A Narrative Review of Patient-reported Outcomes in Overactive Bladder: What is the Way of the Future?

CONTEXT: Debate exists on overactive bladder (OAB) treatment-response assessment in clinical trials and the nature and shortcomings of the different endpoints used in OAB clinical research. OBJECTIVE: To evaluate current evidence and tools that measure OAB treatment response in clinical trials and to inform the development of a new multidimensional patient-reported outcome (PRO) that could be used as a primary endpoint in OAB trials. EVIDENCE ACQUISITION: We conducted a narrative review of OAB literature available in the PubMed database published between January 1, 2004 and June 30, 2015. Eighty articles were selected for full text review. EVIDENCE SYNTHESIS: The assessment of treatment outcomes in OAB is challenging due to the heterogeneity of symptoms and reliance on PROs. OAB studies report a high level of placebo effect and the placebo response is poorly understood. We found significant correlations between PRO measures and bladder diaries. There is evidence of several issues with the bladder diary: burden, over/underestimation, recall period, and lack of validation. Trials for other conditions-interstitial cystitis, benign prostatic hyperplasia, headache, and restless legs syndrome-have used symptom scales rather than diaries to measure treatment outcomes and some now incorporate PRO measures as primary, coprimary, and secondary endpoints. The International Consultation on Incontinence Research Society recommends evaluation of satisfaction, symptoms, health-related quality of life, and adverse events. CONCLUSIONS: There is strong evidence of the shortcomings in current approaches to measuring OAB outcomes in clinical trials and recognition that a new simpler approach which incorporates symptom and health-related quality of life assessment could provide a more comprehensive, standardized approach to OAB assessment. PATIENT SUMMARY: Overactive bladder is a urinary syndrome. Individuals experience different symptoms to varying degrees, which poses difficulties in accurately measuring the effect of treatment. This review found evidence and recommendations that propose a simpler but more comprehensive way to measure treatment outcomes.

Clinical value of a patient-reported goal-attainment measure: the global development of self-assessment goal achievement (SAGA) questionnaire for patients with lower urinary tract symptoms.

AIMS: To discuss the importance of patients' treatment goals and perceived goal attainment to better address expectations in the treatment of lower urinary tract symptoms (LUTS), including overactive bladder (OAB). METHODS: The development of the Self-Assessment Goal Achievement (SAGA) questionnaire was driven by measurement principles from the field of qualitative and psychometric research adapted to elicit patients' treatment goals. At baseline, SAGA solicits individualized responses of patient's treatment expectations and goals, and at follow-up SAGA uses a goal-attainment scale (GAS) to document goal achievement. RESULTS: The SAGA questionnaire provides a basis for the patient and physician to discuss realistic treatment expectations and to measure the alignment between patients' expectations and treatment outcomes in terms of improvement in symptoms and impact on function. Therefore, incorporating the SAGA questionnaire into clinical trials may provide an additional dimension of treatment efficacy by incorporating data on treatment satisfaction from the patient's perspective. CONCLUSIONS: The SAGA questionnaire is a useful tool for patient-centered discussions about the treatment and management of LUTS, including OAB, and assisting physicians in tracking progress and managing patient expectations during therapy.

European content validation of the Self-Assessment Goal Achievement (SAGA) questionnaire in patients with overactive bladder.

