Ebola Vaccine Trial: Pregnant Women's Exclusion in DRC

The exclusion of pregnant women from an Ebola vaccine trial in Boende,
western DRC: Perceptions of female participants who became pregnant and
community members
Maha Salloum
a,b,*
, Ynke Larivi` ere
a,b
, Freddy Bikioli Bolombo
a,b,c
, Tr´ esor Zola Matuvanga
a,b,c
,
Gwen Lemey
a,b
, Vivi Maketa
c
, Hypolite Muhindo-Mavoko
c
, Pierre Van Damme
a
,
Patrick Mitashi
c
, Hilde Bastiaens
b,d
, Jean-Pierre Van Geertruyden
b
, Antea Paviotti
a,b
a
Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
b
Global Health Institute, Department of Family Medicine and Population Health, University of Antwerp, Antwerp, Belgium
c
Tropical Medicine Department, University of Kinshasa, Kinshasa, Democratic Republic of the Congo
d
Primary & interdisciplinary Care, University of Antwerp, Antwerp, Belgium
ARTICLE INFO
Keywords:
Pregnant women
Exclusion
Vaccine trials
DRC
Ebola
ABSTRACT
Pregnant women are often underrepresented in clinical trials. However, there is a growing push for more in-
clusion after multiple disease outbreaks, like COVID-19, Zika, and Mpox disproportionately affected them.
Qualitative research has primarily focused on the experiences of pregnant women who choose to participate or
decline participation in trials. To our knowledge, there has been no research on the perspectives of those who
were excluded from trials upon becoming pregnant. To address this gap, we explored the views of women
excluded from a phase 2 Ebola vaccine trial, as well as those of the broader community in Boende, Democratic
Republic of the Congo. Through individual interviews and focus group discussions, we found that protecting the
foetus was paramount for the women, leading to general acceptance of their exclusion from the trial. Trust in
trial organisers’ knowledge, and the absence of an active Ebola outbreak at the time of the trial, may have
supported this acceptance. Community perceptions generally aligned with those of the excluded women inter-
viewed. However, the exclusion seemed to have impacted the decision to participate for a proportion of women
of reproductive age. This was observed when some interviewed women reported declining participation in the
trial due to their desire to conceive during the trial period. This study illustrates how women made pragmatic
decisions regarding trial participation within the decision space available to them. Our ndings seem to support
established norms of special care for safety during pregnancy and echo sentiments described elsewhere in the
literature. These results, coupled with the growing demands for the inclusion of pregnant women, highlight the
necessity of nding a balance between prioritising the safety of women and their foetuses, and the autonomy of
pregnant women, enabling them to make informed choices through comprehensible informed consent processes.
1. Introduction
Pregnant women have traditionally been excluded from the majority
of clinical trials [1–3]. The primary reason for this exclusion is the
concern for the safety of foetuses exposed to potential side effects of the
investigational products. Incidents such as the teratogenic effects
observed with drugs like Thalidomide and Diethylstilbesterol in the
1960s and 1970s have played an important role in the elaboration of
stringent guidelines for the inclusion of (pregnant) women in trials
[4,5]. In the Food and Drug Administration (FDA) guidelines of 1977,
the exclusion from participation in early-stage clinical trials targeted all
women of reproductive age who were able to get pregnant. Later, the
recommendations slowly became more permissive, and in 1993, the
FDA published new guidelines recommending more gender equality in
clinical trials. However, the lack of inclusion of pregnant women per-
sisted. For example, a 2014 study demonstrated that less than 6 % of US-
approved pharmaceuticals had human pregnancy data [6]. Recent
studies continue to indicate a low percentage of inclusion of pregnant
* Corresponding authors at: Global Health Institute, University of Antwerp, Antwerp, Belgium.
E-mail address: [email protected] (M. Salloum).
