TOTAL URGENCY AND FREQUENCY SCORE AS A MEASURE OF URGENCY AND FREQUENCY

IN OVERACTIVE BLADDER AND STORAGE LOWER URINARY TRACT SYMPTOMS

TOTAL URGENSI DAN FREKUENSI SKOR SEBAGAI UKURAN URGENSI DAN FREKUENSI DALAM GEJALA
OVERAKTIF SALURAN KEMIH BAGIAN BAWAH DAN PENYIMPANAN PADA KANDUNG KEMIH
Christopher R. Chapple, Marcus J. Drake*, Philip Van Kerrebroeck, Linda Cardozo, Ted
Drogendijk, Monique Klaver, Karin Van Charldop, Zalmai Hakimi and Gerhard Compion
Royal Hallamshire, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, *Bristol
Urological Institute, Bristol, UK, Maastricht Medical Center, Maastricht, The Netherlands,
Kings Collage Hospital, London, UK, Astellas Pharma Europe B.V., Leiden, The Netherlands,
and Assiellas Pharma Europe Ltd, Chertsey, UK.

The term lower urinary tract sypmtoms (LUTS) encompasses a range of urinary
symptoms, including storage symptoms (e.g. overactive bladder [OAB]) as well as voiding
and post-micturition symptoms. Although treatment of male LUTS tends to focus on voiding
symptoms, patients typically find storage sypmtoms the most bothersome. The core storage
symptoms is urgency, which drives the other main storage symptoms of increased daytime
frequency, nocturia and incontinencia. Istilah sypmtoms saluran kemih bawah (LUTS) meliputi
berbagai gejala kencing, termasuk gejala yang terjadi pada penyimpanan (misalnya kandung kemih
yang terlalu aktif [OAB]) serta gejala setelah berkemih. Meskipun penanganan LUTS pada laki-laki
cenderung pada gejala berkemih, biasanya pasien memiliki sypmtoms tempat penyimpanan paling
mengganggu. Gejala-gejala inti penyimpanan adalah urgensi, yang mendorong gejala penyimpanan
utama lainnya seperti peningkatan frekuensi siang hari, Nokturia dan incontinencia. Although
several validated questionnaires have been widely used to study urgency, few measure the
two important storage parameters, urgency and frequency, in a single assesment. The total
urgency and frequency, in a single assesment. The total urgency and frequency score (TUFS)
is a new validated tool that captures both variables and is derived from the Patient
Perception of Intensity of Urgency Scale, which has been validated in patients with OAB and
LUTS. The TUFS was first validated in OAB in the phase IIa BLOSSOM study, which was
designed to assess the efficacy and safety of mirabegron, a
3
-adrenoceptor agonist, in 260
patients. The responsiveness of the TUFS to treatment has been confirmed in a further
three large-scale randomized controlled trials of solifenacin in patient with OAB or LUTS.
Meskipun beberapa membenarkan questionnaires telah digunakan secara luas untuk belajar urgensi,
beberapa pengukur dua parameter penting penyimpanan, urgensi dan frekuensi, dalam penilaian
tunggal. Total urgensi dan frekuensi, dalam penilaian tunggal. Urgensi dan frekuensi total score
(TUFS) adalah alat pengukur baru yang menggunakan kedua variabel yang berasal dari persepsi
pasien dan intensitas dari skala urgensi, yang telah disahkan pada pasien dengan OAB dan LUTS.
TUFS pertama divalidasi di OAB dalam tahap IIa BLOSSOM studi, yang dirancang untuk menilai
efektivitas dan keamanan mirabegron,
3
-adrenoceptor agonis pada 260 pasien. Respon dari TUFS
untuk pengobatan telah dikonfirmasi di tiga skala besar secara acak terkontrol solifenacin pada
pasien dengan OAB atau LUTS. Changes in TUFS from baseline to end of treatment were
consistents with changes in micturition diary variables in all four studies. Furthermore, the
TUFS was significantly correlated with several health-related quality-of-life variables in the
phase III NEPTUNE study. Thus, the TUFS appears to be useful for assessing improvements in
major storage symptoms (urgency and frequency) in clinical trials. Perubahan dalam TUFS dari
awal hingga akhir perawatan konsisten dengan perubahan variabel harian berkemih pada seluruh
empat studi. Selain itu, TUFS secara signifikan berkorelasi dan berhubungan dengan kesehatan dan
kualitas hidup variabel dalam studi tahap III NEPTUNUS. Dengan demikian, TUFS tampaknya berguna
untuk menilai perbaikan dalam gejala penyimpanan utama (urgensi dan frekuensi) dalam uji klinis.

