Sickle cell disease (SCD) is a significant contributor to the high childhood mortality in Uganda and other
countries in sub-Saharan Africa. Hydroxyurea has been used safely in the US to moderate the effects of SCD-
related morbidities but is still not widely used in Africa where SCD prevalence is highest. The efficacy and
safety for hydroxyurea in sub-Saharan Africa have now been documented in several efficacy and effectiveness
trials. Based on these results, the Ugandan Ministry of Health (MOH) is invested in making hydroxyurea
available to SCD patients and is in the process of drafting clinical guidelines supporting the use of hydroxyurea
in SCA children. The implementation of routine use of hydroxyurea still has numerous challenges to overcome.
Critical questions to inform an implementation strategy include how to develop and sustain clinical expertise in
routine care settings to support the use of hydroxyurea with acceptable safety and efficacy. Patient and family
barriers to care encountered outside controlled study settings will also inform implementation efforts.
This study will use a broad implementation framework to develop a set of implementation supports for
scaling up hydroxyurea use that can be used in a larger implementation trial while also simultaneously
preparing for the capacity building phase required in ongoing implementation. For Aim 1, the study team will
assemble and pilot an implementation toolkit for use of hydroxyurea in two Ugandan health units: a regional
referral hospital and a district hospital. Clinical experts and trained facilitators will help each site establish
process and outcomes monitoring systems that will both support quality improvement efforts to sustain high
quality services over time and to support the collection of treatment reach, safety, and efficacy data in a
subsequent implementation-effectiveness trial. In Aim 2, the study team will conduct a formative evaluation of
the implementation toolkit and supports. In this evaluation, investigators will identify key barriers and motivating
factors for hydroxyurea use in the Uganda healthcare context and use the information to finalize the toolkit and
overarching implementation strategy. The evaluation will include interviews with MOH to conceptualize
national, regional, and health unit-level implementation factors. Interviews, focus groups, and site observations
with site leaders and staff will illuminate inner setting factors influencing hydroxyurea use. Finally interviews
and focus groups with family members and patients will allow the team to conceptualize the experience of the
direct user of hydroxyurea treatment. Using rapid qualitative coding techniques, we will analyze themes and
map findings to better inform the implementation strategy elements required, including finalizing the toolkit. The
study’s Aim 3 will involve planning for implementation capacity building to support the continued advancement
of hydroxyurea therapy in low resource settings. This planning phase will include assessment of clinical
knowledge strengths and gaps at pilot sites, establishing ideal characteristics and roles for champions, and
identifying strategic advisory board members to guide future implementation.