INTRODUCTION AND HYPOTHESIS: The Self-Assessment Goal Achievement (SAGA) questionnaire is a patient-completed instrument designed to assess goal attainment in the behavioral or pharmacologic treatment of lower urinary tract symptoms (LUTS), including overactive bladder (OAB). The SAGA questionnaire allows patients to identify and rank the importance of treatment goals before treatment is initiated; the follow-up SAGA questionnaire quantifies the achievement of these patient-identified goals. The objective of this qualitative research was to confirm the content validity of the German, Spanish, Swedish, and English (UK) language versions of the SAGA questionnaire in patients with OAB with or without other LUTS. METHODS: The SAGA questionnaire was translated to each language in accordance with a well-established forward and backward harmonization method. Patient interviews were then conducted according to a cognitive debriefing methodology. Qualitative analysis of patients' input allowed assessment of content validity of each linguistically adapted SAGA questionnaire. RESULTS: All patients (n = 29; six to eight per targeted country) found the SAGA questionnaire easy to understand and to complete. Most patients completed the nine prespecified (fixed) treatment goals and were able to add up to five personal goals in the open-ended portion and rate each goal by importance. Differences were identified in how the various languages communicated some of the concepts assessed with the SAGA questionnaire. Rewording of the translated versions of the questionnaire was necessary in some cases. CONCLUSIONS: This linguistic content validation study in four European languages indicates that SAGA is a comprehensive, easy-to-understand, and relevant questionnaire for patient-completed evaluation of LUTS/OAB symptoms and treatment goal attainment.

Effects of drug cessation after flexible-dose fesoterodine in patients with overactive bladder.

OBJECTIVE: To determine the course of overactive bladder (OAB) symptoms after 4 weeks of no treatment following a 12-week study of the efficacy and safety of flexible-dose fesoterodine in patients with OAB who were enrolled in the UK healthcare system. There are limited data available on the natural time course of OAB symptoms after the cessation of treatment. PATIENTS AND METHODS: In the open-label UK Study Assessing Flexible-dose Fesoterodine in Adults trial, patients aged ≥18 years with self-reported OAB symptoms for ≥3 months, a mean of at least eight micturitions per 24 h and three or more urgency episodes per 24 h on a 3-day bladder diary at baseline, and at least moderate bladder-related problems reported on the Patient Perception of Bladder Condition (PPBC) at baseline, were treated with fesoterodine for 12 weeks. All patients received fesoterodine 4 mg once daily for the first 4 weeks, at which time they could choose to increase the dose to 8 mg once daily, based on a discussion of treatment efficacy and tolerability with the investigator, or they could remain on fesoterodine 4 mg for the remaining 8 weeks. The 12-week treatment period was followed by a 4-week follow-up period of no fesoterodine treatment. Patients completed 3-day bladder diaries and the PPBC at baseline, week 4, end of treatment (week 12) and end of the follow-up period (week 16); the King's Health Questionnaire at baseline, end of treatment (week 12) and end of the follow-up period (week 16); and the Benefit, Satisfaction and Willingness to Continue questionnaire at week 12. RESULTS: After 12 weeks of fesoterodine treatment, patients had clinically meaningful improvements in bladder diary variables and King's Health Questionnaire domains; 79% (254/322) of patients reported an improvement on the PPBC. After 4 weeks of no treatment, most patients deteriorated back to week 4 levels or worse on all bladder diary and patient-reported outcomes. Patients who expressed a benefit from fesoterodine treatment, satisfaction with their treatment or a willingness to continue treatment showed greater improvement from baseline to week 12 and greater deterioration from week 12 to week 16 than patients who did not respond positively on the Benefit, Satisfaction and Willingness to Continue questionnaire. Both men and women showed a meaningful deterioration in bladder diary variables and patient-reported outcomes at week 16; baseline symptom severity, age and week 4 dose escalation status did not appear to affect outcome deterioration at week 16. CONCLUSIONS: At 4 weeks after fesoterodine was discontinued, patients showed an increase in the frequency of OAB symptoms, an increase in the severity of bladder-related problems and a reduction in health-related quality of life. Many patients with OAB who respond to antimuscarinics may require treatment for more than 12 weeks because symptoms recur as early as 4 weeks after the cessation of therapy.

Sustained improvement in patient-reported outcomes during long-term fesoterodine treatment for overactive bladder symptoms: pooled analysis of two open-label extension studies.

