Lessons from the field: the conduct of randomized controlled trials in Botswana
Bonsu et al. Trials
Lessons from the field: the conduct of randomized controlled trials in Botswana
Janice M. Bonsu 0 1
Rosemary Frasso 3
Allison E. Curry 2 4
0 Master of Public Health Program, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA
1 370 W. 9th Ave, Columbus, OH 43201 , USA
2 Center for Research Injury and Prevention, Children's Hospital of Philadelphia , Philadelphia, PA , USA
3 College of Population Health, Jefferson University , Philadelphia, PA , USA
4 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA
Background: The conduct of randomized controlled trials (RCTs) in low-resource settings may present unique financial, logistic, and process-related challenges. Middle-income countries that have comparable disease burdens to low-income countries, but greater availability of resources, may be conducive settings for RCTs. Indeed, the country of Botswana is experiencing a rapid increase in the conduct of RCTs. Our objective was to explore the experiences of individuals conducting RCTs in Botswana to gain an understanding of the challenges and adaptive strategies to their work. Methods: We conducted in-depth interviews with 14 national and international individuals working on RCTs in Botswana. Participants included principal investigators, research coordinators, lab technicians, research assistants, and other healthcare professionals. Interviews were audiotaped, transcribed verbatim, and coded for thematic analysis. Results: Five primary themes were identified: ethics board relationships (including delays in the process); research staff management (including staff attrition and career development); study recruitment and retention (including the use of reimbursements); resource availability (including challenges accessing laboratory equipment); and capacity-building (including issues of exporting locally sourced samples). These themes were explored to discuss key challenges and adaptive strategies. Conclusions: This study offers a first-hand account of individuals engaged in conducting RCTs in Botswana, a nation that is experiencing a rapid increase in research activities. Findings provide a foundational understanding for researchers in Botswana and trial managers in similar settings when planning RCTs so that the conduct of research does not outpace the ability to manage, support, and regulate it.
The randomized controlled trial (RCT) is critical to
exploring the impact of interventions and is the ideal study
design to establish causality [
]. Unique to the RCT design
is the random assignment of participants to a treatment
or intervention group, which reduces the potential for
systematic biases that may compromise internal validity in
observational epidemiologic studies [
]. RCTs have been
critical to advancing public health and clinical research;
many important medical treatments such as the
wellknown HIV drug, Tenofovir, have only been approved for
population-wide use after a long series of RCTs [
The advantages of the RCT design have led to its
widespread use. However, the conduct of RCTs in
regions of the world with limited research capacity may
present financial, logistic, and process-related challenges.
For example, investigators in Lebanon faced barriers in
enrollment that stemmed from misconception about
unfamiliar terms such as “randomization” [
]. In Peru,
researchers found that community members were hesitant
to sign study consent forms due to cultural resistance to
foreign documents as a result of past instances of land
being unjustly seized by foreigners [
]. These few
examples tell a greater narrative of cultural and linguistic
challenges associated with the conduct of research in
global settings. Studies have examined the utility of
dedicated trial managers, individuals tasked with managerial
and scientific duties, as critical to the success of trials
]. However, that role is not standard in all studies.
It is critical to identify the factors that promote the
conduct of high-quality RCTs, especially in regions of the
world currently experiencing an increase in research
activities. Botswana – a country in southern Africa – has
undergone this exponential growth, particularly in clinical
trials. This increase in research capacity may be attributed
to the fact that while Botswana is an upper
middleincome country, its diseases of burden such as HIV/AIDS
and tuberculosis, are similar to that of low-income
]. Indeed, numerous research partnerships have
formed between Botswana institutions and U.S.
institutions to address these diseases, such as the: Botswana–
UPenn Partnership, Botswana–Harvard Partnership, and
Gates Foundation’s African Comprehensive HIV/AIDS
]. This convergence of international
partnerships and the Botswana government’s investment
to support research has created a unique opportunity to
not only do clinical trials, but also to study the conduct of
RCTs in Botswana. Previous studies have primarily
focused on the need for improved quality management
systems and resource constraints in the region [
study aims to provide a qualitative account from
individuals who are involved in the day-to-day conduct of trials
in Botswana. Results would provide key insights for
researchers who are engaged in Botswana and might provide
a foundational understanding for those in similar settings.
This qualitative study was conducted between June and
October 2016 and was approved by the University of
Pennsylvania Institutional Review Board (IRB) and the Botswana
Health Research Development Committee (HRDC).
Participant selection and data collection
We employed a snowball sampling approach to recruit
respondents. To do so, the research team identified a
contact organization (Botswana–UPenn Partnership) who
then connected the first author with potential participants,
some of whom facilitated additional contacts. Individuals
were eligible for inclusion if they were involved in the
previous or current conduct of RCTs in the catchment area
of Gaborone, Botswana. The only restriction on
participation was on distance from Gaborone, as recruiting
nationwide would have posed logistic difficulties for interviews.
