Solifenacin in the treatment of overactive bladder syndrome in Italian patients: pharmacoeconomic evaluation

Abstract

Objective: To investigate the pharmacoeconomic performance of treatment with solifenacin, a new antimuscarinic with selectivity for the bladder, when compared to tolterodine and placebo, in Italian patients with overactive bladder (OAB).

Methods: The evaluation was performed using a Markov model. The time horizon of the simulation was 52 weeks, with 1-week cycles. The model simulated outcomes and costs of the treatment with solifenacin (5 mg/day), tolterodine ER (4 mg/day) and no treatment in a cohort representative of the Italian population with OAB. The analysis was conducted mainly from the perspective of the patient, since drugs for the treatment of OAB are not included in the Italian reimbursement list. A supplementary scenario explored the consequences of a hypothetical reimbursement decision by the Italian Health Service to reimburse half of the current retail price in incontinent and responding OAB patients only.

Results: Both treatments produced a reduction in symptoms and improvement in patients' quality of life, with an cost increase of about €540–640/patient/year with solifenacin and €680–780/patient/year with tolterodine. In a cost/utility analysis, solifenacin dominated tolterodine as it resulted in both more effective and less costly treatment; the cost/utility ratio with respect to no treatment was in the range €7,600–18,600/Quality-adjusted life year. The overall expenditure of the hypothesised reimbursement decision was estimated to be about 23 million euros, with a cost/utility ratio of about €600–2,400/Quality-adjusted life year, indicating an efficient allocation of health resources.

Conclusions: While both tolterodine and solifenacin appear to be cost/effective in Italy, the latter has proven to be superior.

Keywords:

Introduction

The micturition cycle can be divided in three phases: filling, pre-micturitional phase (collectively, storage phases) and voiding. During the filling phase, the physical properties of the bladder, in particular its compliance, allow for urine storage without a significant increase in endoluminal pressure. Under physiological conditions during this phase the detrusor muscle, which forms almost the whole muscular wall of the bladder, is maintained in a relaxed state by orthosympathetic stimuli that concurrently induce the bladder neck and urethral sphincters to remain contracted. During the pre-micturitional phase, the increasing pressure in the bladder is consciously perceived by the cerebral cortex, which in response inhibits the micturitional reflex and contracts the intrinsic urethral sphincter, under voluntary control. This inhibition is maintained until it is deemed to be the right time for voiding, which is initiated by concurrent parasympathetic stimulation and orthosympathetic inhibition, resulting in the contraction of the detrusor and the relaxation of sphincters and bladder neck.

Overactive bladder (OAB) syndrome is characterised by an urgency to pass urine and a very short pre-micturitional phase, generally associated with the occurrence of untimely detrusor contractions. OAB is usually accompanied by a high frequency of urination and nocturia, with (OAB wet) or without (OAB dry) incontinence¹. Urgency is defined as a sudden and compelling need to pass urine, which is difficult to defer, while nocturia is the need to get up at least once during the night to empty the bladder. OAB carries with it a profound impairment in health-related quality of life, as it affects physical, psychological, sexual, social and work functionalities. Whilst it is intuitive that bladder incontinence, high frequency and nocturia impair a person's quality of life, it has also been shown that urgency per se has a considerable impact and may even lead to social isolation.

Prevalence data from Europe and the US indicate rates as high as 12–22% in adult populations, increasing with age, similar between genders, which differ, however, in terms of incontinence rates, being much higher in females, allegedly due to anatomical differences^4–6.

Despite its high prevalence and important impact on patients' lives, OAB remains widely underdiagnosed and undertreated; a survey conducted on incontinent women living in Lombardy, Italy, revealed that little more than one-third of the patients consulted a health professional, and that in the majority of cases the proposed solution had been the use of pads. This finding has been explained by the authors as a poor knowledge of available therapies. Furthermore, the Italian Health Service (IHS) does not cover incontinence medications, and only reimburses incontinence devices (pads) to certified, stable incontinent patients. There is widespread opinion among Italian health professionals that only a small minority of OAB patients have access to these reimbursed devices and that most of them manage their problem by personally acquiring pads.

Therapeutic options for the treatment of OAB include behavioural, surgical and pharmacological strategies; the latter, mainly using antimuscarinics, is considered the first-line option.

