Lessons to be learned for gastroenterology from recent issues in clinical trial methodology

Randomized trials are the preferred tool for patient-oriented research, and their main role is to enable the transfer of results from basic research t o routine application. While the need for randomized trials is evident, con ducting these trials is becoming increasingly difficult and complex. This a rticle reviews actual and conflicting issues of clinical trials with respec t to gastroenterology. Major problems in trial design are neglect of previo us research, inadequate sample size calculations and irrelevant outcome cri teria. Significant trial management problems include subversion of random a llocation, and the design of systems and procedures that are inefficient, i neffective and inflexible. One of the major challenges in conducting random ized, controlled trials is obtaining informed consent because of the differ ing perspectives and languages of physicians and patients. Recommendations include practical guidance in obtaining informed consent, feedback of trial results to patients and support of research related to obtaining informed consent. Despite statistical guidance, several critical issues persist with respect to trial analysis. The use of confidence intervals is underreprese nted, the presentation of baseline data is often omitted and postsubgroup a nalysis is performed. Another controversial but relevant issue is the inten tion-to-treat analysis. Despite the formulation of standards, there is cons istently poor quality of trial reporting, poor registration of unpublished trials and limited registration of ongoing trials. The authors conclude tha t there is a need for more randomized trials in gastroenterology. While the complexity of trial conduction has increased, so have the means of methodo logical and practical support. Thus, all problems can be professionally tac kled, resulting in good clinical research.