Potential participants were first contacted via email in
June 2016, with an additional email invitation two weeks
later. Individuals who failed to reply to the contact
attempts were assumed to have declined to participate in
the study. Respondents were interviewed either in person
or by telephone by the first author (JMB) in a private
space away from the individual’s immediate work area, in
order to maximize the privacy of the respondent. All
interviews were audiotaped, transcribed verbatim, and
Qualitative interview instrument
The interview instrument was a semi-structured guide
consisting of open-ended questions. All interviews were
conducted in English with English-speaking respondents;
thus, no translator was necessary. The interview guide
included questions on RCT experience in Botswana and key
aspects of the research process such as the IRB approval
and participant recruitment and follow-up. This guide was
piloted through mock interviews with volunteers prior to
engaging the intended participants. Interviews were
estimated to take 1 h. As is customary in qualitative
research, early interviews informed amendments to
the guide through an iterative process to explore
additional areas of interest. The study team met monthly
throughout the data collection period to assess
saturation and quality control.
The research team employed a directed content analysis
approach through which codes were developed in two
ways: a priori (informed by the interview guide) and
through line-by-line reading of five representative
]. Each code was given an explicit definition in
the codebook to ensure coding accuracy. The first
author (JMB) independently coded all transcripts and a
coding audit of four of the 14 transcripts was
completed by the senior author (RF) to assess coding
accuracy; percent agreement was assessed (range 98–100%).
The analysis of the transcripts was facilitated by NVivo,
a qualitative software analysis program [
Fourteen key informants participated in this study and
their characteristics are described in Table 1. Their roles
on the trial team included: principal investigator (n = 6);
research coordinator (n = 2); laboratory technician (n =
2); research assistant (n = 3); and other healthcare
professional (n = 1). Common themes dominated after 14
interviews, suggesting data saturation. The respondents
had varying number of research projects conducted,
ranging from one trial to twelve.
Analysis revealed the following thematic categories:
ethics approval; research staff management; study
recruitment and retention; and resource availability and
capacity-building. Data were then explored to identify
the challenges within these codes and the adaptive
strategies used by respondents, when possible, to navigate
these challenges. These findings are described below
with selected quotations identified by indentation and
Respondents explained that the first step in conducting
a study in Botswana is seeking ethics approval from the
country’s institutional review board, the Health Research
Development Committee (HRDC). Though their role is
important in regulating studies in the country, many
respondents discussed that the voluntary nature of the
HRDC, whose reviewers have primary clinical and
academic responsibilities, has led to significant delays in
processing applications. As a result, there are no defined
timeline for approval processes in the way that the USA
or UK has, with some respondents citing periods a range
of 6–9 months for determinations.
Respondents shared that the opening of the University
of Botswana’s (UB) IRB has eased some delays in
protocol processing by the HRDC, as the HRDC automatically
approves any protocol approved by UB. However, some
respondents still feel that there needs to be more done
to accommodate the large volume of protocols. One
respondent shared that upon a visit to the HRDC, he
found that the delays in processing were due to a
misplacement of his submission, as all submissions are
handled in paper. Another respondent suggested that the
HRDC should consider instituting financial incentives
for the services of the reviewers, to encourage protocol
determinations in a timely manner.
What they need to do is invest some money in
reform of the HRDC to fix it. Some countries
charge money per protocol, I’m not saying that
helps, but… I think they ask a lot of people’s time,
so it’s hard to get people to engage in it. (Principal
Despite these issues, respondents spoke of the benefits
that have come from the HRDC, such as a mandate that
research conducted by foreign investigators must include
local collaborators. Most respondents felt that these
partnerships with local collaborators greatly enriched
their studies. They reported that local collaborators
bring valuable knowledge from the community,
informing teams on methods to increase acceptability of studies
in the community. However, other respondents believe
the mandate put too many demands on the few available
local investigators, preventing meaningful collaborations.
Research staff management
After gaining approval from the HRDC, the next phase
of conducting a RCT is assembling research staff.
Respondents frequently described issues of staff retention
as a barrier to the conduct of research. Respondents
reported that, as a result of short contracts, usually 6–9
months in length, tensions about job security have come
to the forefront for staff. While employers assumed the
issue of staff retention was a result of the short
contracts, staff attributed the turnover to the lack of career
growth opportunities within some research partnerships.
When people leave [the bosses] don’t know why. People
are leaving because they don’t see career development.
You’re kind of stagnant. You don’t really advance.
As high turnover of staff is costly to the study in terms
of time and money, respondents shared some practices
that are aiding in staff retention. One respondent
acknowledged that some research partnerships offer
bonuses, referred to as “gratuity,” for those who complete
their contracts. This gratuity encourages staff who may
be otherwise looking for longer contracts not to leave
the study prematurely. Additionally, respondents
discussed the career development initiatives some research
partnerships use to retain staff and build capacity.