The older anticholinergics are limited by the lack of bladder selectivity and by the consequent frequent occurrence of systemic side effects (blurred vision, dry mouth, constipation, etc.).

Solifenacin is a new antimuscarinic agent that has been proven to be effective and which has an excellent safety profile in OAB patients treated with single daily doses of 5–10 mg^{7–9,11,12,14}.

The aim of this present study was the pharmacoeconomic evaluation of solifenacin use in Italian OAB patients, conducted by means of cost/effectiveness, cost/utility and budget impact analyses.

Methods

The evaluation was conducted by creating a simple two-state Markov model. The two mutually exclusive states define the possible health states for patients in the cohorts: OAB dry or OAB wet (Figure 1).

The analysis was conducted over a 52-week time horizon, with 1-week cycles. The severity of the illness for every state and for every instant of the simulation is described by two main indices of disease control:

•	Incontinence index → number of incontinence episodes/24 hours
•	Frequency index → number of micturitions/24 hours

The model does not consider the mortality of the simulated cohort because this pathology apparently does not influence survival, and the possibility of a patient dying is negligible because of the short time horizon of the simulation; for the same reason, costs and benefits are not discounted.

Considered treatments and efficacy

The model simulates the clinical and economic outcomes of the treatment with solifenacin (5 mg/day), extended-release tolterodine (4 mg/day), or no treatment in OAB syndrome patients. Treatment efficacy is measured in terms of dry rate (percentage of continent patients among those initially incontinent), episodes of incontinence, micturition frequency and use of medical devices for incontinence; the dry rate substantially represents the transition probability from the OAB-wet to the OAB-dry state of the Markov chain, and the other efficacy parameters describe the temporal evolution of the syndrome and of disposable incontinence pads consumption.

Two alternative scenarios were considered:

•	A base-case scenario which simulated the consequences of the treatments on the general OAB patients population. Efficacy data were derived from registration trials of the two drugs, both obtained versus placebo8–10;
•	A complementary scenario (responders) was developed to represent efficacy in the subgroup of OAB patients that resulted in efficacious treatment. Efficacy data were deduced from results in the patient subgroup from the STAR study11,12 who continued to take solifenacin 5 mg.

Base-case scenario

The base-case scenario was developed to compare outcomes associated with solifenacin 5 mg/day and tolterodine 4 mg/day, referring to placebo-controlled efficacy data from the reference trials of both drugs^8–10. Although the two drugs were compared indirectly, the substantial homogeneity of recruitment criteria, duration of experimentation and endpoint definition in considered randonised controlled trials made this analysis reliable.

For solifenacin, the data from two trials^8,9 have been pooled. Frequency data (number of micturitions/24 hours) from both trials at 4, 8 and 12 weeks show that most of the treatment effect is obtained within the fourth week; therefore, the same time period has been assumed to apply to all other indices.

Neither of the two solifenacin randomised controlled trials report data on the use of pads which, for the purpose of this model, was deduced from information reported in the Summary of Product Characteristics¹³. Dry-rate data, also absent in the placebo-controlled trial reports, were obtained from the STAR study^11,12.

Responders scenario

To evaluate the efficacy of treatments in the OAB patient subgroup who responded to the therapy, the responders subgroup in the STAR study^11,12 was employed. In this trial, symptoms of over 1,000 OAB patients (randomised to solifenacin 5 mg/day or tolterodine ER 4 mg/day) were evaluated for 12 weeks. The experimental design of the study provided solifenacin patients with the possibility of asking for a dose increase (10 mg) after 4 weeks of treatment: 51% of solifenacin-treated patients did not require the increase (NDI – no dose increase group). This is the subgroup that is referred to in the alternative scenario efficacy settings.

Finally, some considerations must be made about data applied to the no treatment arm of the comparison. All the clinical trial data indicate a significant efficacy for placebo treatment; nevertheless, the same level of symptom reduction cannot be expected in patients excluded from every kind of treatment, and ascribing placebo efficacy to the no treatment arm appears to be erroneous. On the other hand, comparing pharmacological treatment to an alternative with null and void efficacy, although probably realistic in many cases, might be too optimistic in terms of incremental efficacy and cost effectiveness. For these reasons, pharmacological therapies were evaluated against both placebo and no treatment in the belief that the ‘true’ result must lie somewhere between these two.