Contents lists available at ScienceDirect
Vaccine
journal homepage: www.elsevier.com/locate/vaccine
https://doi.org/10.1016/j.vaccine.2025.127000
Received 23 September 2024; Received in revised form 17 February 2025; Accepted 6 March 2025
Vaccine 55 (2025) 127000
Available online 22 March 2025
0264-410X/© 2025 Published by Elsevier Ltd.

women in both vaccine and therapeutic trials. For example, around 80 %
of trials registered for COVID-19 non-biological treatments in July 2020,
and over 90 % of late-stage overall vaccine trials between 2018 and
2023 excluded pregnant women [7,8]. Outbreaks of diseases like Mpox
and Zika further underscored the need for tested drugs and vaccines for
pregnant women, as these infections can lead to severe complications,
including congenital anomalies and adverse pregnancy outcomes
[9,10]. However, there seems to be promising progress in this issue, with
advocacy groups and academic researchers sharing actionable recom-
mendations for increased involvement of pregnant women [11,12].
Additionally, the FDA has issued a guidance document on optimal
practices when including pregnant women in clinical research [13].
Public health emergencies like the Ebola Disease (EBOD) outbreaks
in West and Central Africa highlighted the challenges and importance of
including pregnant women in clinical trials. EBOD is a viral haemor-
rhagic illness with a Case Fatality Rate (CFR) that could reach 90 %, and
is caused by either the Ebola virus (EBOV) -previously known as Zaire
Ebola Virus- or a closely related ortho-ebolavirus species [14]. The rst
ortho-ebolavirus species was identied in 1976 in the Democratic Re-
public of the Congo (DRC), which has witnessed since then 15 EBOD
outbreaks, becoming the country most affected by Ebola worldwide
[15]. Treatment of the disease consists of supportive care and rehydra-
tion uids; recently, two monoclonal antibody treatments against EBOV
have been approved by the FDA [16]. In terms of prophylactic in-
terventions, two vaccines (rVSV-ZEBOV, and Ad26.ZEBOV, MVA-BN-
Filo) have been prequalied for use by the World Health Organisation
(WHO) [17].
Despite contrasting reports on EBOD’s association with the possi-
bility of increased disease severity and mortality risk for pregnant
women, there is a consensus that pregnant women experience “an
increased risk of adverse pregnancy outcomes, including foetal loss and
pregnancy-associated haemorrhage” [18]. Nonetheless, the inclusion of
pregnant women in clinical research for Ebola vaccines has been delayed
due to concerns over the unknown potential risks of the investigational
products to pregnant women and their foetuses [19]. This has sparked
numerous debates and calls for their inclusion, especially during the
rollout of the approved rVSV-ZEBOV vaccine in response to the
2018–2020 EBOV outbreak in eastern DRC [20,21]. Eventually, in early
2019, the DRC’s national ethics committee (Comit´ e National d’Ethique de
la Sant´ e) supported including pregnant women in Ebola vaccination
activities in outbreak areas, a decision endorsed by the WHO’s Strategic
Advisory Group of Experts on Immunization (SAGE) [22]. Later in 2019,
a Phase 3 vaccine clinical trial of the Ad26.ZEBOV, MVA-BN-Filo in
DRC’s outbreak-affected regions also included pregnant women [23].
Besides documenting the inclusion of pregnant women in trials and
advocating to increase their participation, researchers have also been
looking into pregnant women’s perceptions of their involvement in
clinical trials [8,24]. Many studies show that pregnant women’s main
fear when considering participating in a clinical trial is the potential
impact on the health of their foetuses [25,26]. However, reports show
that pregnant women’s willingness to participate in clinical trials is, in
most cases, positively correlated with their risk perception of the disease
in question: the more dangerous and locally prevalent a disease or a
medical condition is perceived to be, the more inclined women would be
to enrol in a clinical trial [27,28].
Studies exploring pregnant women’s perceptions mostly interviewed
the ones who chose to participate or declined participation in clinical
trials or asked them questions about hypothetical participation in clin-
ical trials. However, to our knowledge, no existing study attempted to
understand the perceptions of female trial participants who were
excluded from receiving vaccine/drug doses based on their pregnancy
status. To tackle this, our study aimed to explore the perceptions of
women who were excluded from receiving further doses of the Ad26.