Respondents described that these initiatives include
professional training seminars and routes for staff to pursue
Study recruitment and retention
After receiving necessary approval and assembling staff
and research resources, the success of a study rests on
designing and implementing effective recruitment and
retention strategies. Respondents generally suggested
moving away from passive forms of recruitment, such as
admissions forms that are not always updated. Instead,
respondents advocated that a more active form of
recruitment, such as hiring specific recruitment staff,
alleviated the burden from hospital nurses and physicians
and improved recruitment rates. Respondents also found
that integrating technology into the study enrollment
process aided recruitment. One respondent shared that
since the introduction of tablet technology to her
enrollment process, she has been able to increase the speed at
which she enrolls participants and, as a result, she has
been able to recruit three times as many patients as
before. However, these changes to support recruitment
could come with unintended consequences. One
respondent shared the misconception among some
colleagues that effective recruitment was associated to the
termination of employment.
The person who I was working with had a very bad
belief about research. They had the belief that if you
are working in research, if you recruit more you will
reach the target quickly and then you will be jobless.
The most commonly referenced strategy to study
recruitment and retention that was recommended by
respondents was the use of reimbursements to offset the
personal cost incurred for study participants. Respondents
felt that compensating study participants for their time
was a sign of respect and removed barriers to
participating, such as travel. Though compensation increases
retention, some respondents believed that monetary incentives
could be coercive to study participants. To navigate this
tension, a respondent shared that she only reveals the
availability of reimbursements after an individual has
expressed interest in the study.
Sometimes we use [compensation] as part of recruitment.
It should be the last thing. After probing whether I’m
interested or not, then at the end you can say… don’t
worry about coming here, because I’m going to give you
transport money. (Other healthcare professional)
Respondents explained that for some community
members, research was a means to supplement income. One
respondent recalled that participants would show up
outside of their scheduled follow-up appointments because
they were short on money and knew they would be given
a reimbursement. Another respondent talked about
participants who were selling study drugs, unaware of their
randomization group (placebo or drug) and jeopardizing
the health of others as well as the study results.
Participants were very tricky… [they] were selling the
drugs. And what was paining me was that they were not
aware if they were taking the drug or the placebo. So,
they would be selling to HIV-positive people, they would
be coming with many stories: I was in a taxi, my drugs
are taken… or I put them in the house, maybe the
relatives took it. (Other healthcare professional)
Resource availability and capacity-building
As Botswana continues to engage in rigorous research,
resource availability and capacity-building remain high-level
challenges to the conduct of RCTs. Resource availability,
in particular, was highlighted by many respondents.
Respondents recalled study setbacks due to poor
infrastructure and challenges accessing specialized laboratory
equipment. One adaptive strategy that respondents use to
circumvent these issues has been the sharing and
coordination of resources by different research partnerships.
These resources include facilities, equipment, and staff,
which they singled out as the largest cost of any study.
Another respondent asserted that foreign researchers
working in low-resource settings should assume the
responsibility to improve local research capacity. To do so,
the respondent spoke against the practice of exporting
locally collected study samples internationally for
analysis. The respondent also suggested a policy for the
HRDC that would require researchers to send local
research staff abroad when samples are exported, so that
they may learn more about the techniques being used.
I don’t think it’s quite right to take Batswana samples
out of Botswana. I have a fundamental issue with
samples collected from one country and taken to
another, without any justifiable reason except
convenience. (Laboratory technician)
This paper offers an important perspective on research
activities in Botswana and adds to the growing literature
useful for trial managers conducting RCTs in all settings.
Though respondents in our study worked with standard
operating procedures, they discussed challenges in the
“unwritten” parts of the protocol, such as ethics
approval, staff management, and protocol adherence. Prior
studies investigating the conduct of RCTs have reported
Clinical trial managers have recognized the
inefficiencies that lie in reinventing the trial management wheel
and suggest producing standard trial management
guidelines to reduce those challenges. These standard
guidelines would include the utilization of a trial manager in
designing the study, assuring data quality, and ensuring
that recruitment is realistic, practical, and ongoing [
2007 analysis of 114 multicenter trials found that less
than one-third of trials recruited their original target
within the time originally specified [
]. Clinical trial
unit directors in the UK reported that improvements to
trial recruitment, including methods to minimize
attrition, were their highest priority [
]. Respondents in our
study also highlighted recruitment and retention as a
priority, sharing helpful strategies such as community
collaboration in designing study advertisements and the
provision of reimbursements. The use of
reimbursements, however, were variable among our respondents,
with some presenting it at differing points in the
recruitment process (beginning or end). This type of variability
may not only affect recruitment rates, but may also
contribute to a differential selection bias.
