R21TW011554

An implementation toolkit for the use of hydroxyurea in the treatment of sickle cell anemia in Ugandan children - 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.

Global Health Uganda

THE JOHN E. FOGARTY INTERNATIONAL CENTER (FIC) SUPPORTS RESEARCH AND RESEARCH TRAINING TO REDUCE DISPARITIES IN GLOBAL HEALTH AND TO FOSTER PARTNERSHIPS BETWEEN U.S. SCIENTISTS AND THEIR COUNTERPARTS ABROAD. FIC SUPPORTS BASIC BIOLOGICAL, BEHAVIORAL, AND SOCIAL SCIENCE RESEARCH, AS WELL AS RELATED RESEARCH TRAINING AND CAREER DEVELOPMENT. THE RESEARCH PORTFOLIO IS DIVIDED INTO SEVERAL PROGRAMS THAT SUPPORT A WIDE VARIETY OF FUNDING MECHANISMS TO MEET PROGRAMMATIC OBJECTIVES.

93.989 - International Research and Research Training

Fogarty International Center (FIC) [HHS - NIH]

Uganda

Foreign

Dissemination and Implementation Research in Health (R21 Clinical Trial Optional) (PAR-19-275)

Amendment Since initial award the End Date has been extended from 05/31/23 to 05/31/24 and the total obligations have increased 95% from $185,367 to $360,840.