COVID Extension: Material Hardship as a Targetable Measure of Poverty in Pediatric Cancer

项目摘要 这项研究的目的是通过在儿童癌症中放置抗肿瘤药物来降低残余发病率和死亡率。 为设计针对健康结果的社会决定因素的干预措施奠定基础， 贫困连续的临床试验已经导致急性脑梗死儿童的生存率稳步提高， 淋巴细胞白血病（ALL）通过风险分层和风险适应性治疗的逐步进步。 尽管取得了这一成就，但大约20%的ALL儿童会复发，10%的儿童会死于该病 使ALL成为儿童癌症死亡的主要原因。美国每五个孩子中就有一个住在 贫困新的数据表明，尽管有高度标准化的护理， 在美国，所有的童年都存在。这种关系的内在机制尚未确定， 也没有对贫困的目标领域进行调查。这一提议的假设是， 通过将可补救的贫困领域纳入风险领域， 分层和制定针对贫困的干预措施。家庭物质困难-未满足 具体的资源需求，包括食物、住房或能源，是贫困的一个方面， 儿童的健康结果，可以通过干预来补救。 大多数美国儿童被诊断患有急性淋巴细胞白血病（ALL），这是最常见的儿童 将参加临床试验。这种以试验为基础的发现和护理模式允许稳定的 基于生物学的风险分层和风险适应性治疗的改进。该提案利用了 现有的临床试验护理模式，以调查结果的非生物驱动因素的影响。具体 假设HMH通过三种机制影响儿童ALL复发和生存， 化疗：（1）口服化疗依从性降低，（2）儿童基础健康状况较差 导致化疗毒性和随后延迟/剂量减少的状态，以及（3）减少获得 护理导致更高的紧急入院，从而延迟化疗的接受。在她的试点工作的基础上 博纳博士以混合方法利用她的导师团队的跨学科专业知识， 建议评估HMH是否与儿童ALL的不良疾病结局相关，并确定 潜在的行动机制，可作为未来干预措施的目标。在目标1-3）中，博纳博士将 将HMH前瞻性调查研究纳入一项针对新发HMH儿童的III期多中心临床试验 诊断为ALL的患者，以确定HMH与早期复发率和生存率之间的关系（目的1），口服 化疗依从性（目标2a）、化疗实施（目标2b）和护理模式（目标3）。目标4） 博士博纳将通过与家长和供应商的访谈，确定HMH经验中的目标要素， 为临床试验环境中HMH干预的开发提供信息。

PROJECT SUMMARY The objective of the proposed study is to reduce residual morbidity and mortality in pediatric cancer by laying the groundwork for the design of interventions targeting social determinants of health outcomes, specifically poverty. Sequential clinical trials have resulted in steady improvements in survival for children with acute lymphoblastic leukemia (ALL) through incremental advancements in risk stratification and risk-adapted therapy. Despite this achievement, approximately 20% of children with ALL will relapse and 10% will die of their disease making ALL the leading cause of childhood cancer death. One in five children in the United States lives in poverty. Emerging data demonstrate that despite highly standardized care, poverty-related survival disparities exist in childhood ALL in the United States. Mechanisms underlying this relationship have not been defined, nor have targetable domains of poverty been investigated. The hypothesis underlying this proposal is that improved child cancer outcomes are achievable by integrating remediable domains of poverty into risk stratification and developing poverty-targeted interventions. Household material hardship (HMH)—unmet concrete resource needs including food, housing or energy—is a dimension of poverty which predicts general pediatric health outcomes and can be remedied by intervention. A majority of U.S. children diagnosed with acute lymphoblastic leukemia (ALL), the most common childhood cancer, will enroll on a clinical trial. This trial-based paradigm of discovery and care has allowed for steady improvements in biologically-based risk stratification and risk-adapted therapy. This proposal leverages an existing clinical trials model of care to investigate the impact of a non-biologic driver of outcome. The specific hypothesis is that HMH impacts pediatric ALL relapse and survival through three mechanisms affecting chemotherapy delivery: (1) Decreased adherence to oral chemotherapy, (2) Inferior underlying child health status leading to chemotherapy toxicity and subsequent delays/dose reductions, and (3) Decreased access to care leading to higher acuity hospital admissions which delay chemotherapy receipt. Building on her pilot work and leveraging the cross-disciplinary expertise of her mentorship team in a mixed methods approach, Dr. Bona proposes to assess whether HMH is associated with inferior disease outcomes in pediatric ALL, and to identify potential mechanisms of action which can be targeted with future interventions. In Aims 1-3) Dr. Bona will embed a prospective survey study of HMH in a phase III multi-center clinical trial for children with newly diagnosed ALL to identify the association between HMH and rates of early relapse and survival (Aim 1), oral chemotherapy adherence (Aim 2a), chemotherapy delivery (Aim 2b) and patterns of care (Aim 3). In Aim 4) Dr. Bona will utilize parent and provider interviews to identify targetable elements in the experience of HMH to inform the development of an HMH intervention for the clinical trial setting.