Protected to death: systematic exclusion of pregnant women from Ebola virus disease trials

Abstract

BackgroundFor 30 years, women have sought equal opportunity to be included in trials so that drugs are equitably studied in women as well as men; regulatory guidelines have changed accordingly. Pregnant women, however, continue to be excluded from trials for non-obstetric conditions, though they have been included for trials of life-threatening diseases because prospects for maternal survival outweighed potential fetal risks. Ebola virus disease is a life-threatening infection without approved treatments or vaccines. Previous Ebola virus (EBOV) outbreak data showed 89–93% maternal and 100% fetal/neonatal mortality. Early in the 2013–2016 EBOV epidemic, an expert panel pointed to these high mortality rates and the need to prioritize and preferentially allocate unregistered interventions in favor of pregnant women (and children). Despite these recommendations and multiple ethics committee requests for their inclusion on grounds of justice, equity, and medical need, pregnant women were excluded from all drug and vaccine trials in the affected countries, either without justification or on grounds of potential fetal harm. An opportunity to offer pregnant women the same access to potentially life-saving interventions as others, and to obtain data to inform their future use, was lost. Once again, pregnant women were denied autonomy and their right to decide.ConclusionWe recommend that, without clear justification for exclusion, pregnant women are included in clinical trials for EBOV and other life-threatening conditions, with lay language on risks and benefits in information documents, so that pregnant women can make their own decision to participate. Their automatic exclusion from trials for other conditions should be questioned.

Exclusion of Pregnant Women from Clinical Trials during the Coronavirus Disease 2019 Pandemic: A Review of International Registries

“…12 Today, the inclusion of women in clinical trials is both expected and commonplace though usually requires that a subject be nonpregnant and/or compliant with effective contraception. 13 However, pregnant women remain habitually excluded from clinical pharmacologic/ therapeutic trials that do not address obstetric conditions. This is due, in large part, to potential risks of teratogenicity weighed against potential medical benefits to the mother.…”

“…3 The HIV/AIDS epidemic serves as a singular and excellent example of inclusion of pregnant women in the earliest phases of drug development. 13 However, this was predominantly driven by the potential benefit of reduced vertical transmission to the fetus. 14 Unfortunately, the pattern of excluding pregnant women from clinical trials, even during epidemics, is not new.…”

SERINC5 as a New Restriction Factor for Human Immunodeficiency Virus and Murine Leukemia Virus

“…Pregnant women were excluded from receiving the vaccine in West Africa, as there was thought to be insufficient evidence of vaccine safety. This decision led to anger that women were being put at unnecessary risk because of their exclusion (73,90,91).…”

Being Pregnant during the Kivu Ebola Virus Outbreak in DR Congo: The rVSV-ZEBOV Vaccine and Its Accessibility by Mothers and Infants during Humanitarian Crises and in Conflict Areas

“…It is also the largest and most deadly of the ten Ebola outbreaks to occur in DRC [2], the country where Ebola was first identified during the 1976 Yambuku outbreak [3]. Throughout multiple outbreaks of EVD, the infection has had a significant case fatality rate (CFR) among all persons who became infected, but historically the mortality has been especially high among pregnant women, fetuses and infants (less than 1 year of age) [4][5][6][7]. Prior to the West African Ebola epidemic which began in Guinea in December 2013, it was generally believed that EVD occurring in a pregnant woman was close to being non-survivable.…”

“…Prior to the West African Ebola epidemic which began in Guinea in December 2013, it was generally believed that EVD occurring in a pregnant woman was close to being non-survivable. Previous Ebola outbreaks had demonstrated that from 75 to greater than 90 percent of infected pregnant women had died as a result of EVD [4,6,8,9].…”