2009 THE AUTHORS.

JOURNAL COMPILATION 2009 BJU INTERNATIONAL

Original Articles
COST-EFFECTIVENESS OF SOLIFENACIN VS OTHER ANTIMUSCARINICS
CARDOZO

ET AL.

The cost-effectiveness of solifenacin vs

fesoterodine, oxybutynin immediate-release,
propiverine, tolterodine extended-release and
tolterodine immediate-release in the treatment
of patients with overactive bladder in the UK
BJUI BJU INTERNATIONAL
National Health Service
Linda Cardozo, Andrew Thorpe*, Juliet Warner† and Manpreet Sidhu‡
Urogynaecology, Kings’ College Hospital, London, *Urology, Freeman Hospital, Newcastle upon Tyne, †Health
Economics, Abacus International, Bicester, Oxon, and ‡Health Economics and Outcomes Research, Astellas Pharma
Europe Ltd, Staines, Middlesex, UK
Accepted for publication 22 October 2009

opportunity for an economic evaluation of frequency (723.1) and incontinence (695.0).

Please also see BJUI letters on page 586
OBJECTIVE
To assess the cost-effectiveness of solifenacin
vs other antimuscarinic strategies commonly
used in UK clinical practice, based on the
results of a recent published review.
METHODS
Overactive bladder (OAB) syndrome is
characterized by symptoms of urgency,
frequency, incontinence and nocturia.
Pharmacological treatment comprises oral
antimuscarinic agents, which are divided
into older-generation treatments, including
oxybutynin, and new-generation treatments,
comprising solifenacin, tolterodine,
darifenacin and fesoterodine. The latter have
reduced central nervous system penetration
and have better selectivity for the M3
subclass of acetylcholine receptors, resulting
in improved tolerability. A recent systematic
review and meta-analysis of the efficacy and
safety of antimuscarinics provided an
these agents using a rigorous assessment of
efficacy. A cost-utility analysis was
undertaken using a 1-year decision-tree
model. Treatment success was defined
separately for urgency, frequency and
incontinence, with efficacy data taken from
the recent review. Treatment persistence
rates were taken from the Information
Management System database. Utility values
for the calculation of quality-adjusted life-
years (QALYs) were taken from published
sources. The analysis included costs directly
associated with treatment for OAB, i.e.
antimuscarinic therapy, consultations with
general practitioners, and outpatient
contacts. Resource use was based on expert
opinion. Costs were reported at 2007/2008
prices. Extensive deterministic and
probabilistic analyses were conducted to test
the robustness of the base-case results.
RESULTS
Solifenacin was associated with the highest
QALY gains (per 1000 patients) for all three
outcomes of interest, i.e. urgency (712.3),
Solifenacin was dominant relative to
fesoterodine, tolterodine extended-release
(ER) and tolterodine immediate-release (IR),
and cost-effective relative to propiverine ER
for urgency, frequency and incontinence.
Solifenacin was not found to be cost-
effective relative to oxybutynin IR for the
frequency and incontinence outcomes, with
an incremental cost-effectiveness ratio of
>£30 000/QALY threshold.
CONCLUSIONS
Solifenacin provided the greatest clinical
benefit and associated QALYs for all three
outcomes of interest across all therapies
considered, and to be either dominant or
cost-effective relative to all other new-
generation agents, but not cost-effective
relative to oxybutynin for frequency and
incontinence.
KEYWORDS
overactive bladder, solifenacin, cost-
effectiveness, antimuscarinic agents

INTRODUCTION
Overactive bladder (OAB) syndrome is defined
by the ICS as urgency with or without urgency
incontinence, usually with increased
daytime frequency and nocturia [1,2]. The
fundamental symptom is urgency, which is
widely considered to be the driver of other
urological symptoms [3]. Urgency is a sudden
compelling desire to pass urine, which is
difficult to defer [2]. Urgency reduces the time
that voiding can be postponed, thereby
increasing voiding frequency and reducing
voided volumes; it is also believed to be
correlated with incontinence and nocturia,
but this relationship is less consistent [4].
In Europe, OAB is thought to affect
11.8–16.6% of people (>22 million) over
the age of 40 years [5,6]. Even the most
conservative estimates show that the burden
of the condition is considerable, with an
estimated total cost to healthcare systems (in
five European countries) of €4.2 billion, rising
to €5.2 billion by 2020 [7].

