Consensus report: clinical trial guidelines for pharmacological treatment of irritable bowel syndrome E. CORAZZIARI*, P. BYTZER  , M. DELVAUX à , G. HOLTMANN§, J. R. MALAGELADA – , J. MORRIS**, S. MULLER-LISSNER   , R. C. SPILLER àà , J. TACK§§ & P. J. WHORWELL** *Universita ` La Sapienza, Rome, Italy;  Glostrup University Hospital, Copenhagen, Denmark; àGastroenterology Unit, Toulouse, France; §University of Essen, Essen, Germany; –Hospital Universitari Vall d’Hebron, Barcelona, Spain; **Wythenshawe Hospital, Manchester, UK;   Park Klinik Weissensee, Berlin, Germany; ààUniversity Hospital Nottingham, Nottingham, UK; §§University Hospitals Leuven, Leuven, Belgium Accepted for publication 24 June 2003 SUMMARY 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 pathophys- iological 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 assess- ment 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 stop- ping treatment. Subsequent trials with proper withdrawal phase design and duration can then ascertain the drug post-treatment benefit. (d) Consider- ing the intermittent clinical manifestations of irritable bowel syndrome, designing trials with on-demand or repeated cycles of treatment could be envisaged. How- ever, 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. PROCESS FOR THE CREATION OF THE REPORT The process for the development of this report originated from a project by European academic investigators and clinicians who reviewed and discussed the ‘Points to consider on the evaluation of medicinal products for the treatment of irritable bowel syndrome’, released by the European Agency for the Evaluation of Medicinal Products as a draft in April 2002 and as a final document in March 2003. 1 The six-step process for the creation of this report is outlined below. Correspondence to: Dr E. Corazziari, Dipartimento di Scienze Cliniche, Universita ` degli Studi La Sapienza, Policlinico Umberto I, Viale del Poli- clinico 155, 00161 Rome, Italy. E-mail: enrico.corazziari@uniroma1.it Aliment Pharmacol Ther 2003; 18: 569–580. doi: 10.1046/j.0269-2813.2003.01709.x Ó 2003 Blackwell Publishing Ltd 569