Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK.
Ir J Med Sci. 2012 Mar;181(1):1-6. doi: 10.1007/s11845-011-0778-1. Epub 2011 Nov 8.
Although the pathophysiology of sepsis has been extensively studied, the disease remains a common cause of death in the critically ill patient. It thus remains one of the most pressing clinical and economic problems of modern medicine. A vast amount of inflammatory mediators have been identified as key factors in driving sepsis. Therapeutic agents designed to target these mediators have so far failed to demonstrate significant clinical benefit.
Clinical trials are the standard for assessing safety and efficacy of novel agents but are made difficult by the heterogeneous nature of septic patients. This review aims to highlight the complex nature of sepsis and the inherent difficulties encountered in designing clinical trials in these patients. The major factors contributing to the difficulties in improving internal and external validity will be discussed with the aim of guiding future study design.
The design of clinical trials on the septic patient remains a challenge. Methodology must be rigorous if seemingly positive clinical trials which are widely implemented are later discredited as a result of poor study design. Many lessons can be learnt from the study design of the PROWESS trial, however there remains room for improvement. This review serves as a stimulus and guide in motivating much needed high quality clinical trials in sepsis.
尽管脓毒症的病理生理学已经得到了广泛的研究，但它仍然是危重病患者死亡的常见原因。因此，它仍然是现代医学中最紧迫的临床和经济问题之一。大量的炎症介质已被确定为驱动脓毒症的关键因素。迄今为止，旨在针对这些介质的治疗药物未能显示出显著的临床获益。
临床试验是评估新型药物安全性和疗效的标准方法，但由于脓毒症患者的异质性，临床试验变得困难。本综述旨在强调脓毒症的复杂性以及在这些患者中设计临床试验所遇到的固有困难。将讨论导致内部和外部有效性的困难的主要因素，目的是指导未来的研究设计。
脓毒症患者的临床试验设计仍然是一个挑战。如果看似积极的临床试验由于研究设计不佳而被广泛质疑，那么方法学必须严格。从 PROWESS 试验的研究设计中可以吸取许多教训，但仍有改进的空间。本综述旨在为脓毒症的高质量临床试验提供动力，并起到刺激和指导作用。