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TABLE 1 Treatment scenarios
Dose, mg
Muscarinic antagonist 1st line 2nd line
Fesoterodine 4 8
Oxybutynin IR 15 – A new
Propiverine ER 20 – Do not therapy
Solifenacin 5 10
Tolterodine ER 4 –
Tolterodine IR 2 4
The effect of OAB on a patient’s quality of life
and general well-being is profound. Many
studies have shown that OAB is a socially
disabling condition that affects daily physical
activities, social life, sexual relationships and
productivity [8–13]. Sufferers often have
embarrassment, frustration, anxiety,
depression and fear of being away from
home. It is thought that OAB symptoms are
often endured without seeking medical
attention; instead, coping mechanisms, e.g.
reducing fluid intake, avoiding social contacts,
limiting travel and toilet mapping, are very
common [8,13,14].
Various treatment options are available for
OAB, and are aimed at reducing the frequency
and magnitude of symptoms. The mainstay of
treatment for OAB comprises bladder training,
electrical stimulation and biofeedback, as well
as anticholinergic/antimuscarinic drugs.
Muscarinic antagonists block the muscarinic
acetylcholine receptors of the detrusor, thus
reducing its activity [15]. This drug class
includes older-generation therapies including
oxybutynin, propiverine and trospium, and
new-generation therapies, which comprise
solifenacin, tolterodine, darifenacin and
fesoterodine.
New-generation therapies are characterized
by reduced CNS penetration and better
selectivity for the M3 subclass of
acetylcholine receptors, thereby resulting in
better tolerability, especially when compared
with extended- (ER) or immediate-release (IR)
formulations of oxybutynin [16]. The most
recent data suggest that this, combined
with the flexible-dosing regimens of new-
generation antimuscarinics, allow for
individual titration towards optimum efficacy
and tolerability [16]. Once daily formulations
in particular seem to be better tolerated and
potentially more effective for improving OAB
symptoms [16].
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COST-EFFECTIVENESS OF SOLIFENACIN VS OTHER ANTIMUSCARINICS
FIG. 1.
A schematic of the model used.
Treatment
The efficacy and tolerability of antimuscarinic
agents have been under continuous
investigation. The most recent systematic
review and meta-analysis encompassed a
large evidence base from randomized
controlled trials, and covered both well-
established agents and the newly licensed
antimuscarinics darifenacin, fesoterodine and
solifenacin [16].
This systematic review by Chapple et al.
[16] presents a timely opportunity for an
economic evaluation, using a rigorous
assessment of efficacy based on the meta-
analysed data. The aim of the present study
was to assess the cost-effectiveness
of solifenacin vs five alternative oral
antimuscarinic agents commonly used in the
UK, using the results of that review.
METHODS
In our evaluation we estimated the cost-
effectiveness of solifenacin vs fesoterodine,
oxybutynin IR, propiverine, tolterodine IR and
tolterodine ER for the treatment of OAB within
a UK clinical setting over a 12-month period.
This was a model-based evaluation with a
decision-tree structure. Estimates of clinical
effectiveness came from the most recent
systematic review and meta-analysis [16].
The study comprised a cost-utility analysis
(CUA), an advisable approach to economic
evaluation, as it captures a wide range of
health benefits attributable to treatment by
defining these benefits in terms of quality-
adjusted life-years (QALYs), a combined
measure of patient quality and quantity
(years) of life. CUA is typically required
for submissions to Health Technology
Response: Repeat treatment
(Node B)
Adherence
to
treatment Repeat
B
Partial treatment (Node B)
improvement/
No response
(Node A)
repeat
A Stop
treatment
A new therapy (Node A)
Treatment
discontinuation
Stop treatment
3 months
Assessment (HTA) groups such as the National
Institute for Health and Clinical Excellence
(NICE). Unlike other cost-effectiveness
methods, such as cost-per-clinical-effect,
it facilitates a comparison of the cost-
effectiveness of treatments across different
disease areas.
The analysis was conducted from the
perspective of the UK NHS, and encompassed
the costs of pharmacological therapies and
patient management in primary- and
secondary-care settings. All costs were valued
in 2007/2008 in £GB, using official UK prices
and tariffs. Discounting was not applied to
either cost or benefits as the model adopted a
1-year time horizon. (Discounting is a process
whereby future costs or benefits are
transformed into present day values).
A decision-tree model was developed to
compare six treatment scenarios. Patients
were assumed to receive a first-line
antimuscarinic, with those whose symptoms
were not adequately controlled switching to
second-line therapy, which comprised the
higher-dose formulation where available.
Where a higher dose formulation is not
available, patients were assumed to receive no
further treatment. The scenarios considered
are detailed in Table 1. The model structure
was designed to reflect typical UK practice in
OAB management and patient experience
during pharmacological treatment, and was
based on the expert opinion of a UK-based
urogynaecologist and urologist. The model
followed a hypothetical cohort of 1000
patients over 1 year. In each 3-month cycle,
patients could continue with initial treatment,
switch to the next therapy option, where
available, or discontinue treatment (Fig. 1).
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TABLE 2 Model input variables

