Creating and Validating Child Adverse Event Reporting in Oncology Trials

描述：超过60%的被诊断为癌症的儿童将参加临床试验；这些儿童中的绝大多数将经历与治疗相关的多种不良事件，需要强烈的支持性护理。联邦政府规定，所有试验必须报告不良事件(AEs)；美国国家癌症研究所(NCI)将其定义为与使用某种医疗手段暂时相关的任何不良和意外的体征、症状或疾病。肿瘤学试验中的标准做法是临床医生使用不良事件通用术语标准(CTCAE)的标准NCI词典对所有不良事件进行分级，但在成人癌症人群中的多项研究发现，与患者报告的相比，临床医生低估了症状的数量和严重程度。在CTCAE上的790个AEs中，超过三分之一的AEs的识别具有一定的主观因素，需要患者报告来确保AE文件的准确性。鉴于癌症治疗对儿童生活的已知毒性，儿童对主观AEs进行评级的观点必须纳入AE报告中。如果不包括儿童的AE报告，癌症治疗的风险/收益比率将无法准确确定。在比较儿童、父母和临床医生症状评级的少数研究中，临床医生很差，照顾者在识别儿童正在经历的症状方面只略好一些。这项对6个儿童肿瘤学组织(COG)站点的新研究扩展了我们团队目前对儿科临床医生的研究，从CTCAE中确定了62个预期可用于癌症治疗的7至20岁儿童的主观AEs，并可作为设计儿科患者报告CTCAE(PRO-CTCAE)测量的基础。这项为期5年的研究包括3个目标。在目标1中，我们将设计支持CTCAE的儿科和照顾者代理版本的英语和西班牙语版本，将62个主观AE翻译成适合儿童的术语，并创建儿童及其照顾者代理可以理解的配套面试问题。在目标2中，我们将使用认知访谈方法来评估儿童和照顾者代理对支持CTCAE的问题的理解和回答程度。不同的阶层将代表不同的癌症类型和不同的年龄范围。目的3是一项纵向研究，根据年龄和癌症类型对新诊断的儿童癌症治疗中PROCTCAE措施的信度、效度和反应性进行评估。我们还将评估随着时间的推移和临床条件的变化，照料者-代理人、临床医生和儿童对AE评级的一致性。这项研究是朝着我们的长期研究目标迈出的第一步，即当PRO-CTCAE被纳入癌症临床试验时，记录护理管理和结果的差异。

DESCRIPTION: Over 60% of children diagnosed with cancer will participate in a clinical trial; the great majority of these children will experience multiple treatment-related adverse events that require intense supportive care. The Federal Government mandates for safety monitoring that all trials report adverse events (AEs); defined by the National Cancer Institute (NCI) as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medical treatment. The standard practice in oncology trials is for the clinician to grade all AEs using the standard NCI lexicon of the Common Terminology Criteria for Adverse Events (CTCAE), but multiple studies in adult cancer populations found that clinicians underreport the number and severity of symptoms compared to what patients report. More than a third of the 790 AEs on the CTCAE have some subjective aspect to its identification, requiring patient-report to assure accuracy of the AE documentation. Given the known toxicity of cancer treatments on children's lives, the child's perspectives in grading subjective AEs must be integrated into AE reporting. Without including the child's AE reports, the risk/benefit ratio of cancer treatments wil not be accurately established. In a small number of studies comparing child, parent and clinician symptom ratings, clinicians were poor and caregivers only slightly better at recognizing the symptoms the children were experiencing. This new study with 6 Children's Oncology Group (COG) sites extends our team's current research with pediatric clinicians that identified 62 subjective AEs from the CTCAE that 7- to 20- year olds in cancer treatment could be expected to validly rate, and which could serve as the basis for designing a pediatric patient-report CTCAE (PRO-CTCAE) measure. This 5-year study includes 3 aims. In Aim 1, we will design both English and Spanish versions of a pediatric and caregiver-proxy version of the PRO- CTCAE by translating the 62 subjective AEs into child-friendly terms and create companion interview questions that are comprehensible to children and their caregiver-proxies. In Aim 2, we will use cognitive interviewing methods to evaluate how well children and caregiver-proxies understand and respond to the PRO-CTCAE questions. Strata will represent different cancer types and different age ranges. Aim 3 is a longitudinal study to evaluate the reliability, validity and responsiveness of the PRO-CTCAE measures with newly diagnosed children in cancer treatment, stratified by age and cancer types. We will also assess concordance of AE ratings by caregiver-proxies, clinicians and children over time and changing clinical conditions. This study constitutes a first step towards our long term research goal of documenting the differences in care management and outcomes when the PRO-CTCAE is incorporated into cancer clinical trials.