The Urinary Incontinence Treatment Network (UITN) was established in 2000 through a joint initiative of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute of Child Health and Human Development (NICHD). The network consisted of a biostatistical coordinating center and 9 multidisciplinary clinical centers, each with co-principal investigators from both Urology and Urogynecology. The UITN mandate was to design and conduct high impact clinical trials comparing safety and efficacy of treatments for urinary incontinence in women. Additional goals included development of standardized outcome measures and assessment of diagnostic measures used to evaluate urinary incontinence, including preoperative urodynamics.

Between 2001 and 2012, the UITN investigators designed and conducted 4 large randomized controlled trials in which over 2,200 women were randomized. These trials compared treatments for stress urinary incontinence (SUI) and urge urinary incontinence, and assessed the utility of preoperative urodynamics prior to SUI surgery. The 2 surgical trials included extended versions that followed patients for 5 years. The standardized definitions and measurements across all sites provided a unique opportunity to perform secondary analyses of the demographic, clinical and urodynamic variables to better characterize the population of women seeking surgical correction for SUI and to better understand the relationship of these variables to patient outcomes, including efficacy, complications, quality of life and patient satisfaction. The network established processes for designing, conducting and interpreting multicenter urodynamics with high interrater reliability. A brief summary of some of the findings from these studies follows.

The Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr) and its extended followup study (E-SISTEr) found that in women with stress-predominant SUI, the autologous fascial suburethral sling was more efficacious in resolving urinary incontinence, had few surgical retreatments for SUI and yielded higher patient satisfaction rates than the Burch colposuspension at 2 and 5 years.^1,2 However, this increased efficacy was associated with higher rates of urinary tract infection and surgical treatment for voiding dysfunction.³ The SISTEr trial provided the highest level of evidence to date for the 2 most commonly performed procedures for SUI in women. During enrollment of SISTEr, Ward and Hilton had published their landmark study demonstrating similar outcomes between the Burch and the retrobubic midurethral sling (MUS).⁴ By the time the SISTEr results were published, the MUS and its variations had become the most frequently performed surgery for SUI. The UITN investigators designed their next protocol to look more closely at the MUS.

The Trial of Midurethral Slings (TOMUS) randomized 597 women to undergo either a retropubic or transobturator MUS. At 1 year, the 2 procedures were considered equivalent in efficacy, but at 2 and 5 years the difference in efficacy had widened from 3% to 7%, favoring the retropubic approach and no longer meeting the definition of equivalence.^5,6 The 2 approaches differed significantly in the type of complications. The retropubic approach was associated with higher rates of bladder perforation and postoperative voiding dysfunction, while the transobturator approach carried a higher risk of temporary postoperative pain.

SISTEr and TOMUS success rates were significantly lower than the rates reported in the literature at that time. This finding may be related to the use of composite outcome measures, resulting in a stricter definition of success. When the components of the definition were analyzed independently, the failure rates varied widely, highlighting the need for standardized definitions (fig. 1).¹ UITN data demonstrated decreased efficacy over time for all 4 surgical procedures (figs. 2 and 3).^2,6 Interestingly, improvements in quality of life and patients satisfaction decreased at a much slower rate as shown in figure 4 for the SISTEr trial.²

Figure 1. Proportion of patients with treatment failure at 2 years, according to overall composite criteria, composite criteria specific to stress incontinence, and other criteria. Reprinted with permission.¹

Figure 2. Treatment success rates over time for women randomized to Burch colposuspension and pubovaginal rectus fascia sling. Reprinted with permission.²

Figure 3. Treatment success rates over time for women randomized to retropubic and transobturator midurethral sling. Reprinted with permission.²

Figure 4. The percentage of women who reported being satisfied over time in the SISTEr trial. Reprinted with permission.²

The UITN studies provided a wealth of urodynamics data in women with stress-predominant SUI. Over 1,300 patients underwent standardized preoperative and postoperative urodynamics in the SISTEr and TOMUS trials. Through these studies, reference urodynamic values in women with SUI were defined, the relationship between urodynamic variables and efficacy and safety outcomes were described, and a repository of digitally stored urodynamic tracings was created. In this carefully selected population of women with stress-predominant incontinence, preoperative urodynamics were not predictive of incontinence outcomes or postoperative voiding dysfunction.^7,8 The larger question remained unanswered: do urodynamics provide data that lead to better outcomes than an office evaluation alone?

The Value of Urodynamic Evaluation (VaLUE) Trial was designed as a noninferiority trial that randomized 600 women with uncomplicated stress urinary incontinence (defined as SUI or stress-predominant mixed urinary incontinence with no history of SUI surgery) to undergo an office evaluation (post-void residual, urinalysis, urethral mobility assessment, and positive stress test) versus office evaluation and urodynamic testing. The VaLUE study found no difference in treatment success measured by Urinary Distress Inventory and Patient Global Impression of Improvement surveys between the 2 groups.⁹ This Level 1 evidence supporting no preoperative urodynamics in women with uncomplicated SUI leaves urodynamics for the many women with more complicated urinary incontinence.

Urge urinary incontinence treatment was evaluated in the Behavioral and Drug (BE-DRI) trial in which 347 women with urge urinary incontinence were enrolled in a randomized controlled trial with the specific aim to determine whether adding behavioral therapy to antimuscarinic drug therapy improved short-term outcomes of active drug therapy at 10 weeks, and whether reduction of incontinence was sustained after discontinuing drug therapy. The addition of behavioral training to drug therapy reduced incontinence frequency during active treatment but did not improve the ability to discontinue drug therapy and maintain improvement in urinary incontinence.¹⁰

In summary, the UITN trials provide some of the highest level evidence regarding evaluation and treatment of urinary incontinence in women. Rigorous inclusion/exclusion criteria, well-defined outcomes and high statistical power were hallmarks of these trials. The studies were generalizable using multiple sites, with multiple surgeons, including both urogynecologists and urologists.

Multicenter clinical trial networks are expensive and cumbersome. However, the higher levels of evidence obtained in these trials provide patients and their physicians the information needed to make educated decisions based on clear understanding of the risks and benefits of the procedures. The UITN demonstrated that women with urinary incontinence are willing to participate in high quality research needed to answer those questions.