Keywords kata kunci
Urgency, frequency, lower urinary tract symptoms, overactive bladder, total urgency and
frequency score. Urgensi, frekuensi, gejala saluran kemih bagian bawah, overaktif kandung kemih,
urgensi total dan Skor frekuensi.

Introduction pendahuluan
The term LUTS refers to storage symptoms (increased daytime urinary frequency,
urgency, nocturia, urinary incontinence), voiding symptoms (slow stream, intermittency,
hesitency, straining) and postmicturition symptoms (sensation of incomplete emptying,
postmicturition dribble) [1]. The storage subset of LUTS includes overactive bladder (OAB)
symptoms, which, according to the Standardization Subcommittee of the ICS, is a syndrome
characteristic by urinary urgency, usually with urinary daytime frequency and nocturia, in
the absence of an underlying metabolic or pathological condition, and may or may not be
accompanied by urgency incontinence [1,2]. Istilah LUTS mengacu pada gejala penyimpanan
(meningkatkan frekuensi berkemih siang hari, urgensi, Nokturia dan inkontinensia), membatalkan
gejala (lambat streaming, intermittency, hesitency, melelahkan) dan gejala postmicturition (sensasi
menggiring bola postmicturition lengkap mengosongkan,) [1]. Penyimpanan subset dari LUTS
termasuk kandung kemih terlalu aktif (OAB) gejala, yang, menurut subkomite Standardisasi IC,
merupakan karakteristik sindrom oleh urgensi kemih, biasanya dengan frekuensi berkemih siang hari
dan Nokturia, dalam ketiadaan kondisi metabolik atau patologis dasar, dan mungkin atau tidak
disertai oleh urgensi inkontinensia. Prevalence rates range between 12 and 17% in North
America and Europe and are similiar in men and women [3-5]. OAB is a chronic condition
that impairs patients health-related quality of life (HRQoL) [6]. Of the storage symptoms,
incontinence has received the most attentiont in research, but urgency and increased
daytime frequency also have a clinically significant impact on patients HRQoL [4,6]. Urgency
is defined as a sudden compelling desire to pass urine, which is diffcult to defer, while
frequency is the complaint by a patient that they void too often during the day [1].
Traditionally, urinary frequency has been teh primary outcome measure for the evaluation
of LUTS storage symptoms; however, urgency is now regarded as the pivotal symptoms and
is often the focus of investigations [7,8]. Measurement of urinary urgency is challenging,
however, because of its non spesific nature, its association with other storage symptoms,
including frequency, and its subjective nature as experienced and reported by patient [9].
It has been proposed that evaluation of individual storage symptoms in isolation may
not be the best approach. Instead, the treatment response might be better considered as a
composite efficacy endpoint [10], addressing the various clinical variables cited in the ICS
definition of CAB [2]. The total urgency and frequency score (TUFS), previously referred to
as the total urgency score, is a validated measure that capture the two important storage
measure, urgency, and frequency, in a single composite assessment [11,12]. In the present
article, we review existing tools designed to measure the intensity of urgency and
frequency, and describe the validation of the TUFS, including its responsive in randomized
controlled clinical trials.

Measuring Urgency
Urgency is the core LUTS storage symptoms and can lead to increased daytime
frequency, nocturia and urinary incontinance [13]. While the precise mechanisms of how
urgency is perceived remaind unclear, accumulating evidance suggest that it may differ from
the physiological sensation of bladder filling [14]. Possible causes of urgency include
spontaneous smooth muscle cell contraction, detrusor micromotion, increased destrusor
shortening velocity, structural changes in the bladder wall, altered urothelial mediatore
release of neurotrasmitters acting on smooth muscle or afferent nerves, altered central
nervous processing of signal from the bladder and consequent impired central inhibition of
bladder contraction [14].
Several tools have been used to measure urgency. These include the indevus urgency
severity scale (IUSS) [15], the urgency rating scale (URS) [16], the patient perception of
intensity of urgency scale (PPIUS) [17], the urgency perception scale [18] and the urgency
perception score [19]. In each scale, three to five grades of urgency are assigned a score and
with the exception of the URS, each grade is linked to a perceived time interval before
voiding can no longer be postponed. The URS, PPIUS and urgency perception scale also
record urgency incontinence. The definitions for each scale are shown in Table 1.

