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

描述（由申请人提供）：在美国，癌症是1至19岁儿童死亡的头号疾病相关原因；在12,400名新诊断为癌症的儿童中，约有25%将死于疾病。美国国家护理研究所和美国国家癌症研究所的一项优先任务是通过测量患者报告的结果（PROs）来改善儿科癌症患者生命末期的生活质量。当儿童癌症患者的疾病无法治愈时，邀请和测量儿童癌症患者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的继发癌症症状，减少患者的痛苦。PROs被包括在多个以治愈为目标的III期治疗试验中。没有PRO是儿科I期（药物剂量发现和毒性）或II期（药物活性和安全性）试验的组成部分，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PROs的指导意见，以支持药物标签，其中包括明确要求在儿科而不是家长或临床医生代理报告中使用PROs。到目前为止，还没有儿科肿瘤药物适应症是在PRO的基础上确定的；器官和系统的毒性被记录下来，但在参加实验性药物试验时，就症状和生活质量体验而言，没有儿童的声音。我们现在有儿科仪器来测量症状和生活质量（QoL）方面的患者报告在8至18岁，开发和验证作为PROMIS（患者报告的结果测量信息系统）倡议的一部分，由NIH医学研究路线图赞助。这些工具与访谈相结合，将使我们能够超越对患有无法治愈的癌症的儿童和青少年参与I期或II期的单一传统测量收益（肿瘤反应），记录他们在这一护理阶段的症状和生活质量。通过这些工具来衡量儿科PROs，我们将提供知识来帮助临床医生减少患者的痛苦，我们可以定位儿科肿瘤学，以满足FDA的药物标签标准，并在这个两个站点，纵向效度研究(T1，试验入组时间；T2（3 - 4周后），我们将首次评估PROMIS儿科器械的可行性、可接受性、可靠性、有效性和响应性，在多达80名8 - 18岁的无法治愈或难治性癌症患者中进行I期或II期试验。

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.