ZEBOV, MVA-BN-Filo Ebola vaccine when they became pregnant during
a Phase 2 Ebola vaccine trial in the DRC. The objective is to provide
insight from pregnant women in a remote area of a low-income country
on their motivations for trial participation (before becoming pregnant),
and their perception of their exclusion after a positive pregnancy test.
Furthermore, the article incorporates the views of community members
and healthcare workers, including midwives and nurses, as women’s
choices to (not) participate could be (strongly) inuenced by the per-
ceptions of their families and social circles.
2. Methods
2.1. Study setting
Boende is the capital of Tshuapa province, western DRC. From 26
July until 7 October 2014, an Ebola outbreak took place in the Boende
Health Zone, with a total of 69 suspected, probable, and conrmed cases
reported [29]. At that time, no vaccines or treatments were available. To
prepare for potential future EBOV outbreaks, a Phase 2 Ebola vaccine
trial was conducted between 2019 and 2022 in Boende. The trial tar-
geted the recruitment of 700 healthcare and frontline workers (males
and females) to determine the safety and immunogenicity of the two-
dose Ad26.ZEBOV, MVA-BN-Filo vaccine regimen, followed by a
booster dose of Ad26.ZEBOV one or two years after the administration of
the rst vaccine (clinical trial.gov identier: NCT04186000) [30].
Serious adverse events were recorded from the rst dose until six months
after the booster dose.
Alongside the clinical trial, different qualitative sub-studies were
conducted to explore the acceptance of different aspects of the trial. The
vaccine trial and the qualitative study discussed in this paper are part of
the EBOVAC3 project. Led by an international consortium of academic
institutions, research organisations, and private industry partners, the
project aimed to support an essential part of the remaining clinical and
manufacturing activities required for the licensure of an Ebola vaccine
[31].
Recruitment for the Ebola vaccine trial started in December 2019
and excluded pregnant and breastfeeding women from enrolment. This
exclusion aligns with common practices in Phase 2 clinical trials, where
pregnant women are often not included due to limited safety data. In this
case, the trial organisers chose to exclude because the trial involved a
booster dose, and there was insufcient data on the safety of the
(boosted) vaccine regimen yet. Additionally, the initial trial protocol
stated that every participant who became pregnant during the trial
would immediately be excluded. However, this did not consider the fact
that women who became pregnant between dose 2 and their booster
vaccination (administered one to two years later) were not necessarily
still pregnant or breastfeeding at the time of the booster vaccination. The
protocol was therefore amended to ensure that women who became
pregnant between dose 2 and their booster dose could be vaccinated
with a booster if they were no longer pregnant or breastfeeding at the
time of vaccination. Furthermore, if the pregnancy occurred between
dose 1 and dose 2 of the vaccination regimen, women remained in the
study for safety follow-up until delivery; if the pregnancy occurred after
the administration of the two-dose vaccination regimen, women
remained in the study for both safety and immunogenicity follow-up
until the end of the trial. The trial aspired to cover expenses for
related and non-related (serious) adverse events during the entire trial
period but excluded childbirth expenses, as female trial participants
were advised not to become pregnant during trial participation [32].
Female participants were not offered any contraceptives, but they were
informed before trial enrolment that they could not receive the vaccine
while pregnant or breastfeeding and should use adequate contraceptives
from 28 days prior to the rst dose up to one month after the second dose
and from 14 days before the booster dose until 3 months after the
booster dose. If a participant became pregnant during a pre-dened (and
vaccine-dependent) vaccination window, this would be reported as a
protocol deviation [30]. Pregnancies were followed up until the end of
pregnancy period and the pregnancy outcomes were noted (delivery,
still birth, miscarriage). Hereafter, we use the terms ‘excluded’ and
M. Salloum et al.
Vaccine 55 (2025) 127000
2

‘pregnant women’ to refer to female participants who became pregnant
during the trial and therefore did not receive one of the scheduled
regimen doses, even if they remained in the trial for safety (and
immunogenicity) follow-up visits.