OBJECTIVES: • To evaluate the effects of long-term fesoterodine treatment on health-related quality of life (HRQL) and treatment satisfaction in subjects with overactive bladder (OAB) symptoms. • To determine the impact of gender and age on these effects. PATIENTS AND METHODS: • This is a post hoc analysis of data pooled from identically designed open-label extensions of two randomized, double-blind, 12-week fesoterodine studies. • Initial treatment was once-daily fesoterodine 8 mg; subjects had the opportunity to receive open-label fesoterodine for ≥24 months. • After 1 month, subjects could elect dose reduction to 4 mg and subsequent re-escalation to 8 mg; dose reduction and re-escalation were each allowed once annually. • Changes in scores on the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and a Likert scale evaluating severity of bladder-related problems were assessed at open-label baseline and months 12 and 24; treatment satisfaction was assessed at open-label baseline and at months 4, 12 and 24. RESULTS: • A total of 864 enrolled subjects were included (men, n= 182; women, n= 682; aged <45 years, n= 134; 45-64 years, n= 432; 65-74 years, n= 204; ≥75 years, n= 94); most subjects (77%) who continued treatment maintained the 8-mg dose. • Among subjects in the overall population, there were significant improvements in all KHQ domains, ICIQ-SF scores, and bladder-related problems at open-label baseline vs double-blind baseline (P < 0.05); additional significant improvements were observed at months 12 and 24 vs open-label baseline in all outcomes (P < 0.05) except for the KHQ General Health Perception domain. • When data were stratified by gender or age, significant improvements at open-label baseline vs double-blind baseline were further significantly enhanced or sustained at months 12 and 24 for most KHQ domains, and for ICIQ-SF scores and bladder-related problems for all groups. Women had significantly greater improvements than men in the KHQ Emotion (P= 0.0173) and Severity/Coping (P= 0.0112) domains and ICIQ-SF scores (P= 0.0276) during open-label treatment. Subjects aged <45 years had significantly greater improvement in the Personal Relationships domain compared with those aged 45-64 years (P= 0.0357) and in the Sleep/Energy domain compared with all other groups (all P < 0.02). • Treatment satisfaction was high (≥92%) throughout open-label treatment regardless of gender or age. CONCLUSIONS: • Long-term fesoterodine treatment was associated with sustained improvement in measures of health-related quality of life and bladder-related problems and with high treatment satisfaction in subjects with overactive bladder symptoms. • Effects of gender and age were minimal.

Long-term safety, tolerability, and efficacy of fesoterodine treatment in men and women with overactive bladder symptoms.

OBJECTIVE: To evaluate long-term safety, tolerability, and efficacy of fesoterodine for men and women with overactive bladder (OAB) symptoms. RESEARCH DESIGN AND METHODS: This was a post hoc analysis of data pooled from two open-label extensions (NCT00220402, NCT00220376) of double-blind studies. All subjects began open-label treatment with fesoterodine 8 mg once daily, with voluntary dose reduction to 4 mg and re-escalation to 8 mg each permitted once annually. Maximum allowable duration of open-label treatment ranged from 24 to 36 months. MAIN OUTCOME MEASURES: Safety and discontinuations were assessed throughout treatment; subject-reported treatment tolerability and 3-day bladder diaries were evaluated at open-label baseline and months 1, 4, 8, 12, and 24. RESULTS: A total of 185 men and 705 women enrolled; 83 men (45%) and 356 women (50%) continued open-label treatment for ≥ 24 months. Most men (84%) and women (75%) remained on fesoterodine 8 mg throughout open-label treatment. No new or unexpected safety signals were observed. Dry mouth was the most common treatment-emergent adverse event (men, 24%; women, 32%), rates of discontinuation due to dry mouth were low (men, 1%; women, 2%). Most men and women (≥ 91%) reported at least 'good' tolerance. For men and women, statistically significant improvements in urgency urinary incontinence episodes, micturitions, urgency episodes, and mean voided volume per micturition achieved between double-blind baseline and open-label baseline were sustained or further improved through month 24; significant improvements in most OAB symptoms were observed between double-blind baseline and month 24 when subjects were stratified by double-blind treatment (placebo, tolterodine extended release 4 mg, fesoterodine 4 mg, fesoterodine 8 mg). Limitations include the lack of a placebo control and that subjects completing double-blind treatment may have been more likely to tolerate or respond to long-term fesoterodine treatment. CONCLUSIONS: Long-term fesoterodine treatment was well tolerated and associated with sustained improvements in OAB symptoms in men and women.

