Definition of a responder in clinical trials for functional gastrointestinal disorders: report on a symposium.

Introduction On 10 and 11 September 1998, about 125 participants met at a symposium in Vienna, Austria, with the goal of determining whether a consensus could be developed on the definition of responders in clinical trials in the functional gastrointestinal disorders. Present at this meeting were representatives of the Food and Drug Administration (FDA) (Robert Prizont, MD, and John Senior, MD*), a representative of the Japanese International Motility Society (Kei Matsueda, MD, PhD), academic investigators from around the world, and representatives of several pharmaceutical companies currently engaged in the development of therapeutic compounds for the functional gastrointestinal disorders. The discussion centered primarily on the irritable bowel syndrome (IBS), the functional gastrointestinal disorder for which there is the largest development program underway. However, the discussion also addressed the measurement of outcomes in functional constipation. This conference was sponsored by the Multinational Working Teams to Develop Diagnostic Criteria for Functional Gastrointestinal Disorders (MWT). Over a two year period, the executive committee of the MWT held a series of informal meetings with representatives of the FDA, and on one occasion, with a representative of the European Agency for the Evaluation of Medicinal Products. During these meetings, representatives of the regulatory groups indicated that there was a need for a more broad-based consensus on the best ways of defining responders in clinical trials. The MWT organized this conference to meet this need. This conference was unique in several respects. It is the first time representatives of the regulatory agencies, the academic community, and the pharmaceutical research teams have met together with the goal of developing a consensus on outcome measurement. It also represents a milestone in the willingness of diVerent pharmaceutical companies to share data from actual clinical trials for the purpose of developing outcome measures that could be used by all of them. The degree of consensus achieved at this initial meeting was modest. However, this represents the first step in a process that is expected to lead to a broad-based consensus on these issues. The conference was organized as a multi-stage process. Firstly, representatives of the FDA and of the Japanese International Motility Society presented position papers; Dr Drossman described the history of the MWT; and Dr Sander Van Zanten presented the provisional recommendations of the MWT which dealt with the design of clinical trials. Following this, academic investigators described their views on the measurement of outcomes. The representatives of six pharmaceutical companies then presented data. These representatives were asked to select clinical trials completed by their companies in which at least one outcome measure had been found to be significantly diVerent between drug and placebo groups, and to compare the diVerent outcome measures used in these trials on a common scale, making it possible to compare their relative eYcacy and the magnitude of the placebo response. These presentations were followed by an open discussion whose purpose was to assess the degree of consensus among the participants and to summarize their recommendations for measurement. Following the conference, these recommendations, together with a summary of the presentations at the conference, were circulated to the participants and to other members of the scientific community for comment. After this review process was completed, the recommendations were forwarded to the regulatory agencies and to the companies that participated in the conference.