2.2. Qualitative data collection and sampling
This article builds on individual interviews and Focus Group Dis-
cussions (FGDs) conducted in Boende in July/August 2022. In total, 24
women became pregnant during the trial according to pregnancy tests
taken prior to administering any of the vaccine doses. Eight women lived
outside of Boende town. For logistic reasons, we conducted interviews
with 14 women who lived in Boende and had become pregnant during
the vaccine trial. Three of them were excluded from the trial because
they became pregnant before the second dose of the vaccine regimen,
whilst the other 11 became pregnant after the second dose of the vaccine
regimen. Among the latter, 10 women did not receive the booster dose
because they were still pregnant or breastfeeding, while one woman
received the booster dose because pregnancy and breastfeeding ended
before the administration of the booster dose. To enrich the analysis
with broader community perspectives, the study also benetted from
data from four FGDs with nurses and midwives working in Boende who
were sampled by convenience and contacted by the vaccine trial local
study coordinator. Additionally, we drew from secondary data from 30
interviews and FGDs conducted with community members (journalists,
restaurant and hotel managers, and representatives of local human
rights organisations) in Boende who did not participate in the Ebola
vaccine trial. These participants were asked one or two relevant ques-
tions about pregnancy and the Ebola vaccine trial in Boende as part of a
study about the disease and trial perceptions in the community and were
also sampled by convenience. Table 1 shows the gender and profession
of the participants who took part in the interviews and FGDs. Interviews
with the excluded women and FGDs with nurses and midwives were
conducted by MS together with a Lingala-French interpreter, while FB
and AP conducted interviews in Lingala and French with other com-
munity members. The semi-structured interview guide focused on the
perceptions and experiences related to the exclusion decision and
opinions about the trial in general. Some interview questions were
adjusted after the rst three interviews (e.g. changing some probes to
make them clearer to the interviewees). The main interview guide is
uploaded in the supplementary materials. During the data collection
period, peer briengs took place daily to discuss eld notes. The in-
terviews and FGDs were recorded and then transcribed in French with
the support of a translator. All participants provided oral informed
consent. Oral informed consent was chosen for this qualitative study to
accommodate participants with low literacy levels, ensuring compre-
hension and minimising barriers to participation. This approach and the
study protocol received ethics approval from the National Ethics Com-
mittee in DRC (Avis n◦368/CNES/BN/PMMF/2022 du 5/07/2022),
which included approval for the use of oral consent. The data collection
process also involved informal discussions about the study topic with the
interpreter, who was a female doctor living in Boende. We employed the
Consolidated Criteria for Reporting Qualitative Research (COREQ)
checklist to guide our reporting [33].
2.3. Data analysis
French transcripts were uploaded to QSR NVivo V.1.5.1., which was
used to perform the coding. MS and AP used a thematic analysis
approach to analyse and inductively code the data [35,36]. The rst
round of analysis generated initial codes with annotations and a pre-
liminary coding tree. During the second round, codes were rearranged,
renamed, and merged resulting in three main themes. AP and MS
regularly discussed the codes and the major themes identied. Below is a
schematic overview of the three main themes and related subthemes
identied. The quotes reported in the result section of this paper aim to
illustrate the following themes and subthemes.
