Guidance assessment consultation document for HTE10048 Compression products for treating venous leg ulcers: late-stage assessment

The EAG prioritised 15 studies: 14 randomised controlled trials (RCTs) and 1 large UK-based retrospective cohort study comparing different forms of compression for venous leg ulcers in the context of routine NHS practice. Six studies were conducted exclusively in the UK, and 1 other study included some UK sites. Evidence covered all 4 compression products, and head-to-head RCT evidence was available that directly compared different types of product. The clinical evidence was generally considered to be high quality, but the EAG noted that the open-label studies have a higher risk of bias.

Seven prioritised studies compared 4-layer compression bandaging with 2-layer compression bandaging. These showed that 2-layer compression bandaging was at least as effective as 4-layer compression bandaging, with some evidence showing that 2-layer compression bandaging may be more effective. Both 2-layer compression hosiery and compression wraps were shown to be equivalent to 4-layer compression bandaging, but there was only 1 small US-based RCT on compression wraps for this comparison. The VenUS IV study, a UK-based multicentre RCT, compared 2-layer compression hosiery with 4-layer compression bandaging. The EAG considered the evidence available to be high quality and generalisable to the NHS. The EAG acknowledged that all the compression product types evaluated are appropriate treatment options for people with venous leg ulcers.

VenUS 6 was a pragmatic, parallel-group, 3-arm RCT that recruited 637 people in NHS settings across the UK. Data collection was completed in August 2024. It compared 3 types of strong compression: compression wraps, 2-layer bandaging and 'evidence-based compression'. The evidence-based compression included either 2-layer compression hosiery or 4-layer compression bandaging. People were followed up for between 4 and 12 months. The primary endpoint was time to healing. The findings of VenUS 6 were included as individual patient data in a network meta-analysis (NMA) by the VenUS 6 team. Results from the VenUS 6 NMA were shared with the EAG and committee, but are academic in confidence and cannot be reported here.

The EAG requested an additional NMA that includes the VenUS 6 data. This analysis provided by the VenUS 6 team, referred to here as the EAG NMA, was designed to align with the current decision problem and separated the evidence-based care into 2 separate interventions: 2-layer compression hosiery and 4-layer compression bandaging. The results of the EAG NMA are academic in confidence and cannot be reported here.

Despite the overall quality of the evidence, the committee agreed there were several important limitations. In its review of the evidence, the EAG noted that the evidence for studies that included 2-layer compression bandaging was difficult to interpret because the studies used different combinations of bandages. For example, some studies included short-stretch bandages, whereas others used 2-layer multi-component bandages. Expert advice to the committee was that short-stretch bandages and 2-layer multi-component bandages were treated as separate interventions in the NMAs from the VenUS 6 team. There was more limited evidence for compression wraps than for the other interventions. The committee understood this was because compression wraps are a newer technology for this indication. None of the prioritised included studies presented evidence on specific patient subgroups. There was little evidence on patient-reported outcomes, such as ease of use and mobility during treatment.

The committee considered the published results of the VenUS IV study and the academic-in-confidence results from the VenUS 6 NMA. VenUS IV was a multicentre, pragmatic, open RCT in NHS settings that compared the clinical and cost effectiveness of 2-layer compression hosiery and 4-layer compression bandaging. The results from VenUS IV showed that the 2 interventions had similar time to healing, but the 2-layer compression hosiery was cost effective compared with 4-layer compression bandaging. At the time of the committee meeting, the EAG and the committee had seen only the associated NMA and not the detailed results of the VenUS 6 trial. This limited the committee's ability to take these results into account. The committee was aware that the results of the VenUS 6 trial and the associated economic evaluation are being prepared for publication. The committee agreed that the published evidence from VenUS IV and the upcoming results from the VenUS 6 trial will provide important evidence comparing the effectiveness of the compression products in NHS settings.

The committee also discussed the different results of the EAG NMA and the VenUS 6 NMA. It understood that the VenUS 6 NMA assumed equivalence between 4-layer compression bandaging and 2-layer compression hosiery, whereas the EAG NMA treated these interventions separately. The EAG explained that separating the interventions and using the 4-layer compression bandaging as the reference introduced uncertainty in the results of the EAG NMA. Expert advice to the committee was that the different structure in the EAG NMA meant that the results for compression wraps were more uncertain because there was only an indirect link between compression wraps and 4-layer compression bandaging. But the committee understood that the EAG's NMA structure aligned more closely with the decision problem for this assessment. The committee accepted that the results from both NMAs based on the VenUS 6 data are important contributions to the evidence base and considered that the variation in their results highlighted uncertainties in the evidence base. It concluded that the time to healing from the EAG NMA was the most appropriate evidence for the economic modelling, but it noted the uncertainty associated with compression wraps.

The EAG used a Markov model that estimated the costs and quality-adjusted life years (QALYs) accrued for each of the 4 types of compression product. The model included 3 health states: unhealed, healed and dead. People entered the model with an unhealed venous leg ulcer when a healthcare professional applies one of the 4 types of compression product. In each cycle, a person has a probability of transitioning to the healed or dead state. While the venous leg ulcer was unhealed, people were assumed to continue treatment with the same compression product. Once the ulcer was healed the person was offered compression hosiery to provide maintenance compression. The model used a cycle length of 1 week and a time horizon of 5 years. The committee agreed that the structure of the model was appropriate.

