The AUA/SUFU Guideline on the Diagnosis and Treatment of Idiopathic Overactive Bladder.

PURPOSE: The purpose of this guideline is to provide evidence-based guidance to clinicians of all specialties on the evaluation, management, and treatment of idiopathic overactive bladder (OAB). The guideline informs the reader on valid diagnostic processes and provides an approach to selecting treatment options for patients with OAB through the shared decision-making process, which will maximize symptom control and quality of life, while minimizing adverse events and burden of disease. METHODS: An electronic search employing OVID was used to systematically search the MEDLINE and EMBASE databases, as well as the Cochrane Library, for systematic reviews and primary studies evaluating diagnosis and treatment of OAB from January 2013 to November 2023. Criteria for inclusion and exclusion of studies were based on the Key Questions and the populations, interventions, comparators, outcomes, timing, types of studies and settings (PICOTS) of interest. Following the study selection process, 159 studies were included and were used to inform evidence-based recommendation statements. RESULTS: This guideline produced 33 statements that cover the evaluation and diagnosis of the patient with symptoms suggestive of OAB; the treatment options for patients with OAB, including non-invasive therapies, pharmacotherapy, minimally invasive therapies, invasive therapies, and indwelling catheters; and the management of patients with BPH and OAB. CONCLUSION: Once the diagnosis of OAB is made, the clinician and the patient with OAB have a variety of treatment options to choose from and should, through shared decision-making, formulate a personalized treatment approach taking into account evidence-based recommendations as well as patient values and preferences.

Patient and Clinician Challenges with Anticholinergic Step Therapy in the Treatment of Overactive Bladder: A Narrative Review.

Anticholinergics have been used in the treatment of overactive bladder (OAB), but their use is limited by poor tolerability and anticholinergic-related side effects. Increasingly, providers are discontinuing anticholinergic prescribing because of growing evidence of the association of anticholinergic use with increased risk of cognitive decline and other adverse effects. Newer medications for OAB, the ß3-adrenergic receptor agonists mirabegron and vibegron, do not have anticholinergic properties and are typically well tolerated; however, many insurance plans have limited patient access to these newer OAB medications by requiring step therapy, meaning less expensive anticholinergic medications must be trialed and/or failed before a ß3-agonist will be covered and dispensed. Thus, many patients are unable to easily access these medications. Step therapy and other drug utilization strategies (e.g., prior authorization) are often used to manage the growing costs of pharmaceuticals, but these policies do not always follow treatment guidelines and may harm patients as a result of treatment delays, discontinuations, or related increases in adverse events. Medical professionals have called for reform of drug utilization strategies through partnerships that include clinicians and policymakers. This narrative review discusses prescribing patterns for OAB treatment and the effect of switching between drugs, as well as the costs of step therapy and prior authorization on patients and prescribers.

Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder.

BACKGROUND: Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective ß3-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence. METHODS: This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults ≥ 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for ≥ 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence. DISCUSSION: OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting. Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.

Does urinary urgency drive urinary frequency in overactive bladder?

OBJECTIVES: To determine if reduction in urgency in patients with refractory overactive bladder syndrome (rOAB) is correlated with a reduction in voiding frequency and symptom bother. METHODS: Data from a prospective series of women with rOAB undergoing radiofrequency ablation of the subtrigonal tissue, termed selective bladder denervation (SBD), was analyzed. Main outcome measures included urgency voids, nonurgency voids, and urgency urinary incontinence (UUI) epidsodes from a 3-day voiding diary and quality of life (QoL) measures (Overactive Bladder Questionnaire Short Form [OAB-q SF]). RESULTS: The dataset comprised 62 completer subjects at 6 months. Compared to baseline, UUI and urgency voids were lower (P < .001), but nonurgency voids were increased (P < .001) and QoL measures were improved (P < .001), but functional bladder capacity did not increase. At baseline and 6 months post treatment, symptom bother was correlated with urgency voids (P < .05) but inversely correlated with nonurgency voids (P < .001). Urgency and nonurgency voids were inversely related at baseline and at 6 months (P < .0001). Following treatment, urgency voids decreased by 41% and nonurgency voids increased by 33%. CONCLUSIONS: As with other interventions for OAB, SBD resulted in a reduction in OAB symptoms and an improvement in QoL measures. However, the decrease in urgency voids was offset by an increase in nonurgency voids, suggesting that habit or defensive voiding is a significant driver of urinary frequency. It is not certain if this is a unique finding of the SBD effect, but these data do suggest that analyses of outcomes of other OAB interventions are warranted to gain a better understanding of the genesis of OAB symptoms.

