Compression products for treating venous leg ulcers: late-stage assessment

The external assessment group (EAG) took a pragmatic approach in its evidence review. It included studies with compression products delivering 30 to 40 mmHg of pressure at the ankle. This was to ensure that the evidence base reflected most of the comparisons between the types of compression products aiming to give strong compression, as detailed in the scope. The EAG prioritised 15 studies: 14 randomised controlled trials (RCTs) and 1 large UK-based retrospective cohort study comparing different types of compression for venous leg ulcers in the context of routine NHS clinical practice. Six studies were done exclusively in the UK and 1 other study included some UK sites. Evidence covered all 4 compression products. Head-to-head RCT evidence was available that directly compared different types of products. The clinical evidence was generally considered to be high quality, but the EAG noted that the open-label studies had a higher risk of bias.

Seven prioritised studies compared 4_‑layer compression bandaging with 2‑layer compression bandaging. These showed that 2‑layer bandaging was at least as effective as 4‑layer bandaging, with some evidence that 2‑layer 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 pragmatic, 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.

The VenUS 6 study 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. The VenUS 6 clinical trial results, NMA and cost-effectiveness results were available to the committee as early-stage research papers (pre-prints) that were not yet peer reviewed (Arundel et al. 2025; Phung et al. 2025).

The EAG requested an additional NMA that included the VenUS 6 data. This analysis provided by the VenUS 6 team, referred to from here as the 'EAG NMA', was designed to align with the current decision problem and separated 'evidence-based compression' into 2 separate interventions: 2‑layer compression hosiery and 4‑layer compression bandaging.

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 multicomponent bandages. Expert advice to the committee was that short-stretch bandages and 2‑layer multicomponent bandages were treated as separate interventions in the NMA from the VenUS 6 team. There was less 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 studies presented evidence on specific patient subgroups. There was little evidence on patient-reported outcomes, such as ease of use, adherence and mobility during treatment.

The committee considered the results of the VenUS IV and VenUS 6 studies. Both were multicentre, pragmatic, open-label RCTs in an NHS setting. VenUS IV showed that 2‑layer compression hosiery and 4‑layer compression bandaging had a similar time to healing, but 2‑layer compression hosiery was more cost effective than 4‑layer compression bandaging. The VenUS 6 results showed that time to healing was slower in the compression-wrap group than in both the 'evidence-based compression' and the 2‑layer compression bandage groups. The committee agreed that the VenUS IV and VenUS 6 studies provide important evidence comparing the effectiveness of the compression products in NHS settings.

The committee also discussed the different time-to-healing results of the EAG NMA and 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 NMA showed a small, non-statistically significant difference in favour of compression wraps for time to healing, whereas the VenUS 6 NMA showed a small, non-statistically significant difference that compression wraps were less likely to be effective (had a slower time to healing) than 'evidence-based compression'. The EAG explained that separating the interventions and using 4‑layer compression bandaging as the reference introduced uncertainty to 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. Also, the results for 2‑layer compression bandages and compression wraps relied on smaller, lower quality studies within the network. The committee understood that the EAG NMA structure aligned more closely with the decision problem for this assessment, but also considered the uncertainty associated with separating the 'evidence-based compression' arm. The committee accepted that the VenUS 6 NMA included all 4 compression product types and reflected clinical practice. Combining 2‑layer compression hosiery with 4‑layer compression bandaging in an 'evidence-based compression' arm avoids relying on a link in the network based on 2 studies that have been assessed as high risk of bias. It concluded that the time to healing from the VenUS 6 NMA was likely to be associated with less uncertainty.

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, it was assumed that people would continue treatment with the same compression product. For compression wraps, the EAG assumed that 1 pair would last for 6 months. But the EAG assumed that compression hosiery would last for 3 months rather than 6 months while the leg ulcer was unhealed. 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, body mass index, 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 model's results. 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 types of compression product were very small. But, compression wraps and compression hosiery appear to be associated with lower total 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 bandaging. Compression wraps and 2‑layer compression hosiery appear to be of equal clinical effectiveness and lower total 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 relies on smaller, lower quality studies within the network.

The EAG did 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 total 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 cost-effective 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 adopted a lifetime time horizon and included ulcer recurrence and treatment switching. The VenUS 6 cost-effectiveness analysis showed that 'evidence-based compression' dominated short-stretch bandaging and compression wraps, so 'evidence-based compression' is more effective and has lower total costs. It also showed that 2‑layer compression bandaging is not cost effective compared with evidence-based compression, with an incremental cost-effectiveness ratio of £159,641 per QALY gained. The committee concluded that the VenUS IV economic results provided useful additional information to the EAG's results for compression hosiery. But, for compression wraps, the committee concluded that the VenUS 6 economic results provided the most useful information.

Economic modelling suggests that compression hosiery, which enables self-management, is cost effective compared with compression bandaging, which relies on more frequent visits from a nurse to change the compression product. 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, calculated over a 5 year time period, showed that there could be potential savings from using compression hosiery instead of bandaging. Any potential savings would depend on local practice and would be subject to the limitations discussed in the EAG's 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 peoples' lived experience. Taking into account the published VenUS IV results, the VenUS 6 results and the EAG's economic modelling, it agreed there was enough evidence to show that compression hosiery is cost effective compared with compression bandaging. It concluded that price variation is justified for compression hosiery over compression bandaging.

Although compression wraps enable self-management, the VenUS 6 base case showed that compression wraps are not a cost-effective option. The committee concluded that the available evidence does not support price variation for compression wraps over the other compression products. More evidence is needed to show additional value for compression wraps. The committee emphasised that healthcare professionals should have access to an appropriate range of compression products, including compression wraps, to address the clinical needs and preferences of people with venous leg ulcers. The committee was aware that for some people compression wraps might be the only suitable option.