The committee noted that the model did not consider recurrence of ulcers over the 5-year time horizon. The EAG explained that the model's focus was exploring the cost effectiveness of the different treatment options for a venous leg ulcer, rather than capturing all the occurrences of leg ulcers over a person's lifetime. Experts advised that they expect most leg ulcers to heal in a relatively short time (12 to 24 weeks), but some people have ulcers for much longer. The committee also discussed that treatment switching is not included. It heard from the experts that switching between different types of products is relatively common. The EAG believed that excluding treatment switching could bias the analysis in favour of more expensive options, such as compression hosiery and wraps. This is because their higher unit cost means that wastage as a result of switching would have a greater cost impact. The clinical experts advised that people who have compression wraps continue with this treatment in the maintenance phase and do not switch to hosiery. This is different from the model's assumption that all patients move to maintenance hosiery in the healed state.

The key clinical input in the economic model is time to healing. The model assumed that this parameter was unaffected by leg size, BMI, comorbidities, ambulatory status or wound size. Baseline time to healing was estimated for 4-layer compression bandaging using data from the VenUS IV study. Time to healing for the other compression products was calculated by applying hazard ratios from the EAG NMA to the baseline 4-layer compression bandaging survival curve.

The committee noted that for each compression product type, the associated resource use costs are more than the product costs. The committee discussed assumptions about resource use and their effect on the results of the economic model. The EAG used expert advice to estimate the resource use associated with the different products. Experts confirmed that the duration of appointments is fixed in clinic settings. The EAG advised that a scenario analysis that equalised the nurse costs across the products did not affect the results of the model. The committee understood that the frequency of healthcare visits needed is the resource use driver of cost effectiveness.

The results of the economic evaluation suggested that, over 5 years, the differences in QALYs accrued between the 4 compression product types were very small. But, compression wraps and compression hosiery appear to be associated with lower costs. This is the case for all ankle circumferences and whether or not the person with a venous leg ulcer is ambulatory. The committee understood that some of the difference in cost between product types is driven by the frequency of visits needed to change compression bandages. The EAG noted that the economic results should be treated with caution. It explained the results are driven by the clinical evidence suggesting broad equivalence across the product types, with some evidence favouring 2-layer compression bandaging over 4-layer compression bandaging. Compression wraps and 2-layer compression hosiery appear to be of equal clinical effectiveness and lower cost, whereas 2- and 4-layer compression bandaging are more expensive. So, the EAG results showed compression wraps and compression hosiery may offer better value for money than 2- or 4-layer compression bandaging. The committee understood that some of the uncertainty in the EAG's economic modelling was linked to the uncertainties in the EAG NMA results, in which the evidence for compression wraps is limited.

The EAG conducted several scenario analyses that used a lower utility benefit for healed ulcers and similar nurse costs across compression products. These scenarios did not considerably affect the results, and lower costs were still associated with compression wraps and 2-layer compression hosiery compared with 2- and 4-layer compression bandaging. A scenario analysis exploring different time horizons showed that, over shorter time horizons (12 to 52 weeks), 2-layer compression hosiery is the most cost-effective product type. When the time horizon was lengthened, compression wraps became the preferred option.

The EAG advised that the VenUS IV study reported that 2-layer compression hosiery was cost effective compared with 4-layer compression bandaging. This was attributed to its protective effect against recurrence. The committee noted the differences between the VenUS 6 economic modelling and the EAG's economic model. The VenUS 6 model was informed by resource-use data and health-state utilities collected during the study. The VenUS 6 model also adopts a lifetime time horizon and includes ulcer recurrence. The results of the VenUS 6 economic model are academic in confidence. The committee concluded that the VenUS IV and VenUS 6 economic results provided useful additional information to the EAG's results.

Economic modelling suggests that compression hosiery, which enables self-management, is cost effective compared with compression bandaging, which relies on regular visits from a nurse to change the dressing. So, using compression hosiery (if it is clinically appropriate and meets the preferences and needs of the person with the venous leg ulcer) instead of bandaging may be cost-saving for the NHS. A resource impact assessment based on the assumptions and costs from the EAG's economic model showed that there could be potential savings from using compression hosiery instead of bandaging. These were estimated to be £528,000 based on 2,000 people using compression bandaging and assuming that 30% of them switch to compression hosiery. Any potential savings would depend on local practice and would be subject to the limitations discussed in the external assessment report. More details can be found in the resource impact assessment report.

The committee discussed the clinical and economic evidence, the user preference assessment and the lived experience. Taking into account the published VenUS IV results, the VenUS 6 results and the EAG economic modelling, it agreed there was enough evidence to show that compression hosiery is cost effective compared with compression bandaging. It concluded that the price difference is justified for compression hosiery compared with compression bandaging. Although compression wraps facilitate self-management and are a cost-effective option in the EAG's base case, there is considerable uncertainty in these results. The EAG NMA results for compression wraps used in the EAG economic modelling for time to healing were also uncertain. The committee concluded that there is not enough evidence to determine whether price variation is justified for compression wraps over the other products. The committee emphasised that healthcare professionals should have access to an appropriate range of compression products to address the clinical needs and preferences of people with venous leg ulcers.