The AUA/SUFU Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction: Treatment and Follow-up.

PURPOSE: The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management. MATERIALS AND METHODS: A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base. RESULTS: This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of adult patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician. CONCLUSIONS: NLUTD patients may undergo non-surgical and surgical treatment options depending on their level of risk, symptoms, and urodynamic findings. Appropriate follow-up, primarily based on their risk stratification, must be maintained after treatment.

The AUA/SUFU Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction: Diagnosis and Evaluation.

PURPOSE: The clinician treating patients with neurogenic lower urinary tract dysfunction (NLUTD) needs to balance a variety of factors when making treatment decisions. In addition to the patient's urologic symptoms and urodynamic findings, other issues that may influence management options of the lower urinary tract include cognition, hand function, type of neurologic disease, mobility, bowel function/management, and social and caregiver support. This Guideline allows the clinician to understand the options available to treat patients, understand the findings that can be seen in NLUTD, and appreciate which options are best for each individual patient. This allows for decisions to be made with the patient, in a shared decision-making manner, such that the patient's quality of life can be optimized with respect to their bladder management. MATERIALS AND METHODS: A comprehensive search for studies assessing patients undergoing evaluation, surveillance, management, or follow-up for NLUTD was conducted from January 2001 through October 2017 and was rerun in February 2021 to capture newer literature. The primary search returned 20,496 unique citations. Following a title and abstract screen, full texts were obtained for 3,036 studies. During full-text review, studies were primarily excluded for not meeting the PICO criteria. One hundred eight-four primary literature studies met the inclusion criteria and were included in the evidence base. RESULTS: This guideline was developed to inform clinicians on the proper evaluation, diagnosis, and risk stratification of patients with NLUTD and the non-surgical and surgical treatment options available. Additional statements on urinary tract infection and autonomic dysreflexia were developed to guide the clinician. This Guideline is for adult patients with NLUTD and pediatric NLUTD will not be discussed. CONCLUSIONS: NLUTD patients should be risk-stratified as either low-, moderate-, high-, or unknown-risk. After diagnosis and stratification, patients should be monitored according to their level of risk at regular intervals. Patients who experience new or worsening signs and symptoms should be reevaluated and risk stratification should be repeated.

Gene Therapy for Overactive Bladder: A Review of BK-Channel α-Subunit Gene Transfer.

A need exists for local (ie, bladder-specific) interventions to treat overactive bladder (OAB) with low risk of unwanted postprocedural outcomes. Gene therapy targeted to leverage endogenous physiology in bladder cells may assist in restoring normal cell and organ function. Herein, we review the potential promise of gene therapy for treating OAB, focusing on gene transfer of URO-902, a non-viral naked plasmid DNA expressing the big potassium (BK) channel. We searched PubMed for articles concerning functional aspects of the BK channel and its potential use for gene transfer as local OAB treatment. Results from preclinical, phase 1, and phase 2 studies of URO-902 for erectile dysfunction and phase 1 studies of URO-902 for OAB are included. The BK channel has been extensively studied; however, URO-902 is the first gene therapy used in clinical trials directed toward treating OAB via the BK channel. In both URO-902 studies, there were no serious adverse events considered treatment related and no adverse events leading to early withdrawal. Both studies included secondary efficacy endpoints with promising results suggesting improvement in OAB symptoms, and quality of life, with use of URO-902 versus placebo. Gene therapy involving the BK channel, such as gene transfer with URO-902, has demonstrated promising safety and efficacy results in women with OAB. Findings warrant further investigation of the use of URO-902 for OAB treatment.

Persistence with mirabegron or antimuscarinic treatment for overactive bladder syndrome: Findings from the PERSPECTIVE registry study.