Drug Frequency Incontinence Urgency

Treatment effect, per cycle, mean (95% CI) [16]
Fesoterodine 4 mg −0.81 (−1.27, −0.35) −0.81 (−1.27, −0.35) −0.81 (−1.35, −0.27)
Fesoterodine 8 mg −0.93 (−1.37, −0.49) −1.08 (−1.52, −0.64) −1.29 (−1.83, −0.75)
Oxybutynin IR 15 mg −0.92 (−1.43, −0.4) −0.74 (−1.23, −0.26) NA
Propiverine ER 20 mg −0.93 (−1.28, −0.58) −0.53 (−0.92, −0.14) −1.02 (−1.44, −0.6)
Solifenacin 5 mg −0.99 (−1.23, −0.75) −0.77 (−1.02, −0.52) −1.25 (−1.57, −0.93)
Solifenacin 10 mg −1.3 (−1.56, −1.04) −0.81 (−1.06, −0.56) −1.56 (−1.88, −1.23)
Tolterodine ER 4 mg −0.77 (−0.96, −0.58) −0.4 (−0.42, −0.38) −1.05 (−1.37, −0.73)
Tolterodine IR 2 mg −0.67 (−1.07, −0.27) −0.21 (−0.56, 0.14) NA
Tolterodine IR 4 mg −0.71 (−0.93, −0.5) −0.5 (−0.67, −0.32) −0.64 (−1.16, –0.12)
Baseline no. of episodes/24 h, mean (SD) [17] 11.19 (3.39) 3.51 (5.51) 7.66 (3.74)
Health utilities by model state, per cycle*
Response 0.742 0.719 0.742
Partial response 0.715 0.692 0.715
Switch treatment 0.689 0.665 0.689
Stop treatment 0.689 0.665 0.689
No treatment (if applicable) 0.689 0.665 0.689

*The nearer the utility is to 1, the better the patient’s quality of life.

The cycle length was based on the typical

length of clinical trials and corresponded to
the average time between assessment visits in
routine clinical practice.
INPUT DATA
The benefits of treatment were measured
as symptom resolution and subsequent
improvements in health-related quality of life
(HRQL). Treatment success was defined
separately for urgency/24 h, frequency/24 h
and incontinence/24 h as follows: no urge
episodes, eight or fewer voids and no
incontinence episodes, respectively.
To estimate the probability of a complete
response we first calculated the expected
number of symptoms that would be observed
in a cohort of patients after each treatment
cycle and line of treatment, by deducting the
treatment effect from the mean number of
symptoms at a previous observation point
(end of previous cycle or baseline). The
Poisson distribution (discrete probability
distribution that expresses the probability
of a number of events occurring in a fixed
period, assuming that the events occur
independently of the time since the last event
and at a known average rate) was then
applied to the obtained means to derive the
percentage of patients with a complete
response as per the described definitions. This
TABLE 3 Treatment persistence [18]
% of patients who
Drug Discontinued treatment p.a Switched to another treatment p.a
Oxybutynin IR 15 mg 64.32 5.86
Propiverine ER 20 mg 52.48 20.56
Solifenacin 5 mg 39.87 4.64
Solifenacin 10 mg 58.41 9.05
Tolterodine ER 4 mg 66.94 7.21
Tolterodine IR 2 mg 58.33 6.56
Tolterodine IR 4 mg 74.60 7.58
technique is useful when patient distributions [16]. As this review did not report data for
are unknown, as it facilitates a prediction of frequency and urgency at baseline, to ensure
the proportion of patients with a discrete consistency the baseline data for all three
number of events based on the mean number outcomes were obtained from a systematic
of events in a sample population, e.g. the review and meta-analysis conducted on
percentage of patients with 0, 1, 2, 3 or more behalf of Astellas Pharma Europe (available
incontinence episodes/24 h before and after upon request) [17] (Table 2).
treatment. These estimates were obtained
assuming that clinical effectiveness was Drug-specific treatment persistence data, i.e.
constant over time for patients who remained the percentage of patients who discontinue
on therapy, i.e. treatment benefits were the or switch to another muscarinic agent
same in all cycles. regardless of reason, were obtained from the
Information Management System database
Estimates of clinical effectiveness for the and covered the 12-month period ending in
antimuscarinic agents, i.e. the mean number April 2008 [18] (Tables 3,4). The percentage of
of symptom occurrences, for all three patients who stop or switch treatment due to
outcomes were obtained from the systematic poor compliance was based on expert
review and meta-analysis by Chapple et al. opinion. Experts estimated that 70% of

