Voices of children and adolescents with incurable cancer on Phase I or II Trials

描述(申请人提供)：在美国，癌症是1至19岁儿童中与疾病相关的头号死因；在新诊断为癌症的12,400名儿童中，约有25%将死于他们的疾病。国家护理研究所和国家癌症研究所的一项优先任务是通过衡量患者报告的结果(PRO)，部分改善生命末期儿童癌症患者的生活质量。邀请和测量儿科癌症患者在疾病无法治愈时的症状和生活质量报告，将有助于临床医生预测和更好地管理他们继发于癌症的症状，减少患者的痛苦。PRO包括在以治愈为目标的多个III期治疗试验中。没有PRO是儿科第一阶段(药物剂量发现和毒性)或第二阶段(药物活性和安全性)试验的一个组成部分，但正是这两种试验类型有助于新药适应症和标签。最近，美国食品和药物管理局(FDA)发布了关于在试验中使用PRO以支持药物标签的指南，包括明确要求儿科专业人员而不是父母或临床医生的代理报告。到目前为止，还没有基于PRO的儿科肿瘤药物适应症；器官和系统毒性被记录在案，但在参加实验药物试验时，儿童的症状和生活质量体验方面的声音没有得到记录。我们现在拥有儿科仪器，根据8至18岁的患者报告来衡量症状和生活质量(QOL)方面，作为NIH医学研究路线图赞助的PROIS(患者报告的结果测量信息系统)倡议的一部分进行开发和验证。这些工具与访谈相结合，将使我们能够超越无法治愈的癌症儿童和青少年参与第一阶段或第二阶段的单一传统测量益处(肿瘤反应)，记录他们在这一阶段的护理期间的症状和生活质量。有了这些衡量儿科PRO的工具，我们将提供帮助临床医生减少患者痛苦的知识，我们可以将儿科肿瘤学定位为符合FDA的药物标签标准，并且在这项两站点的纵向有效性研究中(T1，试验登记时间；T2，3至4周后)，我们将首次评估PROMIS儿科仪器的可行性、可接受性、可靠性、有效性和响应性，这是有史以来第一次在I期或II期试验中登记的80、8至18岁患有难治性或难治性癌症的儿童。 公共卫生相关性：患有无法治愈的癌症的儿童和青少年可以接受导致他们出现令人担忧的症状的实验性药物。如果在这些年轻患者的报告中直接测量令人不安的症状，临床医生可以更好地管理这些症状，减少患者的痛苦。这项研究将使我们能够测量正在接受实验药物治疗的患有不治之症的儿童和青少年的直接症状和生活质量报告。

DESCRIPTION (provided by applicant): In the United States, cancer is the number one disease-related cause of death in children between the ages of 1 and 19 years; approximately 25% of the 12,400 children newly diagnosed with cancer will die of their disease. A priority of the National Institute of Nursing Research and the National Cancer Institute is to improve the quality of life of pediatric cancer patients at end of life in part by measuring patient- reported outcomes (PROs). Inviting and measuring the pediatric cancer patients' symptom and quality of life reports when their disease is incurable will help clinicians to anticipate and better manage their symptoms secondary to cancer and reduce patient suffering. PROs are included in multiple Phase III therapeutic trials where the objective is cure. No PRO is a component of pediatric Phase I (drug dose finding and toxicity) or Phase II (drug activity and safety) trials, yet it is these two trial types that contribute to new drug indications and labeling. Quite recently, the U.S. Food and Drug Administration (FDA) has released guidance concerning the use of PROs in trials to support drug labeling, including clear language requiring PROs in pediatrics and not parent or clinician proxy reports. To date, no pediatric oncology drug indication has been secured on the basis of a PRO; organ and system toxicities are documented but not the child's voice in terms of symptom and QoL experiences while enrolled on the experimental drug trial. We now have pediatric instrumentation to measure symptoms and aspects of quality of life (QoL) by patient report in 8 to 18 year olds, developed and validated as part of the PROMIS (Patient-Reported Outcomes Measurement Information System) initiative sponsored by the NIH Roadmap for Medical Research. These instruments combined with an interview will allow us to go beyond the single traditionally measured benefit (tumor response) of Phase I or Phase II participation by children and adolescents with incurable cancer to documenting their symptoms and QoL during this phase of care. With these tools to measure pediatric PROs, we will provide knowledge to help clinicians diminish patient suffering and we could position pediatric oncology to meet FDA standards for drug labeling and in this two-site, longitudinal validity study (T1, time of trial enrollment; T2, 3 to 4 weeks later), we will assess the feasibility, acceptability, reliability, validity and responsiveness of the PROMIS pediatric instruments for the first time ever in up to 80, 8 to 18 year olds with incurable or refractory cancer enrolled on Phase I or Phase II trials. PUBLIC HEALTH RELEVANCE: Children and adolescents with incurable cancer can receive experimental drugs that cause them troubling symptoms. Clinicians could better manage these symptoms and reduce patient suffering if the troubling symptoms were measured directly in reports from these young patients. This study will allow us to measure direct symptom and quality of life reports of children and adolescents with incurable cancer who are receiving experimental drugs.