Diagnostic Value of the Symptoms of Stress UI To Distinguish Urodynamic Stress UI Was Low

The diagnostic value of symptoms of stress incontinence compared to multichannel urodynamics for stress UI was examined in 27 studies of 5,780 patients (Appendix Table F5).^{188,189,191,193,195,197,200,202,203,206,207,209,213,217,228,229,238,244,246,251,253,273,279–283} Sensitivity was more than 70 percent, while specificity varied from 10 to 13 percent^213,273,280 to 79 to 88 percent.^197,238

Pooled sensitivity was 93 percent (95 percent CI, 90 to 95 percent) (Appendix Figure F2). The test was not specific with pooled specificity of 41 percent (95 percent CI, 34 to 49 percent) (Appendix Figure F3). Positive predictive likelihood ratio was small at 1.5 (95 percent CI, 1.4 to 1.7) (Appendix Table F6).

Diagnostic Value of Urgency Symptoms of UI To Distinguish Urodynamic Detrusor Overactivity Was Low

The diagnostic value of the symptoms of urgency UI compared to multichannel urodynamics to distinguish detrusor overactivity was examined in 23 studies of 5,485 patients (Appendix Table F7).^{188,191,195,200,202,203,213,216,217,228,229,238,244,246,251,273,279–281,284} Sensitivity varied across the individual studies from 14 percent²⁸⁰ to more than 90 percent.^{188,216,244,251,279,284} Specificity varied across the individual studies from 21 percent²⁰⁷ to more than 90 percent.^203,280 Pooled sensitivity was 82 percent (95 percent CI, 76 to 87 percent) (Appendix Figure F4) for any detrusor overactivity while pooled specificity was as low as 51 percent (95 percent CI, 44 to 59 percent) (Appendix Figure F5). The positive predictive likelihood ratio was small at 1.5 (95 percent CI, 1.4 to 1.7).

Urgency Symptoms of UI Had a Low Diagnostic Value To Distinguish Pure Detrusor Overactivity

The diagnostic value of the symptoms of urgency UI compared to multichannel urodynamics to distinguish pure detrusor overactivity was examined in 17 studies of 3,924 subjects^{191,195,200,203,206,207,209,211–213,217,228,229,244,251,273,279} (Appendix Table F8). Pooled sensitivity was 84 percent (95 percent CI, 78 to 89 percent) (Appendix Figure F6). Pooled specificity was as small as 43 percent (95 percent CI, 36 to 50 percent) (Appendix Figure F7). The positive predictive likelihood ratio was small at 1.5 (95 percent CI, 1.3 to 1.7) (Appendix Table F9).

Urgency Symptoms Alone, With, or Without UI Had a Minimal Diagnostic Value in Distinguishing Detrusor Overactivity in Women

The diagnostic value of urgency symptoms with or without UI compared to multichannel urodynamics to distinguish detrusor overactivity was examined in nine studies of 6,418 patients^{202,206,209,213,217,229,247,279,284} (Appendix Table F10). Pooled sensitivity was 84 percent (95 percent CI, 59 to 95 percent) (Appendix Figure F8). Pooled specificity was as low as 39 percent (95 percent CI, 17 to 67 percent) with substantial heterogeneity across the studies (Appendix Figure F9). The positive likelihood ratio was also low at 1.36 (95 percent CI, 1.2 to 1.6) (Appendix Table F11).

Urgency Symptoms Had Minimal Diagnostic Value to Distinguish Pure Detrusor Overactivity in Women

The diagnostic value of urgency symptoms with or without UI compared to multichannel urodynamics to distinguish pure detrusor overactivity was examined in six studies of 1,598 subjects^{206,209,213,217,229,279} (Appendix Table F12). Pooled sensitivity was 86 percent (95 percent CI, 83 to 89 percent) (Appendix Figure F10). Pooled specificity was as low as 31 percent (95 percent CI, 24 to 39 percent) (Appendix Figure F11). The positive likelihood ratio was also low at 1.21 (95 percent CI, 1.1 to 1.3) (Appendix Table F13).

Mixed Symptoms Had Minimal Diagnostic Value for Urodynamic Criteria of Mixed UI

The diagnostic value of mixed UI symptoms compared to multichannel urodynamics for mixed UI was examined in 11 studies of 2,767 subjects^{191,195,199,200,203,207,228,244,246,251,273} (Appendix Table F14). Pooled sensitivity was 73 percent (95 percent CI, 61 to 82 percent) (Appendix Figure F12). Pooled specificity was as low as 53 percent (95 percent CI, 40 to 66 percent) (Appendix Figure F13). Positive likelihood ratio was also low at 1.5 (95 percent CI, 1.3 to 1.7) (Appendix Table F15). Sensitivity and specificity differed across individual studies. Quality of the studies was not associated with differences in sensitivity or specificity. The results were similar after pooling with random effects models that incorporated heterogeneity across the studies in pooled estimates and bivariate pooling as recommended in cases of detected heterogeneity (Table 3).

Table 3

Diagnostic value of the test for UI in women (pooled with random effects models and bivariate pooling).

Diagnostic Value of Pad Tests Compared to Multichannel Urodynamics

The diagnostic value of a 1-hour pad test compared to multichannel urodynamics for stress UI was examined in three studies of 574 women^207,271,275 (Appendix Table F16). Pooled sensitivity was 84 percent (95 percent CI, 76 to 90 percent) (Appendix Figure F14). Pooled specificity was 77 percent (95 percent CI, 72 to 82 percent) (Appendix Figure F15). The positive likelihood ratio was below 5 (3.6, 95 percent CI, 2.9 to 4.6), pointing out a small increase in the likelihood of urodynamic stress UI in women with positive pad tests (Appendix Table F17).

The diagnostic value of a 1-hour pad test compared to multichannel urodynamics for detrusor overactivity was examined in two studies of 469 subjects. Sensitivity varied in studies with pooled estimates of 72 percent (95 percent CI, 30 to 94 percent)^271,275 (Appendix Figure F16). Pooled specificity was as low as 56 percent (95 percent CI, 38 to 72 percent) (Appendix Figure F17). The positive likelihood ratio was as small as 1.56 (95 percent CI, 0.6 to 3.9) (Appendix Table F18).

Diagnostic Value of Symptoms of UI to Clinical Diagnosis

Clinical diagnosis of UI was based on history, physical examination, pelvic examination, urine culture, Q-tip test, diary, cytometry,²¹⁸ cough stress test, 48-hour home pad test,²⁵⁹ and measurement of postvoid residual volume (by catheter or ultrasonography).^223,266

Women With Urgency Symptoms Had a Small Likelihood of a Clinical Diagnosis of Detrusor Overactivity

The diagnostic value of urgency UI symptoms compared to clinical diagnosis for any detrusor overactivity was examined in four studies of 735 subjects^{218,223,259,266} (Appendix Table F19). Pooled sensitivity was 82 percent (95 percent CI, 73 to 89 percent) (Appendix Figure F18). Pooled specificity was 67 percent (95 percent CI, 53 to 79 percent) (Appendix Figure F19). The positive likelihood ratio was above 2 (2.5, 95 percent CI, 1.8 to 3.5) (Appendix Table F20).

Women With Symptoms of Stress UI Had a Minimal Likelihood of a Clinical Diagnosis of Stress UI

The diagnostic value of symptoms of stress UI compared to a clinical diagnosis of stress UI was examined in five studies of 947 subjects^{218,223,259,266,285} (Appendix Table F19). Pooled sensitivity was 88 percent (95 percent CI, 68 to 96 percent) (Appendix Figure F20). Pooled specificity was 67 percent (95 percent CI, 54 to 78 percent) (Appendix Figure F21). The positive likelihood ratio was above 2 (2.4, 95 percent CI, 2.0 to 2.8) (Appendix Table F21). The diagnostic value of symptoms of mixed UI compared to clinical diagnosis of mixed UI was examined in three studies of 654 subjects. Pooled sensitivity was 65 percent (95 percent CI, 36 to 86 percent) (Appendix Figure F22). Pooled specificity was 54 percent (95 percent CI, 21 to 84 percent) (Appendix Figure F23). The positive likelihood ratio was as small as 1.6 (95 percent CI, 0.7 to 3.6) (Appendix Table F22).

Women With Urgency Symptoms Had a Minimal Likelihood of Having a Clinical Diagnosis of Pure Detrusor Overactivity

The diagnostic value of urgency UI symptoms compared to clinical diagnosis for pure detrusor overactivity was examined in two studies of 551 women (Appendix Table F23). Pooled sensitivity was 70 percent (95 percent CI, 43 to 88 percent) (Appendix Figure F24). Pooled speicificty was 55 percent (95 percent CI, 28 to 79 percent) (Appendix Figure F25). The positive likelihood ratio was as small as 1.6 (95 percent CI, 0.6 to 4.2) (Appendix Table F24).

Individual studies reported diagnostic values of the tests that did not meet pooling criteria (Table 3). One study of 488 women analyzed diagnostic value of the symptoms reported in mailed questionnaires compared to multichannel urodynamics.²⁵⁸ Questionnaires had a minimal diagnostic value for stress (positive likelihood ratio=1.8) and urgency (positive likelihood ratio=1.8) UI.

Diagnostic Value of Complex Clinical Algorithms

The diagnostic values of complex clinical algorithms were high and varied depending on components of algorithms and reference methods to diagnose UI.

Diagnostic Value of a Clinical Algorithm Versus Urodynamics

Diagnostic value of complex clinical algorithms for UI was high when compared to urodynamic evaluation. Two studies examined diagnostic value of algorithms for stress UI. One study of 1,455 women examined diagnostic value of a clinical algorithm versus urodynamics. Included subjects had predominant symptoms of stress UI with more than four episodes of UI per week, normal diurnal and nocturnal frequency, a bladder capacity of 400 ml or greater, and a positive cough stress (sign of stress UI) and stress pad test.²⁵⁴ The authors reported positive predictive values of 90.2 percent for urodynamic stress UI and 76.9 percent for pure urodynamic stress UI.²⁵⁴ Diagnostic accuracy was the same across age categories and among those with previous surgery for stress UI.²⁵⁴ The authors did not report positive predictive likelihood of the clinical algorithm. Another study of 652 women examined the diagnostic value of a clinical algorithm that required the presence of a predominant complaint of stress UI, positive cough stress test results, postvoid residual urine volume of no more than 50 ml, and a functional bladder capacity of at least 400 ml as determined by a completed 24-hour frequency volume chart.²³⁰ This study also used urodynamics as a reference standard test. The algorithm had a positive predictive value of 97 percent when compared to multichannel urodynamics to diagnose stress UI.²³⁰

One study examined diagnostic value of algorithms for urgency UI. The diagnosis of pure detrusor overactivity was accurate when compared to urodynamics in scoring frequency, urgency, nocturia, and self-reported urgency UI.^276,277 The algorithm demonstrated good diagnostic value with a positive predictive likelihood ratio of 12.6 and a diagnostic odds ratio of 27.3. The same study proposed scoring of urodynamic stress UI based on self-reported frequency of incontinent episodes and the amount of protection.^276,277 The diagnostic value of such composite scores was moderate with a positive predictive likelihood ratio of 3.8 and a diagnostic odds ratio of 11.

