Establishing Surveillance of the Pediatric Evidence Base for Drug Therapy

说明(申请人提供)：由于缺乏儿科临床药物试验，高达80%的儿科药物使用被认为是未经批准或“标签外”的。临床医生被迫从成人研究中推断结果，并在没有对剂量、安全性或有效性进行特定年龄研究的情况下，在反复试验的基础上给儿童开药。增加儿科患者在临床试验中的代表性是国家儿童健康与人类发展研究所(NICHD)的一个高度优先领域，该研究所负责监督《儿童最佳药品法》(BPCA)下的活动，最近建立了儿科试验网络(PTN)，以支持根据BPCA进行的临床试验。尽管之前已经认识到缺乏高质量的证据来支持儿科药物治疗，但到目前为止还没有足够的数据来源来全面监测儿科试验组合。这项建议使用独特的资源--ClinicalTrials.gov--并首次开发方法来评估整个儿科研究组合，评估研究与实际疾病负担的相关性和一致性，以及试验的质量和有效性。我们建议利用这一登记系统分析儿科药物试验的三个具体目标：1)确定儿科研究组合与儿科疾病实际负担的对应程度；2)确定儿科患者在药物试验中的患病率以及与儿科患者研究相关的试验特征；3)与成人试验相比，衡量儿科试验设计和报告的质量指标。我们假设，儿科药物研究的重点与实际的全球儿科疾病负担所界定的高度优先领域的对应程度很低。此外，我们假设儿科试验的设计和报告在方法学上不如成人试验严格。由于临床试验的主体在不断演变，这项工作不仅提供了当前儿科药物试验的快照，而且还提供了一个框架和工具包，用于监测未来的证据库。根据这些目标开发的指标将通过ClinicalTrials.gov的基于Web的前端应用程序的原型公开提供，该应用程序自动显示儿科的当前状态 临床试验。 公共卫生相关性：这项建议解决了缺乏高质量的临床试验来支持在儿科人群中循证使用药物的问题。在危重患者、住院患者以及在门诊环境中接受小病治疗的数百万儿童中，标签外药物的使用很普遍。没有高质量的临床数据，儿童 未经测试的药物可能会受到伤害，或者可能会放弃潜在的有效治疗。根据相关性和质量确定儿科药物研究的现状，将允许采取有针对性的措施来改进围绕药物治疗的儿科证据基础。

DESCRIPTION (provided by applicant): Because of a paucity of pediatric clinical drug trials, up to 80% of pediatric drug use is considered unapproved or "off-label". Clinicians are forced to extrapolate findings from adult studies and prescribe medications to children on a trial and error basis without age-specific research on dosing, safety, or efficacy. Increasing representation of pediatric patients in clinical trials is a high priority area for the National Institute of Child Halth and Human Development (NICHD), which oversees activities under the Best Pharmaceuticals for Children Act (BPCA) and recently established the Pediatric Trials Network (PTN) to support clinical trials conducted under the BPCA. Though the lack of high quality evidence to support pediatric drug therapy has been previously recognized, there has not until now been an adequate data source for comprehensive surveillance of the pediatric trial portfolio. This proposal uses a unique resource-ClinicalTrials.gov-and develops methods to, for the first time, take stock of the entire pediatric research portfolio, assessing the relevance and alignment of research with actual disease burden as well as quality and validity of trials. We propose to use this registry to analyze pediatric drug trials in three specific aims: 1) To determine how closely the pediatric research portfolio corresponds to actual pediatric disease burden; 2) To determine the prevalence of pediatric patients in drug trials and trial characteristics associated with the study of pediatric patients; and 3) To measure quality indicators of pediatric trial design and reporting as compared to adult trials. We hypothesize that the focus of pediatric drug research corresponds poorly to high priority areas defined by actual global pediatric disease burden. Further, we hypothesize that the design and reporting of pediatric trials are less methodologically rigorous than adult-based trials. Because the body of clinical trials is constantly evolving, this work provides not only a snapshot of current pediatric drug trials, but also a framework and toolkit for surveillance of the evidence base going forward. Metrics developed under these aims will be made publicly available through a prototype of a web-based front application to ClinicalTrials.gov that automatically displays the current status of pediatric clinical trials. PUBLIC HEALTH RELEVANCE: This proposal addresses the lack of high-quality clinical trials available to support the evidence-based use of medications in pediatric populations. Off-label drug use is prevalent among critically ill, hospitalized patients as well as millions of children treated for minor illnesses in the ambulatory setting. Without high-quality clinical data, children given untested medications may suffer harm or may forgo potentially effective treatments. Defining the current state of pediatric drug research in terms of its relevance and quality will allow directed measures to improve the pediatric evidence-base around pharmacotherapy.