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（ALL）是最常见的儿童癌症。而超过 97% 的儿童 ALL 在最初 28 天的诱导期后进入缓解期，约 20% 的患者在 5 年内复发。此外， 西班牙裔和非裔美国人更有可能复发——这种差异不能完全解释为 临床或遗传因素。挽救效果很差，二线疗法有毒且昂贵。耐用第一 缓解需要 2 年的维持阶段，其中包括每天自行/家长口服 6- 巯基嘌呤（6MP）。 6MP 全身暴露量低的患者观察到复发风险增加 （6MP 代谢物 - 硫鸟嘌呤核苷酸 [TGN] 红细胞水平低）。但个体间差异 红细胞 TGN 水平中观察到的结果可能是由于未能遵守规定的治疗所致。在最近完成的一项 儿童肿瘤小组研究（AALL03N1，R01 CA96670，PI：Bhatia），我们证明了 依从率 <95% 的儿童中复发率明显更高，这使我们能够创建一个定义 不依从性（依从性<95%）。百分之五十二的复发是由于不依从。 66% 的非裔美国人、46% 的西班牙裔美国人、48% 的亚洲人以及 32% 的非西班牙裔白人 不依从（p<0.001）。在调整依从性后，种族造成的最差结果得到了缓解。 错过 6MP 的最常见原因是健忘（年幼孩子的父母双方都认为， 以及青少年患者）。此外，坚持的青少年患者及其父母强调 父母保持警惕作为克服健忘的策略的重要性。这些发现奠定了基础 开发综合干预方案，其中包括多媒体互动患者/家长 教育和基于网络的药物安排，可转化为定制的印刷时间表和文本- 消息提醒，提示指定家长进行直接监督治疗 (DST)。使用随机 临床试验设计，我们将研究这种综合干预方案 (IP) 与教育的影响 单独 (Edu) 观察参与时 d18 岁的 ALL 儿童坚持口服 6MP 的情况。我们将检查 社会人口/社会心理因素的改变效应和健康变化的中介效应 坚持干预的变革信念/知识，并建立基础设施来确定 干预对 ALL 复发的影响。拟议的干预措施解决了一个临床相关问题 - 即，不依从性的高发生率与 ALL 儿童复发风险增加相关， 并了解我们之前研究中确定的依从性障碍/促进因素。干预措施是 全面、技术先进、简单、（因此可传播）且具有成本效益（节省 每年约 1260 万美元至 3280 万美元）。成功实施增强依从性干预措施不仅 提高 ALL 儿童的生存率，但也可能产生深远的益处，因为现代疗法 在许多其他疾病中越来越多地使用口服药物，但不依从是一个重大问题。