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TABLE 4 Resource use by model state, per cycle (expert opinion)
Model state
Response
Partial response
Switch treatment
Stop treatment
No treatment (if applicable)
Event/drug
GP visit
1st outpatient visit, urology
Follow-up outpatient visit, urology
1st outpatient visit, gynecology
Follow-up outpatient visit, gynaecology
Drug costs, per cycle, £ (23)
Fesoterodine 4 mg
Fesoterodine 8 mg
Oxybutynin IR 15 mg
Propiverine ER 20 mg
Solifenacin 5 mg
Solifenacin 10 mg
Tolterodine ER 4 mg
Tolterodine IR 2 mg
Tolterodine IR 4 mg
patients who stop treatment and 2% of
those who switch treatment do so due to
non-adherence. As fesoterodine has only
been on the market since July 2008,
treatment persistence data from longitudinal
databases are not yet available. To
approximate the percentage of patients
stopping and switching treatment with
fesoterodine in the base-case analysis, we
used the persistence rates for tolterodine
ER, the most commonly prescribed new-
generation antimuscarinic. This was
considered the closest proxy, as fesoterodine
is a pro-drug of tolterodine. This assumption
was relaxed in a scenario analysis where
treatment persistence rates for fesoterodine
were estimated as a weighted average
between tolterodine ER and solifenacin.
Patients’ Health-related quality of life (HRQL)
was measured using outcome-related health
utilities, obtained from previous publications.
Health utilities refer to values that represent
an individual’s preference for specific health
states and vary between 0 (death) and 1
(perfect health). Such an approach provides a
uniform base for comparison of patients’
health status across different interventions
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COST-EFFECTIVENESS OF SOLIFENACIN VS OTHER ANTIMUSCARINICS
No. of GP visits No. of outpatient visits
0.5 0
1 0
1 1.5
0 0
0 0
Cost, £GB, per cycle TABLE 5
34.00 Unit costs of healthcare
161 [21,22]
78
138
76
94.61
94.61
9.32
79.68
84.01
109.23
94.61
94.61
99.59
and disease areas. The health utility values for
this study were derived using the EQ-5D, a
generic HRQL instrument, which quantified
the improvement in patient HRQL resulting
from a reduction in voids and incontinence
episodes [19,20].
A Poisson distribution was used to estimate
the proportion of patients with different
numbers of symptoms at model entry.
Obtained distributions were then weighted
by the corresponding utilities to estimate
baseline HRQL. Utilities for treatment
response were assigned as per the definitions
of treatment success. Utilities for partial
response were calculated as the mid-point
between the baseline utility and the utility for
response. It was assumed that patients who
stopped or switched treatments returned to
their baseline state. These patients therefore
adopted a baseline health utility value before
commencing subsequent treatment,
regardless of time spent on therapy, i.e. there
were no residual effects of treatment. Due to
a lack of urgency-related HRQL data suitable
for an economic evaluation, the model
adopted HRQL values for frequency as the
closest proxy (Table 2).
QALYs were calculated by multiplying the
health utilities associated with each model
state by the proportion of patients in that
state in each cycle over the model’s 1-year
time horizon. Half-cycle correction was
applied in all calculations, i.e. transition
between the model states occurred at the
mid-point of a cycle (rather than at the
beginning or at the end), which yields a better
approximation of the average HRQL.
The analysis of resource use and unit costs
was undertaken from the perspective of the
UK NHS and included costs directly associated
with the treatment of OAB, i.e. cost of drugs,
GP consultations and consultations in
outpatient clinics. NHS resource use
associated with OAB management during
pharmacological treatment was estimated by
a UK urogynaecologist and a UK urologist and
costed using UK official tariffs (Table 4)
[21,22]. In calculations, we applied an average
unit cost of the first and follow-up
attendance of two specialities, urology and
gynaecology (Table 5). Drug-cost estimates
were based on recommended dosing
regimens obtained from the British National
Formulary [23] (Table 5).
Due to a lack of quantifiable data on the risk
of OAB-induced comorbidities and associated
resource use, this analysis did not take into
account such additional costs that might be
incurred to the NHS by either adhering or