1. Acceptance of the exclusion rule
a. Foetal safety is paramount
b. Trust in the trial organisers
c. Community trust and concerns
2. Pregnancy concerns
a. Inuence of past experiences
b. Marriage and parenthood options
3. Us and them: trial participants’ sense of superiority
a. Vaccines and sterilisation rumours
b. Medical knowledge and rule acceptance
2.4. Positionality
It is important to look at our results while reecting on the circum-
stances that could have affected the data collected. As the interviewers
were afliated with the trial and the EBOVAC3 project, interviewees’
and participants’ trust in the decision of the trial organisers might have
been emphasised due to desirability bias. Additionally, the fact that two
of the interviewers were (perceived as) white Europeans (MS and AP)
could have encouraged a more positive or accepting sentiment towards
the trial; this was sometimes explicitly mentioned by interviewees and
FGD participants. For example, one participant said: “A white person can
never make a product that can kill people, no. You [white interviewer]
already know how we are, we are suspicious”. The convenience sampling
of participants in community interviews and focus groups may have
introduced some bias, but we tried to mitigate this by conducting a large
number of interviews and focus groups with individuals who live and
work in different parts of Boende.
3. Results
3.1. Acceptance of the exclusion rule
3.1.1. Foetal safety is paramount
Most women who participated in our qualitative study argued that it
Table 1
Gender and profession of the participants of the interviews and FG
a,b
.
Individual interviews
Trial participants who became pregnant 14
School teachers (men) 2
School teachers (women) 2
Hotel and restaurant managers (men) 2
Hotel and restaurant managers (women) 5
Religious leaders (men) 3
Pharmacists (men) 4
Members of a local citizen movement 4
Total 36
Focus Group Discussions 
Vendors (men) 1
Vendors (women) 2
Taximen 1
Relais communautaires (RECO)
a
(women) 1
CODESA
b
(men) 1
Journalists (men) 1
Human rights non-governmental organisation representatives (men) 1
Nurses and midwives (women) (non-participants in the vaccine trial) 4
Total
c
12
a
Relais communautaires are community members who received training in
health communication and volunteer to inform the rest of the community on
different health topics like (non)communicable diseases and vaccination [34].
b
CODESA are committees for the development of the Health Area (sub-divi-
sion of the Health Zone) and represent the institutional link between the health
system and the community.
c
Categories like vendors, restaurant managers, etc.. were identied as
members of relevant social categories to interview to explore how community
members who were not study participants perceived the topic.
M. Salloum et al.
Vaccine 55 (2025) 127000
3

was an appropriate decision to exclude pregnant women from the Ebola
vaccine trial out of concern for the safety of the foetus. During an initial
brieng by the trial team, trial participants were informed that pregnant
and breastfeeding women would not be enrolled in the trial “due to a
lack of sufcient information on the vaccine’s effects on the foetus”.
Therefore, the preventive exclusion of pregnant women seemed
acceptable. As one woman described:
“It was a good decision because the vaccine was [supposed to be] for me
only; we do not know how the baby lives in the womb, and if I take the vaccine
while pregnant, there is a risk that the baby develops malformations”
(interview, trial participant, excluded after becoming pregnant).
3.1.2. Trust in the trial organisers
However, when asked whether they would participate in a vaccine
trial while pregnant if the trial organisers said that pregnant women
could be included, 12 out of 14 of the interviewed excluded women
declared that they would accept to participate. The majority of the fe-
male healthcare workers who did not participate in the trial had the
same view. Their main explanation for this attitude was the desire to be
protected from the disease: “If they invite everybody, without any criteria,
and I happen to be pregnant, I will come to get vaccinated. If they exclude
[pregnant women], I will not come,” one woman concluded (focus group,
non-participant).
These two attitudes -agreeing on the exclusion rule in the Ebola
vaccine trial and accepting to participate in future trials, if allowed-
indicate a signicant degree of trust in the trial organisation. A partic-
ipant excluded from the trial stated that her decision to enrol in future
studies “will depend on the researchers themselves: if they say I can partic-
ipate in their study, then I will participate”.
3.1.3. Community trust and concerns
Among men and women living in Boende who did not participate in
the trial, many saw the decision to exclude pregnant women as appro-
priate out of concern for the safety of the foetus, similar to what was
voiced by the women excluded from the trial after becoming pregnant.
