Creating and Validating Child Adverse Event Reporting in Oncology Trials

描述：超过60%被诊断患有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多种与治疗相关的不良事件，需要强烈的支持性护理。联邦政府要求进行安全监测，要求所有试验报告不良事件（ae）；美国国家癌症研究所（NCI）将其定义为与使用药物治疗暂时相关的任何不利和意外的体征、症状或疾病。肿瘤试验的标准做法是临床医生使用NCI不良事件通用术语标准（CTCAE）的标准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，与患者报告的症状相比，临床医生少报了症状的数量和严重程度。在CTCAE上的790例AE中，超过三分之一的AE在识别上存在一些主观因素，需要患者报告以确保AE文档的准确性。鉴于癌症治疗对儿童生命的已知毒性，儿童对主观不良事件评分的观点必须纳入不良事件报告。如果不包括儿童的不良反应报告，癌症治疗的风险/收益比将无法准确建立。在少数比较儿童、父母和临床医生症状评分的研究中，临床医生和护理人员在识别儿童正在经历的症状方面只是稍微好一点。这项针对6个儿童肿瘤组（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，该研究从CTCAE中确定了62个主观ae， 7至20岁的癌症治疗患者可以预期有效率，这可以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，我们将设计英语和西班牙语版本的PRO- CTCAE儿科和护理人员代理版本，通过将62个主观ae翻译成儿童友好的术语，并创建儿童及其护理人员代理可理解的同伴访谈问题。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PRO-CTCAE问题的理解和回应程度。地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，评估PRO-CTCAE措施对新诊断儿童癌症治疗的信度、效度和反应性，按年龄和癌症类型分层。我们还将评估照顾者代理、临床医生和儿童随时间和临床条件变化对AE评分的一致性。当PRO-CTCAE被纳入癌症临床试验时，我们的长期研究目标是记录护理管理和结果的差异，这项研究是我们的第一步。

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.