Diagnostic Value of Clinical Algorithms Based on the Epidemiology of a Pelvic Organ Prolapse and Incontinence Questionnaire When Compared to Clinical Diagnosis

This comparison was tested in one study of 110 women.²⁶² The questionnaire had a moderate likelihood of identifying women with detrusor overactivity (positive likelihood ratio=7.7) and a large likelihood of identifying women with stress UI (positive likelihood ratio=19).²⁶² One study demonstrated moderate diagnostic value of the Three Incontinence Questions Questionnaire (3IQ) when compared to clinical diagnosis in 301 women to detect those with stress or urgency UI.²⁶⁶

Diagnostic Values of Individual Tests When Compared to Urodynamics

In individual studies, other examined tests using urodynamics as a reference standard, including the Q-tip test,^208,286 UDI-6,^244,287 questionnaire for urinary incontinence diagnosis (QUID) stress score,²⁸⁸ or Bristol Female Lower Urinary Tract Symptoms Questionnaire,²⁵³ demonstrated minimal diagnostic value for UI with positive predictive likelihood ratios less than 2 (Table 3). The studies of the Gaudenz questionnaire reported different results depending on the country where the study was conducted.^220,238

Diagnostic Values of Ultrasound Versus Urodynamics as a Reference Standard

The diagnostic values of ultrasound using urodynamics as a reference standard were examined in five studies of 540 women.^289–293 Perineal ultrasound had a small diagnostic value with a positive predictive likelihood ratio of 3 for urodynamic stress UI.²⁸⁹ Vaginal ultrasound had a moderate diagnostic value with a positive predictive likelihood ratio of 5.3 for urodynamic stress UI.²⁹³ Transrectal ultrasound that detected a decreased angle of UV junction demonstrated a large and conclusive increase in the likelihood of urodynamic stress UI.^291,292

Comparison of Diagnostic Values of Different Tests

The majority of studies demonstrated that the tests had only small diagnostic value in distinguishing women with urodynamic stress or urgency UI. Complex clinical algorithms demonstrated better diagnostic performance. Individual studies suggested a good diagnostic value of the epidemiology of prolapse and incontinence questionnaires. Post-test probability of mixed or urgency UI increased in aging women.²⁹⁴

We compared the accuracy of diagnostic tests for different types of UI across studies (Table 3). Urodynamic stress UI was accurately diagnosed in 80 percent of women using 1-hour pad test, and in 75 percent of women using self-reported symptoms of stress UI (Figure 3). Urge symptoms accurately diagnosed urodynamic urgency UI in 66 percent of women. Pad tests accurately diagnosed urodynamic urgency UI in 61 percent of women. Accuracy of the symptoms of mixed UI to diagnose urodynamic stress UI combined with detrusor overactivity was low (56 percent). Clinical diagnosis of stress UI was accurately detected with self-reported symptoms of stress UI in 80 percent of women. Clinical diagnosis of detrusor overactivity was accurately detected with self-reported symptoms of urgency UI in 73 percent. The pooled diagnostic odds ratio demonstrated the same pattern with the best discriminatory performance of symptoms of stress UI and pad test when compared to urodynamic diagnosis of stress UI (Figure 4). The diagnostic odds ratio was the more than 10 for the symptoms for stress and urgency UI when compared to a clinical diagnosis.

Figure 3

Accuracy of diagnostic methods for female UI (pooled with random effects model results).

Figure 4

Diagnostic odds ratio of diagnostic methods for female UI (pooled with random effects model results).

We also compared predictive values of diagnostic tests for different type of UI across the studies (Table 4). The predictive values in ambulatory settings depend on prevalence of UI in community dwelling women.¹⁶⁷ Positive predictive values were less than 50 percent for most comparisons while negative predictive values were larger than 90 percent. Positive predictive value of the symptoms of mixed UI and urgency UI increased with age. The majority of women without symptoms of UI did not have clinical diagnosis of UI.

Table 4

Predictive value of diagnostic tests for different types of UI by age subgroups.

Clinical Effectiveness of Topical Estrogen Therapy

Evidence from individual RCTs indicated greater continence and improvement in UI with vaginal estrogen formulations and worsening of UI with transdermal patches (Appendix Table F29). Evidence was insufficient to draw conclusions about clinical efficacy of different topical estrogen treatments for UI.

Four RCTs of 640 women examined the effects of topical estrogen formulations compared to placebo on UI (Appendix Table F27). The studies enrolled postmenopausal women with urodynamic stress,^379,380 clinical symptoms of any UI,³⁸¹ clinical symptoms of any UI,³⁸¹ or with urge syndrome.³⁸² Estrogen was administered in vaginal tablets, gel,³⁷⁹ subcutaneous implants,³⁸² intravaginal ovules,³⁸⁰ or transdermal patches.^380,381 The length of treatment varied from 6 months³⁷⁹ to 2 years.³⁸¹ Three studies aimed to treat UI.^379,380,382 One study examined very low dose transdermal estrogen formulation proposed for prevention of osteoporosis in postmenopausal women.³⁸¹

Clinical Effectiveness of Duloxetine

A high level of evidence indicated significant improvement in stress UI with duloxetine, while a low level of evidence suggested that duloxetine did not resolve stress UI when compared to placebo. A low level of evidence suggested improvement in quality of life in women with UI. Evidence was insufficient to conclude benefits of duloxetine in women with urgency UI. The risk of adverse effects was significantly higher with duloxetine than with placebo. Duloxetine resulted in improved UI in 75 to 140 women per 1,000 treated,^{319,364,383–387} while 129 women per 1,000 treated stopped taking duloxetine because of adverse effects.

The 24 publications that reported clinical outcomes with duloxetine^{250,319,364,383–404} included six primary RCTs of 4,292 women,^{319,383,386,387,401,402} collaborative publications from the DESIRE Study group (3,983 subjects),³⁸⁸ Duloxetine Dose Escalation Study Group (516 subjects), ³⁸⁹ Duloxetine OAB Study Group (306 subjects),³⁸⁵ Duloxetine Urinary Incontinence Study Group (2,741 patients),^{250,384,390–392} Duloxetine/Pelvic Floor Muscle Training Clinical Trial Group (201 subjects), pooled analyses of individual patient data (52,891 subjects),^{364,396–400,404} safety evaluation using pooled analysis of 42 placebo-controlled clinical trials of 8,504 patients⁴⁰³ (Appendix Table F27), and nonrandomized prospective observational studies^394,395 (Appendix Table F33).

Improvement in UI

Women experienced more than a 50 percent reduction in the frequency of UI episodes with duloxetine^{319,364,384,386,387} (Appendix Table F36). More women perceived an improvement in UI as either much better or better with duloxetine than with placebo^{319,383–385} (Appendix Table F36). Seven women had to take duloxetine to achieve a 50 percent reduction in UI episodes in one woman (Table 6). Thirteen women (NNT 13, 95 percent CI, 7 to 143) needed to be treated so one woman would perceive an improvement as either much better or better. Improvement in UI was greater with 40 mg/day compared to 20 mg/day³⁹⁰ (Appendix Table F37). Treatment failure did not differ between duloxetine and placebo^{319,383,385,402} (Appendix Table F38).

Table 6

Clinical outcomes with duloxetine treatments (pooled with random effects estimates from head-to-head RCTs).

Improvement in quality of life measures with duloxetine was inconsistent across the studies. Quality of life was examined in eight studies of 5,001 women^{319,364,384–386,390,391,398} (Appendix Table F39). Pooled analysis of two RCTs of 1,133 women with predominant stress UI demonstrated improved Incontinence Quality of Life scores using 80 mg of duloxetine.³⁶⁴ The Multinational Duloxetine UI Study Group found significant improvement in quality of life in North American women,³⁹¹ with no benefit for women in other continents.³⁸⁴ One study indicated significant dose response improvements in the Incontinence Quality of Life questionnaire with 40 mg compared to 20 mg of duloxetine/day.³⁹⁰ Women with severe stress UI³¹⁹ and women with overactive bladder did not experience better quality of life with duloxetine³⁸⁵ compared to placebo.

Clinical Effectiveness of Oxybutynin

A high level of evidence indicated that oxybutynin increased continence rates and improved UI more often than placebo but also resulted in treatment discontinuation due to adverse effects (see Table ES2 in the Executive Summary). Dry mouth was the most common adverse effect. Oxybutynin resulted in resolved UI in 114 women per 1,000 treated, while 63 women per 1,000 treated stopped taking oxybutynin because of adverse effects. Evidence was insufficient to conclude improved quality of life with oxybutynin. A low level of evidence indicated greater rates of adverse effects and dry mouth with immediate release oxybutynin than with controlled release oral or transdermal oxybutynin. A low level of evidence indicated that larger versus lower doses of extended oxybutynin resulted in greater improvement in UI and the same rates of dry mouth, but greater treatment withdrawal.

We identified 15 publications of individual RCTs,^{115,310,322,405–416} one RCT of intravesicular injection of oxybutynin in 52 women,⁴¹⁷ one post hoc analysis of RCTs,⁴¹⁸ and 10 RCTs that compared different doses and formulations of oxybutynin^419–428 (Appendix Table F27). We also reviewed a noncontrolled Ditropan XL study of 256 women,⁴²⁹ a Multicentre Assessment of Transdermal Therapy in Overactive Bladder With Oxybutynin (MATRIX) study of 2,888 women, pooled analysis of dosing studies,^323,430,431 and five observational studies of harms and discontinuation rates of oxybutynin therapy^432–436 (Appendix Table F33).