Goal attainment scaling in patients with lower urinary tract symptoms: development and pilot testing of the Self-Assessment Goal Achievement (SAGA) questionnaire.

INTRODUCTION AND HYPOTHESIS: The Self-Assessment Goal Achievement (SAGA) questionnaire was developed to identify treatment goals and assess goal-achievement in patients with lower urinary tract symptoms (LUTS). METHODS: This study consisted of (1) gathering information on goal setting/attainment concepts, (2) goal elicitation (n = 41 patients with LUTS), (3) cognitive debriefing of draft questionnaire (n = 11), and (4) pilot testing (n = 104). RESULTS: SAGA consists of baseline (goal-assessment; ranking) and follow-up (goal-achievement) modules. In addition to goals most frequently mentioned, patients can list up to five open goals. Goals most commonly reported as "very important" in pilot testing included reducing urgency (72%), incontinence (65%), and nocturia (64%). Treatment goals spontaneously reported as "very important" were reducing incontinence (45%), nocturia (40%), and frequency (26%). CONCLUSIONS: SAGA may be used to identify treatment goals and assess goal-achievement in patients with LUTS in the clinic and for research (with additional validation). This information may promote patient-physician interaction and help patients establish realistic treatment goals, which may in turn improve treatment adherence and outcomes.

Waterbirth and pelvic floor injury: a retrospective study and postal survey using ICIQ modular long form questionnaires.

OBJECTIVE: Benefits attributed to waterbirth (WB) include a shorter second stage of labour and reduction of perineal trauma. The aim of this study is to assess the incidence of perineal trauma and pelvic floor function following WB compared to land birth (LB). STUDY DESIGN: We conducted a retrospective analysis on the incidence of perineal trauma following a spontaneous WB (n=160) or a LB (n=623). Data were collected using the hospital's healthcare database, which codes information on pregnancy outcomes and related variables. ICIQ-VS for vaginal symptoms, and the ICIQ-KH Long Form (KHQ) were used to assess pelvic floor function a year after delivery. RESULTS: Length of 2nd stage was significantly shorter in the WB group. Although this did not translate into less perineal trauma, the incidence of 3rd degree tears appeared to be doubled in the WB group. 77 (38.5%) women from the WB group and 54 (22%) from the LB group answered the postal questionnaires. A significant number of women reported vaginal and urinary symptoms, however the difference between both groups was not statistically significant. CONCLUSION: Waterbirth results in a shorter 2nd stage of labour. This does not lead to less overall perineal trauma or better pelvic floor performance postpartum. Physical limitations in protecting the perineum during the expulsion phase may be associated with an increase in the incidence of 3rd degree tears in the WB population.

Correlations among improvements in urgency urinary incontinence, health-related quality of life, and perception of bladder-related problems in incontinent subjects with overactive bladder treated with tolterodine or placebo.

BACKGROUND: Previous studies demonstrate that tolterodine extended release (ER) significantly improves urgency urinary incontinence (UUI) episodes. Instruments that measure patient-reported outcomes (PROs) provide additional information that is valuable for assessing whether clinical improvements are meaningful to the patient. This study determined the correlation of changes in bladder diary variables and other PROs in subjects with overactive bladder (OAB). METHODS: Subjects with OAB, urinary frequency, and UUI were treated with 4 mg once-daily tolterodine ER or placebo for 12 weeks. Subjects completed 7-day bladder diaries, the Patient Perception of Bladder Condition (PPBC), and the King's Health Questionnaire (KHQ) at baseline and week 12. Only subjects who reported at least some minor bladder-related problems at baseline (PPBC score > or = 3) were included in this analysis. RESULTS: Reductions in UUI episodes per week were significantly greater in the tolterodine ER group (n = 500) compared with the placebo group (n = 487) at week 12 (-71% vs -33%, P < 0.0001). A significantly greater percentage of subjects in the tolterodine ER group reported improvement on the PPBC versus placebo (58% vs 45%, P < 0.0001), and 7 of 10 KHQ domains were significantly improved versus placebo (all P < 0.05). Significant correlations were found for median percentage changes in UUI episodes with changes in PPBC scores (r = 0.35,P < 0.0001) and the 7 improved KHQ domains (r = 0.16-0.32, P < or = 0.0011). Changes in PPBC scores and all KHQ domains were significantly correlated (r = 0.13-0.38, P < or = 0.009) in the tolterodine ER group. Correlations among endpoints in the placebo group were similar to those observed in the tolterodine ER group. CONCLUSION: Improvement in UUI episodes after 12 weeks of treatment with tolterodine ER or placebo was correlated with improvements in patients' perception of their bladder-related problems and health-related quality of life. Correlations were moderate in magnitude but statistically significant, suggesting that PROs are important and relevant measures for evaluating OAB treatment.