OBJECTIVES: This analysis from the PERSPECTIVE (a Prospective, Non-interventional Registry Study of Patients Initiating a Course of Drug Therapy for Overactive Bladder) study evaluated treatment persistence with mirabegron or antimuscarinics over a 12-month period. METHODS: Participants were adults diagnosed with overactive bladder (OAB) by their health care provider (HCP), who were initiating mirabegron or antimuscarinic treatment. The HCP made all treatment decisions, and patients were followed for 12 months with no mandatory scheduled visits. Information requests were sent to patients at baseline and months 1, 3, 6, and 12. Patients were nonpersistent if they switched, discontinued, or added OAB medications/therapies to their initial treatment. Reasons for discontinuation and switching patterns were investigated. RESULTS: Overall, 1514 patients were included (613 mirabegron and 901 antimuscarinic initiators). Persistence rates decreased steadily over time in both groups. A low proportion of patients added or switched medication at each time point. Unadjusted Kaplan-Meier analysis showed similar persistence rates for both groups. When the data were adjusted for patient characteristics (age, sex, and OAB treatment status), mirabegron initiators had higher persistence rates. No significant differences were noted in unadjusted median time to end of persistence. However, end of treatment persistence by any cause was longer with mirabegron (median: 9.5 vs 6.7 months for antimuscarinics). HCPs stated that the most common reasons for nonpersistence were no symptomatic improvement and side effect aversion. CONCLUSIONS: Treatment persistence was longer for mirabegron compared with antimuscarinic initiators after controlling for patient characteristics. End of treatment persistence by any cause was also longer with mirabegron.

Severe urinary tract damage secondary to primary bladder neck obstruction in women.

OBJECTIVE: To present the clinical and radiological characteristics of women with severe structural deterioration of the bladder and upper urinary tract secondary to Primary Bladder Neck Obstruction (PBNO), and their outcomes after bladder neck incision (BNI). METHODS: Retrospective evaluation of adult women who underwent BNI for PBNO at one institution. Patients were assessed for symptoms, renal function, structural abnormalities of the urinary tract and video-urodynamics. PBNO diagnosis was confirmed with video-urodynamics in all patients. BNI was performed at the 4-5 and/or 7-8 o'clock positions. Postoperative symptoms, PVR, uroflowmetry and renal function were evaluated and compared to baseline. RESULTS: Median patient age was 56.5 years (range 40-80). All presented with urinary retention-four were on clean intermittent Catheterization (CIC) and two with a Foley catheter. All patients had bladder wall thickening and diverticula. Four women had elevated creatinine levels, bilateral hydronephrosis was present in five (83.3%). After BNI, all patients resumed spontaneous voiding without the need for CIC. Median Qmax significantly improved from 2.0 [1.0-4.0] mL/s to 15 [10-22.7] mL/s (p = 0.031). Median PVR decreased from 150 to 46 [22-76] mL (p = 0.031). There were no postoperative complications. Creatinine levels returned to normal in 3/4 (75%) patients. CONCLUSION: PBNO in women may result in severe damage to the bladder and upper urinary tract. Despite severe structural abnormalities of the bladder, BNI was effective in reducing symptoms and improving structural and functional abnormalities of the lower and upper urinary tract.

Preparation and Utilization of Freshly Isolated Human Detrusor Smooth Muscle Cells for Characterization of 9-Phenanthrol-Sensitive Cation Currents.

Detrusor smooth muscle (DSM) cells present within the urinary bladder wall ultimately facilitate urine storage and voiding. Preparation of the viable, fresh, and isolated DSM cells presents an important technical challenge whose achievement provides optimal cells for subsequent functional and molecular studies. The method developed and elaborated herein, successfully used by our group for over a decade, describes dissection of human urinary bladder specimens obtained from open bladder surgeries followed by an enzymatic two-step treatment of DSM pieces and mechanical trituration to obtain freshly isolated DSM cells. The initial step involves dissection to separate the DSM layer (also known as muscularis propria) from mucosa (urothelium, lamina propria, and muscularis mucosa) and the adjacent connective, vascular, and adipose tissues present. The DSM is then cut into pieces (2-3 mm x 4-6 mm) in nominal Ca2+-containing dissection/digestion solution (DS). DSM pieces are next transferred to and sequentially treated separately with DS containing papain and collagenase at ~37 °C for 30-45 min per step. Following washes with DS containing enzyme-free bovine serum and trituration with a fire-polished pipette, the pieces release single DSM cells. Freshly isolated DSM cells are ideally suited for patch-clamp electrophysiological and pharmacological characterizations of ion channels. Specifically, we show that the TRPM4 channel blocker 9-phenanthrol reduces voltage-step evoked cation currents recorded with the amphotericin-B perforated patch-clamp approach. DSM cells can also be studied by other techniques such as single cell RT-PCR, microarray analysis, immunocytochemistry, in situ proximity ligation assay, and Ca2+ imaging. The main advantage of utilizing single DSM cells is that the observations made relate directly to single cell characteristics revealed. Studies of freshly isolated human DSM cells have provided important insights characterizing the properties of various ion channels including cation-permeable in the urinary bladder and will continue as a gold standard in elucidating DSM cellular properties and regulatory mechanisms.

