3 Evidence

Clinical evidence

The main clinical evidence comprises 19 studies

3.1 The evidence assessed by the external assessment centre (EAC) included 19 studies, all of which were full-text peer-reviewed publications. Of the included studies, 9 were comparative studies (3 randomised controlled trials and 6 observational studies) and 10 were single-arm observational studies. The comparative evidence included a total of 636 people, of whom 365 had VAC Veraflo Therapy system, 222 had negative pressure wound therapy, and 49 had dressings. For full details of the clinical evidence, see section 3 of the assessment report in supporting documentation.

There are not enough data to make a meaningful comparison with advanced wound care

3.2 Of the 19 studies included by the EAC, only 2 compared VAC Veraflo Therapy system with dressings (Chowdry and Wilhelmi 2019; and Deleyto et al. 2017). Both studies were retrospective, and the EAC said that their methodology and reporting were not high enough quality to have confidence in the results. The EAC concluded that there was not enough evidence to be able to assess the clinical benefit of VAC Veraflo Therapy system over advanced wound care.

The randomised controlled trial by Kim et al. (2020) is the most robust evidence

3.3 The EAC considered the randomised controlled trial by Kim et al. (2020) to be the most informative study. It was in scope, made a relevant comparison (VAC Veraflo Therapy system compared with negative pressure wound therapy), had a relatively large sample size (n=183, randomised), and a relatively high methodological quality. The study included people with acute (28%) or chronic (72%) wounds of various types. These included diabetic ulcers (43%), pressure ulcers (17%) and surgical wounds (13% dehisced and 13% non-dehisced). The EAC considered the other randomised controlled trials by Yang et al. (2017) and Kim et al. (2015) to be of limited relevance.

The observational comparative studies are generally retrospective and of limited methodological quality

3.4 The EAC considered all the comparative observational studies to be of poor methodological quality. It concluded that it was not possible to confidently say that the intervention caused the reported outcomes. Common weaknesses included:

  • poorly reported patient selection

  • small sample sizes

  • use of historical control groups without an adequate description of how these were selected

  • lack of statistical matching

  • lack of confidence in how endpoints were measured, recorded and reported.

    The EAC considered that none of the single-armed studies provided data that could reliably inform estimates of relative treatment effects for wound care in the NHS. This was because several of the studies reported descriptive outcomes only and there was also substantial heterogeneity in study populations and wound characteristics.

Heterogeneity in the study populations and variation in care pathways make it difficult to generalise data to the NHS

3.5 The comparative evidence covered a range of populations. Some studies included people with a specific wound type, while others involved a range. According to the EAC, the heterogeneous nature of the study populations, combined with the relatively small patient numbers for each wound type made interpretation of results in specific patient groups difficult. Also, none of the studies were in the NHS or reported on UK populations.

The available evidence suggests that VAC Veraflo Therapy system reduces bacterial bioburden but the clinical significance of this is unclear

3.6 One randomised controlled trial reported a statistically significant (p=0.02) reduction in bacterial bioburden (the number of bacteria in the wound bed measured in colony forming units) compared with negative pressure wound therapy (Kim et al. 2020). This was measured from the time of initial surgical debridement and first dressing change with VAC Veraflo Therapy system. This was supported by data from a smaller randomised controlled trial (n=20; Yang et al. 2017) and the comparative observational study (Goss et al. 2012), which also reported a reduction in bioburden with VAC Veraflo Therapy system after 7 days of therapy. The EAC highlighted that the clinical significance of this outcome was unclear.

It is not certain if VAC Veraflo Therapy system has better outcomes than negative pressure wound therapy

3.7 One randomised controlled trial reported no significant difference in its primary endpoint: the number of follow-on surgical debridements for VAC Veraflo Therapy system compared with negative pressure wound therapy (Kim et al. 2020). Apart from a reduction in bioburden, there was no significant difference between VAC Veraflo Therapy system and negative pressure wound therapy for any other secondary outcomes. These included the number of inpatient operating room debridements, time until wound closure or coverage, the proportion of wounds closed, and the number of wound complications. The EAC concluded that there was no evidence to support the claims for VAC Veraflo Therapy system of a reduced need for debridement or other follow-on treatments, and improvements in wound healing, compared with negative pressure wound therapy.

The evidence to support claims of a shorter hospital stay is weak

3.8 There was weak evidence to suggest that VAC Veraflo Therapy system is associated with a shorter hospital stay than negative pressure wound therapy in some populations. These included people with acute wounds of the lower limb (Omar et al. 2016), people with infected extremity and trunk wounds (Gabriel et al. 2014, Kim et al. 2014) and people with surgically dehisced wounds (Kim et al. 2020; subgroup analysis only).

There is no published evidence on health-related quality of life or patient-reported outcome measures

3.9 There was no evidence on the following clinical management outcomes: number of dressing changes, number of amputations or skin grafts, staff time, and use of other consumables. There was no published evidence on health-related quality of life or patient-reported outcome measures.

