Optilume for treating recurrent bulbar urethral strictures

3.1 The EAC included 4 publications, 1 unpublished trial report and 10 abstracts as evidence. All publications and abstracts related to 3 studies (ROBUST 1, ROBUST 2 and ROBUST 3). ROBUST 3 is an ongoing randomised controlled trial comparing Optilume with standard endoscopic management (direct visual internal urethrotomy or dilatation). ROBUST 1 and ROBUST 2 were single-arm non-comparative open-label studies. The ROBUST studies have included a total of 196 people, of which 148 have had Optilume. Fourteen studies identified by the company were excluded by the EAC because they did not include Optilume. For full details of the clinical evidence, see section 4 of the assessment report in the supporting documentation.

3.2 ROBUST 3 (n=127; 79 randomised to Optilume and 48 to standard endoscopic management) was most relevant to the decision problem. It is an ongoing multicentre single-blind randomised controlled trial being done in the US and Canada. It becomes open label 6 months after randomisation. Then, people are given the choice to cross over to the Optilume group if they have confirmed stricture recurrence. The study includes adult men with anterior strictures 3 cm or less in length and who have had 2 or more previous endoscopic treatments. People in the intervention group had predilatation before having Optilume.

3.3 ROBUST 1 (n=53) and ROBUST 2 (n=16) included Optilume but had no comparator. ROBUST 1 was done in 4 Latin American centres and ROBUST 2 was done in 5 US centres. They both included adult men with anterior urethral strictures 3 cm or less in length. People in ROBUST 1 had to have had up to 4 previous endoscopic treatments. People in ROBUST 2 had to have had 2 or more previous endoscopic treatments. The EAC concluded that, for both studies, methodological issues reduced the reliability of the findings and recruitment created the potential for selection bias. There were also inconsistencies in defining the primary outcome for follow up in ROBUST 1.

3.4 In ROBUST 3, compared with standard care, Optilume significantly improved anatomical success at 6 months (74.6% compared with 26.8%) and the stricture-free outcome without repeat interventions at 1 year (83.0% compared with 22.0%; p<0.0001). Also, maximum flow rate and postvoid residual both improved after Optilume compared with baseline. These results were supported by findings from ROBUST 1 and 2, with similar rates reported in the 4‑year follow-up data from ROBUST 1.

3.5 Using the international prostate symptom score (IPSS) in ROBUST 3:

3.6 Adverse events were reported in all 3 ROBUST studies. ROBUST 1 and 3 also assessed the safety of Optilume. Urinary tract infection and acute urinary retention were the most reported adverse events. Pharmacokinetic studies found systemic exposure to paclitaxel was minimal. Clinical experts using Optilume acknowledged that there is still limited data on paclitaxel use in the urinary tract for preventing stricture recurrence. Nevertheless, they advised the device was very well tolerated with minimum side effects. Five out of 6 experts said that adverse events happening later than 30 days after the procedure would be unlikely with Optilume. The EAC acknowledged the Medicines and Healthcare products Regulatory Agency safety concerns about the ongoing use of paclitaxel-coated balloons and implantable drug-eluting stents in peripheral artery disease. The systemic paclitaxel concentration after Optilume is low and paclitaxel is primarily localised to the urethra. The EAC concluded that, based on the available evidence, Optilume causes very few adverse events and does not raise safety concerns. For full details of the adverse events, see sections 5.2 and 6 of the assessment report in the supporting documentation.

3.7 The 2‑year evidence showed that Optilume improved clinical and patient-reported outcomes, and is an effective treatment for recurrent bulbar urethral strictures. The results of ROBUST 1 suggested long-term efficacy at a 4‑year follow up but it only included 53 people and was non-comparative. So, there is a lack of long-term comparative data. However, ROBUST 3 is ongoing and will collect 5‑year follow-up data until December 2025.

3.8 The company submitted a new analysis because none of the economic studies identified included Optilume as a comparator. A Markov model compared Optilume with endoscopic management for treating recurrent anterior urethral strictures 3 cm or less in length over a 5‑year time horizon. The model was based on data from ROBUST 3. Additional clinical and cost data was taken from the OPEN trial, a randomised controlled trial comparing urethrotomy with urethroplasty with a 2‑year follow up (Pickard et al. 2020). The company's base case showed a cost saving of £2,502 per person using Optilume. For full details of the cost evidence, see section 9 of the assessment report in the supporting documentation.

3.9 The EAC accepted the company's model structure, comparators, time horizon, and most of the assumptions and parameters. The EAC's initial base case was amended to 100% of day-case procedures. The clinical experts confirmed that Optilume is also being used in an outpatient setting. The EAC's base case was amended to 50% of day cases and 50% of outpatient procedures. The EAC made minor changes to the costs of training with Optilume and readmission to hospital. These changes had a small effect on the incremental cost saving. The cost saving in the EAC's base case increased to £2,510 per person using Optilume.

3.10 The key cost driver in the model was the probability of recurrence, and therefore the expected cost of retreatment. Cost savings were dependent on the savings from reduced repeat interventions being greater than the additional cost of treatment with Optilume when compared with standard endoscopic procedures. The probabilistic sensitivity analysis for the EAC's base case found that 94% of the 1,000 iterations resulted in cost saving.

3.11 The EAC noted that the clinical evidence showed that Optilume improved clinical outcomes in the shorter term. However, there was some uncertainty around the extent and duration of the improvement in the longer term and how this translated to recurrence in the model. This was related to several factors including:

3.12 The clinical experts agreed that there is not a single outcome measure for recurrence that is used consistently. Several additional scenarios using different clinical inputs for the probability of recurrence were provided. The company's and EAC's base cases used the IPSS score to indicate recurrence rates. The company included 2 additional scenarios: 1 using anatomical success from ROBUST 3 and 1 using patient-reported outcome measures from the OPEN trial. When using the EAC's base case, both scenarios decreased the cost saving from £2,510 to £1,127 and £995 respectively. The EAC included an additional scenario that explored using retreatment rates from ROBUST 3. This increased the cost saving from £2,510 to £3,340. All scenarios reported treatment with Optilume to be cost saving at 5 years.

3.13 The company stated that Optilume can be done as a day case and in an outpatient setting. Its base case assumed that 50% of the procedures would be done as a day case and 50% in an outpatient setting. Based on expert advice, the EAC accepted this assumption, which resulted in a cost saving of £2,510. The EAC analysed the effect of varying the proportion of Optilume procedures done as a day case and in an outpatient setting. Results showed that increasing the proportion of day-case procedures decreased cost savings (100%, £1,877), while increasing the proportion of outpatient procedures increased cost savings (100%, £3,142).

3.14 The company's model assumed people initially having Optilume or endoscopic methods would have retreatment using the same method. In practice, it is likely that people who do not have urethroplasty have a mix of sequential endoscopic treatments, including Optilume. This will depend on patient and clinician choice, and availability of resources. The EAC included an additional scenario allowing for a mix of Optilume and endoscopic procedures for retreatment. The results showed that increasing the proportion having retreatment using a standard endoscopic treatment resulted in a moderate decrease in total cost savings.

3.15 The company's base-case time horizon was 5 years. This was because there was a lack of long-term data and because the effect of Optilume would be greater in the initial years of using it. The company included an additional scenario using a 10‑year time horizon and the EAC investigated the effect of a longer time horizon of 20 years. Increasing the time horizon to 20 years had a small effect on the EAC's base case, increasing the cost saving from £2,510 to £3,175. The EAC noted that, because of the lack of longer-term comparative data, the results were uncertain.