Continence

Urinary continence was greater with oxybutynin than with placebo^{409,413,416,437,438} (Appendix Table F47). Pooled results were consistent with nonsignificant heterogeneity across the studies despite differences in populations and doses of the drug. The pooled results, however, were sensitive to one multicenter study at 76 clinics in the United States that demonstrated significant increase in resolved UI with oxybutynin.⁴¹³ The drug needed to be given to nine women to achieve continence in one woman (Table 7).

Table 7

Continence, improvement in UI, treatment failure, and adverse effects with pharmacological interventions compared to placebo (pooled with random effects estimates from head-to-head RCTs).

Clinical Effectiveness of Tolterodine

A high level of evidence indicated increased continence rates and significant improvement in UI with tolterodine treatments than with placebo in women with UI (see Table ES2 in the Executive Summary). A low level of evidence indicated improvement in quality of life with tolterodine treatment. Adverse effects including autonomic nervous system disorders, abdominal pain, dry mouth, dyspepsia, and fatigue were significantly more common with tolterodine than with placebo. Per 1,000 women treated, tolterodine resulted in resolved UI in 85 women, and resulted in adverse effects in 83 women. Discontinuation of the treatment and stopping treatment due to adverse effects did not differ between tolterodine and placebo.

We identified 24 RCTs that examined clinical outcomes with tolterodine versus placebo,^{309,312,314,317,321,343,448–465} publications of secondary data analyses,^87,466–468 multicenter nonrandomized clinical trials,⁴⁶⁹ including the IMPACT study (Appendix Table F27)^470–472 and several noncontrolled observational studies of harms with tolterodine treatments (Appendix Table 33).^473–476

Adverse Effects

Adverse effects were more common with tolterodine than with placebo^{309,312,321,322,343,449,450,453,457,460,465,477} (Appendix Table F47). Active drugs needed to be given to 12 women in order cause adverse effects in one woman (Table 7). Half of the women experienced adverse effects with 4 mg/day of tolterodine in the IMPACT noncontrolled study.^470–472 According to pooled analysis of the aggregate data,^{309,448,450–452} and one pooled analysis of individual patient data, women did not have serious adverse effects more often with tolterodine than with placebo.⁸⁷ The same pooled analysis, however, reported that dose reduction in the case of intolerance was more common with 2 mg twice/day of tolterodine than with placebo⁸⁷ (Appendix Table F52). The rates of all^449,453 or serious adverse effects with different doses and formulations of tolterodine did not differ^451,452 (Appendix Table F53).

Among individual adverse effects, tolterodine significantly increased rates of autonomic nervous system disorders,^448–450 constipation,^{321,449,451–453,455,457,458,477,478} dyspepsia,^{309,322,343,451,452,455,457} and fatigue^309,460,463 (Table 8). Tolterodine also increased rates of abdominal pain.^{309,451–453,455,457} Pooled analysis of individual patient data demonstrated greater rates of abdominal pain,⁴⁵⁶ autonomic nervous system disorder,⁸⁷ fatigue,^88,468 and dry mouth^88,456,468 (Appendix Table F52). Autonomic nervous system disorder was less common with 1 mg twice daily versus 2 mg daily.^87,448 Differences in adverse effects of different doses and formulations of tolterodine were not consistent across the individual studies and pooled data from individual patients (Appendix Table F53). Tolterodine caused dry mouth in one woman among seven treated according to our pooled analysis (Table 7).^{309,312,313,321,322,343,451,453,460,461,463,465,477,478} Increases in the rates of dry mouth were not greater with higher doses of tolterodine (p value for meta-regression >0.5).

Table 8

Rates of adverse effects after drugs vs. placebo (significant differences only, pooled with random effects estimates from head-to-head RCTs).

Treatment discontinuation rates^{309,450,451,454,458,460–462,477,478} and treatment discontinuation due to adverse effects did not differ between tolterodine and placebo^{309,313,321,322,450,452,453,457,458,460,461,463,478} (Table 7). Pooled analyses also demonstrated no differences in discontinuation rates between 2 mg of tolterodine twice daily⁸⁷ and 4 mg of tolterodine once daily⁴⁶⁸ (Appendix Table F52). One pooled analysis reported that treatment discontinuation was lower with 1 mg twice daily than with 2 mg daily of tolterodine (Appendix Table F53). Treatment discontinuation due to adverse effects did not differ in individual RCTs⁴⁵³ and in pooled analyses of individual patient data from RCTs that examined 2 mg of tolterodine twice ^450,452,453 or 4 mg daily^457,458,460 (Appendix Table F54).

Clinical Effectiveness of Darifenacin

A high level of evidence indicated significant improvement in urgency UI episodes and several domains of quality of life with 7.5 and 15 mg of darifenacin compared to placebo. Adverse effects were more common with darifenacin than with placebo. Darifenacin increased rates of constipation, dry mouth, dyspepsia, and headache. Darifenacin improved UI in 117 women per 1,000 treated while 190 women per 1,000 treated experienced various adverse effects. Evidence was insufficient from which to conclude better benefits with 30 mg of darifenacin/day. The largest dose, however, resulted in greater rates of adverse effects. Treatment discontinuation rates due to adverse effects were the same between darifenacin and placebo.

Seven RCTs reported clinical outcomes of darifenacin versus placebo^{306,307,311,479–483} and several publications of secondary data analyses^484–489 (Appendix Tables F27 and F28).

Clinical Effectiveness of Solifenacin

A high level of evidence suggested that solifenacin increased continence rates with greater benefits with the larger dose of the drug in women with urgency and mixed UI. Evidence was insufficient that solifenacin improved quality of life. A high level of evidence suggested greater risk of dry mouth, constipation, and blurred vision with the drug. A high level of evidence suggested that 10 mg of solifenacin increased the risk of severe dry mouth and constipation. Treatment discontinuation due to adverse effects was more common with solifenacin than with placebo. Solifenacin resolved UI in 107 women per 1,000 treated, while 13 women per 1,000 treated stopped taking the drug because of adverse effects.

We identified nine publications of individual RCTs^{477,478,490–496} and pooled analysis of individual patient data from four RCTs^497–499 that examined clinical outcomes with solifenacin compared to placebo (Appendix Table F27). We also reviewed the results from the nonrandomized VOLT flexible-dosing trial (VESIcare Open-Label Trial) that examined quality of life in subjects with OAB and urgency UI at 207 centers in the United States.^500,501

Clinical Effectiveness of Fesoterodine

A low level of evidence indicated a significant increase in continence with fesoterodine. A high level of evidence indicated a significant improvement in urgency UI with fesoterodine compared to placebo, with a better response with 8 mg versus 4 mg. Evidence was low that fesoterodine improved quality of life in women with urgency UI. Fesoterodine treatment resulted in higher rates of adverse effects and related discontinuation of treatment than placebo. Adverse effects were more common with 8 mg than with 4 mg of fesoterodine. Women experienced dry mouth and severe dry mouth with fesoterodine more often than with placebo, with a greater risk with the larger dose of the drug. Fesoterodine resolved UI in 130 women per 1,000 treated, while 31 women per 1,000 treated stopped taking the drug because of adverse effects.

Nine publications of RCTs^{309,313,316,460,461,503–506} and four publications of individual patient data analyses^{88,468,507,508} reported clinical outcomes with fesoterodine compared to placebo (Appendix Table F27). All RCTs were double blinded (Appendix Table F28).

Clinical Effectiveness of Trospium

A high level of evidence indicated increased continence rates with trospium compared to placebo. Individual RCTs found that trospium improved quality of life. Women experienced dry mouth, dry eye, dry skin, and constipation more often with the drug than with placebo. Adverse effects resulted in treatment discontinuation with the drug more often than with placebo. Trospium resolved UI in 114 women per 1,000 treated, while 18 women per 1,000 treated stopped taking the drug because of adverse effects.

Eight publications of RCTs,^{308,325,329,330,509–512} two publications of the Trospium Study Group,^513,514 and one pooled analysis of individual patient data from two RCTs⁵¹² examined the effects of trospium on clinical outcomes compared to placebo (Appendix Table F27).

Clinical Effectiveness of Propiverine

A low level of evidence indicated that propiverine resolved UI. A moderate level of evidence indicated that propiverine improved urgency UI and increased the risk of adverse effects, including abnormal vision, constipation, and dry mouth in a dose responsive manner. Propiverine resolved UI in 163 women per 1,000 treated, while 34 women per 1,000 treated stopped taking the drug because of adverse effects.

Five RCTs examined clinical outcomes of propiverine compared to placebo or to different doses of the drug^{320,502,516–518} (Appendix Tables F27 and F28).

Clinical Effectiveness of Botulinum Toxin

A high level of evidence suggested a reduction in UI episodes due to treatment with botulinum toxin, with an increased risk of elevated post-void residual in patients with severe urgency UI refractory to antimuscarinic drugs.

Four RCTs of 185 subjects reported clinical outcomes after intravesicular injection of botulinum toxin^{315,519–521} (Appendix Table F27). We found one systematic review of the literature about the efficacy and safety of botulinum toxin in the management of OAB.⁵²²

Clinical Effectiveness of Resiniferatoxin

Evidence on the benefits and harms of resiniferatoxin versus placebo in women with urgency UI was insufficient for definitive conclusion about benefits and harms with the drug.

A single RCT enrolled 58 women with idiopathic detrusor overactivity and urgency incontinence to examine clinical outcomes of resiniferatoxin versus placebo (Appendix Table F27).⁵²⁴ The study did not demonstrate benefits of resiniferatoxin versus placebo⁵²⁴ (Appendix Table F67). The rates of the expected adverse effects, including hypogastric pain, dysuria, and minor hematuria, did not differ between resiniferatoxin and placebo.⁵²⁴

Clinical Effectiveness of Nimodipine

Evidence was insufficient for the benefits or harms of nimodipine compared to placebo in older women with predominant urgency UI.

A single RCT enrolled 86 older adult women with urodynamic urgency UI and without clinically important stress UI to examine outcomes after 3 weeks of 30 mg nimodipine twice daily or placebo⁵²⁵ (Appendix Table F27). Nimodipine reduced incontinent episodes but did not improve IIQ scores and American Urological Association symptom scores (Appendix Table F68). Treatment discontinuation did not differ between nimodipine and placebo.⁵²⁵

Comparative Effectiveness of Topical Estrogen on Stress UI

Evidence was insufficient to determine whether an estrogen releasing intravaginal ring was more effective in resolving and improving UI than a pessary or to determine whether an intravaginal tablet was more effective than intravaginal estrogen cream (Appendix Table F69).

