Material Hardship as a Targetable Measure of Poverty in Pediatric Cancer

物质困难作为小儿癌症贫困的有针对性的衡量标准

• 批准号: 9223102
• 负责人: Kira O. Bona
• 金额: $ 13.35万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-20 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9223102
• 关键词: 6-Mercaptopurine; Accident and Emergency department; Achievement; Acute Lymphocytic Leukemia; Address; Adherence; Admission activity; Affect; Area; Biological; Cancer Family; Career Mobility; Caring; Child; Child health care; Childhood; Childhood Acute Lymphocytic Leukemia; Childhood Leukemia; Clinical Trials; Cohort Studies; Collaborations; Communicable Diseases; Dana-Farber Cancer Institute; Data; Development; Diagnosis; Dimensions; Disease; Disease Outcome; Disease remission; Dose; Electronics; Emergency department visit; Enrollment; Environment; Family; Focus Groups; Food; Funding; Future; Goals; Health; Health Services Accessibility; Health Status; Hospitalization; Hospitals; Household; Housing; Indium; Inferior; Intervention; Intervention Trial; Interview; Investigation; Leukemia Acute Lymphoblastic Chemotherapy; Life; Link; Malignant Childhood Neoplasm; Malignant Neoplasms; Measures; Mentors; Mentorship; Methods; Modeling; Modification; Morbidity - disease rate; Multi-Institutional Clinical Trial; Newly Diagnosed; Oral; Outcome; Outcomes Research; Palliative Care; Parents; Pathway interactions; Patterns of Care; Pediatric Oncologist; Pediatric Oncology; Pediatrics; Phase; Physicians; Positioning Attribute; Poverty; Protocols documentation; Provider; Qualifying; Qualitative Research; Randomized Clinical Trials; Relapse; Reporting; Research; Research Infrastructure; Research Personnel; Residual state; Resources; Risk; Series; Stratification; Surveys; Therapeutic; Therapeutic Trials; Time; Toxicity due to chemotherapy; Training; United States; Work; base; cancer care; care delivery; career; career development; chemotherapy; childhood cancer mortality; cohort; design; experience; follow-up; health care delivery; health disparity; improved; improved outcome; leukemia; monitoring device; mortality; oncology; outcome prediction; prospective; psychosocial; research and development; screening; social; social health determinants; standardize measure; standardized care; therapy design; therapy development; trial design

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. Up to 30% of pediatric cancer families report HMH during the first 6 months of chemotherapy; its impact on child cancer outcomes is unknown. 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. Social determinants of health as contributors to outcome have not been systematically incorporated into therapeutic trial design. 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. Together, these data will inform the subsequent development of an HMH intervention for the clinical trial setting. Poverty crosses all risk group stratifications in pediatric ALL; as such, targeting this predictor of outcomes has the potential to impact a significant proportion of children with cancer. This project will facilitate the candidate's training in three areas central her career development and transition to independence: 1) conduct and design of qualitative research; 2) collaboration on multi-center clinical trials; and 3) understanding the social and biological pathways underlying health inequities. Dr. Bona is pediatric oncologist and outcomes researcher in the richly supportive research setting of the Dana-Farber Cancer Institute (DFCI), an environment ideally suited to the successful conduct of this study. Dr. Bona's research and career development are supported by highly qualified and deeply committed mentors: Dr. Joanne Wolfe, a leader in pediatric palliative care investigation, and Dr. Smita Bhatia a leader in pediatric oncology outcomes research. A dynamic team of advisors with multi-disciplinary expertise in pediatric leukemia, outcomes, disparities, palliative care and psychosocial oncology will oversee the successful conduct of this proposal. Leveraging the research infrastructure of DFCI, the expertise of her mentorship team, and the proposed career development goals Dr. Bona will be well positioned to successfully complete the proposed aims, compete for future R01 funding to support an intervention trial and transition to a career as an independent physician investigator dedicated to reducing health disparities in childhood cancer.

