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

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

© 2010 THE AUTHORS


506 JOURNAL COMPILATION © 2 0 1 0 B J U I N T E R N A T I O N A L | 1 0 6 , 5 0 6 – 5 1 4 | doi:10.1111/j.1464-410X.2009.09160.x
COST-EFFECTIVENESS OF SOLIFENACIN VS OTHER ANTIMUSCARINICS

FIG. 1. Response: Repeat treatment


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

© 2010 THE AUTHORS


JOURNAL COMPILATION © 2010 BJU INTERNATIONAL 5 07
C A R D O Z O ET AL.

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


TABLE 3 Treatment persistence [18]
length of clinical trials and corresponded to
the average time between assessment visits in
% of patients who
routine clinical practice.
Drug Discontinued treatment p.a Switched to another treatment p.a
Oxybutynin IR 15 mg 64.32 5.86
INPUT DATA
Propiverine ER 20 mg 52.48 20.56
Solifenacin 5 mg 39.87 4.64
The benefits of treatment were measured
Solifenacin 10 mg 58.41 9.05
as symptom resolution and subsequent
Tolterodine ER 4 mg 66.94 7.21
improvements in health-related quality of life
Tolterodine IR 2 mg 58.33 6.56
(HRQL). Treatment success was defined
Tolterodine IR 4 mg 74.60 7.58
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.
technique is useful when patient distributions [16]. As this review did not report data for
To estimate the probability of a complete are unknown, as it facilitates a prediction of frequency and urgency at baseline, to ensure
response we first calculated the expected the proportion of patients with a discrete consistency the baseline data for all three
number of symptoms that would be observed number of events based on the mean number outcomes were obtained from a systematic
in a cohort of patients after each treatment of events in a sample population, e.g. the review and meta-analysis conducted on
cycle and line of treatment, by deducting the percentage of patients with 0, 1, 2, 3 or more behalf of Astellas Pharma Europe (available
treatment effect from the mean number of incontinence episodes/24 h before and after upon request) [17] (Table 2).
symptoms at a previous observation point treatment. These estimates were obtained
(end of previous cycle or baseline). The assuming that clinical effectiveness was Drug-specific treatment persistence data, i.e.
Poisson distribution (discrete probability constant over time for patients who remained the percentage of patients who discontinue
distribution that expresses the probability on therapy, i.e. treatment benefits were the or switch to another muscarinic agent
of a number of events occurring in a fixed same in all cycles. regardless of reason, were obtained from the
period, assuming that the events occur Information Management System database
independently of the time since the last event Estimates of clinical effectiveness for the and covered the 12-month period ending in
and at a known average rate) was then antimuscarinic agents, i.e. the mean number April 2008 [18] (Tables 3,4). The percentage of
applied to the obtained means to derive the of symptom occurrences, for all three patients who stop or switch treatment due to
percentage of patients with a complete outcomes were obtained from the systematic poor compliance was based on expert
response as per the described definitions. This review and meta-analysis by Chapple et al. opinion. Experts estimated that 70% of

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508 JOURNAL COMPILATION © 2010 BJU INTERNATIONAL
COST-EFFECTIVENESS OF SOLIFENACIN VS OTHER ANTIMUSCARINICS

QALYs were calculated by multiplying the


TABLE 4 Resource use by model state, per cycle (expert opinion)
health utilities associated with each model
state by the proportion of patients in that
Model state No. of GP visits No. of outpatient visits
state in each cycle over the model’s 1-year
Response 0.5 0
time horizon. Half-cycle correction was
Partial response 1 0
applied in all calculations, i.e. transition
Switch treatment 1 1.5
between the model states occurred at the
Stop treatment 0 0
mid-point of a cycle (rather than at the
No treatment (if applicable) 0 0
beginning or at the end), which yields a better
approximation of the average HRQL.