Likewise, many community members explained that their opinion on
whether pregnant women should participate in future trials would
depend on the recommendations of the medical professionals organising
clinical trials as one restaurant manager stated: “Only you doctors know if
pregnant women should not take [the vaccine]. Me, I do not know a lot”
(interview, non-participant). This level of trust, among community
members, may derive from the perception of medical doctors as persons
who are highly educated in matters of health [37]. Nevertheless, some
expressed the concern that pregnant women, if excluded, would not be
protected in the face of possible future Ebola epidemics. For example, a
pharmacist argued that pregnant and breastfeeding women should be
given the vaccine after the end of their pregnancy or breastfeeding
period: “If they are not immunised, when there will be another outbreak, they
will be the rst victims.” He hoped that a vaccine would be developed and
made accessible to everyone, as “the disease does not spare anybody.”
Similarly, an activist working for a human rights organisation under-
lined that pregnant women also deserve a chance at protection: “They
are human beings like us! We were recommended the vaccine, but when is it
going to be recommended for them as well?”. Both quotes show the
importance of pregnant women’s health and protection for the
community.
3.2. Pregnancy concerns
3.2.1. Inuence of past experiences
Whilst most of the interviewed women indicated that they would
have enrolled if pregnant and given the possibility, three women
declared that they would not participate in a future vaccine trial if they
were pregnant. In particular, these women expressed concerns about the
potential effects of the vaccine on the foetus’s health. Two of these three
were trial participants who became pregnant and had complications or
miscarriages during the trial. Following this, they suspected that the
vaccine may have caused their complications. As one woman explained:
“This time, when I became pregnant, I had too many [health issues] […]
and I told myself that it was maybe because of the vaccine. [I had taken] two
doses already, it might have been what has brought me these issues. Then, I
told myself that if there will be another study, if I will be pregnant, I will not
accept any more.” (interview, trial participant, excluded after becoming
pregnant).
Nevertheless, these three women, like the rest of the women inter-
viewed, explicitly stated that if there were an Ebola outbreak, they
would take the risk of participating in the trial even if they were preg-
nant. The search for protection seemed to prevail in the context of an
active outbreak, which is much more fearsome than normal circum-
stances, and thus changed these women’s decision-making process. As
one woman who did not participate in the trial summarised: “Well,
everybody is afraid of dying; if there is an outbreak, I will accept to receive the
vaccine, to be protected!” (focus group, non-participant).
3.2.2. Marriage and parenthood options
The “out if pregnant” exclusion criterion at enrolment, in combina-
tion with the relatively long duration of the trial (two years and 6
months), did not only automatically exclude pregnant women at the
time of recruitment, it also inuenced the decision-making process of
certain non-pregnant women who attended the introductory brieng
sessions of the trial. Certain women explained that they decided not to
participate in the trial because it would have prevented them from
getting pregnant for two years:
“I [decided not to participate] because I saw that I am still young. I do not
know, I might get pregnant during these two years; I am a woman, [and] I can
get married. If my husband demands that we make a child… this is what made
me take a step back and not enrol” (focus group, non-participant).
Meanwhile, other women argued that despite their husbands’
opposing opinions, they chose to enrol and possibly withdraw from the
trial if they became pregnant:
“My husband said: ‘You are a married woman, you want to have children;
why would you want to participate in a study that advises against preg-
nancy?’. But I answered: ‘If I will ever get pregnant, I will stop [participating
in] this study” (interview, trial participant, excluded after becoming
pregnant).
These views demonstrate that the exclusion criterion not only
inuenced women’s decisions regarding trial participation but also
showed their ability to make pragmatic choices that best suited their
circumstances. Rather than being passive, women exercised agency—-
whether by opting out to prioritise future pregnancies or enrolling with
a plan to withdraw if necessary—demonstrating autonomy in balancing
personal goals with trial requirements.
