Spiller R C
Department of Therapeutics, University Hospital, Queens Medical Center, Nottingham, United Kingdom.
Am J Med. 1999 Nov 8;107(5A):91S-97S. doi: 10.1016/s0002-9343(99)00086-8.
The last two decades have seen many studies that are of inadequate design and power. This report focuses on what we have learned from the 25 randomized, controlled studies that included at least 30 patients during the period 1976-1998. The most important finding has been that the median placebo response was 47% (range, 0-84%), which is approximately three times the size of the difference between placebo and drug response, median 16% (range, -17-64%). This tells us the importance of reassurance and the powerful nonspecific therapeutic effects of entering patients into clinical trials in irritable bowel syndrome (IBS). Patients should be stratified according to the dominant symptoms that are relevant to the drug's intended effect. A randomized, double-blind, controlled, parallel group study appears the most robust design. Minimizing the placebo response reduces the numbers needed to detect a significant difference. The optimum length of trial is probably >3 months, because the placebo effect takes approximately 12 weeks to start to recede. Dose titration should maximize the chance of detecting a benefit.
在过去二十年里，出现了许多设计和效能不足的研究。本报告聚焦于我们从1976年至1998年期间进行的25项随机对照研究中所学到的内容，这些研究每项至少纳入了30名患者。最重要的发现是，安慰剂反应的中位数为47%（范围为0 - 84%），这大约是安慰剂与药物反应差异（中位数为16%，范围为 - 17 - 64%）的三倍。这向我们表明了安慰的重要性以及让患者参与肠易激综合征（IBS）临床试验所具有的强大非特异性治疗效果。患者应根据与药物预期效果相关的主要症状进行分层。随机、双盲、对照、平行组研究似乎是最为可靠的设计。尽量减少安慰剂反应可降低检测到显著差异所需的样本量。试验的最佳时长可能超过3个月，因为安慰剂效应大约需要12周才开始消退。剂量滴定应使检测到疗效的机会最大化。
