Irritable bowel syndrome is characterized by recurrent abdominal pain and altered bowel function. In designing studies to evaluate new treatments for this disease, however, it is difficult to select appropriate endpoints to reflect improvement in the range of symptoms of the syndrome. In the present study we evaluated the parameter of adequate relief of abdominal pain and discomfort, as perceived by the patients, as a key endpoint for efficacy in the treatment of patients with irritable bowel syndrome. Abdominal pain and bowel function data were collected daily from 370 patients with the disease during treatment with placebo or a novel potent 5HT3 receptor antagonist. Once every 7 days adequate relief of pain and discomfort was assessed. Quality-of-life data were collected using self-administered questionnaires. The endpoint of adequate relief was significantly (P < 0.05) correlated with improvement in pain severity scores, percentage of pain-free days, percentage of days with urgency, improvement in stool frequency and consistency, and quality-of-life parameters. Adequate relief of pain and discomfort is significantly correlated with changes in multiple parameters associated with irritable bowel syndrome and can be used as an endpoint for assessing response to therapy in these patients.

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OBJECTIVES: Treatment effects are often evaluated by comparing groups in terms of the proportion of “responders”, i.e., patients who achieve some prospectively defined outcome. In the absence of additional data, it is assumed that responders in different treatment groups achieve comparable benefits and therefore that the treatment benefit is fully described by the responder rates. This study compared the HRQOL changes of responders in two treatment groups. METHODS: In two identical randomized, double‐blind, placebo‐controlled studies (S3BA3001; S3BA3002) in women evaluating 12 weeks of treatment with alosetron 1mg BID, patients completed the Irritable Bowel Syndrome Quality of Life Questionnaire (IBSQOL) at baseline and at the final treatment visit. A patient was classified as a responder if she achieved adequate relief of IBS pain and discomfort on at least 2 of 4 weeks for all 3 months. This post‐hoc analysis compared responders from the two treatment groups in terms of IBSQOL change from baseline scores at the final visit using analysis of covariance. The analysis focused on patients with diarrhea‐predominant IBS. RESULTS: Our analyses included 154 patients (96 alosetron and 58 placebo) in S3BA3001 and 172 (110 alosetron and 62 placebo) in S3BA3002. Compared with placebo responders, those in the alosetron group had significantly higher (p < .05) scores on 5 of 9 IBSQOL scales (sleep; energy; physical functioning, food and role‐physical) in S3BA3001 and on 4 scales (sleep, energy, food and social functioning) in S3BA3002. CONCLUSIONS: Adequate relief responders in the alosetron group experienced significantly greater HRQOL improvements relative to placebo group responders. This suggests that treatment benefits may be underestimated when described only in terms of the additional proportion of responders. Reporting HRQOL differences between responders in the treatment groups provides a more comprehensive characterization of the treatment effect.