Indevus Urgency Sevently Scale
The IUSS, a four-point qualitative scale, was developed to capture urgency severity per
void during completion of a 7-day micturition diary. It consists of four distinct subjective
degrees of urgency linked to the level of impairment as measured by the ability to complete
activities (Table 1). The IUSS has been validated using data from a 12-week phase III clinical
trial evaluating the efficacy of trospium chloride in 658 patients with OAB [15].

Urgency Rating Scale
The URS is a five-point scale intended to be used concurrently with a 7-day micturition
diary to grade the level of urgency associated with each micturition. The URS was developed
based on the guidance from the European Medicines Agency Committe for Proprietary
Medicinal Products for the clinical investigation of medicinal products for the treatment of
urinary incontinence [20]. Levels of urgency are defined as: 1=no urgency; 2=mild urgency;
3=moderate urgency; 4=severe urgency; and 5=urgency incontinence (Table 1). The URS was
used during a extended-release tolterodine clinical trial [16] and in a study comparing
extended-release tolterodine or tamsulosin monotherapy with both extended release
teltoradine and tamsulosin togetherin the treatment of patient with OAB and LUTS [21].

Patient Perception of Intensity of Urgency Scale
The PPIUS is a five point scale designed to rate the level of urinary urgency for each
void during completion of a micturition diary [17]. The PPIUS was developed based on the
guidance from the ICS [2] and the European Medicines Agency: Commite for Proprietary
Medicinai Products for the clinical investigation of medical product for the treatment of
urinary incontinance [20]. Patient record each micturition in a paper diary with the degree
of associated urgency from 0 (no urgency) to 4 (urgency incontinence). Urgency episodes
with or without incontinence are measured by adding the number of severe urgency (grade
3) and urgency incontinence (grade 4) episodes.
The content validity and excellent test-retest reliability of the PPIUS have recently
been demonstrated in a non-interventional study of 39 patients with stable OAB [22]. In
addition, the reliability of PPIUS has been extensively evaluated, both in healthy volunteers
and in patients with OAB and LUTS, in trial investigating the effect of solifenacin, mirabegron
and the oxybutynin patch [8,23-27].
In the Solifenacin in the Treatment of Urgency Symptoms of Overactive Bladder in a
Rising-Dose, Randomized, Placebo Controlled, Double-Blind, Efficacy (SUNRISE) trial in
patients with OAB symptoms, changes in PPIUS score related to patients perception of
bladder condition (PPBC), indicating its value in assessing improvements in major OAB
symptoms (frequency and urgency) [8]. Further evaluation of the PPIUS was undertaken in a
phase II study of mirabegron for the treatment of OAB (urinary frequency and urgency) in
male and female patients, in which the degree of urgency for each episode of micturition or
incontinence episode was recorded by patients over a 3-day period [24].
Data collected from a 4-week, double blind, placebo-controlled trial of 96 Patients
with OAB, randomized to transdermal oxybutinin or matching placebo patches [17].
Indicated thaat the PPIUS had good test-retest reliability and responsiveness [17]. The PPIUS
also correlated with other measures of condition severity and distinguished between
patient groups [17]. In addition, data were collected as part of tge 12-week Solifenacin and
Tamsulosin in Males with Lower Urinary Tract Symptoms Associated with Benign Prostatic
Hyperplasia (SATURN) study, which was designed to evaluate the efficacy and safety of
Solifenacin plus an oral controlled absorption system (OCAS
TM
) formulation of Tamsulosin
(TOCAS) [28]. Used as part of a 3-day micturition diary, the PPIUS demonstrated good test-
retest reliability, responsivenees, and know-groups and concurrent validity in the SATURN
trial [12].

Urgency Perception Scale
The urgency perception scale was designed to measure urgency on a three-point scale
[18]. Patients are asked to describe their typical experience whe they feel the desire to pass
urine. Three categories of the desire to void are described as follows: 1= i am usually not
able to hold urine; 2= i am ussally able to hold urineuntil i reach the toilet if i go
immediatelly; 3= i am usually able to finish what i am doing before going to the toilet.
Construct validity was established by correlating urgency perception scale scores with
clinical and patient assessment data from three tolterodine clinical trial [18,29,30]. The
urgency perception scale correlates well with PPBC and micturition diary variables.

