Wounds research theme: treatments in wound care
Members of the Wounds research group have been involved in several large randomised controlled trials (RCTs) funded by the National Institute of Health Research.
We have also been involved in evidence synthesis research using methods such as network meta-analysis and decision analytical modelling to explore clinical and cost effectiveness in wound care (funded by the MRC and NIHR).
Some projects used these advanced methods where RCT evidence was limited, while others used the approaches to combine new RCT data with existing evidence to give a comprehensive overview of evidence and outstanding uncertainty that might influence decision making.
We have also used value of information analysis to assess the value for money future research options might offer given current levels of uncertainty around treatment choices in wound care.
Some examples of studies we have been involved in are given below.
Venous Ulcer Study I (VenUS I)
Iglesias C, Nelson EA, Cullum NA, Torgerson DJ; VenUS Team.
VenUS I: a randomised controlled trial of two types of bandage for treating venous leg ulcers. Health Technol Assess. 2004 Jul;8(29).
Funded by: NIHR-HTA
Chief Investigator: Professor Dame Nicky Cullum
This RCT compared the four-layer compression bandage to the short stretch bandage in 387 participants with a venous leg ulcer. The primary outcome was time to healing.
Overall, the trial found a reduced time to healing and lower costs associated with the four-layer bandage compared with the short stretch bandage.
NIHR Journals Library: HTA, Vol. 8, Issue 29
This result was re-enforced in a collaborative individual patient data meta-analysis of all RCTs comparing four layer and short stretch bandages.
Venous Ulcer Study II (VenUS II)
Dumville JC, Worthy G, Soares MO, Bland JM, Cullum N, Dowson C, et al.
VenUS II: a randomised controlled trial of larval therapy in the management of leg ulcers. Health Technol Assess2009;13(55).
Funded by: NIHR-HTA
Chief Investigator: Professor Dame Nicky Cullum
This RCT compared larval therapy with a standard treatment (Hydrogel) in 267 participants with leg ulcers that had at least 25% sloughy/necrotic tissue. The primary outcome was time to healing; there were a number of secondary outcomes measured, including with time to debridement and ulcer pain.
VenUS II found that larval therapy significantly reduced the time to debridement of sloughy and/or necrotic chronic leg ulcers compared with hydrogel. However, larval therapy did not increase the rate of healing of the ulcers and was associated with significantly more ulcer pain.
It was impossible on the basis of the RCT evidence to distinguish between larval therapy and hydrogel in terms of cost-effectiveness.
NIHR Journals Library: Health Technology Assessment, Vol. 13: No. 55 (PDF)
Venous Ulcer Study III (VenUS III)
Watson JM, Kang'ombe AR, Soares MO, Chuang LH, Worthy G, Bland JM, et al.
VenUS III: a randomised controlled trial of therapeutic ultrasound in the management of venous leg ulcers. Health Technol Assess 2011;15(13)
Funded by: NIHR-HTA
Chief Investigator: Professor Andrea Nelson
This RCT compared low-dose ultrasound delivered in conjunction with standard care with standard care alone in 337 participants with hard-to-heal venous leg ulcers. The primary outcome was time to ulcer healing.
VenUS III found that low-dose ultrasound, delivered weekly during dressing changes, added to the package of current best practice (dressings, compression therapy), did not increase ulcer healing rates, affect quality of life or reduce recurrence. It was associated with higher costs and more adverse events.
There is no evidence that adding low-dose ultrasound to standard care for 'hard-to-heal' ulcers aids healing, improves quality of life or reduces recurrence. It increases costs and adverse events.
NIHR Journals Library: Health Technology Assessment, Vol. 15: No. 13 (PDF)
Venous Ulcer Study IV (VenUS IV)
Funded by: NIHR-HTA
Chief Investigator: Dr Jo Dumville
This RCT compared use of the four-layer compression bandage with compression stockings (both treatments aiming to deliver 40mmHg at the ankle) in the management of venous leg ulcers in 457 participants. The primary outcome was time to healing – with time to ulcer recurrence one of a number of secondary outcomes assessed.
The study went on to synthesise the RCT findings with all other relevant trial data on the use of high compression for healing venous leg ulcers, using a combination of individual patient data and aggregate data within a network meta-analysis. Finally, cost effectiveness and value of information analyses were conducted.
Overall, RCT data found no evidence of a difference in venous ulcer healing between compression stockings and the four layer bandage. Compression stockings may reduce ulcer recurrence rates compared with the bandaging and be a cost-effective treatment.
When all available high-compression treatments were considered, a two-layer compression bandage had the highest probability of being clinically effective and cost-effective. However, the underpinning evidence was sparse and more research is needed and value of information suggested that further research should focus on establishing, in a high-quality trial, the effectiveness of this compression system.
NIHR Journals Library: Health Technology Assessment, Vol. 18: Issue 57 (PDF)
Negative pressure wound therapy for the treatment of severe pressure ulcers
Funded by: Medical Research Council
Chief Investigator: Professor Dame Nicky Cullum
This work systematically reviewed and synthesised evidence on negative pressure wound therapy (NPWT) as a treatment for severe pressure ulcers. The work considered the decision to adopt NPWT given a range of alternative treatments, using a decision analytic modelling approach.
Literature searches were conducted to identify existing evidence on model parameters. Given the limited evidence base, a second source of evidence, beliefs elicited from experts, was used. Judgments from experts on relevant (uncertain) quantities were obtained through a formal elicitation exercise.
Additionally, data derived from a pilot trial we conducted were also used to inform the model. The three sources of evidence were collated, and the impact of each on cost-effectiveness was evaluated.
Analysis of the value of further information indicated that a randomised controlled trial may be worthwhile in reducing decision uncertainty, where from a set of alternative designs, a 3-arm trial with longer follow-up was estimated to be the most efficient.
The analyses presented demonstrate how allocation decisions about medical technologies can be explicitly informed when data are sparse and how this kind of analyses can be used to guide future research prioritisation, not only indicating whether further research is worthwhile, but also what type of research is needed and how it should be designed.