Urethral diverticulum: A systematic review.

Objective: To present a review of the current literature regarding the presentation, diagnosis, and treatment of female urethral diverticula (UD). Methods: A systematic search of the PubMed database was performed to identify studies evaluating female UD. Article titles, abstracts and full-text manuscripts were screened to identify relevant studies, which then underwent data extraction and analysis. Results: In all, 50 studies evaluating the presentation, diagnosis and treatment of female UD were deemed relevant for inclusion. Almost all studies were retrospective single-arm case series. Female UD are outpouchings of the urethral lumen into the surrounding connective tissue. The presentation of female UD is diverse and can range from incidental findings to lower urinary tract symptoms, frequent urinary tract infections, dyspareunia, urinary incontinence (UI), or malignancy. Repair of UD begins with an accurate assessment and diagnosis, which should include adequate radiographic imaging, usually including magnetic resonance imaging. Once the diagnosis is confirmed, the usual treatment is surgical excision and reconstruction, most often through a transvaginal approach. The principles of transvaginal urethral diverticulectomy include: removal of the entire urethral diverticulum wall, watertight closure of the urethra, multi-layered and non-overlapping closure of surrounding tissue with absorbable suture, and preservation or creation of continence. Results of surgical repair are usually excellent, although long-term recurrence of these lesions may occur. Complications of urethral diverticulectomy include urethrovaginal fistula, UI, and rarely urethral stricture. Conclusion: Whilst urethral diverticulectomy excision and reconstruction is a challenging procedure, it is ultimately satisfying for the patient and the surgeon when relief of bothersome symptoms is achieved. Adherence to principles of reconstructive surgery is important to ensure a satisfactory result. Abbreviations: PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; UD: urethral diverticulum/diverticula; UI: urinary incontinence; US: ultrasonography; VCUG: voiding cystourethrogram.

One-year results with selective bladder denervation in women with refractory overactive bladder.

AIMS: To report 1-year results with selective bladder denervation (SBD) of the trigone in women with refractory overactive bladder (OAB). METHODS: In this prospective, international, multicenter case series, women with refractory OAB underwent a single SBD treatment of the bladder subtrigone region using temperature-controlled radiofrequency. Patients were followed for 1 year and evaluated for changes in OAB symptoms and adverse events. RESULTS: Among 35 women, 29 (83%) returned for 1-year follow up. Median symptom reductions based on 3-day bladder diaries were 68% for urgency urinary incontinence ( P < .001), 67% for urinary incontinence ( P < .001), 43% for urgency episodes ( P < .001), 5% for urinary frequency ( P = .19), and 33% for the total urgency and frequency score ( P < .001), with the majority of treatment benefit realized in the first month. Treatment benefit was reported in 72% of patients, the clinical success rate (≥50% reduction in urgency urinary incontinence) was 69%, and the dry rate was 10%. Statistically significant improvements occurred on Symptom Bother and Health-related Quality of Life scales on the Overactive Bladder questionnaire, and on 6 of 9 King's Health Questionnaire domains. Patients with less severe baseline symptoms had similar quality of life improvements as those with more severe baseline symptoms. Device- or procedure-related adverse events were reported in 6 (17%) patients. CONCLUSIONS: A single treatment with selective bladder denervation is durable for 1-year in a significant proportion of women with refractory overactive bladder.

Factors Associated with Improvements in Patient-Reported Outcomes During Mirabegron or Antimuscarinic Treatment of Overactive Bladder Syndrome: A Registry Study (PERSPECTIVE).