3.3. Us and them: trial participants’ sense of superiority
3.3.1. Vaccines and sterilisation rumours
Contrary to other settings where sterilisation rumours strongly
accompanied vaccine trials and vaccination activities [38], this type of
rumour did exist but did not seem to be widespread in Boende. After
having decided to participate in the trial, women dismissed rumours that
the vaccine could sterilise them. As one participant explained: “Those
who speak are rather those who do not know. But we, who are in the study, we
know that it is not what they say” (interview, trial participant, excluded
after becoming pregnant). Another participant described her reaction to
rumours of sterilisation: “I told them: ‘I told you that the vaccine was not
made to prevent pregnancies. The proof? I got pregnant. So, your rumours are
not true’” (interview, trial participant, excluded after becoming
pregnant).
This goes to show that the participants regarded themselves as more
knowledgeable about the trial compared the rest of the population
which could be the reason why they dismissed some rumours.
M. Salloum et al.
Vaccine 55 (2025) 127000
4

3.3.2. Medical knowledge and rule acceptance
During our conversations with nurses and midwives, we observed a
sense of relative epistemic superiority regarding how their medical
knowledge compared to the rest of the population. This perceived su-
periority may have facilitated their acceptance of the trial’s “pregnancy
exclusion rule”, as adhering to it reinforced their alignment with the
professional standards upheld by the trial staff and organisers. The trial
staff included local doctors and nurses from Boende, professors from
Kinshasa, and international researchers who were only intermittently
present over the course of the study. By accepting the rule, the in-
terviewees might have thought that they could signal their inclusion
within the broader medical community, which contributed to enhancing
the local community’s preparedness for potential lethal healthcare
threats like Ebola. It could also explain the relative scarcity of rumours
surrounding pregnancy and the trial vaccine among this category of trial
participants. One interviewee articulated this sentiment by saying: “It is
important to realise that as a healthcare worker, my reasoning has to be
different from other people’s” (Interview, trial participant, excluded after
becoming pregnant). The same feeling of having different knowledge
levels was expressed by some healthcare providers who did not partic-
ipate in the trial: “I think they [community members] were scared, but as
healthcare workers we have always told them that these people [trial orga-
nisers] do not take blood for [no reason], they are here to protect us.” (focus
group, non-participant).
4. Discussion
The exclusion of pregnant women from the Ebola vaccine trial in
Boende did not seem to face signicant local controversy. Participants
and residents of Boende largely viewed this decision as appropriate,
reecting established social and historical norms regarding the unique
physiology of pregnancy and the potential risks of introducing new in-
terventions during this period [39,40]. Additionally, the absence of an
active Ebola outbreak at the time of the trial may have facilitated the
acceptance of the exclusion rule. All the women interviewed agreed that
in the case of an active Ebola outbreak, they would take the risk of
participating in the trial, even if they were pregnant. This seems to be in
line with the concerns raised by pregnant women in Beni, DRC, excluded
from the Ebola vaccine roll-out during the rst months of the Kivu
outbreak, who claimed that depriving pregnant women of the vaccine
would mean “sending them to death” [41]. Some pharmaceutical com-
panies, however, are beginning to acknowledge and respond to calls for
greater inclusion of pregnant women in clinical trials. While systematic
change remains slow, isolated efforts show growing attention to this
issue. In Rwanda, for instance, where no outbreak exists at the moment,
the pharmaceutical company manufacturing the Ad26-ZOBOV, MVA-
BN-Filo is sponsoring a trial to examine the safety of the vaccine in
pregnant women [42].
Our results also highlighted a great reliance on what trial organisers
allow or suggest. This emerged clearly in answers like “if they say yes, I
participate; if they say no, I do not” that we most often received when
asking about participation in a future hypothetical vaccine trial. This
showed an important externalisation of decision-making and risk man-
agement, within which no other factors like the type of vaccine, the
pregnancy trimester, or other types of information seemed to be taken
into account. Noteworthy is the fact that many of the interviewees were
nurses and midwives, who have a relatively high degree of medical
education and knowledge of women’s health. This could suggest that
other participants who have lower (medical) literacy levels -compared
to the ones we interviewed- could practice even higher levels of
decision-making externalisation. This was observed in a study by Hol-
lander et al. in Accra (Ghana), where pregnant women without a med-
ical background showed reliance on medical doctors’ advice or religious
factors (God’s will) when deciding to participate in clinical trials [43].