Two RCTs of 291 women compared different estrogen formulations (Appendix Table F27).^526,527 The studies enrolled postmenopausal women with lower urinary tract symptoms including UI.^526,527 The first study compared an intravaginal tablet with intravaginal conjugated estrogen cream administered for 8 weeks.⁵²⁶ The second study compared an estrogen releasing ring with an estrogen pessary administered for 24 weeks.⁵²⁷ Continence rates did not differ between the intravaginal tablet and the intravaginal cream⁵²⁶ (Appendix Table F70). Women treated with an estrogen releasing ring did not experience urgency UI more often than those treated with a pessary.⁵²⁷ The rates of resolved stress UI did not differ between estrogen rings and pessaries.⁵²⁷ Women were satisfied with the estrogen ring more often than with the estrogen pessary.⁵²⁷

An estradiol vaginal ring and oral oxybutynin demonstrated similar effects in decreasing the number of daily voids in postmenopausal women with overactive bladder.⁵²⁸ Quality of life score did not differ with two drugs.⁵²⁸ Women experienced constipation and dry mouth more often with oxybutynin than with an estrogen ring.⁵²⁸ Bothersome adverse effects leading to treatment discontinuation did not differ between the drugs.⁵²⁸

Comparative Effectiveness of Darifenacin and Oxybutynin on Urgency UI

Evidence was insufficient from which to conclude comparative effectiveness between darifenacin and oxybutynin on continence or improved UI. A low level of evidence indicated lower rates of total adverse effects and dry mouth with darifenacin, with no differences in adverse effects leading to treatment discontinuation.

Two RCTs^446,529 compared clinical outcomes of oxybutynin and darifenacin.

Adverse Effects

Darifenacin was safer than oxybutynin. Total rates of adverse effects were lower with darifenacin than with oxybutynin⁵²⁹ (Appendix Table F71). Rates of dry mouth were lower with darifenacin than oxybutynin.⁴⁴⁶ Severe dry mouth was less common with 7.5 mg/day of darifenacin than with 7.5mg/day of oxybutynin, and lower with 15 mg/day of darifenacin than with 15 mg/day of oxybutynin⁵²⁹ (Appendix Table F72). Only one adverse effect, constipation, was more common with 30 mg of darifenacin than with 15 mg of oxybutynin⁵²⁹ (Appendix Table F73). Discontinuations from the study due to treatment-related adverse effects were lower with darifenacin than with oxybutynin in one RCT⁴⁴⁶ (Appendix Table F74). Pooled analysis of two RCTs found no significant differences between the two drugs in adverse effects leading to treatment discontinuation (Table 9).

Table 9

Discontinuation due to adverse effects with pharmacological treatments for urgency UI (pooled with random effects estimates from head-to-head RCTs).

Comparative Effectiveness of Oxybutynin and Tolterodine on Urgency UI

Evidence was insufficient from which to draw conclusions about comparative effectiveness between oxybutynin and tolterodine on continence. A moderate level of evidence indicated no difference between the drugs for UI improvement. A high level of evidence indicated more frequent treatment discontinuation due to adverse effects with oxybutynin than with tolterodine. Women experienced dry mouth and several other adverse effects more often with oxybutynin than with tolterodine. Thus, the drugs offered equal benefits, but tolterodine resulted in fewer harms.

We identified 15 publications that compared clinical outcomes of oxybutynin and tolterodine,^{87,322,408,411,441,442,450,530–537} including secondary data analyses,^87,535,536 OBJECT Study group,⁵³⁰ OPERA Study group (Overactive bladder: Performance of Extended Release Agents),⁵³³ Transdermal Oxybutynin Study Group,⁴¹¹ and Japanese and Korean Tolterodine Study Group⁴⁴¹ (Appendix Table F27).

Continence

Urinary continence was reported in the OPERA trial of 790 women.⁵³³ Ten mg/day of oxybutynin, compared to 4mg/day of tolterodine, resulted in greater rates of continence⁵³³ (Appendix Table F75). Drugs had to be given to 16 women to achieve continence in one (Table 10).

Table 10

Continence with pharmacological treatments for urgency UI.

Improvement in UI

We found no difference between the two drugs^322,441,531 (Figure 5). Treatment-related rates of improved bladder condition did not differ between the two drugs in a pooled analysis of individual patient data from four RCTs⁸⁷(Appendix Table F76).

Figure 5

Comparative effectiveness of oxybutynin vs. tolterodine (pooled results from individual RCTs).

Comparative Effectiveness of Propiverine and Oxybutynin on Urgency UI

Evidence was insufficient from which to draw conclusions about comparative effectiveness and safety of propiverine and oxybutynin.

One RCT compared clinical outcomes of propiverine and oxybutynin.⁴³⁹

Improvement in UI and subject satisfaction did not differ between the two drugs (Appendix Table F76). Total adverse effects did not differ between the two drugs (Appendix Table F71). Fewer subjects experienced severe dry mouth with propiverine than with oxybutynin.⁴³⁹ No studies compared rates of treatment discontinuation due to adverse effects between the two drugs.

Comparative Effectiveness of Flavoxate and Oxybutynin on Urgency UI

Evidence was insufficient from which to draw conclusions about comparative effectiveness and safety of flavoxate and oxybutynin.

A single RCT of 100 subjects compared clinical outcomes of 1,200 mg/day of flavoxate hydrochloride and 15mg/day of oxybutynin.⁵³⁸ Neither urinary continence nor improvement in UI differed between the two drugs⁵³⁸ (Appendix Tables F75 and F76). Neither treatment failure with worsening of UI nor total number of adverse effects differed between the two drugs.⁵³⁸ Rates of dry mouth and dry eyes were significantly lower with flavoxate than with oxybutynin. Nausea was also significantly less common with flavoxate than with oxybutynin.⁵³⁸

Comparative Effectiveness of Tolterodine and Propiverine on Urgency UI

Evidence was insufficient from which to draw conclusions about comparative effectiveness and safety of propiverine and tolterodine.

We identified one RCT of 202 patients treated with 15 mg of propiverine twice daily or 2 mg of tolterodine twice daily.⁵³⁹ No studies compared continence and improvement in UI with the two drugs.⁵³⁹ Improvement in urodynamic criteria of detrusor overactivity did not differ between the two drugs.⁵³⁹ Both drugs improved quality of life scores without significant differences between them. The rates of total adverse effects did not differ between the two drugs (Appendix Table F71).

Comparative Effectiveness of Tolterodine and Fesoterodine on Urgency UI

A low level of evidence indicated greater continence rates with fesoterodine than with tolterodine. A high level of evidence indicated greater rates of improvement in UI with fesoterodine than with tolterodine. A moderate level of evidence indicated higher rates of adverse effects that led to treatment discontinuation with fesoterodine than with tolterodine.

Six publications of RCTs compared clinical outcomes of fesoterodine and tolterodine.^{88,309,313,460,461,468}

Comparative Effectiveness of Solifenacin and Tolterodine on Urgency UI

Comparative effectiveness evidence was insufficient for solifenacin and tolterodine. A moderate level of evidence indicated that adverse effects leading to treatment discontinuation did not differ between the two drugs.

Six publications of RCTs compared clinical outcomes of solifenacin and tolterodine,^{114,477,478,541–543} including the Solifenacin and Tolterodine as an Active comparator in a Randomized STAR study group that compared clinical outcomes of 5 or 10 mg of solifenacin and 4 mg of extended-release tolterodine.^541,542 The studies examined different doses of the drugs on a variety of outcomes that hampered the synthesis of evidence.

Comparative Effectiveness of Solifenacin and Darifenacin on Urgency UI

Evidence was insufficient from which to conclude comparative effectiveness and safety of solifenacin and darifenacin.

One unpublished RCT, the Solidair study, compared solifenacin and darifenacin.⁵⁴⁴

No studies compared continence and improvement in UI with solifenacin and darifenacin.

The Solidair study found that women taking solifenacin had to increase the dose of the drug more often than women taking darifenacin.⁵⁴⁴ The Solidair study found that the rates of treatment discontinuation due to adverse effects did not differ between solifenacin and darifenacin.

Comparative Effectiveness of Solifenacin and Oxybutynin on Urgency UI

Evidence was insufficient from which to conclude comparative effectiveness and safety of solifenacin oxybutynin.

A single RCT, the VECTOR trial, compared 5 mg solifenacin once daily versus 5 mg oxybutynin immediate release three times daily.⁵⁴⁵ Both drugs improved results in the Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire, without evident differences between them.

Rates of adverse effects were lower with solifenacin than with oxybutynin.⁵⁴⁵ Dry mouth was less common with solifenacin than with oxybutynin.⁵⁴⁵ Rates of dry mouth leading to treatment discontinuation were lower with solifenacin than with oxybutynin.⁵⁴⁵ Rates of other adverse effects resulting in treatment discontinuation did not differ between the two drugs.⁵⁴⁵

Comparative Effectiveness of Solifenacin and Propiverine on Urgency UI

Evidence was insufficient from which to conclude comparative effectiveness and safety of solifenacin and propiverine.

A single RCT compared clinical outcomes of solifenacin and propiverine.⁵⁰²

This study reported a significant reduction in UI episodes with both drugs, without significant differences between them.⁵⁰²

The highest dose of solifenacin, 10 mg daily, caused greater rates of constipation and dry mouth than propiverine.⁵⁰²

The rates of dry mouth did not differ between 5mg/day of solifenacin and propiverine.⁵⁰²

Adverse effects leading to treatment discontinuation did not differ between the two drugs.

Comparative Effectiveness of Trospium and Oxybutynin on Urgency UI

Evidence was insufficient from which to conclude comparative effectiveness between trospium and oxybutynin. Individual studies found lower rates of dry mouth with trospium than with oxybutynin. A low level of evidence indicated no differences in treatment discontinuation due to adverse effects between the two drugs.

Two RCTs compared clinical outcomes of oxybutynin and trospium chloride.^305,546

Comparative Effectiveness of Trospium and Tolterodine on Urgency UI

Evidence was insufficient from which to conclude the comparative effectiveness and safety of trospium and tolterodine.

