Lessons from PrEP: A Qualitative Study Investigating How Clinical and Policy Experts Weigh Ethics and Evidence When Evaluating Preventive Medications for Use in Pregnant and Breastfeeding Women

Kristin M Beima-Sofie,Grace C John-Stewart,Maureen Kelley,Susan Brown Trinidad,Kenneth Ngure,Renee Heffron,Jared M Baeten

doi:10.1007/s10461-018-2361-5

Abstract

This study explored how multinational HIV experts weigh clinical, evidential, and ethical considerations regarding pre-exposure prophylaxis in pregnant/breastfeeding women. Semi-structured interviews were conducted with experts in HIV policy, research, treatment, and implementation from three global regions. A constant comparative approach identified major themes. Experts noted that exclusion of pregnant women from research limits evidence regarding risks/benefits, emphasizing that underinclusion of pregnant women in RCTs shifts the onus of evidence-building to clinical care. Experts discussed approaches for weighing evidence to make decisions, including triangulating evidence from sources other than RCTs. Likelihood and severity of disease strongly influenced decisions. Less effective interventions with limited fetal risk were preferred over interventions of uncertain safety, unless the disease was serious. Experts resisted the dichotomous choice between protecting maternal and fetal interests, arguing that these interests are intertwined and that more holistic approaches to maternal–fetal balance support greater inclusion of pregnant women in research.

Highlights

The development of safe and effective biomedical interventions for women during pregnancy and breastfeeding is critical
Pregnant women have been considered a vulnerable population meaning that the ethical threshold for inclusion in research is higher than nonpregnant participants given concerns about potential risks to the developing fetus
Participants self-identified as a mixture of clinicians/healthcare workers, researchers and ethicists, and some (14%) identified as experts from multiple domains

Summary

Introduction

The development of safe and effective biomedical interventions for women during pregnancy and breastfeeding is critical. Pregnant women have been considered a vulnerable population meaning that the ethical threshold for inclusion in research is higher than nonpregnant participants given concerns about potential risks to the developing fetus. This position placed pregnant women in the same category as other dependent populations considered to be more susceptible to harms or exploitation in research, such as children, prisoners, or those suffering from mental illness. Despite recent ethics and policy arguments advocating a shift away from classifying pregnant women as a vulnerable population in research, significant barriers remain to the inclusion of pregnant women in clinical trials given persistent concerns about risks to the fetus [1,2,3,4]. In the absence of randomized control trial (RCT)-derived data on safety and efficacy in pregnancy, implementation studies and clinical decisions regarding medications in pregnancy/ breastfeeding can be ethically and clinically challenging for health providers, researchers, and policy makers [5,6,7,8,9].

Results

Discussion

Conclusion