Including Pregnant Women in Clinical Research: Practical Guidance for Institutional Review Boards

Abstract

Scanty evidence exists about the safety and effectiveness of drugs—and of their efficacious dosing—that women may need to treat acute and chronic health issues during their pregnancies. This lack of evidence puts pregnant women and their fetuses at risk of harm from the use or avoidance of drugs during pregnancy. In light of the protectionist approach in regulations governing research with pregnant women and fetuses, trial sponsors, researchers, clinicians, and institutional review boards (IRBs) have been reluctant to include pregnant women in clinical drug trials, applying ethical reasoning for exclusions that reflects a default exclusionary approach. Yet in recent years, many clinicians, researchers, bioethicists, and professional societies have called for a reexamination of the routine practice of excluding pregnant women from clinical research. This paper proposes a practical approach to an ethical framework for IRBs that supports fair inclusion, rather than routine exclusion, of pregnant women in clinical research. This guidance will aid IRBs in ethically including and appropriately protecting pregnant women in research.

Using maternal and neonatal data collection systems for coronavirus disease 2019 (COVID-19) vaccines active safety surveillance in low- and middle-income countries: an international modified Delphi study

“…Exclusionary criteria imposed by IRBs, federal guidelines, and codes of regulation have further contributed to this challenge [31][32][33] . This emerging consensus that systematic exclusion of pregnant women from study involvement ultimately leaves these women and their fetuses susceptible to potentially substantially higher harm due to the lack of rigorous clinical data on the safety of drugs and other treatments have pushed clinicians, academics, bioethicists, and professional societies to increasingly call for a re-examination of the routine procedure of excluding pregnant women from clinical research in recent years 34 . This panel's dissent regarding the effect of regulatory requirements on the feasibility of including pregnant women in the target population for COVID-19 vaccine R&D activities suggests that additional guidance and regulation may be required to assist IRBs and research sponsors move toward an equitable, ethical, and adequately protected inclusion of pregnant women in vaccine R&D in the context of COVID-19.…”

The Promise, Problems, and Pitfalls of Including Pregnant Women in Lassa Fever Vaccine Clinical Trials: A Qualitative Analysis of Sub-Sahara Africa Investigators' Perception

“…Given the explorative nature of the research questions and the limited understanding of the factors responsible for the reluctance in including pregnant women in vaccine clinical trials despite the publication of guidelines [4,20], and enhanced advocacy, we, therefore, adopt a qualitative approach utilizing the participatory research (action inquiry) paradigm to answer the research questions. Data collection occurred between 17-21 September 2018 at the ninth EDCTP Forum in Lisbon, Portugal.…”

The COVID-19 vaccine evidence gap: Decisions without data for pregnant and breastfeeding women

“…9,22,23 Additional studies suggest that pregnant women with more severe COVID-19 disease are at increased risk of preterm delivery,²⁰ which is itself associated with poor fetal outcomes.²⁴ Safe and effective vaccines against COVID-19 will be instrumental in controlling the spread of SARS-COV-2 and putting an end to the pandemic. 25,26 Although four COVID-19 vaccines have been approved for use in Canada as of March 2021, 27 pregnant and breastfeeding women have been systematically excluded from all COVID-19 vaccine trials to date 20,22 Indeed, decisions about enrolling pregnant and lactating women in clinical research requires prudent considerations about the risks and benefits of the intervention being studied.⁸ These discussions are frequently characterized as "ethically complicated",¹⁵ as considerations need to be made for both of the mother and fetus 11,15 Often, the result is a decision to exclude all women of reproductive age out of fear for harming the fetus, which elicits considerable concern about financial and legal liability 14,28 Judgements of this type align with the widely accepted "precautionary principle" approach to medical ethics, i.e., reduce the risk of harm even before evidence of harm exists 11,29 As noted by others, 8,16,22,23 however, when it comes to vaccine trials for COVID-19, this 'exclude all' approach does not align with the ethical principles (namely autonomy, beneficence, and justice) purported to be upheld by decision makers. This is especially true for pregnant and lactating women with comorbid conditions that are known to increase their risk of severe disease.¹² To understand how best to protect pregnant women from COVID-19, we have to understand how their immune system reacts to vaccine candidates throughout the course of pregnancy.…”