A single unpublished study compared clinical outcomes of trospium and tolterodine.⁴⁶⁵

The rates of total adverse effects and dry mouth were the same with trospium and tolterodine.⁴⁶⁵

Indirect Evidence of Comparative Effectiveness of Pharmacological Treatments on Urgency UI

Indirect evidence did not indicate substantial differences in resolving or improving UI with different drugs. Differences in discontinuation due to adverse effects, including dry mouth, were more evident than differences in benefits. However, head-to-head comparisons were rarely available in more than one study, and the studies used different definitions of treatment success and different tools to measure quality of life.

We compared relative benefits and harms of drugs compared to placebo. Such indirect evidence from all RCTs that examined clinical outcomes of active drugs versus placebo indicated that trospium was the most effective to resolve UI (Figure 6), but the differences across the drugs were not significant. Absolute rates of continence were the highest with solifenacin and fesoterodine (Figure 7). Indirect statistical comparisons were difficult because of substantial variability in continence rates with placebo. For instance, women became continent with placebo in RCTs of fesoterodine (48 percent), oxybutynin (16 percent), solifenacin (28 percent), tolterodine (44 percent), and trospium (17 percent).

Figure 6

Continence with drugs for overactive bladder when compared to placebo (pooled with random effects estimates from head-to-head RCTs).

Figure 7

Continence rates (%) with drugs vs. placebo (pooled results from RCTs). Vertical axis = percentage of continent with treatments Horizontal axis = treatments with drug or placebo

We analyzed which factors might contribute to such differences in continence with placebo. The studies that did not report whether they included cases of mixed incontinence had lower rates of continence with placebo (18 percent) than studies that excluded women with stress UI (30 percent). The studies that included women with severe daily UI reported higher rates of continence with placebo (28 percent) than the studies that omitted baseline daily frequency of UI (15 percent).

From quality criteria of the studies, masking of treatment would be the most obvious candidate to explain continence with placebo. All drug studies that examined continence, however, were double blinded. From other quality criteria, the studies that reported justification of the sample size had higher continence with placebo (28 percent) than the studies that did not justify sample size (17 percent). Considering substantial variability in continence rates with drugs and placebo, but comparable relative effectiveness of the drugs, comparative safety of the drugs may influence decisions on which drug offers a better balance between benefits and harms.

Compared to placebo, all drugs except darifenacin and tolterodine led to more treatment discontinuation due to adverse effects. The number needed to treated was the highest with solifenacin (NNT=78) and the lowest with oxybutynin (NNT=16). The absolute rates of adverse effects leading to treatment discontinuation were the highest with oxybutynin, and were comparable between other drugs (Figure 8). Dry mouth was the most common adverse effect (Figure 9). Rates of dry mouth were the highest with oxybutynin. Among other adverse effects, constipation and blurred vision were the most common (Figure 10).

Figure 8

Discontinuation of treatments due to adverse effects (%) with drugs vs. placebo (pooled results from RCTs). Vertical axis = percentage of those who discontinued treatments due to adverse effects Horizontal axis = treatments with drug or placebo

Figure 9

Dry mouth rates (%) with drugs vs. placebo (pooled results from RCTs). Vertical axis = percentage of subjects with dry mouth with treatment Horizontal axis = treatments with drug or placebo

Figure 10

Rates (%) of the most common (>10%) adverse effects with drugs vs. placebo (pooled results from RCTs). Horizontal axis = percentage of subjects with adverse effects

Indirect comparisons indicated comparable effectiveness of the drugs on continence. Oxybutynin had higher rates of dry mouth and treatment discontinuation due to adverse effects than other drugs.

Several retrospective observational studies analyzed comparative effectiveness and safety of pharmacological treatments for UI. The evidence-based cost utility analysis reported that more than half of patients stop taking drugs for UI after 1 year of treatment (Figure 11).⁵⁴⁸ The lowest rates of treatment discontinuation were with 5 mg of solifenacin.⁵⁴⁸ The authors estimated quality adjusted life years using treatment response rates and discontinuation rates for all drugs and demonstrated the largest gain in quality adjusted life years per 1,000 treated with solifenacin (Figure 12). Trospium, which demonstrated the highest continence rates, was not included in this analysis (Appendix Figure F26).

Figure 11

Treatment persistence during 1 year of followup of the drugs for UI.

Figure 12

Clinical outcomes with duloxetine vs. placebo in age subgroups (pooled analysis of individual data on women from four RCTs). PGI-I = Patient Global Impression of Improvement

Age

The rates of clinical outcomes were similar in age subgroups. Clinical outcomes in age subgroups were reported in four studies involving duloxetine,³⁹⁸ solifenacin,⁴⁹⁷ tolterodine,³¹⁴ and oxybutynin.^{314,398,497,534} Active and control treatments, outcomes, and definitions of age subgroups varied across the studies. We describe clinical outcomes in age subgroups treated with the drugs from individual studies and pooled analyses of individual subject data.

In 1,913 women ages 22 to 83 years with predominant stress UI, duloxetine compared to placebo did not improve UI in older women (Figure 12).³⁹⁸

In contrast, younger women reported improvement in UI more often with duloxetine than with placebo.³⁹⁸ Duloxetine prevented worsening of UI in older women, but was not better than placebo in women younger than 50 years of age.³⁹⁸

Solifenacin increased continence rates more often than placebo in all age groups (Figure 13).⁴⁹⁷ The drug tended to benefit older women more than younger women. For instance, the relative increase in continence with 5 mg was 38 percent in younger and 69 percent in older individuals.⁴⁹⁷ We observed the same tendency with 10 mg of solifenacin, with a relative increase in continence of 49 percent in younger people and of 63 percent in older people.⁴⁹⁷ This tendency was not statistically significant.

Figure 13

Urinary continence with solifenacin when compared to placebo (pooled analysis of individual patient data from four RCTs).

Tolterodine extended release, when compared to placebo in 1,015 individuals with urgency UI, improved UI more than placebo in older but not younger subjects³¹⁴ (Figure 14).

Figure 14

Clinical outcomes with tolterodine vs. placebo in age subgroups (individual RCTs).

Oxybutynin reduced the number of urgency and total UI episodes more often than tolterodine in women younger than 64 years with urgency or mixed UI in one RCT.⁵³⁴ The rates of adverse effects did not differ between age groups.

Several studies did not directly compare the outcomes among treatment groups but aimed to test treatment effects in older populations. Oxybutynin, trospium, and darifenacin improved UI in older women. Oxybutynin reduced UI frequency and produced subjective benefits compared to placebo in frail community-dwelling older people.⁴⁰⁶ Darifenacin was examined in older populations in two RCTs^479,480 and one pooled analysis of three RCTs.⁴⁸⁷ Darifenacin resulted in improvement in UI when compared to placebo in the older women.⁴⁷⁹ The drug needed to be given to eight older patients to achieve more than a 50 percent reduction in UI episodes in one person. Cognitive function changes did not differ between darifenacin and placebo in short-term (2-week) treatment.⁴⁸⁰ Dry mouth, constipation, and dyspepsia were the most common adverse effects in the older subjects.

Evidence suggested that age did not modify the effects of the tested drugs on examined clinical outcomes. Trospium was effective improving UI and quality of life in older subjects with overactive bladder.⁵⁴⁹ A high level of evidence suggested that duloxetine was no better than a placebo in improving UI in older women. A high level of evidence suggested that solifenacin increased continence rates more often than placebo, regardless of age. Oxybutynin, trospium, and darifenacin improved UI in older women.

Race

Evidence was inconclusive about differences among racial groups in the effects of duloxetine for stress UI. Only one study, DESIRE (Duloxetine Efficacy and Safety for Incontinence in Racial and Ethnic Populations) examined clinical outcomes in different race groups.³⁸⁸ Women with stress UI were treated with 80 mg of duloxetine per day. Weekly UI episodes were reduced compared to baseline in all race groups, by 65.7 percent in African Americans, by 73.0 percent in Hispanics, and by 75.0 percent in Caucasian women. Clinical outcomes rarely differed between racial subgroups (Figure 15).³⁸⁸ African American women reported improvement in UI more often than Caucasian women. Hispanic women experienced a reduction in UI by more than 50 percent less often than Caucasian women. Several adverse effects, including dizziness, headache, and somnolence, were less common among African American women and more common among Hispanic women than among Caucasian women. The biological plausibility of such differences is not clear.

Figure 15

Clinical outcomes with duloxetine in racial subgroups of women with stress UI, DESIRE (Duloxetine Efficacy and Safety for Incontinence in Racial and Ethnic populations).

Baseline Type of UI

Evidence was not sufficient for individualized prediction of benefits by the urodynamic type of UI.

The studies of antimuscarinic drugs enrolled subjects with overactive bladder and predominant urgency UI. The studies of duloxetine enrolled subjects with predominant stress UI. Few studies compared the outcomes in subgroups with the predominant type of UI. One RCT of tolterodine compared continence rates, reduction in UI episodes, and pad utilization in subjects with predominant urgency and pure urgency UI, and concluded the same treatment benefits in all subjects regardless of the type of UI.⁴⁶⁹ Two pooled analyses of individual patient data compared clinical outcomes between 5 or 10 mg of solifenacin and placebo.^497,498

Both doses of solifenacin increased continence rates compared to placebo. Solifenacin increased continence rates in subjects with pure urgency and mixed UI. The effect size did not differ between subgroups with different types of UI (Figure 16). The relative increase in continence rates was greater with 5 mg of solifenacin in patients with pure urgency UI than those with mixed UI. One pooled analysis demonstrated that 5 mg of solifenacin was not better than placebo in achieving continence in subjects with mixed UI.⁴⁹⁸ Individuals with mixed UI required longer treatment duration to achieve greater benefits from solifenacin. At the end of 40 weeks of treatment, 52 percent of the people with mixed UI reported regaining continence, and 34 percent reported resolution of symptomatic urgency on uncontrolled extension in one RCT.⁴⁹⁹

Figure 16

Continence with solifenacin compared to placebo in patients with mixed or pure urgency UI (pooled analyses of individual patient data).

Clinical outcomes of tolterodine and solifenacin did not differ in individuals with baseline mixed or pure urgency UI. Individuals with mixed UI may require a larger dose and longer treatment than women with urgency UI to achieve clinical benefits from solifenacin.

