Economic evaluation of Optilume, a drug‐coated balloon for recurrent anterior male urethral stricture

Abstract Objectives We aim to conduct an economic evaluation of the Optilume urethral drug‐coated balloon (DCB) compared with endoscopic management for the treatment of recurrent anterior male urethral stricture in England. Patients and Methods A cohort Markov model was developed to estimate the costs and savings to the NHS over a 5‐year time horizon of adopting Optilume for the treatment of anterior urethral male stricture versus current endoscopic standard of care. A scenario analysis was conducted which compared Optilume to urethroplasty. Probabilistic and deterministic sensitivity analyses were performed to estimate the impact of uncertainties in model parameters. Results When compared with current endoscopic standard of care Optilume resulted in an estimated cost saving of £2502 per patient if introduced in the NHS for the treatment of recurrent anterior male urethral stricture. In the scenario analysis, the use of Optilume compared with urethroplasty resulted in an estimated cost saving of £243. Results were robust to changes in individual input parameters as demonstrated in the deterministic sensitivity analyses, with the monthly probability of symptom recurrence associated with endoscopic management the only exception. Probabilistic sensitivity analysis results demonstrated that Optilume was cost saving in 93.4% of model iterations, when running 1000 iterations. Conclusion Our analysis suggests that the Optilume urethral DCB treatment can be a cost‐saving alternative management option for the treatment of recurrent anterior male urethral stricture within the NHS in England.

reconstruction of the urethra via plastic surgery. Although urethroplasties are becoming more common in England, there is still a limitation on their availability to patients because the procedure requires a specialist centre with a trained urethroplasty surgeon.
Recurrence of male urethral stricture after receiving endoscopic treatment is common, reported to be as high as 16% after 1 month. 4,5 Recurrences of a urethral stricture often require further treatment, resulting in increased costs to the health system and impacting on patient's quality of life. 6 Optilume was designed for the treatment of anterior male urethral strictures for people aged 18 years or older for stricture length equal to, or less than, 3 cm. Optilume is a surgical intervention that has a lower male urethral stricture recurrence rate than endoscopic management. 4 This is the first analysis that attempts to estimate the cost impact of implementing Optilume as an alternative treatment for male urethral stricture in the England.

| Objective
The aim of this study was to conduct an economic evaluation of the Optilume urethral drug-coated balloon (DCB) compared with endoscopic management for the treatment of recurrent anterior male urethral stricture in England. The following assumptions were used in the modelling. Firstly, patients could remain in the recurrence health state for more than one cycle. This was based on literature showing that the time to treatment following recurrence is longer than 1 month 6 ; the waiting time to treatment was also assumed to be equivalent between endoscopic management and Optilume. Another assumption made was that the F I G U R E 1 Patients entering the model underwent treatment with Optilume or endoscopic management. Patients transitioned to the treatment-dependent cured health state after a one monthlycycle where they remained until experiencing a recurrence. A proportion of patients then transition into a recurrence health state that is dependent on the last treatment received. The number of cycles in which patients remain in the treatment-dependent recurrence state is dependent on the median time to treatment following recurrence. A small proportion of recurrent patients are assumed to receive no treatment following stricture recurrence and will remain in this state for the remainder of the model time horizon or until death. The remainder of patients have a repeat procedure following recurrence, and patients can receive either a repeat endoscopic procedure or a urethroplasty procedure. Patients in the Optilume treatment arm given a repeat endoscopic procedure are assumed to have another Optilume treatment. Following retreatment, patients were assumed to transition to the cured health state, and any treatment failure was assumed to be captured by recurrence rates. At any point in the model time horizon, patients could transition and remain in the death health state. efficacy of treatments was the same irrespective of whether it was an initial or repeat procedure. Evidence suggests that the efficacy of endoscopic management may diminish after the first treatment. However, the expected decrease of efficacy with each additional treatment is not clearly defined in the literature. 7,8 To support the assumption of keeping efficacy the same, the population that the model parameters are based on is heterogeneous, and patients may have had different numbers of previous endoscopic treatments at the time of recruitment into the study.

