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。高达30%的儿童癌症家庭报告 在化疗的前6个月使用HMH;其对儿童癌症结局的影响尚不清楚。 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 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。健康问题社会决定因素 作为结果的贡献者，尚未系统地纳入治疗试验设计。这 该提案利用现有的临床试验护理模型来调查非生物驱动因素对 结果。具体的假设是，HMH通过以下三个方面影响儿童ALL复发和生存率： 影响化疗递送的机制：（1）对口服化疗的依从性降低，（2） 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，和（3） 获得护理的机会减少，导致更高的紧急住院率，从而延迟化疗的接受。 在她的试点工作的基础上，利用她的导师团队的跨学科专业知识， 方法的方法，博纳博士建议评估是否HMH与劣疾病的结果， 儿童ALL，并确定潜在的作用机制，可以与未来的干预措施为目标。在 目标1-3）博纳博士将在III期多中心临床试验中嵌入HMH的前瞻性调查研究， 新诊断的ALL儿童，以确定HMH与早期复发率之间的关系， 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 (Aim 3）。在目标4）中，博纳博士将利用家长和提供者访谈来确定 HMH的经验。总之，这些数据将为HMH干预的后续发展提供信息， 临床试验环境。贫困跨越儿科ALL的所有风险组分层;因此，针对这一点， 预测结果有可能影响很大一部分癌症儿童。 该项目将促进候选人在三个方面的培训， 独立性：1）定性研究的实施和设计; 2）多中心临床试验的合作; （3）了解造成卫生不公平现象的社会和生物学途径。博纳医生是儿科医生 丹娜-法伯癌症研究中心（Dana-Farber Cancer）的肿瘤学家和结果研究员 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 职业发展得到了高素质和坚定的导师的支持：Joanne Wolfe博士， Smita Bhatia博士是儿科姑息治疗研究的领导者，Smita Bhatia博士是儿科肿瘤学成果的领导者 research.一个充满活力的顾问团队，在儿科白血病，结果， 性别差异、姑息治疗和心理社会肿瘤学将监督这项建议的成功实施。 利用DFCI的研究基础设施，她的导师团队的专业知识，以及拟议的职业生涯 发展目标博纳博士将处于有利地位，成功地完成拟议的目标， 未来的R 01资金，以支持干预试验和过渡到职业生涯作为一个独立的医生 致力于减少儿童癌症健康差异的研究人员。