discontinuing patients. The cost of adverse
events was also excluded for this reason.
We further assumed that patients who
discontinued treatment incurred no further
cost to the NHS, i.e. the analysis excluded the
cost of further interventions in those who
failed to respond to or to comply with
treatment.
BASE-CASE ANALYSIS
Point estimates for all model variables were
used to conduct the base-case CUA. The cost
and benefits of each treatment alternative
were reported separately and then
incremental cost-effectiveness ratios (ICERs)
were calculated to compare the relative cost-
effectiveness of different treatment scenarios.
ICERs were obtained by dividing the
incremental (or additional) cost of an
intervention by the incremental (or
additional) QALY gains. The ICERs were
compared against the threshold for cost-
effectiveness of £30 000/QALY, which is
generally accepted by HTA groups such as
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NICE (Fig. 2). The results are presented per
1000 patients.
In some instances a therapy might be less
costly and less effective than the alternative. In
this analysis, we assumed that if the payer is
willing to pay up to £30 000 per QALY gained,
that they will, conversely, be willing to accept
a loss of one QALY if the cost saving exceeds
£30 000 gained. This means that therapies that
are less costly and less effective than the
alternative will be deemed cost-effective if
they have an ICER greater than £30 000.
SENSITIVITY ANALYSIS
Uncertainty around the base-case cost-
effectiveness results was tested in univariate
deterministic and probabilistic sensitivity
analyses (PrSA). Within the PrSA, 1000 Monte
Carlo simulations were generated by varying
the model parameters simultaneously
according to generally accepted distributions.
PrSA included the percentage of patients
stopping treatment, the percentage of
patients switching treatments, number of
symptoms observed at baseline, i.e. frequency,
incontinence, urgency, and treatment effects.
1000 combinations of incremental costs and
benefits from the PrSA were plotted on the
cost-effectiveness plane to indicate a likely
quadrant for ICERs (Fig. 2). Because data for
the variance around point estimates for
health utilities and the cost of patient
management per cycle were not available,
these variables were excluded from the PrSA.
To determine whether variability in these
parameters was likely to alter the conclusions
of the base-case analysis, all model variables
including health utilities and the cost of
patient management per cycle were varied
across an arbitrary 20% range around the
point estimate in a one-way sensitivity
analysis. Any variable excluded from the PrSA
that was shown to be a driver of cost-
effectiveness was subjected to additional
threshold analysis to identify the threshold
values at which the ICERs exceeded £30 000/
QALY. We excluded the drug unit cost from
the sensitivity analysis as any significant
changes in current pricing was considered
unlikely.
RESULTS
Patients treated with solifenacin were
shown to benefit most from treatment.
Solifenacin was associated with the highest
QALY gains (per 1000 patients) for urgency
(712.3), frequency (723.1) and incontinence
(695.0). Treatment persistence data indicated
that patients treated with solifenacin were
also likely to stay on treatment for longer,
due to the low discontinuation rates,
and therefore had a higher chance of
improvement in their OAB symptoms
(Table 6).
Among new-generation antimuscarinics,
treatment with solifenacin was associated
with the lowest cost. The total estimated
annual cost of treating OAB symptoms with
solifenacin ranged from £443 000 (frequency)
to £470 000 (urgency) per 1000 patients.
However, the least expensive treatment
option of all therapies considered was
treatment with oxybutynin IR, the only non-
proprietary antimuscarinic agent. The drug
cost of 1 year of treatment with oxybutynin
was estimated to be £32.60 per patient. Its
total annual cost was estimated to be
£159 000–172 000 per 1000 patients. Drug
costs in the oxybutynin IR scenario accounted
for 20% of the overall cost of OAB treatment,
while drug costs with other antimuscarinics
were responsible for 60–70% of the overall
cost (Table 6).
FIG. 2. The cost-effectiveness plane.
Costs
Less effective, more More effective, more
costly costly
Dominated Cost-effective if
ICER below
£30,000/QALY
QALYs
Less effective, less More effective, less
costly costly
Cost-effective if Dominant
ICER above
£30,000/QALY

