1. Pharmacologic Treatment of Overactive Bladder: Defining a Success and When is Improvement ‘Enough’
Jeffrey P. Weiss, MD, FACS
Professor and Chair
Department of Urology
SUNY Downstate College of Medicine
VA NY Harbor Healthcare System
Brooklyn, NY

2. OAB: Definition
Urgency, with or without urge incontinence, usually with frequency and nocturia

3. Two Types of Urgency
Urgency is comprised of at least two different sensations:
An intensification of the normal urge to void (69%)
A sudden urge that is a different sensation (31%)
May have different etiologies
May respond differently to treatment
In contradistinction
Blaivas, AUGS, 2006

4. Classification of Urge
Type 0 - no urge
Type 1 - mild urge (delay for > 1H)
Type 2 - moderate (delay for 10 – 60 m)
Type 3 - severe (delay for < 10 m)
Type 4 - precipitous urge (must void immediately)
Blaivas, J Urol. 2007:177, 199
DeWachter, Neurourol & Urodynam, 2004

5. OAB: Urodynamic Classification
Type I: symptoms of overactive bladder, no IDC at urodynamics
Type II: IDC present; patient is aware and can abort the IDC
Type III: IDC patient aware, cannot abort but can temporarily maintain continence by contracting the sphincter
Type IV: IDC, no awareness or control

6. Urodynamic classification of OAB
So far there is no data available to determine the validity or usefulness of this new classification as regards outcome of therapy of OAB

7. PRO as outcomes in medical research*
“While we can measure a biological response, we may not be able to determine whether that response makes a noticeable difference to the patient”
*Fairclough DL: Stat Methods Med Res 13: , 2004

8. OAB: Outcome analysis
OAB is a syndrome, with several symptoms together determining the severity of this condition.
Clinical trials typically report single-outcome variables
Endpoints including multiple key symptoms including QoL would better reflect Rx outcome

9. OAB: Evaluable endpoints
Urgency (# episodes/24 hours, grading)
Incontinence (# episodes/24 hours, grading)
Nocturia severity
Voiding frequency/24 h
HRQoL specific to bladder symptoms

10. OAB: outcomes analysis
Great challenge pertaining to health-related QoL research is to translate statistically significant HRQoL changes into those of clinical, not just statistical, significance
Payne CK and Kelleher C: BJUI 9 9 , 101 – 10 6, 2007

11. OAB Diagnosis
Does not rely on urodynamic evaluations, but arises solely from patient symptoms
Urgency is recognized as the hallmark symptom of OAB
Clinical trials do not normally report reductions in urgency as a primary outcome variable, mainly because there is no commonly agreed method for evaluating this key symptom (so far)

12. Kings Health Questionnaire
Multi-dimensional questionnaire
Part of the International Consultation on Incontinence Questionnaire (ICIQ)
The KHQ is fully validated to assess HRQoL in both women and men with lower urinary tract dysfunction, including OAB
Consists of 29 items across 9 domains; 7 of these domains contain items for which there are multiple questions (role limitations, physical limitations, personal relationships, emotions, sleep/energy and severity measures)
Remaining 2 domains are single-question items (incontinence impact and general health perception)

13. Kings Health Questionnaire
Δ 12–15 points represents a moderately clinically meaningful difference for all domains except symptom severity; this domain only requires a difference of ≥2 points to be considered minimally clinically meaningful
Kelleher CJ, Pleil AM, Reese PR, Burgess SM, Brodish PH. How much is enough and who says so? BJOG 2004; 111: 605–12

14. OABq: overactive bladder questionnaire
33-item, condition-specific measure developed to assess the impact of OAB on HRQoL
Consists of a symptom bother scale (8 items) and four HRQoL subscales (coping, concern, sleep and social interaction; 25 items).
All items are scored on a 6-point Likert scale, and scores are transformed to a 0-to 100-point scale.
Higher symptom bother scores indicate greater symptom severity, while lower HRQoL subscale scores indicate greater impact.
Threshold of 10 points thought to represent MID on OAB-q*
*Khullar V: Int Urogynecol J (2012) 23:179–192

