Approximately 1 in 500 African American births are diagnosed with sickle cell disease (SCD), which is associated with substantial morbidity and risk of early mortality. Among affected individuals, sickling of the red blood cells causes excruciating, chronic pain, which is the most common symptom of SCD. The presence of pain indicates suboptimal disease management and results in substantial financial burden on the healthcare system. Over 50% of children with SCD have at least one pain crisis a year; these pain crises are associated with substantially lower quality of life, as well as inadequate sleep, more school absences, chronic depression, and impaired peer relationships. The frequency, intensity, and duration of pain crises can only be controlled through appropriate disease management using the medication hydroxyurea. Use of hydroxyurea therapy by children with SCD is associated with lower rates of initial and recurrent episodes of pain, hand-foot syndrome (dactylitis), acute chest syndrome, and hospitalization compared with no hydroxyurea therapy. Given the substantial potential of hydroxyurea therapy to reduce pain crises and other clinical complications among children with SCD, the National Heart, Lung, and Blood Institute (NHLBI) released (2014) recommendations for its use among children. All children (9 months or older) with specific subtypes of SCD should be offered hydroxyurea therapy to reduce its health-related complications, irrespective of disease severity. The existing body of evidence regarding the use of hydroxyurea therapy among children with SCD is based on studies conducted prior to the NHLBI recommendation for use among all children. Consequently, there is a complete gap in knowledge regarding use of hydroxyurea therapy post NHLBI recommendations. Using administrative claims from states with the highest prevalence of SCD, complemented by focus groups with key stakeholders, this research project will identify multiple levels of opportunities for improvement in appropriate use of hydroxyurea therapy among children with SCD. In addition, this project provides the framework to enable me to become a successful independent investigator and a leader in reducing health disparities among children with severe chronic conditions through development of expertise in comparative effectiveness, qualitative methods, and medication adherence theory. Combined, these research and training activities will provide a crucial foundation for a subsequent application to conduct an R01-funded comparative effectiveness trial to gauge the effectiveness of interventions targeted at SCD patients, their caregivers, and providers of SCD services to increase appropriate use of hydroxyurea therapy among this vulnerable population. To this end, the following aims will be investigated:
Research Aim 1 : Quantify hydroxyurea therapy prevalence prior to NHLBI guidelines, and changes in prevalence post-NHLBI guidelines among children with SCD using Medicaid administrative claims data, as well as predictors of hydroxyurea initiation and adherence.
Specific Aim 1 a: Assess baseline hydroxyurea therapy prevalence among children with SCD prior to NHLBI guidelines (2005-2012).
Specific Aim 1 b: Evaluate changes in hydroxyurea therapy prevalence among children with SCD post- NHLBI guidelines (2011-2017).
Specific Aim 1 c: Identify characteristics associated with hydroxyurea initiation and subsequent adherence among children with SCD.
Research Aim 2 : Evaluate the comparative effectiveness of hydroxyurea therapy among adherent users on reducing the incidence of pain crises, adverse outcomes, and use of health services, compared with those having limited or no use of hydroxyurea therapy.
Research Aim 3 : Identify barriers to initiation and adherence of hydroxyurea therapy through focus groups conducted among adolescents with SCD, caregivers of children with SCD, and SCD health services providers in Michigan. Overall Career Development Aim: To acquire the skills and experience necessary to conduct an R01-funded comparative effectiveness trial to increase appropriate use of hydroxyurea therapy in children with SCD.
These aims will be achieved during 3 phases of research over 5 years under the guidance of a multi- disciplinary team of experienced mentors. Through the conduct of high quality research, formal coursework, and interaction with mentors, this K01 award will provide the PI with the necessary training to become a successful independent investigator and to develop a future R01 grant application. If successful, this line of inquiry will improve health outcomes and quality of life among children with SCD.
Severe pain episodes are the most common, debilitating, and costly morbidity of sickle cell disease (SCD). Use of hydroxyurea is the only method to prevent these pain crises among children, and interventions to increase its use are urgently needed. This project will identify of opportunities to develop targeted interventions to increase the use of hydroxyurea among this high-risk population.