Overactive bladder is associated with erectile dysfunction and reduced sexual quality of life in men.

INTRODUCTION: The prevalence of sexual dysfunction, including erectile dysfunction (ED), is greater in men with lower urinary tract symptoms (LUTS), including overactive bladder (OAB), than in men without LUTS. AIM: To evaluate the prevalence of ED, the impact of urinary symptoms on sexual activity and sexual enjoyment, and sexual satisfaction in men with OAB. METHODS: A nested case-control analysis was performed on data from a subset of men with (cases) and without (controls) OAB frequency-matched for age (5-year age strata) and country from the EPIC study. Respondents were asked about OAB symptoms (using the 2002 International Continence Society [ICS] definitions) and sexual activity. Sexually active respondents were asked about ED, sexual enjoyment, and overall satisfaction with their sex lives. Conditional logistic regression was used to assess factors associated with ED. MAIN OUTCOME MEASURES: The percentage of cases and controls reporting ED, a reduction in the frequency of sexual activity or enjoyment of sexual activity because of urinary symptoms, and overall satisfaction with their sex lives was determined for cases and controls. RESULTS: A total of 502 cases and 502 controls were matched for age strata and country. Significantly more cases (14%) reported reduced sexual activity because of urinary symptoms compared with controls (4%; P

Impact of fesoterodine on quality of life: pooled data from two randomized trials.

OBJECTIVE: To evaluate the effect of fesoterodine on health-related quality of life (HRQoL) in patients with overactive bladder (OAB) syndrome. PATIENTS AND METHODS: Pooled data from two randomized placebo-controlled phase III studies were analysed. Eligible patients with frequency and urgency or urgency urinary incontinence were randomized to placebo or fesoterodine 4 or 8 mg for 12 weeks; one trial also included tolterodine extended release (tolterodine-ER) 4 mg. HRQoL was assessed using the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), a six-point Likert scale measuring the severity of bladder-related problems, and treatment response. RESULTS: By the end of treatment, all active-treatment groups had significantly improved HRQoL compared with those on placebo, as shown by an improvement in the KHQ and ICIQ-SF scores, treatment response rate, and a major improvement in self-reported bladder-related problems. The fesoterodine 8-mg group had statistically significant improvements over placebo in eight of nine KHQ domains. Fesoterodine 4 mg and tolterodine-ER produced statistically significant improvements in seven of nine KHQ domains. Fesoterodine 8 mg gave better results than 4 mg in two domains; Emotions and Symptom Severity (P < 0.05). A major improvement (>or=2 points) in bladder-related problems was reported by 33% of patients on fesoterodine 4 mg, 38% on fesoterodine 8 mg, and 34% on tolterodine-ER, vs 21% on placebo (P < 0.001). CONCLUSIONS: Fesoterodine significantly improved HRQoL in patients with OAB. Both fesoterodine 4 and 8 mg produced significant improvements on most KHQ domains, the ICIQ-SF, treatment response rate, and a Likert scale measuring bladder-related problems.

The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: results from the EPIC study.