Other studies have found success in recruiting from
diverse populations when they integrate knowledge
from local collaborators such as an RCT of
indigenous people in four countries (New Zealand, Australia,
Canada, and the United States). The inclusion of local
collaborators, integration of community engagement
groups to inform key study decisions, and the
incorporation of local staff were strategies that our
respondents also found to facilitate recruitment and
]. Other factors that have been associated
with good trial recruitment include having a
dedicated trial manager, being a drug trial, and trials that
address clinically important questions at a timely
]. Collectively, these studies highlight the
importance of the role of local trial managers who are
able to work collaboratively with partners in foreign
This paper also uncovered issues of non-adherence to
treatment protocols that threaten to undermine the
RCT design. A review of 100 RCT publications from the
BMJ, New England Journal of Medicine, the Journal of
the American Medical Association, and The Lancet
found that 98% of the trials studied reported
nonadherence to treatment protocols [
]. The review found
that adherence to randomized intervention is poorly
considered in the reporting and analysis of published
RCTs and often simply labeled as modified intention to
treat. While researchers are still struggling on methods
to optimize adherence, it is likely that using trial
managers to investigate the causal factors of non-adherence
could aid in the challenge.
Along with issues of study recruitment and ethics
approval, the concept of capacity-building has been
on the forefront of those engaging in international
research. In our study, respondents identified tensions
from behaviors such as exporting locally derived
samples and the lack of career development as hindrances
of capacity-building. The required capacity-building
measures are diverse. Some efforts to build capacity
in African countries experiencing a progressive rise in
clinical trials include the creation of data safety
monitoring boards to assist local researchers [
These boards contribute to capacity-building as they
train nationals in data safety monitoring and research
skills training for research staff. It is critical for future
work to encourage and evaluate such measures to
establish progresses and shortcomings in
capacitybuilding. Overall, we are encouraged by the adaptive
strategies that respondents described and believe it is
imperative that the conduct of research not only
contributes to the generation of knowledge, but also to
the strengthening of research systems.
Strengths and limitations
The primary strength of this study is its inclusion of
individuals representing a variety of roles within the
trial team, resulting in a comprehensive collection of
perspectives. This led to the collection of many
themes, each of which can be further explored
through subsequent studies (e.g. a study that narrowly
focuses on exporting locally derived samples).
Nonetheless, our findings must be considered in light of
some limitations. In terms of transferability, we
interviewed a convenience sample of individuals working
on RCTs near the capital of Botswana, Gaborone.
Though we believe this study can provide
foundational understanding for researchers dealing with
universal issues such as staffing, ethics approval, and
recruitment, different regions may yield additional
challenges and, thus, may reveal new adaptive
practices. A final limitation rests in the exploratory nature
of the study, as the authors are not currently based
in Botswana with extensive work in the region, but
rather, partnered with colleagues of the Botswana–
UPenn Partnership to conduct this study. That said,
this partnership served as a strength for this study as
we were able to navigate our own ethics approval
with guidance from nationally based research staff.
Additionally, as we stated before, this partnership
aided in our recruitment by providing us a platform
to communicate with other researchers and research
partnerships in the area.
RCTs are a research design that is widely used to
critically evaluate clinical treatments and
interventions. This study assesses the conduct of RCTs in
Botswana and provides meaningful, front-line data
that can be shared with those working and
regulating research in the region. Trial managers may find
insight from this context that may be applicable to
and potentially improve in their own trials. It is
recommended that investigators systematically chronicle
these experiences in papers to directly inform the
work of the larger research community. This practice
would have tremendous value for individuals who
are engaged in building capacity in research
infrastructure in global settings so that the conduct of
research does not outpace the ability to manage,
support, and regulate it.
HRDC: Botswana Health Research Development Committee; IRB: Institutional
Review Board; RCT: Randomized controlled trial; UB: University of Botswana
The authors would like to acknowledge the support of the Botswana–UPenn
Partnership who made this research possible and thank the individuals in
this study who candidly shared their experiences.
This work was supported by the Center for Public Health Initiatives and the
Masters of Public Health Program at the University of Pennsylvania.
JMB and RF designed this study. JMB was the lead investigator, collected the
data, analyzed the data, and drafted the manuscript. This work formed JMB’s
Master of Public Health thesis. RF and AEC aided in interpretation of the
results. All authors contributed to the editing of the manuscript. All authors
read and approved the final manuscript.
Ethics approval and consent to participate
This study was approved by the University of Pennsylvania Institutional
Review Board (824631) and the Botswana Human Resources Development
Council (HPDME 13/18/1 X (533)). Information about the study and an
invitation to participate was sent by email to each respondent. All
respondents provided written consent in accordance with the ethical
approval received for the study.
Consent for publication
Respondents were asked for permission for the interview to be taped and
for quotes to be used anonymously.
The authors declare that they have no competing interests.
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