To obtain efficacy data for the placebo group, results of the three randomised controlled trials versus placebo were pooled^8–10. The placebo group dry rate, not published, was derived by maintaining the mean observed proportion between the reduction in incontinence episodes and the dry rate in the active treatment groups (28%).

In the trials, discontinuation rates were low: over 90% of active treated patients reached the final evaluation in the two solifenacin trials, and only 9% and 7.3% of patients interrupted the treatment with solifenacin or tolterodine, respectively, in the STAR study.

All efficacy data in the model refer to a modified intent-to-treat population: only patients who began receiving the treatment and who had at least one visit in the following 12 weeks were evaluated. These efficacy values account for the discontinuation rate, and therefore no adjustment was applied. The trials reported efficacy data at 12 weeks; in order to extrapolate these results to the established time horizon (52 weeks), it was conservatively assumed that no further improvement or worsening in mean pathology indices would occur in the remaining 40 weeks. This assumption is supported by the results of two open-label, 40-week, safety and tolerability extension studies, which showed only a small improvement compared with the results obtained at 12 weeks¹⁴.

For tolterodine, an open 52-week extension study in Japanese and Korean patients randomised to tolterodine, oxybutynin or placebo^15,16 confirmed this assumption.

Health-related quality of life

Computation of quality-adjusted life years (QALYs) for the cost/utility analysis was based on utility weights originally defined by Kobelt and colleagues in a 1998 model that has been used in every major cost/utility model published on OAB patients since its publication^17–19.

The Kobelt weights are defined by combining two pathology indices: incontinence and frequency. In the original model, these weights were obtained by correlating urinary symptoms with scores from the EQ–5D questionnaire, which was completed by 461 Swedish patients with OAB (dry and wet) enrolled in a willingness-to-pay study²⁰ (Table 4).

The original data were expanded by taking into account a recent UK population study performed on 609 OAB subjects²¹; in this way the differences between quality of life of continent and incontinent subjects were examined. These new utilities (in function of the symptom index) were estimated by comparing the mean utility of the Swedish cohort (dry + wet: 0.672) with the UK study utilities (dry: 0.72; wet: 0.604). On this basis, it was estimated that utilities must be increased by about 15% for OAB-dry patients and decreased by 7% for OAB wet patients.

In the present model, the symptom index is a continuous variation, while in the original Kobelt model it was a discreet parameter. Using linear regression, a new analytic relation to determine utilities in function of the combined index was calculated and the original relationship between symptoms and utilities replicated (Table 5).

Costs

Costs considered in this model include drugs, pads for incontinent patients, medical examinations, creams and other local treatments, productivity loss and costs caused by falls or fractures. Composition and amounts applied change in function of the adopted perspective, as shown in Table 6.

In this study, the primary perspective was the patient point of view, because in Italy patients have to bear the two main costs – drugs and pads – themselves.

Anticholinergic drugs are not reimbursed by the IHS, and it is impossible to estimate precisely the share of pad costs covered by the IHS. Patients gain access to public reimbursement in different ways in different regions, but the assessment of invalidity (diagnosis of chronic, stable incontinence) is always necessary. Nevertheless, from interviews with pharmacists it has emerged that, in practice, only the most severe cases of incontinence obtain public reimbursement, and more moderately incontinent patients (probably, the majority of OAB patients) pay for their pads out of their own pockets. This observation is further supported by an investigation conducted in 2003 by Bernasconi and colleagues on a female population resident in Monza, Italy²², from which it emerged that all purchased pads were paid for by the patients.

The analysis was also performed from the IHS perspective in order to investigate the budget impact and the allocation efficiency of a hypothetical reimbursement decision for the two study drugs. In this scenario, both drug and pad costs were assumed to have been borne by the IHS.

Pharmaceutical costs were calculated on the basis of solifenacin and tolterodine ER public prices reported in the national formulary (Prontuario Farmaceutico Nazionale, November 2007), and on the doses used in reference trials.

Only packages which determine the lowest cost per year of therapy were considered; this cost was €735.16 for solifenacin 5 mg/day and €852.80 for tolterodine ER.