OBJECTIVES: To examine the effect overactive bladder (OAB) and other lower urinary tract symptoms (LUTS) on health-related quality of life (HRQoL) in a population sample, as OAB often occurs in conjunction with many other LUTS. SUBJECTS AND METHODS: A nested case-control analysis was performed on men and women with (cases) and without (controls) OAB, from the EPIC study. OAB was assessed using 2002 International Continence Society definitions. Based on their responses to questions about LUTS, cases were classified into five groups; continent OAB, OAB with incontinence, OAB + postmicturition, OAB + voiding, and OAB + postmicturition + voiding. Both cases and controls were asked questions about symptom bother (OAB-q), generic QoL (EQ-5D), work productivity (Work Productivity and Activity Impairment, WPAI), depressive symptoms (Center for Epidemiologic Studies Depression Scale), sexual satisfaction, and erectile dysfunction (men only) using the Massachusetts Male Aging Study. Cases answered additional condition-specific questions HRQoL (OAB-q short form), Patient Perception of Bladder Condition and work productivity related to a specific health problem (WPAI-SHP). General linear models were used to evaluate group differences. RESULTS: Of the EPIC participants, 1434 identified OAB cases were matched by age, gender and country, with 1434 participants designated as controls. Cases and controls were primarily Caucasian (96.2% and 96.7%, respectively), and most (65%) were female; the mean age was 53.8 and 53.7 years, respectively. Comorbid conditions differed significantly by case/control status, with cases reporting significantly greater rates of chronic constipation, asthma, diabetes, high blood pressure, bladder or prostate cancer, neurological conditions and depression. There were significant differences between the cases and controls in all reported LUTS. The OAB + postmicturition + voiding group reported significantly greater symptom bother, worse HRQoL, higher rates of depression and decreased enjoyment of sexual activity, than the other subgroups. CONCLUSION: OAB has a substantial, multidimensional impact on patients; OAB with additional LUTS has a greater impact. The diagnosis and treatment of OAB should be considered in conjunction with other LUTS, to maximize treatment options and optimize patient outcomes.

The validation of patient-rated global assessments of treatment benefit, satisfaction, and willingness to continue--the BSW.

OBJECTIVE: This study evaluated the validity of three single-item, patient-rated, interviewer-administered, global assessments of treatment benefit, satisfaction with treatment and willingness to continue treatment, collectively referred to as the BSW. METHODS: The BSW, micturition diaries, the Overactive Bladder Questionnaire (OAB-q) and the King's Health Questionnaire (KHQ) were included in part or in total in three OAB clinical trials. Discriminant validity for full and dichotomized responses was assessed with anovas models and correlations were used to evaluate construct validity. RESULTS: The BSW demonstrated significant differences among the majority of the response levels on all measures of micturitions in all studies. The BSW also demonstrated discriminant validity with the OAB-q and the KHQ. BSW measures demonstrated significant differences among the change scores for all subscales of the OAB-q and the majority of the KHQ domains with both full and dichotomized responses. Patients who were dissatisfied with treatment and those unwilling to continue treatment also reported significantly worse OAB-q and KHQ scores compared with those who were satisfied with treatment or willing to continue treatment. BSW measures were moderately correlated with the micturition variables, moderate to strongly correlated with the OAB-q and weak to moderately with the KHQ, providing support for the construct validity of the BSW measures. CONCLUSIONS: The BSW is a useful tool to capture patients' global impressions of three key elements of treatment outcome: a perceived benefit, satisfaction with treatment, and the willingness to continue treatment, and can facilitate patient-physician communication as well as be informative to researchers.

Improved quality of life in patients with overactive bladder symptoms treated with solifenacin.