INTRODUCTION: Patient-reported outcomes (PROs) provide valuable insights about the effectiveness of overactive bladder (OAB) treatments. The aim of PERSPECTIVE (a Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder) was to provide real-world evidence from the USA and Canada on patient-perceived effectiveness and safety of mirabegron and antimuscarinics for treating OAB symptoms. METHODS: This prospective, non-interventional registry followed adult patients with OAB who were starting treatment with mirabegron or antimuscarinics. All treatment decisions were made at the discretion of the treating healthcare provider with no mandatory visits after enrollment. The primary objective was to identify factors associated with improved treatment effectiveness from a patient perspective mainly using the OAB Questionnaire Short-Form (OAB-q SF). The form was sent to patients via email link at baseline and months 1, 3, 6, and 12. Treatment-emergent adverse event (TEAE) data were collated from investigator reports. RESULTS: Overall, 1514 patients were included (female 73.5%, mean age 62.2 years). Mirabegron was initiated by 613 patients and antimuscarinics by 901 patients. A PRO response rate of approximately 60% was achieved (575 patients did not complete baseline PROs). Similar improvements in OAB-q SF symptom bother score and health-related quality of life (HRQoL) total score were observed for mirabegron and antimuscarinic initiators. Covariate-adjusted models demonstrated that worse baseline PRO score, Hispanic ethnicity, being treatment naïve, and use of complementary/supportive OAB therapies at baseline were significantly associated with greater improvements in both scores. The most frequent TEAEs were gastrointestinal disorders (dry mouth, constipation, and nausea) and nervous system disorders (headache, somnolence, and dizziness). CONCLUSION: There are no differences between mirabegron and antimuscarinics in terms of patient-reported OAB symptom bother and HRQoL. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02386072. FUNDING: Astellas Pharma Global Development, Inc. Plain language summary available for this article.

The Use of Tissue Flaps in the Management of Urinary Tract Fistulas.

Urinary tract fistulas represent a complex group of pathologies that present significant management challenges. While most such fistulas ultimately require definitive surgical management, compromised local tissue quality or other factors often render straightforward simple one layered closure challenging with a substantial risk of failure. Interpositional tissue flaps have become a mainstay of treatment in these circumstances, enabling the delivery of healthy tissue from other locations to the site of pathology. Herein, we present an overview of the assessment and management of complex urinary tract fistulas involving the reproductive and gastrointestinal organs, and the decision to utilize flaps. We review the underlying principles of tissue flaps and classify different types of flaps. We conclude with a discussion of the indications, advantages, disadvantages, and harvesting techniques for the most commonly utilized flaps in urinary tract fistula repair.

Six-Month Results of Selective Bladder Denervation in Women with Refractory Overactive Bladder.

PURPOSE: We report 6-month efficacy and safety outcomes of selective bladder denervation in women with refractory overactive bladder. MATERIALS AND METHODS: Women with refractory overactive bladder and urgency urinary incontinence were enrolled in 2 prospective feasibility studies with the same entry criteria. They underwent selective bladder denervation of the subtrigonal region containing afferent sensory nerves. Patients were followed for 6 months and assessed for adverse events, overactive bladder symptoms and health related quality of life measures. RESULTS: In the 35 women with a mean age of 66 years who were enrolled in the study all selective bladder denervation procedures were completed successfully. During 6 months of followup the symptom improvement based on 3-day bladder diaries was 59% for urgency urinary incontinence (p <0.001), 59% for urinary incontinence (p <0.001), 39% for urgency (p <0.001), 9% for urinary frequency (p = 0.01) and 27% for the total urgency and frequency score (p <0.001). Most of this treatment benefit was realized in the first month. The rate of clinical success, defined as a 50% or greater reduction in urgency urinary incontinence, was 70%, treatment benefit was reported in 75% of patients and the dry/cure rate was 27%. Statistically significant improvements during 6 months were identified on the symptom bother and health related quality of life scales on the OAB-q (Overactive Bladder Questionnaire) and on all KHQ (King's Health Questionnaire) domains except general health perception. Device or procedure related adverse events were reported in 6 patients (17%). CONCLUSIONS: Pooled results of 2 prospective feasibility studies suggest that selective bladder denervation is a promising minimally invasive treatment option in women with refractory overactive bladder.