The cost of incontinence devices (pads) was calculated by valorising simulated consumption with a unitary cost estimate based on the mean cost obtained from pharmacies (TENA Lady, 12 items, €8) for patients (€0.67/pad) and the IHS (€0.28/pad). This last figure was calculated taking into account the annual sales turnover of the incontinence devices market divided by the number of pieces sold, as reported in Assobiomedica (Italian Association of Biomedical Products Manufacturers) data²³.

Two medical visits were included in the model: an initial examination and a follow-up examination during the year for all patients in the simulated cohort. An additional visit for every severe adverse event caused by the pharmacological therapy was also allowed for. Visits were presumed to be equally divided between the GP and the medical specialist (urologist or gynaecologist). In accordance with a opportunity cost evaluation of Garattini and colleagues²⁴, the cost of a GP visit was estimated to be €12.32 for the IHS, whilst the cost of the specialist examination was determined using the last published maximum national value (€20.66)²⁵. The patient co-payment (ticket) is variable at the regional level in Italy, so an indicative value (€18.60) from the Piedmont region was estimated²⁶.

The costs of local treatment and of fractures in aged patients are only for the incontinent patient subgroup. A value of €11.11/year for creams and local treatments, including those used in urinary infections, was based on the analysis by Bernasconi et al²². A mean value of €15.58/year for the increased incidence of fractures in aged incontinent patients was obtained from an economic analysis by Reeves et al ²⁷.

Simulated population

The size of the simulated cohort was calculated by using the OAB prevalence rate reported for Italy (12% males and 13% females) in a large population study⁴ of 16,776 subjects from six European countries; this rate was then applied to the Italian resident population (January 2006)²⁸. In this way, a population of over 3.9 million subjects was obtained, about 2.2 million of whom were females. This cohort was divided into OAB-dry and OAB-wet groups by applying rates of incontinence (25.9% and 42.3%) to men and women with OAB as reported by the multinational prevalence study in the original⁴ and subsequent publication²⁷.

Considering that the OAB syndrome is notoriously under-diagnosed and under-treated, the rate of seeking medical care was set at 35.9% (from Bernasconi and colleagues), which yielded a population of 1,403,343 OAB subjects eligible for pharmacological therapy (base-case scenario, patient perspective), of whom 491,319 were wet patients (alternative scenario, IHS perspective). In the absence of Italian data, the same clinical characteristics (micturition frequency, incontinence episodes, mean pad consumption) as patients recruited in the reference trials were applied. For frequency, the value of 11.57 micturitions/24 hours (weighed mean of the data of three clinical trial data^8,10,11) was used. The number of incontinence episodes was obtained using the only study that reported an incontinence rate at enrollment⁸; the mean value was calculated by dividing incontinence episodes by incontinent patients, thus obtaining a value of 2.75 episodes/24 hours. Pad consumption was obtained by calculating the mean consumption in STAR, and applying a process similar to the one used for incontinence episodes, which assumed that the incontinent patient rate was identical to the one reported in the solifenacin versus placebo trial⁸. Thus a value of 3.32 pads/24 hours was obtained.

Sensitivity analysis

The robustness of the results was tested by a series of one-way sensitivity analyses, i.e. by varying main parameter values in the range ±20% and observing the resulting variation in the incremental cost/utility estimate. Parameters whose influence on the final result was tested include the efficacy of active treatments (percentage reduction in the wet/dry OAB ratio, incontinence rates, micturition frequency and pad use), costs (unit prices of drugs, pads, visits and local treatments) and utility variables (baseline values from Kobelt et al 19 and adjustments made to discriminate between OAB-wet and OAB-dry subjects according to data from Currie et al ²¹).

Results

Table 8 displays the main cost/effectiveness results for the base-case scenario.

The number of patients freed from incontinence symptoms is the main efficacy measure, whereas utility is quantified as the mean QALY increase per patient. Incremental cost/effectiveness and cost/utility were calculated versus both placebo and no treatment.