Baseline Frequency of UI

The baseline frequency of UI demonstrated no significant or consistent association with clinical outcomes of any drug. Individuals with more frequent UI had slightly greater benefits with drugs than with placebo. Variability in definitions of baseline severity and clinical outcomes lowered the level of evidence.

Three secondary data analyses of drug trials examined clinical outcomes among subgroups with different baseline frequency of UI.^467,497,508 The results indicated that baseline frequency of UI tended to modify the treatment effects of the drugs; however, statistical significance of such modifications was not consistent across the definitions of baseline severity, drugs, and treatment outcomes.

Several drugs resulted in greater benefits for patients with more frequent baseline UI. In a post hoc analysis of an RCT, tolterodine extended-release increased continence rates compared to placebo in patients with symptoms of urinary frequency and pure urgency UI. Urinary continence rates varied by diary-recorded duration and frequency of UI at baseline (Figure 17).⁴⁶⁷ Individuals with more frequent baseline UI had a larger relative benefit with the drug than with placebo. Five or 10 mg of solifenacin per day increased the rates of continence regardless of baseline frequency of UI in a pooled analysis of 1,873 people with OAB.⁴⁹⁷ Those with more than three episodes of urgency UI per day at baseline experienced a slightly larger relative benefit than those with less frequent UI.⁴⁹⁷ Patients with more than two urgency UI episodes per day experienced a greater reduction in the number of urgency UI episodes with 8 mg of fesoterodine in a pooled analysis of two RCTs.⁵⁰⁸ In contrast, trospium was better than placebo at resolving UI only in subjects with fewer than five UI episodes/day.⁵⁵⁰ Trospium did not resolve UI in subgroups with more than five episodes of UI/day.⁵⁵⁰

Figure 17

Complete continence with tolterodine, extended release of 4 mg/day vs. placebo in groups with different baseline frequency UI (episodes/week).

Adverse effects leading to discontinuation were more common with 8 mg of fesoterodine in patients with two to four episodes of urgency UI per day (Figure 18).⁵⁰⁸

Figure 18

Adverse effects of fesoterodine compared to placebo in subgroups with different baseline frequency of urgency UI (pooled analysis of four RCTs).

Prior Treatment Status

Solifenacin was effective regardless of the response to previous treatments, even though poor responders did not benefit from increasing the dose of the drug (high level of evidence). One study reported that darifenacin was effective in those for whom previous treatments failed. Tolterodine was no better than placebo in achieving clinical benefits among poor responders to the previous muscarinic antagonists in one RCT.

Many studies reported prior treatment status, but very few reported clinical outcomes in subgroups by the response to previous treatments. In a pooled analysis of individual patient data from four RCTs, solifenacin increased continence rates when compared to placebo, regardless of the response to previous treatments (Figure 19).⁴⁹⁷ Previous nonresponders experienced a greater relative benefit than those who responded to previous treatments.⁴⁹⁷ Patients who did not respond to previous treatments did not benefit from increasing the dose of solifenacin.⁴⁹⁷ Post hoc analysis of the OPERA trial demonstrated greater rates of continence with oxybutynin than with tolterodine in patients with prior treatments with antimuscarinic drugs, but no difference was demonstrated between the two drugs in treatment of naïve patients.⁵⁵¹ In one RCT, tolterodine was not better than placebo among poor responders to the previous muscarinic antagonists.⁴⁵³

Figure 19

Continence with solifenacin vs. placebo in subgroup by response to the previous treatment with antimuscarinic medications (pooled analysis of RCT).

In one nonrandomized study, darifenacin improved clinical outcomes in OAB patients who expressed dissatisfaction with prior extended-release (ER) oxybutynin or tolterodine therapy.⁴⁸⁵ Darifenacin improved the Patient’s Perception of Bladder Condition regardless of previous treatments by 108 percent (OR 2.08, 95 percent CI, 1.48 to 2.92) in oxybutynin treated patients and by 77 percent (OR 1.77, 95 percent CI, 1.29 to 2.43) in tolterodine treated patients.⁴⁸⁵

Concomitant Treatments

Trospium reduced the number of urgency UI episodes irrespective of concomitant medications. Adverse effects were more common in those taking seven or more concomitant medications.⁵⁵²

Comorbidities

Duloxetine was no better than placebo in women with stress UI and comorbidities (one RCT).

One RCT examined clinical outcomes with duloxetine compared to placebo in women with comorbidities (Figure 20).³⁹⁸ Duloxetine was not better than placebo in women with depression, diabetes, and chronic lung diseases, nor was it better than placebo in preventing worsening of UI in underweight women and women with depression, diabetes, and chronic lung diseases.³⁹⁸

Figure 20

Patient global impression of improvement rating as “better” with duloxetine when compared to placebo in subgroups with different comorbidity status (duloxetine urinary incontinence study group).

Obesity

Baseline obesity did not modify the effect of trospium in pooled analysis of individual patient data from RCTs (Table 11).⁵⁵³ Trospium was more effective than placebo in achieving continence in obese and nonobese adults.⁵⁵³ The magnitude of the benefit was similarly low in subgroups with different baseline body mass index (BMI). Trospium resolved urgency UI in 140 per 1,000 treated adults with normal weight or obesity.

Table 11

Continence with 60 mg once daily of trospium vs. placebo in obese and nonobese adults with overactive bladder (pooled results from RCTs using the WHO criteria for obesity).

Clinical Effects of Pelvic Floor Muscle Training (PFMT)

A high level of evidence indicated significant benefits from PFMT for women with UI. Compared to regular care, PFMT increased urinary continence rates and improvement in UI. Benefits were consistent across different regimens of training and definitions of improvement in UI.

Eleven studies^554–564 examined PFMT compared to regular care or no active treatment.

Clinical Effects of Vaginal Cones and Pessaries

Evidence was insufficient to draw valid conclusions about the benefits of vaginal cones. Two RCTs compared clinical outcomes with vaginal cones and no active treatment^558,563 (Appendix Table F81). One study treated women with clinical and urodynamic stress UI with vaginal cones of 20, 40, and 70g for 20 minutes per day.⁵⁵⁸ Another study examined nine cones of equal shape and volume, increasing in weight from 20 to 100g.⁵⁶³

Clinical Effects of PFMT With Biofeedback Using Vaginal Electromyography (EMG) Probe

A low level of evidence indicated increased urinary continence with PFMT with biofeedback when compared to usual care. Evidence was high that this treatment improved UI.

Four RCTs examined PFMT with biofeedback using a vaginal EMG probe.^{440,556,557,560}

The studies included women over 55 years of age with urodynamic UI^{440,556,557,560} (Appendix Table F81).

Clinical Effects of Electrical Stimulation

A high level of evidence suggests increased continence rates and improvement in UI with electrical stimulation.

Nine studies examined intravaginal electrical stimulation.^{558,577–584} The studies included women with predominant urgency UI,^581,583 clinical^579,580 or urodynamic stress UI,^558,577 or urodynamic mixed UI⁵⁷⁸ (Appendix Table F81). Few studies excluded women with detrusor overactivity.^577,579 Electrical stimulation was described with different levels of detail and had variable stimulation parameters, depending on the UI type being treated, including the use of 4 Hz,⁵⁸³ 10 Hz,⁵⁸¹ 20 Hz,⁵⁷⁸ or 50 Hz^558,579,580 frequency for 4 weeks,^558,581 7 to 8 weeks,^578,583 12 weeks,⁵⁷⁹ or 15 weeks.⁵⁷⁷

Continence

Electrical stimulation increased continence rates more often than sham stimulation (Appendix Table F96).^{558,563,577,579–581,584} The benefit was consistent across the studies, despite differences in women and treatment characteristics. One RCT reported significantly higher rates of continence with electrical stimulation.⁵⁸⁴ Increase in continence did not differ across the studies with mixed versus pure stress UI. Electrical stimulation needed to be administered in nine women to achieve continence in one (Table 12).

Table 12

Continence with nonpharmacological treatments compared to no active treatment (pooled with random effects estimates from head-to-head RCTs).

Clinical Effects of Magnetic Stimulation

A moderate level of evidence indicated that magnetic stimulation improved UI but did not increase urinary continence more than sham stimulation. Evidence of improved quality of life was low.

Five RCTs examined magnetic stimulation.^587–591 The studies of magnetic stimulation included women with UI,⁵⁸⁸ stress UI,^587,590 mixed,⁵⁹⁰ or predominant urgency UI⁵⁸⁹ (Appendix Table F81). Magnetic stimulation was described with different levels of detail using 10 Hz,^588,591 15Hz,^587,590 or 18.5Hz⁵⁸⁹ for 1,⁵⁸⁷ 2,⁵⁹⁰ 6,⁵⁹¹ or 8 weeks.^588,589 The studies compared active with sham stimulation using double blind,^587,589,590 single blind,⁵⁸⁸ or open label⁵⁹¹ designs.

Clinical Effects of Medical Devices

Evidence was insufficient to draw valid conclusions about the benefits of using intravaginal and intraurethral devices. Uncontrolled studies demonstrated improvement in UI, but also high discontinuation rates due to adverse effects.

Clinical outcomes with a variety of medical devices were reported in nonrandomized, noncontrolled studies^{568–572,574,575,593–608} (Appendix Table F26). Continence rates were 82 percent after using the CapSure (Re/Stor) continence ⁵⁹³ and 20 percent⁵⁹⁴ to 54 percent⁵⁹⁵ after using the Contiform intravaginal device. Rates of continence and improved UI were 58 percent⁵⁹⁸ to 69 percent^596,597 after using the Conveen Continence Guard. Improvement in quality of life was reported by 50 percent⁶⁰⁰ to 59 percent⁶⁰¹ of women after using the FemAssist silicone cup. The continence rate was 93 percent at 48 months after using the FemSoft urethral insert.⁶⁰² Some studies reported discontinuation rates that varied from 27 percent⁶⁰¹ to 41 percent.⁶⁰² A few studies reported adverse effects in women after using the devices, including urinary tract infection in 31.3 percent, mild trauma in 6.7 percent, hematuria in 3.3 percent,⁶⁰² local discomfort in 62 percent,⁵⁹⁷ acute bacterial cystitis in 5 percent, a small degree of fracture of the curvature of the device in 22 percent,⁵⁹⁴ or residual volume >100 ml in 5.4 percent.⁵⁹⁵

Clinical Effects of Bulking Agents for Refractory Stress UI

A low level of evidence suggests that bulking agents did not demonstrate improvement in UI when compared to placebo. Evidence was insufficient to draw valid conclusions about improvement in quality of life. Uncontrolled studies reported high rates of improvement, but also adverse effects.