Urgency Perception Score
The urgency perception score is a single-item question that was designed to
determine the underlying reasons why an individual patient usually voids, and is not meant
to serve as an index of the frequency or severity of urgency episodes [19]. Patients are
asked: what is the reason that you usually urinate? the urgency perception score is scored
on a five-point scale ranging from voiding out of convenience (no urgency = 0) to desperate
urgency (score=4) (table 1), and has been validated in a asymptomatic normal volunteers
(n=83), patients with LUTS (n=62) and patients with OAB (n-80) [19]. The urgency perception
scale wa shown to be a valid adn reliable means a grading urgency based on test-retest
reliability, making it a clinically useful measureof urgency [19].

Measuring Frequency
In a population-based prevalence study increased urinary frequency (85%) was the
most commonly reported symptoms in adults aged 40 years with OAB, followed by
urgency (54%) and urgency incontinence (36%) [3]. Frequency can be measured
quantitatively with micturition diaries, which have been shown to be reliable and
reproducible [7]. These provide quantitative measurements of all voiding episodes, and the
pattern of voiding over times however, no single diary is in wide use, and different diaries
can vary hugely. Some include micturition charts, recording only the time of micturition,
others include a measure of the volume voided at each void or ask for additional
information such as fluid intake, incontinence episodes, degree of urgency and pad usage
[31]. Furthermore, the duration of micturition diaries varies significantly typically ranging
from 3 to 7 days. While a short duration may fail to capture rarer events, e.g. incontinence
episodes, patient complience is known to decrease with longer diary duration [32,33].
Micturition diaries, when completed in real time, are not subject to recall bias and can
provide an accurate reflection of lower urinary tract function [34,35].

Measuring Urgency and Frequency Using a Single Efficacy Measure
Increased frequency often occurs as a behavioral response to urgency, as patients
attempt to reduce the incidence of incontinence or to reduce discomfort or distress
associated with urgency, so it is appropriate that they should be considered together when
evaluating storage LUTS. Consequently, urgency severity per void may not always fully
describe the impact of urgency, especially when learned behaviours and coping strategies
lead patients to void when convenient or out of fear of leakage, rather than because of
sudden compelling desire to void that is difficult to defer. Increased frequency is likely to
cause sosial difficulty or embarrassment for patient and affect quality of life. Measures that
incorporate changes in both urgency and frequency have been found to be useful for
assessing the efficacy of therapies designed to reduce OAB or LUTS storage symptoms.
These are typically based on existing measures used to measure urgency, and iclude: the
OAB Symptom Composite Score (OAB-SCS), based on the IUSS; the URS sum urgency score;
and the TUFS, based on the PPIUS.

OAB Symptoms Composite Score
The IUSS, discused above, was combined with measure of daily frequency and daily
urgency incontinence episodes to create teh OAB-SCS. Teh tool was developed during the
post hoc analysis of two clinical trials and uses the IUSS to numerically rate each void
recorded in the micturition diary [36]. OAB-SCS point values were assigned to the
corresponding IUSS value/void as follows: 1= no urgency; 2= mild urgency; 3= moderate
urgency; 4= severe urgency; and 5=urgency incontinence not associated with a urinary void.
The OAB-SCS aims to capture the influence of daily frequency and daily urgency
incontinence episodes, in addition to measuring urgency severity as a surrogate measure of
OAB severity. The OAB-SCS accounts for the effect of urgency on the interval between voids
(and hence increased frequency) by summation of all daily voiding events, however, this
score is not validated, and few studies have used this measure.




Table 2. Details of the phase II-III studies in patients with OAB or LUTS that have included
TUFSas an endpoint