Cost evidence

The company's comparators are negative pressure wound therapy and advanced wound care in 4 clinical scenarios

3.10 The company presented a cost calculator model that compared VAC Veraflo Therapy system with negative pressure wound therapy or advanced wound care. The model evaluated 4 clinical scenarios (lower limb, mixed wounds, prosthetic implant and surgical site infections) and combined the data to estimate a total cost for the whole population (the base case). The model assumed that surgical debridement was needed after treatment and that operating room visits and operations were for debridement only. It also assumed that consumables needed changing 3 times per week. Nurse training time on VAC Veraflo Therapy system was believed to be negligible and was not included. The main clinical parameters driving the model related to length of hospital stay, length of therapy, and the number of surgical debridements needed. Parameters were derived from 7 comparative studies. When all 3 parameters could not be sourced from the same study, the company applied scaling factors using data from another study. The 3 sources of costs in the model were from the therapies themselves, surgical debridement and hospital stay.

The company's estimates show cost savings over the comparators

3.11 The company's base case results estimated a cost saving using VAC Veraflo Therapy system of £3,251 per patient compared with negative pressure wound therapy. It was £8,312 per patient compared with advanced wound care. The main driver for these cost savings was a shorter hospital stay in the VAC Veraflo Therapy system arm. The company's sensitivity analyses reported that the technology was cost saving in all of the individual scenarios that were used to inform the base case (from £300 to over £13,000). Results from a one-way deterministic sensitivity analysis found that changing individual parameters did not affect the overall direction of cost savings, but that cost savings were most sensitive to parameter or cost changes in length of stay. For full details of the cost evidence, see section 4 of the assessment report in supporting documentation.

The overall modelling approach used by the company is not appropriate

3.12 The EAC said that combining results from different clinical scenarios is not a usual method of establishing a base case. It said that a more appropriate approach would be to use a broader population as the base case, followed by scenario analyses for different subgroups. The EAC did not believe the model population was well defined, noting that the different populations included were likely to overlap. The EAC also noted that the company had used simple averages to estimate parameters in the base case, and these had not been weighted by study sample size or by underlying prevalence. The EAC did not agree with the company's method of estimating missing clinical parameters using scaling factors based on data from different studies. The EAC believed that, because of the amount of structural and parameter uncertainty, the results from the company's sensitivity analyses were uninformative.

There is a lack of confidence in the informing clinical data

3.13 The EAC noted that most of the clinical parameters used in the company model were derived from retrospective studies with low methodological quality. Some of the studies involved people who did not match the scenario described. Three of the studies used by the company were excluded by the EAC in the clinical evaluation because they used a previous version of the technology (VAC Instill).

The EAC's changes to the model result in VAC Veraflo Therapy system costing more than negative pressure wound therapy

3.14 The EAC revised the company's model to address some potential limitations by:

  • Including 2 new scenarios using relevant data from 2 additional studies (Kim et al. 2020 and Omar et al. 2016). The randomised controlled trial by Kim et al. (2020) was regarded by the EAC as the most robust evidence and was the closest to being considered appropriate for populating parameters on clinical effectiveness.

  • Only using data reported within a single study for each scenario. In the absence of data, length of stay was assumed to be the same as length of therapy. When a study did not report the number of surgeries or debridements in both arms, no debridement costs were incurred.

  • Updating technology costs to reflect current prices and excluding additional procedural costs that the company had included for the 'prosthetic implant subgroup'.

  • Modifying some inputs concerning resource use and rounding techniques.

    The EAC's base case (which used data from Kim et al. 2020 only) found VAC Veraflo Therapy system to be more costly than negative pressure wound therapy for all cost domains (length of stay, therapy and debridement), with an overall cost difference of £480 per patient. The EAC did not report a base case for VAC Veraflo Therapy system compared with advanced wound care because there were not enough data to inform this analysis.

It is not certain that VAC Veraflo Therapy system is cost saving

3.15 Although the EAC made changes to the company model that aimed to improve accuracy and consistency, its analyses had similar limitations to the company's because there was not enough clinical evidence. The EAC's scenario analyses showed that VAC Veraflo Therapy system was cost saving in all scenarios except for the EAC base case and that cost savings were mainly from shorter hospital stay. Results from probabilistic sensitivity analyses on the base case scenario showed a point estimate cost difference of £471 (95% credible interval -£1,085 to £2,015). The EAC highlighted that, because the credible interval crossed zero, it is not possible to draw conclusions from this analysis. The EAC's probabilistic sensitivity analysis at a scenario level showed that cost savings with VAC Veraflo Therapy system were highly likely in 3 out of 9 scenarios. But there was considerable uncertainty in the other 6 scenarios. Based on these results, the EAC concluded that the cost saving potential is highly uncertain.

  • National Institute for Health and Care Excellence (NICE)