Clinical outcomes after bulking agents compared to placebo or sham treatments were reported in two RCTs of 241 women^609,610 (Appendix Table F81). The studies enrolled women with urodynamic stress UI and without detrusor overactivity. Women were treated with periurethral injections of autologous fat.⁶¹⁰ Active treatments did not improve UI^609,610 (Appendix Table F104). Periurethral injections of autologous fat did not improve the mean incontinence quality of life score⁶¹⁰ (Appendix Table F105).

Uncontrolled studies reported outcomes after injection of copolymer system⁶¹¹ or nonendoscopic injection of nonanimal stabilized hyaluronic acid/dexranomer (NASHA/Dx) gel.^612,613 Improvement rate after NASHA/Dx was 76 percent,⁶¹³ improvement in quality of life was 67 percent,⁶¹² but 36 percent had adverse effects.⁶¹³

Clinical Effects of Bladder Training

A low level of evidence indicated an improvement in UI with bladder training compared to usual care. Evidence of benefits from bladder training for urinary incontinence was insufficient.

Two RCTs examined bladder training compared to no active treatment.^614,615

Clinical Effects of Percutaneous Tibial Nerve Stimulation

Percutaneous tibial nerve stimulation improved UI in adults with OAB.

Four RCTs examined clinical effects of percutaneous tibial nerve stimulation,^617–620 including the Study of Urgent PC versus Sham Effectiveness in Treatment of Overactive Bladder Symptoms (SUmiT) trial⁶¹⁷ and the Overactive Bladder Innovative Therapy Trial (OrBIT)^618,621 (Appendix Table F108). The studies treated adults with either active stimulation with a current level of 0.5 to 9 mA at 20 Hz, or with sham stimulation.

Clinical Effects of PFMT Combined With Bladder Training

A high level of evidence indicated significant benefits from PFMT combined with bladder training on urinary continence and improvement in UI. The evidence was low that this treatment reduced bother of UI and was insufficient that it improved quality of life.

Six publications of five RCTs examined PFMT combined with bladder training in adults with mixed UI.^627–632

Improvement in UI

PFMT combined with bladder training resulted in a significant improvement in UI in all studies that examined this outcome (Appendix Table F97).^{627–629,631} PFMT combined with bladder training had to be administered in three women to improve UI in one woman.

PFMT combined with bladder training reduced severity of UI (Appendix Table F110).^627,632,633 One study found that self-reported severe UI was reduced by 82 percent.⁶²⁷ Another study demonstrated that self-reported bothersome UI was reduced by 31 percent.⁶³³ Use of absorbent pads for UI was reduced by 29 percent in one study.⁶³³ One study found a significant reduction in stress and urgency UI, but not in mixed UI⁶³² (Appendix Table F100).

Quality of life was examined in one study that reported significant changes in IIQ score after treatment and at the 6 month-followup⁶³² (Appendix Table F111). Evidence was insufficient to determine improvement in quality of life with PFMT combined with bladder training (Table 13).

Table 13

Improvement in severity of incontinence and quality of life with nonpharmacological treatments compared to no active treat.

Clinical Effects of Continence Services That Were Implemented by Specialized Health Care Providers

A low level of evidence indicated no consistent benefits from continence services implemented by specialized health care providers on continence and improvement of UI when compared to usual care. Promising results on improved quality of care need further confirmation. Comparison across the studies was difficult because of the variety of interventions that constituted complex continence services.

Clinical outcomes were reported in four RCTs that compared continence services with usual care^634–637 (Appendix Table F81). Continence services were described with different levels of detail and usually included advice on diet and fluids, bladder training, pelvic floor muscle education and awareness, lifestyle advice,⁶³⁴ use of an audiovisual program, calendar, counseling, voiding schedule recommendations, and assessing self-care methods.⁶³⁵ The services were implemented by continence nurse advisors^636,637 and consulting urogynecologists.⁶³⁶ The studies included subjects with any UI.

Clinical Effects of Group Behavioral Modification Program (BMP)

Group BMP was a combination of PFMT and bladder-training education.⁶⁴¹ Evidence from one RCT was insufficient for valid conclusions about the effectiveness of behavioral modification programs in women with mixed UI.

A single study randomized 44 adult women with mixed UI to a behavioral modification program consisting of a group lecture by two trained urology nurses with individualized meetings and assessment of knowledge and modification of behavior.⁶⁴¹ The control group received no treatments for UI. The behavioral modification program significantly improved UI (ARD 0.38, 95 percent CI, 0.13 to 0.63).⁶⁴¹ The program improved UI in every third woman (NNT 3 95 percent CI, 2 to 8) when compared to no active treatment.⁶⁴¹ Improvement in UI was achieved in 379 per 1,000 treated women (95 percent CI, 126 to 632).

Clinical Effects of Weight Loss

A moderate level of evidence indicated improvement in UI after weight loss and exercise in obese women. The evidence was insufficient to conclude if there was an increase in continence or improved quality of life.

Three studies reported clinical outcomes after weight loss programs (Appendix Table F116).^642–644 One RCT compared an intensive 6-month weight loss program to no active treatment.⁶⁴² The trial enrolled women with a BMI of 25 to 50kg/m² with any daily UI. The program included self-administered diet, exercise, and behavior modification, and aimed to produce an average loss of 7 to 9 percent of initial body weight. The second study treated women with a BMI between 25 and 45 kg/m² and at least four incontinent episodes per week.⁶⁴³ A diet study provided a 3-month standard low calorie liquid diet (800 kcals/day or less), increased physical activity to 60 minutes/day, and training by a nutritionist, exercise physical therapist, or behavioral therapist.⁶⁴³

Clinical Outcomes of Soy-Enriched Diet

One study tested the effects of the soy-enriched diet on urogenital symptoms in perimenopausal and postmenopausal Thai women, and demonstrated no reduction in UI (Appendix Table F119).⁶⁴⁶

Clinical Effects of Acupuncture

Evidence was insufficient to conclude improvement in UI after acupuncture. Low evidence suggested possible improvement in quality of life after active acupuncture.

Clinical outcomes of active acupuncture versus acupuncture of inactive points were reported in two RCTs of 137 women^647,648 (Appendix Table F81) and one uncontrolled study.⁶⁴⁹ The RCTs enrolled women with symptoms of overactive bladder with urgency incontinence⁶⁴⁷ or with stress UI.⁶⁴⁸ Active acupuncture did not resolve urgency UI⁶⁴⁷ (Appendix Table F120). An uncontrolled study reported an improvement rate of 80 percent in older women for whom previous treatments had failed.⁶⁴⁹ Improvement in quality of life was inconsistent across two RCTs^647,648 (Appendix Table F121).

Comparative Effectiveness of Supervised PFMT and Self-Administered PFMT

A high level of evidence indicated no difference in UI outcomes between supervised PFMT combined with bladder training and self-administered PFMT.

Supervised PFMT combined with bladder training was not more effective than self-administered PFMT^650–654 (Appendix Table F122). Continence rates were similar between the two interventions (Table 15).^650–654 Improvement in UI was similar between supervised and self-administered PFMT (Appendix Table F123).^650–654 Rates of treatment failure and treatment discontinuation did not differ between the two treatments (Appendix Table F122).^650–653 One RCT reported better patient satisfaction with supervised versus self-administered PFMT in 44 women with urodynamic stress UI.⁶⁵²

Table 15

Continence rates compared between nonpharmacological treatments (pooled with random effects estimates from head-to-head RCTs).

Differences in quality of life were inconsistent across studies. One RCT did not demonstrate better quality of life with supervised versus self-administered PFMT in 88 women with mixed UI⁶⁵⁵ (Appendix Table F125). Supervised PFMT versus self-administered PFMT worsened two domains of King’s Health Questionnaire (physical limitations and physical activity limitations), with no differences in other domains in 61 women with urodynamic stress UI⁶⁵¹ (Appendix Table F126).

Prevalence of UI did not differ between supervised and self-administered PFMT.^{650,655–657} Only one RCT of intensive PFMT under the supervision of a physical therapist for 6 months in 52 women with urodynamic stress UI demonstrated no sustained reduction in prevalence of severe UI (RR 0.18, 95 percent CI, 0.02 to 1.33) and urgency UI (RR 0.37, 95 percent CI, 0.12 to 1.18) at 15 years (Appendix Table F125).⁶⁵⁰

The studies of individual PFMT did not report better outcomes than group PFMT in individual RCTs of women with different types of UI (Appendix Table F127).^658,659

Comparative Effectiveness of PFMT With and Without Biofeedback Using Vaginal EMG Probe

A high level of evidence indicated no differences in clinical outcomes between PFMT with or without biofeedback using vaginal EMG probe.

The studies that compared PFMT with or without biofeedback using vaginal EMG probe found no consistent differences in continence (Table 15, Appendix Table F124). Nor did quality of life rates differ.^660,661 Scores of Leakage Index,^660,662 Social Activity Index,⁶⁶⁰ Incontinence Impact Questionnaire,⁶⁶³ or IIQ-7 scores⁶⁶⁴ did not differ between PFMT with and without biofeedback (Appendix Table F128). Prevalence and impact of UI did not differ between treatments, either^660,663 (Appendix Table F129).

Comparative Effectiveness of PFMT and Electrical Stimulation

A moderate level of evidence suggested no differences in UI with PFMT and electrical stimulation. PFMT did not result in better outcomes than electrical stimulation^563,665,666 (Appendix Table F130). Rates of improvement in UI and treatment failure also did not differ between the two treatments^563,665,666 (Appendix Table F123).

Comparative Effectiveness of PFMT Combined With Electrical Stimulation Versus PFMT

Evidence was insufficient to draw conclusions about comparative effectiveness of PFMT combined with electrical stimulation versus PFMT alone. A combination of PFMT with electrical stimulation reduced the frequency of UI and improved quality of life more often than PFMT alone⁶⁶⁷ (Appendix Table F131).