The analysis of resource use and unit costs


Event/drug Cost, £GB, per cycle TABLE 5 was undertaken from the perspective of the
GP visit 34.00 Unit costs of healthcare UK NHS and included costs directly associated
1st outpatient visit, urology 161 [21,22] with the treatment of OAB, i.e. cost of drugs,
Follow-up outpatient visit, urology 78 GP consultations and consultations in
1st outpatient visit, gynecology 138 outpatient clinics. NHS resource use
Follow-up outpatient visit, gynaecology 76 associated with OAB management during
Drug costs, per cycle, £ (23) pharmacological treatment was estimated by
Fesoterodine 4 mg 94.61 a UK urogynaecologist and a UK urologist and
Fesoterodine 8 mg 94.61 costed using UK official tariffs (Table 4)
Oxybutynin IR 15 mg 9.32 [21,22]. In calculations, we applied an average
Propiverine ER 20 mg 79.68 unit cost of the first and follow-up
Solifenacin 5 mg 84.01 attendance of two specialities, urology and
Solifenacin 10 mg 109.23 gynaecology (Table 5). Drug-cost estimates
Tolterodine ER 4 mg 94.61 were based on recommended dosing
Tolterodine IR 2 mg 94.61 regimens obtained from the British National
Tolterodine IR 4 mg 99.59 Formulary [23] (Table 5).

Due to a lack of quantifiable data on the risk


of OAB-induced comorbidities and associated
patients who stop treatment and 2% of and disease areas. The health utility values for resource use, this analysis did not take into
those who switch treatment do so due to this study were derived using the EQ-5D, a account such additional costs that might be
non-adherence. As fesoterodine has only generic HRQL instrument, which quantified incurred to the NHS by either adhering or
been on the market since July 2008, the improvement in patient HRQL resulting discontinuing patients. The cost of adverse
treatment persistence data from longitudinal from a reduction in voids and incontinence events was also excluded for this reason.
databases are not yet available. To episodes [19,20]. We further assumed that patients who
approximate the percentage of patients discontinued treatment incurred no further
stopping and switching treatment with A Poisson distribution was used to estimate cost to the NHS, i.e. the analysis excluded the
fesoterodine in the base-case analysis, we the proportion of patients with different cost of further interventions in those who
used the persistence rates for tolterodine numbers of symptoms at model entry. failed to respond to or to comply with
ER, the most commonly prescribed new- Obtained distributions were then weighted treatment.
generation antimuscarinic. This was by the corresponding utilities to estimate
considered the closest proxy, as fesoterodine baseline HRQL. Utilities for treatment BASE-CASE ANALYSIS
is a pro-drug of tolterodine. This assumption response were assigned as per the definitions
was relaxed in a scenario analysis where of treatment success. Utilities for partial Point estimates for all model variables were
treatment persistence rates for fesoterodine response were calculated as the mid-point used to conduct the base-case CUA. The cost
were estimated as a weighted average between the baseline utility and the utility for and benefits of each treatment alternative
between tolterodine ER and solifenacin. response. It was assumed that patients who were reported separately and then
stopped or switched treatments returned to incremental cost-effectiveness ratios (ICERs)
Patients’ Health-related quality of life (HRQL) their baseline state. These patients therefore were calculated to compare the relative cost-
was measured using outcome-related health adopted a baseline health utility value before effectiveness of different treatment scenarios.
utilities, obtained from previous publications. commencing subsequent treatment, ICERs were obtained by dividing the
Health utilities refer to values that represent regardless of time spent on therapy, i.e. there incremental (or additional) cost of an
an individual’s preference for specific health were no residual effects of treatment. Due to intervention by the incremental (or
states and vary between 0 (death) and 1 a lack of urgency-related HRQL data suitable additional) QALY gains. The ICERs were
(perfect health). Such an approach provides a for an economic evaluation, the model compared against the threshold for cost-
uniform base for comparison of patients’ adopted HRQL values for frequency as the effectiveness of £30 000/QALY, which is
health status across different interventions closest proxy (Table 2). generally accepted by HTA groups such as

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C A R D O Z O ET AL.