OBJECTIVE: To assess the effect of solifenacin succinate treatment on quality of life (QoL) measured in clinical trials in patients with overactive bladder (OAB). PATIENTS AND METHODS: QoL data using the King's Health Questionnaire (KHQ) were analysed from two phase-3, 12-week studies (1984 patients) and a long-term extension of these studies (1637 patients) where patients received solifenacin for up to an additional 40 weeks (i.e. a 52-week exposure to solifenacin). The 12-week studies were multinational, multicentre, randomized, double-blind, and placebo-controlled. The 10 domains from the KHQ evaluated were general health perception, incontinence impact, role limitations, physical limitations, social limitations, personal relationships, emotions, sleep/energy, severity measures, and symptom severity. Changes from baseline to endpoint in QoL variables were assessed by analysis of variance, and from pooled outcomes of the 12-week studies by analysis of covariance. Descriptive statistics were used to evaluate data in the extension study. RESULTS: In the two 12-week studies (1033 and 857 patients), those receiving once-daily solifenacin had statistically significantly better QoL than those on placebo. Changes in the KHQ were statistically significantly (P < 0.05) different from placebo for both solifenacin 5 and 10 mg once daily on five of the 10 KHQ domains in each of the studies. Pooled data from the two 12-week studies showed statistically significant (P < 0.05) differences from placebo for both solifenacin doses in nine of the 10 domains. Improvements in QoL scores for solifenacin were 35-48% in nine of the 10 domains for the 1347 patients providing QoL data in the extension study. About two-thirds of this overall improvement occurred during the original 12-week study, with an additional third reported during the extension, with an improvement in QoL over time in patients treated with solifenacin. CONCLUSIONS: Results from the KHQ in study participants in the two double-blind studies showed that solifenacin significantly improved the QoL in patients with OAB symptoms after 12 weeks of treatment, with further improvements during long-term administration up to 1 year. Clinical trial outcomes show a favourable balance of efficacy and tolerability with solifenacin; the present report further supports this efficacy and tolerability by providing evidence for both short- and long-term improvements in QoL.

How much is enough and who says so?

BACKGROUND: One of the challenges of health-related quality of life research is to translate statistically significant health-related quality of life changes into interpretable clinical or medically important ones. OBJECTIVE: To calculate the minimal important difference of the King's Health Questionnaire, a condition-specific health-related quality of life questionnaire for the assessment of men and women with lower urinary tract dysfunction. METHODS: The King's Health Questionnaire was administered to patients suffering from overactive bladder enrolled in two multinational studies. Minimal important differences were calculated using an anchor-based approach with both a global rating of patient-perceived treatment benefit and one of perceived disease impact. A distribution-based method using effect size was calculated for comparison purposes. RESULTS: Minimal important difference values varied slightly with each method. Using the anchor-based approach, the King's Health Questionnaire minimal important difference ranged between 5-10 points when the calculation factored out patients who reported no change and 6-12 points for patients who experienced a small improvement. The effect size method indicated a minimal important difference of 5 to 6 points for a small effect and 10 to 15 points for a medium effect. CONCLUSIONS: In the case of the King's Health Questionnaire, the anchor-based approaches and the distribution-based approach provide similar results. A change from baseline of at least 5 points on King's Health Questionnaire domains indicates a change that is meaningful to patients and is indicative of a clinically meaningful improvement in health-related quality of life after treatment. Convergence of the estimates using different approaches should give us confidence in the values derived for the quality of life domains measured by the King's Health Questionnaire.

Multinational study of reliability and validity of the King's Health Questionnaire in patients with overactive bladder.

OBJECTIVE: Overactive bladder (OAB) has substantial impact on health-related quality of life (HRQoL). The purpose of this research was to evaluate the psychometric properties of the King's Health Questionnaire (KHQ). METHODS: The KHQ (n = 1284) was administered at baseline and 12 weeks post-treatment in a multinational, double-blind, randomized clinical trial of tolterodine for treatment of OAB. Country-specific psychometric analyses of HRQoL instruments were performed. Countries demonstrating marginal psychometric properties on the KHQ were pooled with same-language countries, re-evaluated, and aggregate analysis performed on the pooled data. RESULTS: Internal consistency of the KHQ was high, item characteristics were good, most assumptions of summed scales were met, and it is externally valid and consistent. Few problems with the KHQ were noted although the performance of the personal relationships domain was complicated by the 'not applicable' response category. CONCLUSIONS: Psychometric testing supports the reliability and validity of the KHQ as an OAB-specific measure of HRQoL.