BLOSSOM (24) Phase Iia, Randomized
controlled, double-blind,
4 weeks
Mirabegron 100/150 mg
twice daily, tolteradine 4
mg once daily or placebo
314 patient with
symptoms of OAB for 3
months, 8
micturitions/24 h, 3
urgency episodes (grade
3 or 4)/24 h using a 3-
day diary
Primary endpoint :
number of
micturition/24 h.
Secondary endpoints:
micturition diary
varibles,
HRQoLmeasures.
SUNRISE (11) Phase Iib, randomized
controlled, double-blind,
16 weeks
Solifenacin 5/10 mg or
placebo
863 patient with
symptoms of OAB for 3
months and 3 episodes
of urgency
incontinence using a 3-
day diary
Primary endpoint : PPIUS
3 + 4 episodes .
Secondary endpoints:
micturition diary
variables, HRQoL
meauseres, TUFS
SATURN (28) Phase II randomized
controlled, double-blind,
12 weeks
Solifenacin 3, 6, or 9 mg;
solifenacin 3, 6, or 9 mg
plus TOCAS; TOCAS 0,4
mg; or placebo
937 men with LUTS (3
months, total IPSS 13
and maximum urinary
flow rate of 4,0-15,0
mL/s)
Primary endpoint: total
IPSS.
Secondary endpoints:
IPSS sub-scale scores,
micturition diary
variables, HRQoL
measures, TUFS (Post
hoc)
NEPTUNE (26) Phase III, randomized
controlled, double-blind,
12 weeks
Solifenacin 6 or 9 mg
plus TOCAS; TOCAS 0,4
mg: or placebo
1334 men with LUTS (3
months) with voiding
and storage symptoms
(2 urgency episodes/24
h (PPIUS grade 3 or 4)
and 8 micturition/24 h.
Primary endpoint: total
IPSS and TUFS.
Secondary endpoints:
IPSS, IPSS sub-scale
scores, micturition diary
variables, HRQoL
parameters.

URS Sum Urgency Score
The URS was applied during a extended-release tolterodine clinical trial [16] and post
hoc was analyses were performed to assess three different analytical methodologies: mean
(sum of urgency rating/ number of micturition), mode (most frequent urgency rating) and
sum of urgency ratings in measuring urgency outcomes [16]. When comporing pre-and post-
treatment scores, improvements were only apperent in the sum score. The study concluded
that mean and mode urgency per 24 h were not sensitive indicators of treatment-related
change, while sum urgency per 24 h appeared to be responsive, probably owing to its ability
to account for both the frequency and urgency components of OAB. This score has also
been termed the frequency-urgency sum in trials with tolterodine [37-38].