As expected, the drug-based strategies were more effective but also more expensive than placebo or no treatment, because drug cost is only partially compensated by other cost savings (essentially pads). On average solifenacin dominated tolterodine ER: in other words the drug was more effective and less expensive. Benefits implied by the use of solifenacin in OAB patients required a mean cost increase of €540–640 per patient per year, while with tolterodine ER the annual increase was about €680–780. Considering the improvement in quality of life, the cost increase implies a mean cost/utility ratio of €7,600–18,600/QALY for solifenacin.

Figures 2 and 3 show the results of the sensitivity analyses conducted on incremental cost/utility ratios in this scenario. Figure 2 shows that, under all tested hypotheses, the solifenacin cost/utility estimate remains in the ‘very cost/effective’ area (dark grey – incremental cost/utility <€26,000/QALY), regardless of the comparator chosen (placebo vs. no treatment), while the tolterodine cost/utility is stable in this area when compared to no treatment and always in the ‘cost/effective area’ (light grey, incremental cost/utility between 1 and 3 per capita gross domestic products[GDPs]) if the chosen comparator is placebo. No single 20% variation in parameters inverts the relative convenience of tolterodine and solifenacin (lines in the diagram never cross). In Figure 3, the magnitude of the influence of single parameters on the cost/utility of solifenacin versus placebo is shown in greater detail by means of a tornado diagram, which orders parameters according to the decreasing sensitivity of the final estimate to their variations.

In the responders scenario there are greater clinical benefits and lower cost increases, as shown in Table 9. A hypothetical incontinent and responding patient who decides to continue solifenacin therapy can expect a cost increase of €100–400 per year, with a reduction in episodes of urgency and micturition frequency of about one-quarter, and a 65% probability of returning continence.

As mentioned above, the IHS perspective in this analysis was included in order to be able to explore the impact of a hypothetical policy of reimbursement of anticholinergic drugs. A restricted form of reimbursement for the drug was presumed, only to incontinent and responding OAB patients, excluding all patients for whom the therapy did not result in a satisfactory outcome. In addition, a 50% discount was applied to the public price of these drugs.

On the basis of these settings, the model estimates that a pharmacological intervention with solifenacin on all Italian incontinent OAB patients seeking medical care can free more than 150,000 patients from incontinence, if compared to no treatment, with a cost to the IHS of about 23 million euros. This results in a favourable cost/utility ratio, ranging from €600 to €2,500/QALY. The sensitivity analyses conducted on this ratio (Figure 4) indicate that the estimate is substantially stable under a wide range of parameter settings. Both drugs have an estimated cost/utility ratio that is consistently between €5,000 and €10,000/QALY. The only exception is the case where solifenacin is compared to no treatment where it would become dominant (white area in Figure 4) if its cost was reduced by a further 20%, or if pad prices were higher. As in the main scenario, no single parameter variation changes the relative convenience of solifenacin and tolterodine.

Conclusions

Currently, in Italy, OAB syndrome is mainly managed with the use of incontinence pads instead of medical therapy. This therapeutic attitude, which is caused by historical-cultural reasons (poor sensitivity and poor patient and physician knowledge) and contextual difficulties (firstly, the coverage of devices versus the non-coverage of drugs), is suboptimal in terms of acceptability, quality of life impact and general wellbeing. Furthermore, many authors have suggested that a more proactive approach has the potential of being economically advantageous for patients and society, and may even be so from the point of view of the healthcare provider^7,17–19.

The pharmacoeconomic analyses presented here indicate that the use of pharmaceutical treatments for OAB syndrome can be expected to be associated with a significantly better clinical outcome and improved quality of life, at a relatively modest increase to healthcare costs. Both evaluated drugs cause an increase in expected costs and utility, although solifenacin appears to dominate tolterodine ER, as it is estimated as being associated with lower costs and higher effectiveness. From the fundamental point of view of the patient, which currently carries the clinical and economical burden of the illness, the benefits of solifenacin are to be weighed against a net annual cost of about €600, and even less (€100–400/year) for the incontinent and respondent patient.