Surgery for urinary incontinence in women: Report from the 6th international consultation on incontinence.

Urinary incontinence is a prevalent condition worldwide and causes a tremendous impact on a woman's quality of life. While conservative and non-surgical therapies are options for treatment, surgery for stress urinary incontinence (SUI) is common. Options include colposuspension, slings (pubovaginal and midurethral), and periurethral bulking. While evidence supports each of these options in the treatment of SUI, each is associated with various rates of success and unique adverse event profiles. Urgency urinary incontinence (UUI) is initially treated with behavioral modification and pharmacologic means, with surgery reserved for those with refractory symptoms or significant complications from medication use. At present, intravesical onabotulinumtoxinA injections, percutaneous tibial nerve stimulation, and sacral neurostimulation are all viable options for refractory UUI/overactive bladder. As with surgical interventions for SUI, each of these is, likewise, associated with unique outcomes and adverse event profiles. Herein, we summarize the findings and conclusions from the 6th International Consultation on Incontinence (ICI) regarding surgical treatment of urinary incontinence in women.

Study design and outcomes measures: The influence of composite endpoints and other design variables on outcomes in a study of a novel device for stress urinary incontinence.

OBJECTIVES: To perform a post hoc analysis of the outcome data from a phase III study of a novel incontinence therapy for female stress incontinence (SUI) and to understand the pitfalls inherent to performing trials in SUI. METHODS: Results of the SUCCESS Trial, a multicenter, prospective, single-blinded, randomized, sham-controlled study were assessed post hoc for parameters and variables consistent with changes in the symptoms or signs of SUI. Subjects were randomized to either the investigative device (Vesair Balloon) placement or placebo. The efficacy endpoint analysis herein evaluated a composite of both a >50% reduction from baseline on 1-hour provocative pad weight test and a ≥10-point improvement in symptoms on the Incontinence Quality of Life (I-QOL) questionnaire assessed at the three-month study visit. Further analysis was performed utilizing more challenging success criteria for each endpoint and a subset of subjects with more severe baseline symptoms. RESULTS: The three-month composite efficacy endpoint was achieved in 42.1% of treatment group subjects compared with 28.1% of control subjects on an intention-to-treat analysis (P = .046). This difference between groups was not evident when analyzing each component of the composite endpoint separately. These endpoints diverged from endpoints involving improvement in PGI-I score and a 50% reduction of incontinence episode frequency as reported by subjects on a diary. CONCLUSIONS: Individual endpoints may not demonstrate a significant treatment effect as standalone SUI measures but may as components of a composite endpoint. Defining patient selection and outcomes assessments is a critical aspect of study design, experimental flaws, and therapeutic accuracy.

A Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder (PERSPECTIVE): Rationale, design, and methodology.

INTRODUCTION: Pharmacotherapy of overactive bladder (OAB) typically involves treatment with an antimuscarinic or mirabegron, a ß3-adrenoceptor agonist, but real-world evidence on their use, including treatment access, persistence, and switching, is limited. Here, we describe the design of a prospective, multicenter, non-interventional registry of patients beginning a new course of OAB pharmacological therapy in routine clinical practice. METHODS: Adults with an OAB diagnosis for at least 3 months who either initiated a new course of mirabegron or antimuscarinic, or who switched therapy were enrolled into PERSPECTIVE (a Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder). The primary objective was to identify factors associated with improved OAB treatment effectiveness from a patient perspective. Secondary objectives were to compare persistence rates, reasons for discontinuation, and switching patterns between patients taking mirabegron or antimuscarinics. Healthcare centers and sites involving medical specialties who routinely participate in the care and treatment of patients with OAB (e.g., gynecology, urology, and primary care practices) were targeted for recruitment. Patient-reported outcomes (PROs), including quality of life, symptom bother, and treatment satisfaction from OAB-validated scales, were collected at baseline, months 1, 3, 6, and 12, and when patients switched or discontinued their current OAB medication. CONCLUSIONS: PERSPECTIVE is the first real-world observational study in the United States and Canada on clinical and patient perspectives in OAB management. Recruitment was reflective of centers where patients are treated for OAB to maximize generalizability to the real-world population. TRIAL REGISTRATION: ClinicalTrials.gov, ID number NCT02386072 (date of registration March 6, 2015).