Multiple Medical Therapies for Pediatric TBI; Comparative Effectiveness Approach

描述（由申请人提供）：创伤性脑损伤（TBI）是儿童的主要杀手，2005年在美国有超过7000人死亡。除了这些生命损失之外，在美国，创伤性脑损伤每年对儿童健康和福利的成本超过20亿美元，用于急性护理，超过100万人的生命年可能处于危险之中。对患有严重脑外伤的儿童的治疗进展缓慢，令人失望。新治疗药物和方法的随机对照试验（rct）在多中心应用时普遍失败。基于证据的指南不足以产生有意义的建议，因为文献未能证明创伤性脑损伤护理的大多数方面的最佳实践。在当代临床实践中，诸如颅内高压控制、减轻继发性损伤和代谢支持等实践差异很大，导致患者结果差异很大，并可能最终淹没在设计良好的随机对照试验中可能观察到的治疗效果。我们建议在美国、英国和欧盟的一个国际联盟中对1000名严重TBI儿童进行观察性队列研究，以比较儿科TBI治疗的有效性。我们将测试3个具体目标，包括总共6种TBI治疗方法——(i)颅内高压策略——脑脊液分流

DESCRIPTION (provided by applicant): Traumatic brain injury (TBI) is the leading killer of children with over 7000 deaths reported in the US in 2005. In addition to this loss of life, the yearly costs of TBI on the health and welfare of children in the US is over $2 billion for acute care along and more than a million life-years are potentially at risk. Advances in care for children with severe TBI have been disappointingly slow. Randomized controlled trials (RCTs) of novel therapeutic agents and approaches have universally failed when applied in multiple centers. Evidenced-based guidelines are not sufficiently robust to generate meaningful recommendations because the literature has failed to demonstrate best practices for most aspects of TBI care. Variations in practices such as intracranial hypertension control, mitigation of secondary insults and metabolic support are substantial in contemporary clinical practice, leading to wide variations in patient outcomes and may ultimately overwhelm treatment effects that might be observed in a well-designed RCT. We propose an observational cohort study of 1000 children with severe TBI to compare the effectiveness of pediatric TBI therapies within an international consortium from the US, UK and EU. We will test 3 specific aims that encompass a total of 6 TBI therapies - (i) intracranial hypertension strategies - cerebrospinal fluid diversion and hyperosmolar therapies; (ii) secondary insult detection - prophylactic hyperventilation and brain tissue oxygen monitoring (PbO2); (iii) metabolic support - nutritional support and glucose management. Several statistical approaches, often used in comparative effectiveness research (CER) to control for confounders, will be employed including propensity score adjustments, regression analyses and novel statistical modeling. Successful completion of this proposal would provide compelling evidence to change clinical practices, provide evidence for several new recommendations for future guidelines and lead to improved research protocols that would be limit variability in TBI treatments - helping children immediately through better clinical practices and ultimately through more effective investigation.