NICE (Fig. 2). The results are presented per management per cycle were not available, Among new-generation antimuscarinics,
1000 patients. these variables were excluded from the PrSA. treatment with solifenacin was associated
To determine whether variability in these with the lowest cost. The total estimated
In some instances a therapy might be less parameters was likely to alter the conclusions annual cost of treating OAB symptoms with
costly and less effective than the alternative. In of the base-case analysis, all model variables solifenacin ranged from £443 000 (frequency)
this analysis, we assumed that if the payer is including health utilities and the cost of to £470 000 (urgency) per 1000 patients.
willing to pay up to £30 000 per QALY gained, patient management per cycle were varied However, the least expensive treatment
that they will, conversely, be willing to accept across an arbitrary 20% range around the option of all therapies considered was
a loss of one QALY if the cost saving exceeds point estimate in a one-way sensitivity treatment with oxybutynin IR, the only non-
£30 000 gained. This means that therapies that analysis. Any variable excluded from the PrSA proprietary antimuscarinic agent. The drug
are less costly and less effective than the that was shown to be a driver of cost- cost of 1 year of treatment with oxybutynin
alternative will be deemed cost-effective if effectiveness was subjected to additional was estimated to be £32.60 per patient. Its
they have an ICER greater than £30 000. threshold analysis to identify the threshold total annual cost was estimated to be
values at which the ICERs exceeded £30 000/ £159 000–172 000 per 1000 patients. Drug
SENSITIVITY ANALYSIS QALY. We excluded the drug unit cost from costs in the oxybutynin IR scenario accounted
the sensitivity analysis as any significant for 20% of the overall cost of OAB treatment,
Uncertainty around the base-case cost- changes in current pricing was considered while drug costs with other antimuscarinics
effectiveness results was tested in univariate unlikely. were responsible for 60–70% of the overall
deterministic and probabilistic sensitivity cost (Table 6).
analyses (PrSA). Within the PrSA, 1000 Monte
Carlo simulations were generated by varying RESULTS FIG. 2. The cost-effectiveness plane.
the model parameters simultaneously
according to generally accepted distributions. Patients treated with solifenacin were Costs
PrSA included the percentage of patients shown to benefit most from treatment. Less effective, more More effective, more
stopping treatment, the percentage of Solifenacin was associated with the highest costly costly
patients switching treatments, number of QALY gains (per 1000 patients) for urgency Dominated Cost-effective if
symptoms observed at baseline, i.e. frequency, (712.3), frequency (723.1) and incontinence ICER below
incontinence, urgency, and treatment effects. (695.0). Treatment persistence data indicated £30,000/QALY
1000 combinations of incremental costs and that patients treated with solifenacin were QALYs
benefits from the PrSA were plotted on the also likely to stay on treatment for longer, Less effective, less More effective, less
cost-effectiveness plane to indicate a likely due to the low discontinuation rates, costly costly
quadrant for ICERs (Fig. 2). Because data for and therefore had a higher chance of Cost-effective if Dominant
the variance around point estimates for improvement in their OAB symptoms ICER above
health utilities and the cost of patient (Table 6). £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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COST-EFFECTIVENESS OF SOLIFENACIN VS OTHER ANTIMUSCARINICS

TABLE 7 Base-case ICERs comparing solifenacin with other antimuscarinic therapies

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 dominant NA £8087 – dominant NA
Frequency dominant £80 009 £4457 – dominant dominant
Incontinence dominant £87 162 £2639 – dominant dominant

QALY gains and cost of treatment with


TABLE 8 Univariate sensitivity analysis of treatment persistence rates for fesoterodine
fesoterodine, the overall results and cost-
effectiveness conclusions did not change
Variable Urgency Frequency Incontinence
(Table 8).
Total QALYs 710.6 719.8 693.9
Total cost, GB£ 495 447 471 904 478 857
The model was robust to simultaneous
Drug cost 339 913 339 913 339 913
variations of the model inputs within the
Health care cost 155 534 131 990 138 944
PrSA. The probability of solifenacin being
a cost-effective or dominant treatment
Solifenacin remained the dominant treatment strategy relative to fesoterodine 4 mg/8 mg, i.e. it is
strategy for all treatment outcomes
associated with higher QALY gains and lower costs than fesoterodine (solifenacin, QALYs; cost): urgency
relative to fesoterodine, propiverine,
(712.3; 470 840); frequency (723.1; 443 282); incontinence (695; 456 048).
tolterodine IR and tolterodine ER was >75%
(Table 9).