| Inputs
The following input data were used to populate the model, and full details are in Table 1. Transition probabilities were derived for each   health state based on data from the ROBUST III trial and OPEN RCT. 4,6 The monthly probability of recurrence after endoscopic management or Optilume was taken from the ROBUST III trial. 4 The ROBUST III study utilised a subjective outcome at the 12-month follow up, symptom recurrence without intervention. Responder rates at Value Source (IPSS) improvement of ≥30% without repeat intervention. The recurrence rate at 12 months was 88.1% for the standard of care arm and 26.9% for Optilume; these were then converted into monthly probabilities that could be used in the model. The reported outcomes of the ROBUST III were used for the transition probabilities as it directly compared Optilume and endoscopic management. The monthly probability of stricture recurrence with urethroplasty was taken from the OPEN RCT, using the outcome of recurrence at 24 months then converted to a monthly probability. 6 The probability of having further treatment following a recurrence of a urethral stricture and the distribution of the different available treatments given was taken from the OPEN RCT. 6 The study reported that 90% of patients received treatment following a recur-

| Scenario analysis
In scenario analysis, the effect of using urethroplasty as the comparator instead of endoscopic management was explored. To compare Optilume with urethroplasty, no inputs associated with Optilume were changed from the base case. The monthly probability of recurrence with urethroplasty was taken from the OPEN RCT, which stated a recurrence of 0.9%. 6 The cost of urethroplasty (£4716) was taken from the NHS reference costs (10).

| Sensitivity analysis
Sensitivity analyses were used to assess the level of confidence associated with the results of our economic evaluation. Both probabilistic sensitivity analysis (PSA) and deterministic sensitivity analysis (DSA) were conducted. A PSA was undertaken using 1000 iterations, because that was the number of iterations needed to produce stability in the results of the model. Distributions were fitted and used confidence intervals reported from the data sources. In the absence of data on the variability around the sampling distribution of mean values, the standard error was assumed equal to 25% of the mean. A summary of the distributions used for the DSA and PSA is available in Table S2.

| RESULTS
The base case result followed a hypothetical cohort of men aged 59 with an anterior urethral male stricture. The mean cost per patient given Optilume, mean cost per patient given endoscopic management and the incremental difference are shown in Table 2. The total cost per person over a 5-year time horizon was £9122 for endoscopic management and £6620 for Optilume. The result is a cost-saving of £2502 when using Optilume when compared with endoscopic management in the NHS in England.

| Scenario analysis
A scenario analysis demonstrates cost differences with the use of Optilume compared with urethroplasty.

| Sensitivity analysis
The PSA demonstrates that the results are robust to joint parameter uncertainty. The majority of parameters were varied in the PSA by distributions based on confidence intervals reported in the literature.
As Figure 2 shows, Optilume was cost saving in 93.4% of 1000 iterations.
The results of the DSA are presented in Figure 3, as a tornado diagram. The DSA shows that the monthly probabilities of symptom recurrence for endoscopic management and Optilume are the primary drivers of the incremental cost per patient. A table of the DSA results are available in Table S3.

| DISCUSSION
The main findings of our analysis indicated that for the treatment of The main strength associated with this analysis is the use of robust model inputs adopted from publicly available data sources.
Costs were taken from the BNF and NHS reference costs, sources that are widely adopted for economic evaluations in England. 9,10 The effectiveness of Optilume was modelled based on data from the pivotal, phase III, single-blind, randomised controlled study ROBUST III. 4 The ROBUST III consisted of 127 subjects. From the ROBUST III, our analyses estimated the probability of stricture recurrence and safety of Optilume compared with endoscopic management. The results of this trial are supported by a single arm study of Optilume looking over a longer 3-year time period, the ROBUST I. 12 These key model assumptions were then extensively explored via sensitivity analyses.
The PSA and DSA showed that the model results are robust to plausible changes in input parameters.
There were some limitations identified in our analyses. The ROBUST III trial, used for treatment recurrence rates of Optilume Another limitation in our analyses was the lack of robust data to inform the comparison between Optilume and urethroplasty. Urethroplasty was included in the scenario analysis as the comparator to Optilume. There was not any head to head data available that directly compared the effectiveness of both treatments, in the absence of data

| CONCLUSION
In conclusion, the findings of this analysis support the use of Optilume urethral drug-coated balloon as an alternative to the standard of care Patrick.