TABLE 6 Cost (GB£) and QALY gains associated with the treatment alternatives: results of the base-case CUA

Symptom Feso 4 mg/8 mg Oxy IR 15 mg Prop ER 20 mg Sol 5 mg/10 mg Tol ER 4 mg Tol IR 2 mg/4 mg
Urgency
Total QALYs 709.6 NA* 708.9 712.3 709.7 NA
Total cost 484 553 – 443 455 470 840 480 090 –
Drug cost 332 113 – 271 191 312 078 328 020 –
Healthcare cost 152 440 – 172 264 158 762 152 071 –
Frequency
Total QALYs 718.3 719.6 718.0 723.1 718.1 718.5
Total cost 462 230 159 896 420 377 443 282 458 720 472 183
Drug cost 332 113 32 630 271 191 312 078 328 020 338 107
Healthcare cost 130 117 127 266 149 186 131 204 130 700 134 076
Incontinence
Total QALYs 692.5 691.7 688.0 695.0 688.0 688.1
Total cost 469 062 171 891 437 683 456 048 476 167 490 554
Drug cost 332 113 32 630 271 191 312 078 328 020 338 107
Healthcare cost 136 949 139 261 166 492 143 970 148 147 152 447

*Chapple et al. did not identify data for the urgency outcome for oxybutynin IR 15 mg and tolterodine IR. NA, not available.