The cost-effectiveness of solifenacin vs the Efficacy data for the incontinence outcome DISCUSSION
treatment alternatives was analysed for were available for all six antimuscarinic
each outcome of interest separately. When agents. Solifenacin was dominant compared Few published reports have considered
comparing the economic value of new- with fesoterodine, tolterodine ER and the cost-effectiveness of the newer
generation antimuscarinic agents, solifenacin tolterodine IR, and cost-effective relative to antimuscarinic agents, such as solifenacin. An
was found to be the dominant treatment propiverine ER. Again, solifenacin was not economic evaluation by Ko et al. [24] assessed
strategy, i.e. it was associated with the highest cost-effective for the incontinence outcome the cost per clinical response of solifenacin,
QALY gains and the least cost (Table 7). vs oxybutynin, as the ICER was above the darifenacin, trospium, oxybutynin IR,
£30 000/QALY threshold. oxybutynin ER, transdermal oxybutynin,
Efficacy data for the urgency outcome were tolterodine IR, and tolterodine ER. Clinical
only available from Chapple et al. [16] for SENSITIVITY ANALYSES response was defined as the percentage of
solifenacin, fesoterodine, propiverine ER and patients with complete continence for seven
tolterodine ER. Among the therapies with data, The univariate sensitivity analysis showed sequential days. That study concluded that
solifenacin was shown to be the preferred that the base-case results of all pair solifenacin was a dominant treatment
treatment strategy. It was found to be less comparisons with solifenacin were robust. strategy relative to all other treatment
costly and more effective (dominant) relative While in some cases the model was sensitive alternatives, followed by transdermal
to fesoterodine 4 mg/8 mg and tolterodine ER, to utility values, treatment effects and oxybutynin, darifenacin, oxybutynin ER,
and cost-effective compared with propiverine discontinuation rates, a 20% variation of the tolterodine ER, tolterodine IR, trospium and
ER, with an ICER of £8087/QALY, with a higher point estimates did not alter the conclusion oxybutynin IR. Two previous CUAs, comparing
QALY and slightly higher costs. on the relative cost-effectiveness of this solifenacin and tolterodine ER, also showed
intervention. Further threshold analyses on that treatment with solifenacin was less
Efficacy data for the frequency outcome were the utility values did not yield plausible costly and more effective, i.e. dominant
available for all six muscarinic agents. results. All generated values fell outside [25,26].
Solifenacin was a dominant treatment option clinically relevant ranges at the £30 000/QALY
compared with fesoterodine, tolterodine ER threshold. The present research offers an economic
and tolterodine IR, and cost-effective relative evaluation of solifenacin vs five alternative
to propiverine ER, with an ICER of £4457/ A further scenario analysis was conducted muscarinic antagonists commonly used for
QALY. When considering the £30 000/QALY around persistence data for fesoterodine. We treating OAB in the UK clinical setting based
threshold, as used by NICE, the added benefits relaxed the base-case assumption and used on a CUA. Three outcomes were considered,
(in respect of QALYs) would be offered at a weighted averages between tolterodine i.e. urgency, frequency and incontinence.
much greater cost for solifenacin than ER and solifenacin to approximate the
oxybutynin IR, and would therefore result in a percentage of patients stopping and We found that solifenacin was associated
less cost-effective position for solifenacin switching treatment with fesoterodine. While with the highest QALY gains for urgency,
than oxybutynin. it had an effect on the estimate of total frequency and incontinence across all

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six therapies included in the analysis.