Total Urgency and Frequency Score
The TUFS captures the two important storage symptoms, urgency and frequency, in a
single measure [11] and has been validated in patient with OAB and LUTS [12]. Subjects
grade each void according to the PPIUS scale from no urgency (0) to urge incontinence (4).
The score is calculated by adding the PPIUS scores of every void in a patients urinary diary,
and dividing this by the number of days recorded in the diary [11].
The TUFS was validated in patients with OAB in the phase Iia BLOSSOM study, which
was designed to assess the efficacy and safety og mirabegron, a
3
-adrenoceptor agonist
[24]. The TUFS has also been shown to have good psychometric properties, with high
responsiveness, a link with the number of micturition and high stability. It showed a low
(r=0.28) but significant correlation with the PPBC score [12]. Subsequently, the TUFS was
used in three large phase II-III studies of the oral antimuscarinic Solifenacin in patients with
OAB or LUTS [11,26,28] (Table 2).
The phase IIIb SUNRISE study evaluated the effect of Solifenacin 5/10 mg in 863
patients who had symptoms of OAB for at least 3 months [8,11]. The primary endpoint was
the mean change from baseline to end of treatment (16 weeks) in the number of urgency
episodes with or without urgency incontinence per 24 h, defined as grade 3 + 4 on the five-
point PPIUS. The TUFS was included as a secondary efficacy endpoint. Solifenacin 5/10 mg
was significantly mo effective than placebo in reducing the mean number of episodes of
PPIUS grade 3+4 per 24 h from baseline to end of treatment (-2.6 vs -1.8, P<0.001), and also
significantly more effective than placebo in reducing mean TUFS from baseline to end of
treatment (-9.0 vs -6,4, P< 0.001). both efficacy measures correlated with PPBC score at end
of treatment (Spearmen rank correlation: 0.41 for PPIUS 3+4 and 0.47 for TUFS; P<0.001 for
both). The authors concluded that TUFS appears to be useful for assessing improvements in
major OAB symptoms (urgency and frequency) in clinical trials.
The phase II SATURN study was designed to evaluate the combination of Solifenacin
and TOCAS versus TOCAS alone in the treatment of 937 men with LUTS [28]. The primary
endpoint was the mean change from baseline to end of treatment (12 weeks) in total IPSS,
and TUFS was included as a post hoc endpoint. Improvements in total IPSS were very small
in all combination therapy groups and were similar to TOCAS; however, greater decreases in
TUFS were absorbed with combination therapy versus TOCAS alone, consistent with other
micturition diary variables. Although al men included in the SATURN trial had voiding
symptons and some degree of storage symptoms , only approximately half had storage
symptoms severe enough to warrant the addition of an antimuscarinic to -blocker
monotherapy; therefore, the result were further analysed to evaluate treatment effects in
the subgroup of patient with 2 urgency episode per 24 h (PPIUS grade 3 or 4) and 8
micturitions per 24 h at baseline. This analysis showed numerically greater improvements in
both total IPSS and TUFS with Combination therapy than with TOCAS alone. There was a
significant additional benefit from increasing doses of Solifenacin (in combination with
TOCAS) on the change from baseline in the TUFS per 24 h compered with TOCAS alone
(dose-response slope -0.48; P<0.001), with similar patterns observed for micturition
frequency and voided volume.
The pahse III NEPTUNE study [26] was designed to assess the efficacy of fixed dose
combination tablet of 6 or 9 mg Solifenacin plus TOCAS vs Placebo or vs TOCAS
monotherapy in men with moderate-to-severe storage symptoms and voiding symptoms.
The TUFS was included as one oh the primary endpoints in that study, along with total IPSS.
Compared with placebo all three active treatments significantly improved change from
baseline to end of treatment in both total IPSS (P<0.05, for all) and TUFS (P<0.001, for all;
Fig.2), and this pattern of improvement was absorbed for other micturition diary variables,
including micturition frequency, urgency episodes and voided volume. Furthermore,
significant correlation were absorbed between changes from baseline to end of treatment
in TUFS and all HRQoL endpoints in invetigated, including the patient and clinician global
impression, the IPSS HRQoL and the OAB questionnaire symptoms bother score, irrespective
of treatment received (P<0.001, for all [Table 3]) [39].
Some limitation of the TUFS and the PPIUS, on which the TUFS is based, should be
considered when interpreting scores. Firstly, as the TUFS is calculated from patient-
completed urinary diaries, it accuracy is dependent on the ability of patients to understand
and interpret the questions as intended, and to complete the diaries correctly. Furthermore,
the PPIUS/TUFS assesses incontinence as either present or absent, without considering that
incontinence may be present alongside various levels of urgency and incontinence may
consist of just a small leakage or larger incident. These differences are not captured with the
TUFS. Finally, the duration of a voiding diary can result in compromise between patient
burden, and therefore risk of incomplete or inaccurate entries, and inability to adequately
capture more infrequent events, e.g. incontinence [34].

Table 3. Correlation between the mean change in TUFS from baseline to end of treatment
and the HRQoL endpoints in the NEPTUNE study.
Spearmen Rank
Correlation
PGI: overall bladder symptoms 0.432
PGI: general health 0.356
CGI: overall bladder symptoms 0.382
IPSS: HRQoL score 0.338
OAB questionnaire symptoms bother
score
0.351
*All correlation P<0.001. PGI, patient global impression; CGI, clinician global impression.

Conclusions
While urgency typically leads to increased frequency in patients with storage LUTS or
OAB, only a subset of these patient experience urgency incontinence. Thus, urgency is the
core symptoms of storage LUTS and OAB and is often the focus of investigation; however,
measures of urgency, as obtained with the URS, PPIUS, ISS, urgency perception scale and
the urgency perception score, are unable to capture the broad impact of this symptoms,
and not all are validated. There is a need to capture more storage variables in one measures
for a better overview of the level of disease and impact of treatment on patients.
Of three scones that aim to measure urgency and frequency in a single assessment,
the OAB-SCS, URS and TUFS, the TUFS is the most widely used and has been validated
during the development programme of several drugs. The responsiveness of the TUFS has
been confirmed in four large phase II-III trials of mirabegron and solifenacin in patients with
OAB or LUTS, and was able to discriminate between placebo and active treatment groups in
all studies. In conclusion, the TUFS appears to be a useful tool for the assessment of
improvements in urgency and frequency in patients with storage symptoms attributable to
LUTS or OAB.

Acknowledgements
The study was funded by Astellas Pharma Europe Ltd. Medical writing and editorial
assistance was provided by Sorcha Wahlkvist and Lindsay Napier from Darwin Healtcare,
and funded by Astellas Pharma Europe Ltd.