Identifying Opportunities to Improve Hydroxyurea Therapy Initiation and Adherence among Children with Sickle Cell Disease

 描述（由申请人提供）：摘要大约每500名非洲裔美国人中就有1名被诊断患有镰状细胞病（SCD），这与大量发病率和早期死亡风险相关。在受影响的个体中，红细胞的镰状化会导致痛苦的慢性疼痛，这是SCD最常见的症状。疼痛的存在表明不理想的疾病管理，并导致医疗保健系统的巨大经济负担。超过50%的SCD儿童每年至少有一次疼痛危机;这些疼痛危机与生活质量显著降低，睡眠不足，更多的缺课，慢性抑郁症和同伴关系受损有关。疼痛危象的频率、强度和持续时间只能通过使用药物羟基脲进行适当的疾病管理来控制。与未使用羟基脲治疗的SCD儿童相比，使用羟基脲治疗的SCD儿童疼痛、手足综合征（趾炎）、急性胸部综合征和住院的初始和复发率较低。鉴于羟基脲治疗在减少SCD儿童疼痛危象和其他临床并发症方面的巨大潜力，美国国家心肺血液研究所（NHLBI）发布了（2014）儿童使用建议。所有患有SCD特定亚型的儿童（9个月或以上）都应接受羟基脲治疗，以减少其健康相关并发症，无论疾病严重程度如何。关于在SCD儿童中使用羟基脲治疗的现有证据是基于在NHLBI建议在所有儿童中使用之前进行的研究。因此，在NHLBI建议后，关于使用羟基脲治疗的知识完全空白。使用SCD患病率最高的州的行政索赔，辅以与关键利益相关者的焦点小组，本研究项目将确定在SCD儿童中适当使用羟基脲治疗的多个级别的改善机会。此外，该项目提供了一个框架，使我能够成为一个成功的独立调查员和领导者，通过发展比较有效性，定性方法和药物依从性理论的专业知识，减少严重慢性病儿童的健康差距。结合起来，这些研究和培训活动将为后续申请提供关键的基础，以进行R 01资助的比较有效性试验，以评估针对SCD患者，其护理人员和SCD服务提供者的干预措施的有效性，以增加该弱势人群中适当使用羟基脲治疗。为此，将研究以下目标：研究目标1：使用Medicaid行政索赔数据，量化NHLBI指南之前的羟基脲治疗患病率，以及SCD儿童NHLBI指南后患病率的变化，以及羟基脲开始和依从性的预测因素。 具体目标1a：评估NHLBI指南（2005-2012）之前SCD儿童的基线羟基脲治疗患病率。具体目标1b：评价NHLBI指南（2011-2017）后SCD儿童中羟基脲治疗流行率的变化。具体目标1c：确定SCD儿童中与羟基脲开始治疗和随后依从性相关的特征。研究目的二：评价与有限或未使用羟基脲治疗的患者相比，在依从性使用者中使用羟基脲治疗在降低疼痛危象发生率、不良结局和使用卫生服务方面的比较有效性。研究目标3：通过在密歇根州SCD青少年、SCD儿童的照顾者和SCD卫生服务提供者中进行的焦点小组，确定启动和坚持羟基脲治疗的障碍。总体职业发展目标：获得进行R 01资助的比较有效性试验所需的技能和经验，以增加在SCD儿童中适当使用羟基脲治疗。这些目标将在一个由经验丰富的导师组成的多学科团队的指导下，在5年的3个研究阶段中实现。通过进行高质量的研究，正式的课程，并与导师的互动，这个K 01奖将提供必要的培训PI成为一个成功的独立调查员，并制定未来的R 01补助金申请。如果成功的话，这条调查路线将改善SCD儿童的健康结果和生活质量。

 DESCRIPTION (provided by applicant): SUMMARY 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 1a: Assess baseline hydroxyurea therapy prevalence among children with SCD prior to NHLBI guidelines (2005-2012). Specific Aim 1b: Evaluate changes in hydroxyurea therapy prevalence among children with SCD post- NHLBI guidelines (2011-2017). Specific Aim 1c: 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.