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TABLE 7 Base-case ICERs comparing solifenacin with other antimuscarinic therapies
Symptom Feso 4 mg/8 mg
Urgency dominant
Frequency dominant
Incontinence dominant
TABLE 8 Univariate sensitivity analysis of treatment persistence rates for fesoterodine
Variable Urgency
Total QALYs 710.6
Total cost, GB£ 495 447
Drug cost 339 913
Health care cost 155 534
Solifenacin remained the dominant treatment strategy relative to fesoterodine 4 mg/8 mg, i.e. it is
associated with higher QALY gains and lower costs than fesoterodine (solifenacin, QALYs; cost): urgency
(712.3; 470 840); frequency (723.1; 443 282); incontinence (695; 456 048).
The cost-effectiveness of solifenacin vs the
treatment alternatives was analysed for
each outcome of interest separately. When
comparing the economic value of new-
generation antimuscarinic agents, solifenacin
was found to be the dominant treatment
strategy, i.e. it was associated with the highest
QALY gains and the least cost (Table 7).
Efficacy data for the urgency outcome were
only available from Chapple et al. [16] for
solifenacin, fesoterodine, propiverine ER and
tolterodine ER. Among the therapies with data,
solifenacin was shown to be the preferred
treatment strategy. It was found to be less
costly and more effective (dominant) relative
to fesoterodine 4 mg/8 mg and tolterodine ER,
and cost-effective compared with propiverine
ER, with an ICER of £8087/QALY, with a higher
QALY and slightly higher costs.
Efficacy data for the frequency outcome were
available for all six muscarinic agents.
Solifenacin was a dominant treatment option
compared with fesoterodine, tolterodine ER
and tolterodine IR, and cost-effective relative
to propiverine ER, with an ICER of £4457/
QALY. When considering the £30 000/QALY
threshold, as used by NICE, the added benefits
(in respect of QALYs) would be offered at a
much greater cost for solifenacin than
oxybutynin IR, and would therefore result in a
less cost-effective position for solifenacin
than oxybutynin.
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COST-EFFECTIVENESS OF SOLIFENACIN VS OTHER ANTIMUSCARINICS
Oxy IR 15 mg Prop ER 20 mg Sol 5 mg/10 mg
NA £8087 – dominant
£80 009 £4457 – dominant
£87 162 £2639 – dominant
Frequency Incontinence
719.8 693.9
471 904 478 857
339 913 339 913
131 990 138 944
Efficacy data for the incontinence outcome
were available for all six antimuscarinic
agents. Solifenacin was dominant compared
with fesoterodine, tolterodine ER and
tolterodine IR, and cost-effective relative to
propiverine ER. Again, solifenacin was not
cost-effective for the incontinence outcome
vs oxybutynin, as the ICER was above the
£30 000/QALY threshold.
SENSITIVITY ANALYSES
The univariate sensitivity analysis showed
that the base-case results of all pair
comparisons with solifenacin were robust.
While in some cases the model was sensitive
to utility values, treatment effects and
discontinuation rates, a 20% variation of the
point estimates did not alter the conclusion
on the relative cost-effectiveness of this
intervention. Further threshold analyses on
the utility values did not yield plausible
results. All generated values fell outside
clinically relevant ranges at the £30 000/QALY
threshold.
A further scenario analysis was conducted
around persistence data for fesoterodine. We
relaxed the base-case assumption and used
weighted averages between tolterodine
ER and solifenacin to approximate the
percentage of patients stopping and
switching treatment with fesoterodine. While
it had an effect on the estimate of total
Tol ER 4 mg Tol IR 2 mg/4 mg
NA
dominant
dominant
QALY gains and cost of treatment with
fesoterodine, the overall results and cost-
effectiveness conclusions did not change
(Table 8).
The model was robust to simultaneous
variations of the model inputs within the
PrSA. The probability of solifenacin being
a cost-effective or dominant treatment
strategy for all treatment outcomes
relative to fesoterodine, propiverine,
tolterodine IR and tolterodine ER was >75%
(Table 9).
DISCUSSION
Few published reports have considered
the cost-effectiveness of the newer
antimuscarinic agents, such as solifenacin. An
economic evaluation by Ko et al. [24] assessed
the cost per clinical response of solifenacin,
darifenacin, trospium, oxybutynin IR,
oxybutynin ER, transdermal oxybutynin,
tolterodine IR, and tolterodine ER. Clinical
response was defined as the percentage of
patients with complete continence for seven
sequential days. That study concluded that
solifenacin was a dominant treatment
strategy relative to all other treatment
alternatives, followed by transdermal
oxybutynin, darifenacin, oxybutynin ER,
tolterodine ER, tolterodine IR, trospium and
oxybutynin IR. Two previous CUAs, comparing
solifenacin and tolterodine ER, also showed
that treatment with solifenacin was less
costly and more effective, i.e. dominant
[25,26].
The present research offers an economic
evaluation of solifenacin vs five alternative
muscarinic antagonists commonly used for
treating OAB in the UK clinical setting based
on a CUA. Three outcomes were considered,
i.e. urgency, frequency and incontinence.
We found that solifenacin was associated
with the highest QALY gains for urgency,
frequency and incontinence across all
5 11
C A R D O Z O ET AL.
six therapies included in the analysis.
Furthermore, treatment with solifenacin was
dominant relative to fesoterodine, tolterodine
ER and tolterodine IR, being associated
with improved patient outcome and a lower
cost, and cost-effective relative to propiverine
ER.
Oxybutynin IR was found to be dominant
relative to fesoterodine (frequency),
propiverine, tolterodine ER and tolterodine
IR (frequency and incontinence). The
incremental cost-effectiveness ratios for
solifenacin vs oxybutynin IR (for the
frequency and urgency outcomes for which
data were reported for oxybutynin IR in
Chapple et al. [16]) were above the £30 000/
QALY threshold generally accepted by groups