The hypothetical scenario in which the IHS reimburses solifenacin, paying half of its retail price for incontinent and responding OAB patients, is expected to raise health expenditures by about 23 million euros and to reduce the rate of incontinence in this population by two-thirds, without considering the benefits in terms of urgency and frequency. The authors estimate a cost/utility of about €2,500/QALY for this strategy, which is an extremely favourable value when compared to accepted thresholds. In fact, according to the WHO, health interventions whose cost for year of life gained is below the annual per capita GDP are to be considered very cost/effective, and cost/effective where they have a cost/year of life between 1 and 3 times the per capita GDP²⁹. To facilitate the evaluation of the present study's results according to these parameters, it is useful to keep in mind that a QALY corresponds to a year of life in the best imaginable health state, and that the per capita GDP in Italy was about €26,000 in 2007³⁰.

Two previous pharmacoeconomic evaluations of OAB treatments that included solifenacin have been published in the international literature.

In the first, a decision-analytic model of antimuscarinics used for OAB treatment that was conducted from the perspective of a US third-party payer, solifenacin dominated all other alternatives, being concurrently less expensive and more effective³¹. The second³² was a Markov model constructed to simulate the clinical and economical outcome of treating UK OAB patients with tolterodine or solifenacin. This latter model was based on the results of the STAR study¹¹. The base-case analysis shows that solifenacin is the dominant strategy; the extended sensitivity analyses confirmed that solifenacin is either dominant or cost/effective (incremental cost/utility always less than £30,000/QALY). Therefore, the overall results and conclusions reported in these papers compare well to the ones presented here, despite the use of different methodologies, data sources and settings.

In conclusion, the authors believe that pharmaceutical treatment of OAB syndrome is capable of improving patient quality of life at an acceptable cost, and that it should be proposed to all patients referring to a health professional seeking a solution to their condition. It appears that solifenacin economically outperforms tolterodine ER in Italy as well as in the different healthcare settings for which studies have been performed.

Figure 1. Graphical representation of the simple Markov chain used for the analyses.

Figure 2. Radar diagram of sensitivity analyses on incremental cost/utility estimates (patient perspective) in the main scenario.

Figure 3. Tornado diagram of sensitivity analyses on the incremental cost/utility (patient perspective) of solifenacin 5 mg vs. placebo in the main scenario.

Figure 4. Radar diagram of sensitivity analyses on incremental cost/utility estimates (IHS perspective) in the responders scenario.

Table 1. Solifenacin efficacy (means) in clinical trials vs. placebo^8,9.

	SOL 5 mg	Placebo
Chapple et al, 2004
Evaluated patients, n	266	253
Efficacy
Episodes of incontinence/24 hours (%)	–59	–29
Micturitions/24 hours (%)	–17	–8
Cardozo et al, 2004
Evaluated patients, n	286	281
Efficacy
Episodes of incontinence/24 hours (%)	–60.7	–27.9
Micturitions/24 hours (%)	–19.6	–12.8

SOL, solifenacin.

Table 2. Tolterodine efficacy (means) in the placebo-controlled trial¹⁰.

Van Kerrebroeck, 2001 study	TOL ER	Placebo
Evaluated patients, n	507	508
Micturitions/24 hours
Baseline mean	10.9	11.3
Decrease	–1.8	–1.2
Percentage change	–17	–11
Incontinence episodes/week
Baseline mean	22.1	23.3
Decrease	–11.8	–6.9
Percentage change	–53	–30
No. pads/24 hours
Baseline mean	1.4	1.5
Decrease	–0.5	–0.2
Percentage change	–36	–13

TOL ER, tolterodine extended release.

Table 3. Efficacy (mean percent variation) in the STAR study^11,12.

STAR study	All patients group (week 4)		All patients group (week 12)		NDI group (week 4)
	SOL 5/10 mg	TOL ER 4 mg	SOL 5/10 mg	TOL ER 4 mg	SOL 5 mg	TOL ER 4 mg
Micturitions/24 hours(%)	–14.5	–12.6	–20.8	–19.2	–22.3	–21.9
Episodes of incontinence/24 hours(%)	–46.9	–35.3	–57.8	–43.5	–67.2	–61.2
Use of pads/24 hours(%)	–37.2	–27.3	–52.9	–40.6	–57.0	–53.4
Dry rate (%)	39.00	34.00	59.00	49.00	65.40	58.30

TOL ER, tolterodine extended release; SOL, solifenacin; NDI, no dose increase.

Table 4. Utilities from the Kobelt et al model¹⁹ by symptom index.

