific monitoring expected for clinical studies involving pregnant and lactating women. The report also recommends that the Office for Human Research Protections provides clarity and guidance that helps clinical researchers, institutional review boards, and data and safety monitoring boards ensure that pregnant and lactating women who participate in clinical research are adequately protected without creating undue burdens for their participation.

• Incentives, Funding, and Accountability for Research: Utilizing as a model legislation passed in the early 2000s to spur innovation in pediatric populations, the report鈥檚 recommendations include a call for Congress to develop incentives, such as extended market exclusivity or tax breaks, to encourage the conduct of clinical studies with pregnant and lactating women. Additionally, the recommendations call for Congress to expand FDA鈥檚 authority to require that sponsors submit dosage, safety, and efficacy data in pregnant and lactating women for new medical products.

• Data and Safety Monitoring: Real-world data collection in the postmarket setting is an important source of information regarding the safety and efficacy of medical products. Increased clinical studies with pregnant and lactating women will not lessen the need for the collection of these real-world data. The report calls for the US Department of Health and Human Services to establish an interagency task force that can promote more efficient collection and use of these data.

• Research Participants鈥� Privacy: Following the US Supreme Court decision in Dobbs v Jackson Women鈥檚 Health Organization, research participants may be exposed to potential civil or criminal liability should they experience a spontaneous abortion or seek an elective abortion. While the legal landscape post Dobbs is still shifting, the potential for civil and criminal liability in states with statutes that confer personhood on the fetus could further discourage the conduct of clinical research with pregnant women. To protect the privacy of research participants, the report recommends that principal investigators apply for a certificate of confidentiality from the National Institutes of Health, if not already automatically granted one from a federal research sponsor.

Over the last several decades, there have been enormous advances in science, therapeutic agent development, and clinical care. However, pregnant and lactating women and their children have been left behind and have not experienced the benefits afforded to other people. It is time to allow pregnant and lactating women the same opportunities. The committee鈥檚 recommendations are one step toward this goal.

Corresponding Author: Margaret Foster Riley, JD, School of Law, Miller Center, University of Virginia, 580 Massie Rd, Charlottesville, VA 22903-1738 (mimiriley@law.virginia.edu).

Published Online: April 10, 2024. doi:10.1001/jama.2024.6874

Conflict of Interest Disclosures: The author is the chair of the National Academies of Sciences, Engineering, and Medicine consensus report Advancing Clinical Research With Pregnant and Lactating Populations: Overcoming Real and Perceived Liability Risks discussed in this article. No other disclosures were reported.