Corazziari E, Bytzer P, Delvaux M, Holtmann G, Malagelada J R, Morris J, Muller-Lissner S, Spiller R C, Tack J, Whorwell P J
Università La Sapienza, Rome, Italy; Glostrup University Hospital, Copenhagen, Denmark.
Aliment Pharmacol Ther. 2003 Sep 15;18(6):569-80. doi: 10.1046/j.1365-2036.2003.01709.x.
Appropriate guidelines for clinical trials in irritable bowel syndrome are needed because of the inadequacy of previously performed trials, the use of new and more adequate patient definition, new emerging pathophysiological models and the unique requirements related to the assessment of treatment outcome that, in the absence of a biological marker, can rely only on the evaluation of clinical manifestations. This consensus report highlights the following points. (a) A 4-week period is considered to be adequate to assess drug efficacy for the control of symptoms. (b) For the cyclic and non-life-threatening nature of the disease, a long-term study of 4-6 months or more of active treatment to establish efficacy is considered to be inappropriate in the large majority of patients. (c) In the initial assessment phase of drug efficacy, the withdrawal effect of treatment can be ascertained during a follow-up period prolonged for a sufficient time (4-8 weeks) after stopping treatment. Subsequent trials with proper withdrawal phase design and duration can then ascertain the drug post-treatment benefit. (d) Considering the intermittent clinical manifestations of irritable bowel syndrome, designing trials with on-demand or repeated cycles of treatment could be envisaged. However, the lack of a definition of what constitutes an exacerbation is a major obstacle to the design of such trials. In the absence of an established gold standard, appropriately justified novel trial designs are welcome. (e) Patients eligible for inclusion should comply with the Rome II diagnostic criteria for irritable bowel syndrome. (f) The main efficacy outcome of the treatment should be based on one primary end-point. (g) The primary efficacy end-point could combine, in a global assessment, the key symptoms (abdominal pain, abdominal discomfort, bowel alterations) of irritable bowel syndrome or rate any single symptom for drugs considered to target specific symptoms. (h) A 50% improvement in the primary efficacy end-point seems to be a reasonable definition of a responder.
由于既往进行的试验存在不足、采用了新的且更合适的患者定义、新出现的病理生理模型以及与治疗结果评估相关的独特要求（在缺乏生物标志物的情况下，只能依靠临床表现的评估），因此需要制定针对肠易激综合征临床试验的适当指南。本共识报告强调了以下几点。(a) 4周时间被认为足以评估药物控制症状的疗效。(b) 鉴于该疾病具有周期性且不危及生命的性质，对于绝大多数患者而言，进行4至6个月或更长时间的积极治疗以确定疗效的长期研究被认为是不合适的。(c) 在药物疗效的初始评估阶段，治疗的撤药效应可在停药后延长足够时间（4至8周）的随访期内确定。随后进行具有适当撤药期设计和时长的试验，便可确定药物治疗后的益处。(d) 考虑到肠易激综合征临床表现的间歇性，可以设想设计按需或重复治疗周期的试验。然而，缺乏对病情加重的定义是设计此类试验的主要障碍。在没有既定金标准的情况下，欢迎有充分理由的新颖试验设计。(e) 符合纳入条件的患者应符合肠易激综合征的罗马II诊断标准。(f) 治疗的主要疗效结果应基于一个主要终点。(g) 主要疗效终点在整体评估中可综合肠易激综合征的关键症状（腹痛、腹部不适、肠道改变），或者对被认为针对特定症状的药物对任何单一症状进行评分。(h) 主要疗效终点改善50%似乎是对有反应者的合理定义。