Comparative Effectiveness of PFMT and Medical Devices

A moderate level of evidence indicated no difference in outcomes for UI treated with PFMT compared to vaginal cones. Evidence was insufficient to draw valid conclusions about comparative effectiveness of PFMT and vaginal rings and balls.

Relative benefits of PFMT compared to medical devices were inconsistent across the studies. The rates of continence or improvement in predominant stress UI did not differ between PFTM and vaginal cones^561,563,668 (Appendix Table F132). PFMT combined with biofeedback did not result in greater continence rates than use of vaginal cones⁶⁶⁹ (Appendix Table F131). Rates of treatment discontinuation did not differ between the two treatments.⁶⁶⁹ PFMT with biofeedback resulted in the same quality of life as vaginal cones^670,671 (Appendix Table F133).

PFMT using weighted vaginal balls 50 to 100 g resulted in increased continence rates and improvement in UI compared to regular PFMT in one study that examined this association⁶⁷² in 37 women with stress UI (Appendix Table F131).

PFMT resulted in greater improvement in UI and lower treatment discontinuation than vaginal rings⁶⁷³ (Appendix Table F131).

PFMT combined with the use of a vaginal ring resulted in greater improvement in UI and lower rates of treatment discontinuation than a ring alone⁶⁷³ (Appendix Table F131).

PFMT and the use of a vaginal ring did not differ from PFMT alone in causing improvement of UI or treatment discontinuation⁶⁷³ (Appendix Table F131).

Comparative Effectiveness of Circular Muscle Exercises and PFMT

Evidence was insufficient to draw valid conclusions about comparative effectiveness of muscle training regimens.

Continence and improvement in predominant stress UI were greater with circular muscle exercises (Paula method) than PFMT⁶⁷⁴ in women with UI (Appendix Table F134). Quality of life was reported in two RCTs that compared circular muscle exercises with PFMT, with no consistent differences^674,675 (Appendix Table F135). With circular muscle exercises, women experienced less “leakage annoyance” but not less frequency of UI⁶⁷⁴ (Appendix Table F136). Back pain was more common with the Paula method than with regular PFMT.⁶⁷⁴

Quality of life did not differ significantly in studies that compared PFMT with other active treatments^{561,660,661,674,676} (Appendix Tables F137 and F138).

Comparative Effectiveness of Interventions To Increase Adherence to PFMT

Evidence was insufficient to draw valid conclusions about comparative effectiveness of interventions to increase adherence to PFMT.

Adding personal reminders to enhance adherence to PFMT did not improve outcomes in 129 women with UI⁶⁷⁷ (Appendix Table F139). Providing women with an audiocassette tape to enhance adherence to PFMT increased routine pelvic floor muscle exercise more often than usual verbal instructions for PFMT.⁶⁷⁸ Women performed pelvic floor exercises twice per day more often after listening to audiocassette tapes.⁶⁷⁸ Providing audiocassette tapes resulted in better adherence to PFMT in 698 women per 1,000 treated (Appendix Table F139).

Comparative Effectiveness of PFMT in Different Positions

Available evidence did not indicate differences in benefits between different regimens and combinations of PFMT treatments.

PFMT with EMG biofeedback in both supine and upright positions versus supine position resulted in the same outcomes in 44 women with stress UI.⁶⁷⁹

Comparative Effectiveness of Electrical Stimulation Methods

Evidence was insufficient to conclude comparative effectiveness of electrical stimulation and other nonpharmacological treatments for UI.

Comparative effectiveness of once versus three times per week posterior tibial nerve simulation resulted in the same outcomes in 35 subjects with urgency UI who failed oxybutynin treatment.⁶²³

Frequency of UI episodes, pad test, quality of life, and treatment discontinuation rates did not differ between intravaginal electrical stimulation with or without biofeedback⁶⁸⁰ (Appendix Table F131).

Electrical stimulation compared to the use of vaginal cones resulted in the same rates of continence, improvement in UI, and discontinuation of treatments due to failure to improve UI⁵⁶³ (Appendix Table F131).

Physical therapy that included PFMT in combination with biofeedback compared to physical therapy alone increased rates of continence and improvement in UI in one study of 40 women with stress UI.⁶⁶¹

Comparative Effectiveness of Medical Devices

Evidence was insufficient to conclude comparative effectiveness of examined medical devices.

Clinical outcomes were examined in seven RCTs of vaginal cone therapy, Contrelle Continence Tampon, CCT, Conveen Continence disposable Intravaginal device Guard, CCG, Hodge pessary with support and Durasphere and Urethral device (NEAT), sterile urethral insert^{561,670,681–684} (Appendix Table F140). The studies did not demonstrate significant differences in outcomes. One RCT of 94 women with the predominant symptom of stress UI found that women reported “no bother from UI” more often after Contrelle Continence Tampon versus Conveen Continence Disposable Intravaginal Device Guard.⁶⁸¹ Quality of life did not differ after examined devices^561,670,683 (Appendix Tables F141 and F142). One cross-over RCT of 20 women with light UI examined patient comfort, absorbency, and leakage performance after different pads, and found no significant differences⁶⁸⁵ (Appendix Table F143).

Comparative Effectiveness of Various Bulking Agents for Refractory Stress UI

Evidence was insufficient to conclude comparative effectiveness of examined bulking agents.

Seven RCTs examined clinical outcomes after different bulking agents in women with pure stress UI and did not find consistent differences^686–692 (Appendix Table F144). Continence was greater after Macroplastique versus Contigen^® in 260 women⁶⁹³ and after autologous myoblasts and fibroblasts versus collagen in 63 women.⁶⁹⁰ Autologous myoblasts and fibroblasts versus collagen improved quality of life scores in 63 women with intrinsic sphincter insufficiency or stress UI⁶⁹⁰ (Appendix Table F145). Adverse effects were more common with Zuidex Implacer than with Contigen Endoscopic guidance in 344 women with stress UI⁶⁹² (Appendix Table F146). Continence rates were greater with durasphere than with contigen in one RCT in 52 women with stress UI.⁶⁸³

Comparative Effectiveness of Bladder Training

Evidence indicated that continence did not differ between bladder training combined with PFMT and bladder training alone. Evidence was insufficient to draw conclusions based on other tested comparisons.

Bladder training by listening to an audiotape daily improved UI more often than bladder training without the audiotape⁶⁹⁴ (Appendix Tables F131 and F147).

Continence did not differ between bladder training and PFMT.⁶⁶⁰ Satisfaction with current UI and feelings of no impact from UI on quality of life did not differ between bladder training and PFMT.⁵⁶¹ Transcutaneous tibial nerve combined with bladder and PFMT increased rates of continence or clinically important reduction in daily UI episodes in older women with urgency UI compared to bladder and PFMT (Appendix Table F148). Bladder training combined with PFMT did not increase continence or improve UI more often than bladder training alone^93,695 (Appendix Table F149). Bladder training did not increase continence more often than use of vaginal cones (Appendix Table F131).⁵⁶¹

Comparative Effectiveness of Continence Services Implemented by Specialized Health Care Providers

Evidence was insufficient to draw valid conclusions about comparative effectiveness of continence services and other tested individual treatments (Table 14).

Table 14

Continence with nonpharmacological treatments.

Outpatient continence services involving bladder retraining and physical therapy resulted in the same continence as treatment with an inpatient 5-day hospital stay in 74 women with any UI⁶⁹⁶ (Appendix Table F131).

The Continence Efficacy Intervention Program increased continence rates more often than PFMT in 48 women with stress or mixed UI.⁶³⁵ Quality of life scores, however, did not differ between the two treatments⁶³⁵ (Appendix Table F150). Face-to-face behavioral consultation by the nurse specialist giving digital assessment feedback on pelvic floor contraction resulted in the same continence as video conferences with continence nurses in 32 older women with symptoms of urgency or stress incontinence⁶⁹⁷ (Appendix Table F131).

Comparative Effectiveness of Group Versus Individual Physical Therapy Sessions

Evidence was insufficient to draw conclusions about comparative effectiveness of group versus individual therapy for UI.

Women reported lower benefits from group versus individual physical therapy sessions for mixed UI at 5 months of followup (RR 0.79, 95 percent CI, 0.65 to 0.98) in one RCT.⁶⁹⁸ Symptom severity or quality of life outcomes did not differ between treatment groups.⁶⁹⁸

Comparative Effectiveness of Behavioral Weight Loss and Education

Evidence was insufficient to conclude comparative effectiveness between behavioral weight loss intervention and education. Women reported more frequent improvement in mixed UI (defined as more than 70 percent reduction in weekly UI episodes) at 12 months with a behavioral weight loss intervention than with education⁶⁹⁹ (Appendix Table F131). The differences remained significant only for urgency UI at 18 months posttreatment.⁶⁹⁹

Indirect Evidence of Comparative Effectiveness of Nonpharmacological Treatments

Indirect comparisons indicated similar effectiveness of nonpharmacological treatments on continence.

We evaluated the effectiveness of different nonpharmacological treatment compared to no active treatment. Such indirect evidence from all RCTs indicated that all active treatments increased continence rates without evident differences (Figure 21). Absolute rate differences were significant for electrical stimulation, PFMT, and PFMT combined with bladder training. Attributable cases of continence were 299 per 1,000 for PFMT compared to 162 cases for electrical stimulation, and 166 cases for PFMT combined with bladder training. Rates of continence were similar between different treatments: 38 percent of women became continent with PFMT, 23 percent became continent with electrical stimulation, and 21 percent became continent with PFMT combined with bladder training.

Figure 21

Continence with nonpharmacological treatments for UI when compared to no active treatment (pooled with random effects estimates from head-to-head RCTs).

Statistical indirect comparisons were difficult because of substantial variability in continence rates with control treatment (Figure 21). We analyzed which factors potentially contribute to such differences in continence with the control treatment, and found no statistically significant associations.

Comparative Effectiveness of Nonpharmacological Treatments When Compared to Drugs or Combined Modalities

Evidence was insufficient to draw valid conclusions about comparative effectiveness and safety of nonpharmacological treatments compared to drugs or combined modalities (Table 16).

Table 16

Continence with pharmacological treatments compared to nonpharmacological treatments or combined modalities.

Comparative Effectiveness of Nonpharmacological Treatments When Compared to Drugs or Combined Modalities for Stress UI

Comparative Effectiveness of Nonpharmacological Treatments When Compared to Drugs or Combined Modalities for Urgency UI