Aims of Study:

This study compared the health-related quality of life (HRQOL) as measured by the Kings Health Questionnaire (KHQ) in overactive bladder (OAB) patients receiving treatment with tolterodine 4mg once-daily (tolterodine) or placebo in the largest intervention trial in OAB to date.  

Methods: 
A randomized, parallel groups, double-blind, multinational study compared the efficacy and safety of tolterodine with placebo.  OAB patients (n = 1015) with a minimum of eight micturitions/24hrs and > 5 urge incontinence episodes/wk received tolterodine 4 mg once-daily or placebo. The KHQ, self-administered at baseline and end of treatment (12 weeks), is a 33-item, disease-specific HRQoL measure designed to evaluate the impact of urinary incontinence on HRQoL, including areas of physical and emotional function shown to be important to patients [1,2]. It is a valid, reliable measure with 20 validated language translations making it ideal for multicentre multinational clinical trials  [1,2,3].  The KHQ is scored 0-100 where 0 indicates the best possible HRQoL.

Treatment comparisons were based on two primary dimensions (Role Limitations and Incontinence Impact)selected a priori and tested using an intent-to-treat population for whom KHQ translations were available.  The Hochberg procedure was used to control for multiple comparisons[4].

Results: 

The tolterodine group experienced statistically significant improvement in both Incontinence Impact and Role Limitations scores compared with the placebo group.  Role Limitations includes the ability to perform household tasks, perform work, and carry out other normal daily activities. Patients in the tolterodine group also experienced statistically significant improvement in the Severity (coping) Measures,  Physical Limitations, Sleep and Energy, and Symptom Severity scores versus the placebo group. 

 

 End of Treatment Differences (Adjusted for Age, Gender, and Baseline Score)

 

KHQ Domains	Tolterodine   vs Placebo	p-value
Incontinence Impact               -6.75*                0.0002 Role Limitations                  -7.36*                0.0001 Physical Limitations              -6.43*                0.0003 Social Limitations                -2.50                 0.0622 Personal Relationships            -1.38                 0.4460 Emotions                          -2.40                 0.1062 Sleep and Energy                  -3.85*                0.0060 Severity (coping) Measures        -5.58*                0.0001 General Health Perception         -0.13                 0.8995 Symptom Severity                  -1.46*                0.0001

 

* Statistically significant using Hochberg procedure with an initial p<0.05 and rejection of H0 if pk < a/k

Conclusions:

Compared to placebo, tolterodine 4mg once-daily significantly improves the quality of life of patients with overactive bladder, as evidenced by the statistically significant changes in the key dimensions of Role Limitations and Incontinence Impact. Tolterodine patients also experienced statistically significant changes in the Severity (coping) Measures, Physical Limitations, Sleep and Energy, and Symptom Severity domains compared with the placebo group. These results also reconfirm that the KHQ is a sensitive condition-specific HRQoL questionnaire which can be utilized successfully in multinational multicentre studies of OAB.

 

References
1.  Quality of life and urinary incontinence.  Curr Opin Obstet.Gynecol. 1995;7:404-408.
2. A new questionnaire to assess the quality of life of urinary incontinent women.  Br J Obstet.Gynaecol. 1997;104:1374-1379.
Quality-of-life aspects of the overactive bladder and the effect of treatment with tolterodine.  BJU Int 1999;83:583-590.
4.  Some comments on frequently used multiple endpoint adjustment methods in clinical trials.  Stat Med 1997;16:2529-2542.

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