Methods for a multicenter randomized trial for mixed urinary incontinence: rationale and patient-centeredness of the ESTEEM trial

Abstract

Introduction Mixed urinary incontinence (MUI) can be a challenging condition to manage. We describe the protocol design and rationale for the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence (ESTEEM) trial, designed to compare a combined conservative and surgical treatment approach versus surgery alone for improving patient-centered MUI outcomes at 12 months. Methods ESTEEM is a multi-site, prospective, randomized trial of female participants with MUI randomized to a standardized perioperative behavioral/pelvic floor exercise intervention plus midurethral sling versus midurethral sling alone. We describe our methods and four challenges encountered during the design phase: defining the study population, selecting relevant patient-centered outcomes, determining sample size estimates using a patient-reported outcome measure, and designing an analysis plan that accommodates MUI failure rates. A central theme in the design was patient-centeredness, which guided many key decisions. Our primary outcome is patient-reported MUI symptoms measured using the Urogenital Distress Inventory (UDI) score at 12 months. Secondary outcomes include quality of life, sexual function, cost-effectiveness, time to failure and need for additional treatment. Results The final study design was implemented in November 2013 across 8 clinical sites in the Pelvic Floor Disorders Network. As of February 27, 2016, 433 total /472 targeted participants have been randomized. Conclusions We describe the ESTEEM protocol and our methods for reaching consensus for methodological challenges in designing a trial for MUI by maintaining the patient perspective at the core of key decisions. This trial will provide information that can directly impact patient care and clinical decision-making.

The urinary microbiome in women with mixed urinary incontinence compared to similarly aged controls

“…Furthermore, we discouraged participants from engaging in vaginal intercourse/douching/using vaginal sprays or wipes for 48 hours prior to study visits and specimens were collected at least 48 hours following cessation of menses. MUI participants consisted of a subset of women enrolled in a randomized trial of MUI treatment comparing efficacy of mid-urethral sling (MUS) surgery alone to MUS surgery and behavioral therapy (NCT# 01959347) [2]. For this supplementary study, we also recruited controls who were of similar age as the MUI cases, as described in the methods paper [6].…”

“…Women with MUI face a therapeutic dilemma because of the dual nature of their condition; treatment of stress urinary incontinence (SUI) symptoms may exacerbate urgency while treatment of urgency urinary incontinence (UUI) symptoms may worsen SUI. The study, Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence (ESTEEM), was designed to compare stress, urgency and MUI symptom outcomes in an MUI population treated with surgery alone versus surgery and behavioral/pelvic floor therapy [2]. The ESTEEM study’s population provided a singular opportunity to evaluate the urinary microbiome as a biologically plausible contributor to MUI.…”

Methodology for a vaginal and urinary microbiome study in women with mixed urinary incontinence

“…The ESTEEM trial methods have been published previously [11]. The ESTEEM parent trial enrolled women with MUI who reported at least “moderate bother” for both UUI and SUI components of the Urinary Distress Inventory (UDI) questionnaire [12].…”

“…The ESTEEM trial was designed to compare urinary incontinence symptom outcomes in women randomized to a standardized perioperative behavioral/pelvic floor exercise intervention plus midurethral sling versus midurethral sling alone [11]. While ESTEEM interventions are aligned with traditional treatment approaches to SUI and UUI, the ESTEEM population provides a unique opportunity to explore alternative hypotheses regarding the etiology of MUI as well as MUI treatment response.…”

Structured behavioral treatment research protocol for women with mixed urinary incontinence and overactive bladder symptoms

“…The ESTEEM trial was designed to compare a combined conservative and surgical treatment approach versus surgery alone for improving patient‐centered MUI outcomes at 12 months. It is a multi‐site, prospective randomized trial of female patients with MUI randomized to a standardized perioperative behavioral/pelvic floor exercise intervention plus MUS versus MUS alone . Sung and colleagues describe the inclusion and exclusion criteria and primary and secondary outcomes .…”