Comprehensive Approach to Improve Medicine Adherence in Pediatric Leukemia

提高小儿白血病用药依从性的综合方法

• 批准号: 8626018
• 负责人: SMITA BHATIA
• 金额: $ 74.79万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-07 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8626018
• 关键词: 6-Mercaptopurine; Accounting; Acculturation; Acute Lymphocytic Leukemia; Address; Adherence; Adolescent; African American; Age; Area; Asians; Behavioral; Belief; Child; Childhood; Childhood Leukemia; Children' s Oncology Group; Chronic; Clinical; Clinical Trials Design; Cues; Data; Development; Disease; Disease remission; Distress; Dose; Education; Educational Intervention; Electronics; Elements; Erythrocytes; Ethnic Origin; Evaluation; Event; Exposure to; Failure; Family; Genetic; High Prevalence; Hispanics; Household; Individual; Ingestion; Intervention; Intervention Trial; Knowledge; Life; Maintenance; Malignant Childhood Neoplasm; Measures; Mediating; Mediator of activation protein; Medicine; Minority Groups; Monitor; Not Hispanic or Latino; Nucleotides; Online Systems; Oral; Outcome; Parenting Education; Parents; Patients; Perception; Pharmaceutical Preparations; Phase; Population; Printing; Psychological reinforcement; Psychosocial Factor; Randomized Clinical Trials; Relapse; Research Infrastructure; Risk; Savings; Schedule; Self Efficacy; Severity of illness; Single Parent; Staging; Subgroup; Symptoms; System; Text; Therapeutic Intervention; Thioguanine; Time; Translating; arm; base; behavior change; clinically relevant; cohort; cost effective; depressive symptoms; follow-up; health belief; health knowledge; improved; interactive multimedia; older patient; parental involvement; pill; public health relevance; vigilance

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. While over 97% of children with ALL enter remission after an initial 28-day induction period, ~20% relapse within 5 years. Furthermore, Hispanics and African Americans are more likely to suffer relapse - a difference not entirely explained by clinical or genetic factors. Salvage is poor, and second-line therapies are toxic and expensive. Durable first remissions require a 2-year maintenance phase that includes daily oral self/parent-administration of 6- mercaptopurine (6MP). Increased risk of relapse is observed in patients with low systemic exposure to 6MP (low red cell levels of 6MP metabolite - thioguanine nucleotide [TGN]). However, the inter-individual variability observed in red cell TGN levels could be due to failure to adhere to prescribed therapy. In a recently completed Children's Oncology Group study (AALL03N1, R01 CA96670, PI: Bhatia), we demonstrated that the risk of relapse was significantly higher among children with adherence rates <95%, allowing us to create a definition of non-adherence (adherence <95%). Fifty-two percent of the relapses were attributable to non-adherence. Sixty-six percent of African Americans, 46% of Hispanics, 48% of Asians, and 32% of non-Hispanic whites were non-adherent (p<0.001). The worse outcome by ethnicity was mitigated after adjusting for adherence. The most common reason for missing 6MP was forgetfulness (on part of both parents of younger children as well as adolescent patients). Furthermore, adherent adolescent patients and their parents emphasized the importance of parental vigilance as a strategy to overcome forgetfulness. These findings have formed the basis for developing a comprehensive intervention package that consists of multimedia interactive patient/parent education, and web-based medication scheduling that translates into customized printed schedules and text- message reminders to prompt directly supervised therapy (DST) by a designated parent. Using a randomized clinical trial design, we will study the impact of this comprehensive intervention package (IP) vs. education alone (Edu) on adherence to oral 6MP in children with ALL who are d18 years at participation. We will examine the modifying effect of sociodemographic/ psychosocial factors and the mediating effects of change in health beliefs/knowledge on change in adherence with intervention, and establish the infrastructure to determine the impact of intervention on relapse of ALL. The proposed intervention addresses a clinically relevant problem - i.e., high prevalence of non-adherence that is associated with an increased risk of relapse in children with ALL, and is informed by the barriers/facilitators to adherence identified in our previous studies. The intervention is comprehensive, technologically sophisticated, yet simple, (hence disseminable) and cost-effective (savings of ~$12.6M to $32.8M/y). Successful implementation of the adherence-enhancing intervention will not only improve survival in children with ALL, but could also have far-reaching benefits, since contemporary therapies are increasingly incorporating oral agents in many other diseases, and non-adherence is a significant problem.

急性淋巴细胞白血病（全部）是最常见的儿童癌症。超过97％的儿童 全部在最初的28天诱导期后进入缓解，5年内〜20％复发。此外， 西班牙裔和非裔美国人更有可能遭受复发 - 差异并非完全解释 临床或遗传因素。打捞很差，二线疗法有毒且昂贵。先耐用 汇款需要为期2年的维护阶段，其中包括每天的口服自我/父级管理6-- 胃嘌呤（6MP）。在6MP的全身性暴露中，观察到复发的风险增加 （6MP代谢物的低红细胞水平 - 硫代氨酸核苷酸[TGN]）。但是，个体间的变异性 在红细胞TGN水平上观察到的可能是由于未能遵守规定的治疗所致。在最近完成的 儿童肿瘤学组研究（AALL03N1，R01 CA96670，PI：BHATIA），我们证明了有风险 依从率<95％的儿童的复发明显更高，使我们能够创建一个定义 不遵守（依从性<95％）。 52％的复发归因于不遵守。 66％的非洲裔美国人，46％的西班牙裔，48％的亚洲人和32％的非西班牙裔白人 是不遵循的（p <0.001）。在调整依从性后，减轻了种族的结果。 失踪6MP的最常见原因是健忘（在年幼的孩子的父母都是一部分 以及青春期患者）。此外，遵守青少年患者及其父母强调了 父母警惕作为克服健忘的策略的重要性。这些发现构成了基础 用于开发由多媒体互动患者/父母组成的综合干预套件 教育和基于Web的药物计划，这些计划转化为自定义的印刷时间表和文本 - 消息提醒指定父母直接监督治疗（DST）。使用随机 临床试验设计，我们将研究此综合干预措施（IP）与教育的影响 单独（EDU）遵守所有参加活动的儿童的口服6MP。我们将检查 社会人口统计学/社会心理因素的修改作用以及健康变化的中介作用 关于与干预依从性变化的信念/知识，并建立基础设施以确定 干预对所有人复发的影响。拟议的干预措施解决了与临床相关的问题 - 即，与所有人的儿童复发风险增加有关的不遵守的高患病率 并由障碍/促进者告知我们以前的研究中确定的遵守。干预是 全面的，技术上的精致，但简单，（因此是可观的）和成本效益（节省了 〜1260万美元至3280万美元/y）。成功实施依从性增强干预不仅将 改善所有人的儿童生存，但也可能会带来深远的好处，因为当代疗法 越来越多地将口服剂纳入许多其他疾病中，而不遵守是一个重大问题。