Forensic dissection of a clinical trial: lessons learned in understanding and managing interstitial cystitis.

A pharmaceutical company-sponsored post-registration clinical trial designed to determine the most effective dose of pentosan polysulfate for the treatment of interstitial cystitis (IC) reported negative results. However, because of a priori trial design features, important posthoc analyses were able to answer many of the important clinical issues on the epidemiology, diagnosis, and treatment of IC that to date had remained unanswered. Seven published follow-up reports based on data and outcomes from the original study evaluated the clinical significance of a positive Potassium Sensitivity Test, confirmed the O'Leary-Sant Interstitial Cystitis Symptom Index as a valid and sensitive outcome measure, and determined that doses of pentosan polysulfate higher than the standard US Food and Drug Administration-approved dose of 300 mg/d did not increase efficacy although increased duration of therapy increases the chance of symptom amelioration. Further analyses determined that sexual dysfunction is an important parameter to assess in IC and that successful therapy can improve sexual functioning. Finally, the data showed that symptom severity, quality of life (QoL), and sleep function are interrelated. Consequently, symptom improvement with therapy correlates with improvement in both sleep function and QoL. This post hoc forensic dissection of a clinical trial initially undertaken for simple regulatory reasons has significantly improved our understanding and management of the enigmatic condition we call IC.