Towards precision medicine in clinical trials for the treatment of urologic chronic pelvic pain syndrome: lessons from the MAPP Research Network

Abstract

Randomized clinical trials have resulted in few approved therapies for the treatment of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urologic chronic pelvic pain syndrome. Heterogenous patient populations, mismatches of treatments to patient phenotypes, non-specific outcomes and use of standard study designs not leveraging phenotypic heterogeneity might have contributed to the inability of previous trials to demonstrate existing efficacy. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network has identified important phenotypic characteristics associated with differential symptom severity and treatment responsiveness. Based on Multidisciplinary Approach to the Study of Chronic Pelvic Pain findings and external research, empirically informed strategies were generated for defining patient populations, specifying treatments and selecting primary outcomes for future randomized clinical trials in urologic chronic pelvic pain syndrome. Explicitly specifying the scope of eligibility criteria across heterogeneous patient subgroups defined by pain widespreadness, the presence of Hunner lesions, the presence of pain with bladder filling or relieved by voiding, the extent of chronic overlapping pain conditions, and pelvic floor tenderness is needed. Therapies should be selected based on the mechanism of action and relevance to the mechanism of pain and dominant symptomology that the patient experiences. Evidence suggests that pain and urinary symptoms should be evaluated separately. Promising trial designs for identifying effective therapies in this heterogeneous patient population include sequential multiple assignment randomized trials and adaptive designs.