such as NICE as cost-effective.
There are several limitations to this study. The
first is that the analysis conducted was
limited to a comparison of therapies for which
the outcomes frequency, urgency and
incontinence/24 h were reported in Chapple
et al. [16]. On this basis, the current analysis
excludes trospium and darifenacin; an
analysis which included these therapies
would add further to knowledge in this area.
This analysis did not include the effect on
HRQL or costs associated with the side-effects
of therapy, which might be higher in the
older-generation antimuscarinics such as
oxybutynin. As such the comparative cost-
effectiveness of solifenacin vs oxybutynin
IR in clinical practice cannot be concluded
from this analysis. As with any economic
evaluation, this study also made several
assumptions and simplifications to integrate
the best available evidence.
This evaluation is limited to consideration
of treatment scenarios with a single oral
antimuscarinic agent, albeit including both
lower and higher dose formulations where
they are available. In clinical practice,
prescribers switch between agents and
identifying the most common treatment
pathways and the relative cost-effectiveness
of these would increase knowledge in this
area. In addition, the efficacy data used in this
analysis were taken from clinical trials, where
adherence to antimuscarinic therapy is known
to be higher than that in clinical practice.
Lower adherence to therapy would be
expected to result in a lower level of efficacy
for all therapies used in clinical practice.
However, levels of adherence in clinical
512
TABLE 9 Results of the PrSA: the probability (%) of solifenacin being dominant, cost-effective or
dominated
Drug comparison
Solifenacin 5 mg/10 mg vs fesoterodine 4 mg/8 mg
Urgency
Frequency
Incontinence
Solifenacin 5 mg/10 mg vs propiverine ER
Urgency
Frequency
Incontinence
Solifenacin 5 mg/10 mg vs tolterodine ER
Urgency
Frequency
Incontinence
Solifenacin 5 mg/10 mg vs tolterodine IR 2 mg/4 mg
Urgency
Frequency
Incontinence
*Estimated applying net benefit framework.
practice might be lower in older-generation
therapies traditionally associated with a
higher incidence of side-effects.
Due to a lack of published data, our analysis
used expert-based estimates for healthcare
resources involved in the management of
OAB. These estimates were conservative, and
an extensive sensitivity analysis showed that
the model was not sensitive to this input
variable. However, estimates of resource use,
based for example on a patient registry, would
provide valuable additional information on
the true cost of patients with OAB.
HRQL data in this analysis were also limited to
that published previously. Future studies
would benefit from seeking to use not only
the efficacy data available from randomized
controlled trials, but also the HRQL data
collected within these trials wherever
possible.
This analysis focuses only on patients
receiving pharmacological treatment and
does not include the cost of life-style
interventions, behavioural therapies or
further surgical or non-surgical procedures
for those who fail to respond to or comply
with antimuscarinic therapy. The analysis also
excludes the cost of pads, which account for a
significant cost burden in patients with OAB.
In a study investigating the economic burden
JOURNAL COMPILATION
Dominant Cost-effective*
98.30 98.7
96.80 99.0
70.50 77.9
4.40 90.4
0.20 90.0
10.70 98.5
96.7 97.5
100 100
100 100
NA NA
99.2 100
100 100
on healthcare systems in Germany, Italy,
Spain, Sweden and the UK, it was estimated
that pads account for 63% of the annual per
patient cost of OAB management [7].
The general applicability of the results from
this analysis and the comparison of the
findings with previous studies is difficult due
to possible variations among countries in
treatment pathways, cost of medications, and
type and volumes of healthcare resources
included. Furthermore, existing economic
evaluations vary considerably in terms of
methodology, time horizon, perspective on
cost, background study population and
outcome measures. For example, most studies
report cost-effectiveness ratios as cost per
clinical effect (such as complete continence,
expected continent days, total incontinence
episodes per day/annual, total number of days
in complete response, number of voids/day,
etc.) [24,27–29]. Only a few of the existing
studies conducted a CUA [19,20,30].
The principal contribution of the present
study is that, to our knowledge, it is the first
economic evaluation to appraise solifenacin
against five of the most commonly used oral
antimuscarinic drugs in the UK healthcare
setting. It extended the findings of previous
studies by adopting the cost-utility approach
to cost-effectiveness. Importantly, the study
used a wide base of evidence on efficacy from
© 2010 THE AUTHORS
© 2010 BJU INTERNATIONAL

a recently published systematic review and
meta-analysis, presenting the most robust
estimates of efficacy for the treatment
alternatives.
ACKNOWLEDGEMENTS
Marina Grishchenko MSc MPH. This analysis
was conducted with financial support from
Astellas Pharma Europe.
CONFLICT OF INTEREST
Linda Cardozo and Juliet Warner are both paid
consultants for Astellas, Manpreet Sidhu is an
employee of Astellas and Andrew Thorpe is a
stock holder in Astellas.
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49
Correspondence: Juliet L. Warner, Abacus
International – Health Economics, 4 Market
Square, Bicester, Oxon OX26 6AA, UK.
e-mail: juliet.warner@abacusint.com
Abbreviations: OAB, overactive bladder;
ER, extended-release; IR, immediate-release;
CUA, cost-utility analysis; QALY, quality-
adjusted life-year; HTA, Health Technology
Assessment; NICE, National Institute for
Health and Clinical Excellence; HRQL, health-
related quality of life; ICER, incremental cost-
effectiveness ratio; PrSA, probabilistic
sensitivity analysis.

© 2010 THE AUTHORS

514 JOURNAL COMPILATION © 2010 BJU INTERNATIONAL