PubMed2007
OBJECTIVE: To evaluate three potential definitions of treatment response in overactive bladder (OAB) syndrome, based on the International Continence Society (ICS) definition of OAB, using pooled data from two large clinical trials of the antimuscarinic agent solifenacin succinate. PATIENTS AND METHODS: As the ICS definition of OAB does not rely on urodynamic observations for a diagnosis, the use of composite endpoints, such as in the definitions examined here, might provide a more relevant measure of patient benefits. Each definition was tested to assess the impact of pharmacotherapy, comparing treatment response rates based on composite endpoints. Responder definitions were validated based on the impact on quality of life (QoL). Pooled data from two 12-week multinational, multicentre, double-blind randomized studies of solifenacin, a once-daily oral antimuscarinic for treating OAB symptoms, were used for this analysis. Based on the symptom data from these studies (episodes of urgency, incontinence, nocturia and voiding frequency per 24 h), response was defined as being: (i) a reduction by half or more in all baseline symptoms; (ii) a reduction by half or more in urgency and at least one other symptom; or (iii) resolution of urgency episodes and at least one other symptom. Health-related QoL changes were recorded using the King's Health Questionnaire (KHQ). RESULTS: Solifenacin at 5 mg or 10 mg once daily resulted in significantly higher response rates than with placebo, irrespective of the definition of a responder (P < or = 0.001). When assessing the most challenging definition of response (resolution of urgency and at least one other symptom), solifenacin at 5 mg and 10 mg resulted in 20% and 25% of patients, respectively, meeting the response criteria, vs 12% of placebo-treated patients (P < or = 0.001 for both solifenacin doses). For all three definitions of response, responders showed greater improvements in all KHQ domains than did nonresponders, and the differences were statistically significant. CONCLUSIONS: The two strictest definitions of response (halving or more in all baseline symptoms or resolution of urgency and more than one other symptom) appeared to capture QoL changes most effectively. Establishing the most appropriate definition to assess treatment-related changes in OAB will require further investigation, but it is clear from this analysis that composite clinical endpoints, based on the ICS definition of OAB, are a valid approach for assessing the effect of treatments for OAB.