Comprehensive Approach to Improve Medicine Adherence in Pediatric Leukmia

提高小儿白血病药物依从性的综合方法

• 批准号: 8987413
• 负责人: SMITA BHATIA
• 金额: $ 57.08万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 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 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8987413
• 关键词: 6-Mercaptopurine; Accounting; Acculturation; Acute Lymphocytic Leukemia; Address; Adherence; Adolescent; African American; Age; Area; Asians; Behavioral; Belief; Child; Childhood; 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; Health; 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; Pediatric Oncology Group; 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; adolescent patient; 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; vigilance

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：急性淋巴细胞白血病（ALL）是最常见的儿童癌症。虽然超过 97% 的 ALL 儿童在最初 28 天的诱导期后进入缓解期，但约 20% 的儿童在 5 年内复发。此外，西班牙裔和非裔美国人更有可能复发——这种差异不能完全用临床或遗传因素来解释。挽救效果很差，二线疗法有毒且昂贵。持久的首次缓解需要 2 年的维持阶段，其中包括每天口服 6-巯基嘌呤 (6MP)。在全身暴露于 6MP 较低（6MP 代谢物 - 硫鸟嘌呤核苷酸 [TGN] 红细胞水平较低）的患者中观察到复发风险增加。然而，红细胞 TGN 水平观察到的个体间差异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学小组研究（AALL03N1，R01 CA96670，PI：Bhatia）中，我们证明依从率<95％的儿童复发的风险显着较高，这使我们能够创建不依从性（依从性<95％）的定义。百分之五十二的复发是由于不依从。 66% 的非洲裔美国人、46% 的西班牙裔美国人、48% 的亚洲人和 32% 的非西班牙裔白人不遵守规定 (p<0.001)。在调整依从性后，种族造成的最差结果得到了缓解。缺少 6MP 的最常见原因是健忘（年幼儿童的父母以及青少年患者均如此）。此外，坚持的青少年患者及其父母强调了父母保持警惕作为克服健忘的策略的重要性。这些发现为开发综合干预方案奠定了基础，该方案包括多媒体交互式患者/家长教育和基于网络的药物安排，该药物安排可转化为定制的印刷时间表和短信提醒，以提示指定家长进行直接监督治疗（DST）。我们将使用随机临床试验设计，研究这种综合干预方案 (IP) 与单独教育 (Edu) 对 18 岁 ALL 儿童坚持口服 6MP 的影响。我们将研究社会人口/社会心理因素的改变效应以及健康信念/知识变化对干预依从性变化的中介效应，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，并且由我们之前的研究中确定的依从性障碍/促进因素告知。该干预措施全面、技术先进，但简单（因此可传播）且具有成本效益（每年节省约 1260 万至 3280 万美元）。成功实施增强依从性的干预措施不仅可以提高 ALL 儿童的生存率，而且还可能产生深远的益处，因为当代疗法越来越多地将口服药物纳入许多其他疾病中，而不依从性是一个重大问题。