项目概要 拟议研究的目的是通过降低儿童癌症的残余发病率和死亡率 设计针对健康结果社会决定因素的干预措施的基础，特别是 贫困。连续的临床试验已使患有急性疾病的儿童的生存率稳步提高。 通过风险分层和风险适应治疗的不断进步，预防淋巴细胞白血病（ALL）。 尽管取得了这一成就，但大约 20% 的 ALL 儿童会复发，10% 会死于疾病 使 ALL 成为儿童癌症死亡的主要原因。美国五分之一的儿童居住在 贫困。新数据表明，尽管护理高度标准化，但与贫困相关的生存差距 ALL 存在于美国的童年时期。这种关系背后的机制尚未确定， 也没有对目标贫困领域进行调查。该提案的假设是 通过将可补救的贫困领域纳入风险范围，可以改善儿童癌症的结果 分层并制定针对贫困的干预措施。家庭物质困难（HMH）——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，它预示着普遍的贫困 儿科健康结果，可以通过干预来补救。高达 30% 的儿童癌症家族报告 化疗前 6 个月期间的 HMH；它对儿童癌症结果的影响尚不清楚。 大多数美国儿童被诊断患有急性淋巴细胞白血病 (ALL)，这是最常见的儿童期疾病 癌症，将参加临床试验。这种基于试验的发现和护理范式使得稳定的 基于生物学的风险分层和风险适应治疗的改进。健康的社会决定因素 因为对结果的贡献因素尚未系统地纳入治疗试验设计中。这 该提案利用现有的护理临床试验模型来调查非生物驱动因素的影响 结果。具体假设是，HMH 通过三个方面影响儿科 ALL 复发和生存： 影响化疗的机制：(1) 口服化疗的依从性降低，(2) 较差 潜在的儿童健康状况导致化疗毒性和随后的延迟/剂量减少，以及（3） 获得护理的机会减少，导致入院的严重程度更高，从而延迟了化疗的接受。 以她的试点工作为基础，并利用她的指导团队的跨学科专业知识，以混合方式 Bona 博士建议评估 HMH 是否与以下疾病的不良结局相关： 儿科 ALL，并确定未来干预措施的潜在作用机制。在 目标 1-3) Bona 博士将在一项 III 期多中心临床试验中嵌入一项 HMH 前瞻性调查研究，用于 患有新诊断 ALL 的儿童以确定 HMH 与早期复发率和 生存率（目标 1）、口服化疗依从性（目标 2a）、化疗给药（目标 2b）和护理模式 （目标 3）。在目标 4) 中，博纳博士将利用家长和提供者访谈来确定项目中的目标要素 HMH的经验。总之，这些数据将为 HMH 干预措施的后续发展提供信息 临床试验设置。儿童 ALL 的所有风险组均存在贫困问题；因此，针对这个 结果的预测因素有可能影响很大一部分癌症儿童。 该项目将促进候选人在职业发展和转型的三个核心领域的培训 独立性：1）进行和设计定性研究； 2）多中心临床试验合作； 3) 了解健康不平等背后的社会和生物学途径。博纳医生是儿科医生 丹娜—法伯癌症研究所 (Dana-Farber Cancer) 的肿瘤学家和结果研究员，拥有丰富的支持性研究环境 研究所（DFCI），一个非常适合成功进行这项研究的环境。博纳博士的研究和 职业发展得到高素质且忠诚的导师的支持：Joanne Wolfe 博士， Smita Bhatia 博士是儿科姑息治疗研究领域的领导者，Smita Bhatia 博士是儿科肿瘤学结果领域的领导者 研究。一个充满活力的顾问团队，在儿科白血病、结果、 差异、姑息治疗和社会心理肿瘤学将监督该提案的成功实施。 利用 DFCI 的研究基础设施、导师团队的专业知识以及拟议的职业 发展目标 博纳博士将处于有利地位，能够成功完成所提出的目标，竞争 未来的 R01 资金将用于支持干预试验并过渡到独立医生的职业生涯 致力于减少儿童癌症健康差异的研究人员。