15. Urogenital distress inventory (UDI)
Assesses the impact of incontinence on the HRQoL in women
UDI consists of 19 symptom items and a 4-point Likert scale (0-3, total 57) to assess the level of bother to the patient (not at all, slightly, moderately and greatly)
UDI-6 (shortened version) uses the four point Likert scale to assess the impact of LUTS in women: incontinence, lower abdominal pain, difficulty emptying the bladder
UDI-6 often used in conjunction with the Incontinence Impact Questionnaire (IIQ), which provides information on the impact of LUTS on activities, roles and emotional status
UDI (entire form): statistically significant improvements of ≥11 points (MID) have been considered clinically important
Barber MD, et al. Am J Obstet Gynecol 200:580–587

16. EPIC: population-based, cross-sectional telephone survey of adults aged ≥18
OAB cases divided into five subgroups (SG) based upon symptom report: Continent OAB (SG1); OAB+UI Sxs(SG2), OAB + post-micturition Sxs (SG3), OAB+voiding Sxs (SG4), or OAB+post-micturition+voiding Sxs(SG5)
PPBC: single item assesses patients’ subjective impression of current urinary problems
Patients rate their perceived bladder condition on a six-point scale ranging from 1 (‘no problems at all’) to 6 (‘many severe problems’)
36% of SG5 reported that their bladder condition caused ‘moderate- very severe problems’, vs 21.0% in SG4, 18.0% in SG3, 18.4% in SG2 and 3.9% in SG1
Coyne KS et al: BJUI 101: , 2008

17. Effect of solifenacin on male and female patients with OAB: Re Nocturia
Assessed utilizing pooled data from four phase III randomized clinical trials
3032 patients included in the analysis; 2534 reported nocturia at baseline
Patients without nocturnal polyuria experienced a statistically significant reduction in nocturia
Translated to a numeric difference of only 0.18 episodes of nocturia less per night than placebo
Statistical significance clearly not same as clinical significance
Brubaker L et al: Int Urogynecol J Pelvic Floor Dysfunct 2007;18: 737–41

18. IPSS: MID
Studied 150 consecutives patients treated for LUTS associated with BPH*
Related the change in the IPSS at 3 months to a global rating scale of change made of 5 categories: worse, stable, slight, moderate and marked improvement
Mean absolute MID could be estimated approximatelly 3 points on the IPSS
Results similar to those presented by Barry MJ et al J Urol. 154: , 1995
*Ruffion A et al: Eur Urol Suppl: S (08)

19. Oxybutynin IR cf propantheline cf placebo*
Oxy-IR but not propantheline: significant reduction in voids/24 hrs and increases in volume at first involuntary contraction and max cystometric capacity vs placebo
Pt responses to VAS re: symptom severity % improvement for Oxy-IR, 45% for propantheline and 43% for placebo.
Thus subjective results mirrored objective endpoints through diaries and UDS
*Thuroff et al J Urol 145: , 1991

20. Detrol-ER cf Oxy-IR cf placebo*
Perception of bladder condition improvements:
Detrol 72%; Oxy-IR 73%; placebo 59%
Both active treatments significantly reduced weekly UUI and #24 hour voids and increased volume/void cf placebo
King’s Health Questionnaire, validated for assessment of QoL in patients with LUTS:
None of the KHQ domains could distinguish between active Rx groups
Hence objective outcomes via diaries or UDS do not always agree with subjective outcomes
*Kelleher CJ et al: Br J Obst Gyn 104: , 1997

21. Conclusions
Ultimately, patient satisfaction and improved QoL define success in therapy of OAB
Currently it is impossible to determine the ideal outcome measure for use in OAB
Endpoints should focus on changes in urgency [grade], with or without other symptoms, and QoL*
Payne CK and Kelleher C. BJUI 99: 101-6, 2007