Utilities in function of the combination index = (micturitions + incontinence episodes)/24 hours
Index	<9	9–<12	12–<15	15–<18	≥18	Dropout
Utilities	0.742	0.712	0.676	0.64	0.598	0.672

Table 5. Modification of utilities from the model of Kobelt et al based on Currie et al ²¹.

Index	<9	9–<12	12–<15	15–<18	≥18
Continent patients utilities	0.853	0.819	0.778	0.736	0.688
Incontinent patients utilities	0.690	0.662	0.628	0.595	0.556

Table 6. Costs calculated for every considered perspective.

Costs	Patient perspective	IHS perspective
Drugs	x	x
Pads	x	x
Examinations	x	x
Creams and local treatments	x
Falls and fractures		x

HIS, Italian Health Service.

Table 7. Retail prices of tolterodine ER and solifenacin.

Generic name	Manufacturer and proprietary name	Cost
Tolterodine	Pfizer Detrusitol Caps Retard 14 caps 2 mg	€32.80
	Pfizer Detrusitol Caps Retard 14 caps 4 mg	€32.80
Solifenacin	Astellas Vesiker 10 cpr 5 mg	€21.73
	Astellas Vesiker 30 cpr 5 mg	€60.59

Table 8. Results (means) from the base scenario: patient perspective.

OAB patient perspective	SOL 5 mg	TOL ER 4 mg	Placebo	No treatment
Efficacy (patients freed from incontinence)	289,878	240,746	135,584
Utility (QALY/patient)	0.810	0.800	0.776	0.740
Costs for patient (€/patient)
Drugs	735.16	852.80	0	0
Pads	87.41	114.86	182.72	283.47
Examinations	18.63	18.76	18.60	18.60
Creams and local treatments	1.88	2.22	2.95	3.89
Total	843.08	988.64	204.27	305.96
	SOL 5 mg	TOL ER 4 mg
Incremental cost/effectiveness (€/patient freed)
CE vs. placebo	5,810.13	10,467.10
CE vs. NoT	2,600.26	3,979.42
Incremental cost/utility (€/QALY)
CU vs. placebo	18,612.95	33,309.27
CU vs. NoT	7,634.15	11,457.30

SOL, solifenacin; TOL ER, tolterodine extended release; CE, incremental cost/effectiveness; CU, incremental cost/utility; NoT, no treatment; QALY, quality-adjusted life years.

Table 9. Results (means) in the incontinent and responder subgroup: patient perspective.

Incontinent patient perspective	SOL 5 mg	TOL ER 4 mg	Placebo	No treatment
Costs (€/patient)	931.52	1,089.89	548.93	839.39
Increase vs. placebo	382.59	540.96
Increase vs. NoT	92.13	250.49
Cost/utility (€/QALY)
CU vs. placebo	4,221.63	7,013.95
CU vs. NoT	576.51	1,712.11

SOL, solifenacin; TOL ER, tolterodine extended release; CU, incremental cost/utility ratio; NoT, no treatment.

Table 10. Results in the incontinent and responders patients subgroup; IHS perspective.

IHS perspective	SOL 5 mg	TOL ER 4 mg	Placebo	No treatment
Efficacy (patients freed from incontinence)	163,874	146,084	69,148
Utility (QALY/patient)	0.775	0.761	0.684	0.615
Costs (€/patient)	479.59	556.07	262.90	386.93
Budget impact (€ million)	120.17	139.34	65.88	96.95
Increase vs. placebo	54.29	73.46
Increase vs. NoT	23.22	42.38
			SOL 5 mg	TOL ER 4 mg
Incremental cost/effectiveness (€/patient freed)
CE vs. placebo			573.17	954.83
CE vs. NoT			141.67	290.13
Incremental cost/utility (€/QALY)
CU vs. placebo			2,390.93	3,801.20
CU vs. NoT			579.79	1,156.08

IHS, italian Health Service; QALY, quality-adjusted life years; SOL, solifenacin; TOLER, tolterodine extended release; CE, incremental cost/effectiveness ratio CU, incremental cost/utility ratio; NoT, no treatment.

Acknowledgement

Declaration on interest: This study was funded by an unrestricted research grant from Astellas Pharma s.r.l.

Notes