On the contrary, a study conducted in Canada reported different answers
to the question about participation in a future hypothetical vaccine trial,
with the majority of women indicating that they “would need to seek
information beyond what the researchers would provide” [26]. This
would put additional ethical responsibility on the researchers in settings
where trial participants regard them as the main source of health in-
formation, as was observed in our study. Women having less access to
health information, which might lead to medical decision externalisa-
tion, appears to be a phenomenon observed in many LMIC settings,
possibly due to connectivity and nancial accessibility challenges, as
well as other barriers [44]. For example, a 2014 survey of demographics
and health (DHS) in the Equateur province in DRC (now administra-
tively restructured into ve provinces including Tshuapa province with
Boende as its provincial capital) revealed that over 40 % of women aged
15–45 do not know how to read and over 80 % in the province do not
access media outlets (radio, newspaper, tv, etc.) for periods of at least
one week at a time [45]. Although these numbers have likely changed in
the past years with the increased reach of the internet and smartphones,
they still give an estimate of literacy and media access in the rural setting
of Boende and possibly in similar settings elsewhere in low-income
countries Such challenges would require trial organisers to pay further
attention, in these settings, to the informed consent and recruitment
process, particularly when recruiting pregnant women. Although the
Ebola vaccine trial in Boende did not include pregnant women, infor-
mation sessions on informed consent were organised in the local lan-
guage prior to inclusion, allowing all (potential) participants to ask
questions. Furthermore, and given the long duration of the trial, the
participants had to re-consent and take the test of understanding again
before getting the booster dose one or two years following the rst dose
[46].
When analysing pregnant women’s attitudes towards clinical trial
participation, we need to discern between trials for therapeutic medi-
cines and those for vaccines targeting healthy populations. Prior
research suggests that pregnant women might be more accepting of
therapeutic trials compared to vaccines [26,47]. This could be due to the
difference in perceived risks; therapeutic trials aim to alleviate existing
conditions and recruit patients already suffering from specic illnesses,
whereas vaccines aim to provide protection from possible future in-
fections and target healthy volunteers. However, the risk perception
may also be inuenced by the prevalence and lethality of the disease
against which the vaccine is being tested, and our ndings support this
argument. In Boende, an area with a history of Ebola and Mpox out-
breaks, most women indicated a willingness to participate in a hypo-
thetical vaccine trial. Conversely, interviews with women from
European countries revealed a general reluctance to participate in
maternal vaccine trials [25]; notably, these interviews were conducted
before the COVID-19 pandemic, when no large threat of active infectious
disease existed in Europe. On the other hand, a survey of 128 women in
the United States around the time of the Zika virus epidemic in South
America showed that over 77 % of pregnant women and new mothers
would accept to participate in a vaccine trial for the Zika virus [48].
These observations highlight that disease prevalence and risk perception
can inuence pregnant women’s decisions regarding clinical trial
participation. In some settings, pregnant women are more compelled or
have no other choice but to participate, due to higher disease risk. This
being said, the calls for more inclusion of pregnant women in vaccine
research do not assume that all pregnant women at serious risk of con-
tracting a prevalent disease would want to participate in clinical trials
[49]. Rather, the calls aim to provide these women with the tools and
opportunities necessary to make informed health decisions.
The Ebola vaccine trial in Boende excluded a priori pregnant women,
putting women of childbearing potential in front of the choice between
pregnancy and participation in the trial. Our ndings suggest that
women strategically utilised the limited “decision space” they had in the
way that they believed served them best. They made pragmatic choices
based on their understanding of the trial’s one-to-two-year no-preg-
nancy requirement. This involved weighing their desire for children in
the next two years against potential trial benets. For some women of
M. Salloum et al.
Vaccine 55 (2025) 127000
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