Health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.

OBJECTIVE: To compare the health-related quality of life (HRQoL) of overactive bladder (OAB) patients foilowing treatment with tolterodine extended-release (ER) 4 mg once daily versus placebo. STUDY DESIGN: Multinational, placebo-controlled, randomized, double-blind 12-week study. POPULATION: Patients with urinary frequency ( > or = 8 micturitions/24 hours over a 7-day period), urge incontinence ( > or = 5 episodes/week), and symptoms of OAB for at least 6 months were eligible for inclusion. Patients (81% female) received oral therapy with tolterodine ER (n = 507) or placebo (n = 508) for 12 weeks. OUTCOMES MEASURED: HRQoL was assessed using the King's Health Questionnaire (KHQ) and Medical Outcomes Study Short Form 36-item questionnaire (SF-36). Patients also rated their bladder condition. Assessments were performed at baseline and at the end of treatment. RESULTS: At end of treatment, KHQ domains selected a priori as primary HRQoL end points (incontinence impact and role limitations) significantly improved (P < or = .001) with tolterodine ER. Domains selected a priori as secondary end points (physical limitations, sleep and energy, severity [coping] measures, and symptom severity) were also significantly improved (P < or = .006) following treatment with tolterodine ER. The tolterodine ER group had decreased symptom severity and statistically significant improvements in patient rating of bladder control compared with the placebo group at end of treatment. No treatment differences were detected using the SF-36. CONCLUSION: Many aspects of HRQoL, as measured by the KHQ, showed statistically significant improvement following treatment with tolterodine ER. These HRQoL improvements were consistent with clinical efficacy benefits. Patients receiving tolterodine ER experienced overall improvement in their condition that was associated with an important impact on their HRQoL.

Long-term health-related quality of life of patients receiving extended-release tolterodine for overactive bladder.

OBJECTIVE: To evaluate the long-term effects of tolterodine on the health-related quality of life (HRQoL) of patients diagnosed with overactive bladder with incontinence. METHODS: Patients who completed a 12-week randomized, double-blind, safety and efficacy trial comparing tolterodine with placebo were invited to enroll in a 12-month open-label continuation trial to assess the long-term safety and efficacy of tolterodine. This study reports the HRQoL results from the King's Health Questionnaire (KHQ) and the Short Form-36 (SF-36) that were administered at baseline, at the end of the 12-week trial, and 3 and 12 months following open-label treatment with tolterodine. RESULTS: One thousand seventy-seven patients were included in the intent-to-treat (ITT(B)) population. KHQ translations were available for 838 patients (mean age, 61.1 years; 80.9% women) in the ITT(B) population. HRQoL, as measured by the KHQ, significantly improved from baseline to months 3 and 12 on the following domains: incontinence impact, role limitations, physical limitations, social limitations, personal relationships, emotions, sleep and energy, severity (coping) measures, and symptom severity. Improvements were generally consistent across all analyses for the 3- and 12-month measurements and for the ITT(B) and completer (C(B)) populations. Patients receiving tolterodine in the double-blind study showed additional improvement at the 3-month open-label assessment on all but the general health domain. At 12 months from treatment rollover, all improvements from rollover to 3 months were sustained with additional improvement seen on the incontinence impact and role limitations domains. The general health perceptions domain showed a slight decline from rollover that might be attributable to a natural decline in patients' health status at this life stage. These findings were consistent with other efficacy results whereby efficacy was maintained over the 12-month open-label period. SF-36 results were consistent with previous experience of reduced sensitivity, as population groups were similar to the SF-36 Physical Component and Mental Component scores at various time points and with all populations. CONCLUSION: Continued treatment with tolterodine provides additional benefits in HRQoL as measured by the KHQ. Of particular importance are improvements on the psychological aspects after longer-term treatment not detected after a short-term trial. Treatment effects on HRQoL are evident even after a 12-week placebo run-in supporting the true clinical effect of active treatment.