TABLE 9 Results of the PrSA: the probability (%) of solifenacin being dominant, cost-effective or
Furthermore, treatment with solifenacin was
dominated
dominant relative to fesoterodine, tolterodine
ER and tolterodine IR, being associated
Drug comparison Dominant Cost-effective*
with improved patient outcome and a lower
Solifenacin 5 mg/10 mg vs fesoterodine 4 mg/8 mg
cost, and cost-effective relative to propiverine
Urgency 98.30 98.7
ER.
Frequency 96.80 99.0
Incontinence 70.50 77.9
Oxybutynin IR was found to be dominant
Solifenacin 5 mg/10 mg vs propiverine ER
relative to fesoterodine (frequency),
Urgency 4.40 90.4
propiverine, tolterodine ER and tolterodine
Frequency 0.20 90.0
IR (frequency and incontinence). The
Incontinence 10.70 98.5
incremental cost-effectiveness ratios for
Solifenacin 5 mg/10 mg vs tolterodine ER
solifenacin vs oxybutynin IR (for the
Urgency 96.7 97.5
frequency and urgency outcomes for which
Frequency 100 100
data were reported for oxybutynin IR in
Incontinence 100 100
Chapple et al. [16]) were above the £30 000/
Solifenacin 5 mg/10 mg vs tolterodine IR 2 mg/4 mg
QALY threshold generally accepted by groups
Urgency NA NA
such as NICE as cost-effective.
Frequency 99.2 100
Incontinence 100 100
There are several limitations to this study. The
first is that the analysis conducted was
*Estimated applying net benefit framework.
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 practice might be lower in older-generation on healthcare systems in Germany, Italy,
analysis which included these therapies therapies traditionally associated with a Spain, Sweden and the UK, it was estimated
would add further to knowledge in this area. higher incidence of side-effects. that pads account for 63% of the annual per
patient cost of OAB management [7].
This analysis did not include the effect on Due to a lack of published data, our analysis
HRQL or costs associated with the side-effects used expert-based estimates for healthcare The general applicability of the results from
of therapy, which might be higher in the resources involved in the management of this analysis and the comparison of the
older-generation antimuscarinics such as OAB. These estimates were conservative, and findings with previous studies is difficult due
oxybutynin. As such the comparative cost- an extensive sensitivity analysis showed that to possible variations among countries in
effectiveness of solifenacin vs oxybutynin the model was not sensitive to this input treatment pathways, cost of medications, and
IR in clinical practice cannot be concluded variable. However, estimates of resource use, type and volumes of healthcare resources
from this analysis. As with any economic based for example on a patient registry, would included. Furthermore, existing economic
evaluation, this study also made several provide valuable additional information on evaluations vary considerably in terms of
assumptions and simplifications to integrate the true cost of patients with OAB. methodology, time horizon, perspective on
the best available evidence. cost, background study population and
HRQL data in this analysis were also limited to outcome measures. For example, most studies
This evaluation is limited to consideration that published previously. Future studies report cost-effectiveness ratios as cost per
of treatment scenarios with a single oral would benefit from seeking to use not only clinical effect (such as complete continence,
antimuscarinic agent, albeit including both the efficacy data available from randomized expected continent days, total incontinence
lower and higher dose formulations where controlled trials, but also the HRQL data episodes per day/annual, total number of days
they are available. In clinical practice, collected within these trials wherever in complete response, number of voids/day,
prescribers switch between agents and possible. etc.) [24,27–29]. Only a few of the existing
identifying the most common treatment studies conducted a CUA [19,20,30].
pathways and the relative cost-effectiveness This analysis focuses only on patients
of these would increase knowledge in this receiving pharmacological treatment and The principal contribution of the present
area. In addition, the efficacy data used in this does not include the cost of life-style study is that, to our knowledge, it is the first
analysis were taken from clinical trials, where interventions, behavioural therapies or economic evaluation to appraise solifenacin
adherence to antimuscarinic therapy is known further surgical or non-surgical procedures against five of the most commonly used oral
to be higher than that in clinical practice. for those who fail to respond to or comply antimuscarinic drugs in the UK healthcare
Lower adherence to therapy would be with antimuscarinic therapy. The analysis also setting. It extended the findings of previous
expected to result in a lower level of efficacy excludes the cost of pads, which account for a studies by adopting the cost-utility approach
for all therapies used in clinical practice. significant cost burden in patients with OAB. to cost-effectiveness. Importantly, the study
However, levels of adherence in clinical In a study investigating the economic burden used a wide base of evidence on efficacy from

© 2010 THE AUTHORS


512 JOURNAL COMPILATION © 2010 BJU INTERNATIONAL
COST-EFFECTIVENESS OF SOLIFENACIN VS OTHER ANTIMUSCARINICS

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30 O’Brien BJ, Goeree R, Bernard L, Rosner Correspondence: Juliet L. Warner, Abacus CUA, cost-utility analysis; QALY, quality-
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514 JOURNAL COMPILATION © 2010 BJU INTERNATIONAL