Cost-effectiveness of treatments for superficial venous refluxin patients with chronic venous ulceration.

Background Venous leg ulcers impair quality of life significantly, with substantial costs to health services. The aim of this study was to estimate the cost‐effectiveness of interventional procedures alongside compression therapy versus compression therapy alone for the treatment of chronic venous leg ulceration. Methods A Markov decision analytical model was developed. The main outcome measures were quality‐adjusted life‐years (QALYs) and lifetime costs per patient, from the perspective of the UK National Health Service at 2015 prices. Resource use included the initial procedures, compression therapy, primary care and outpatient consultations. The interventional procedures included superficial venous surgery, endothermal ablation and ultrasound‐guided foam sclerotherapy (UGFS). The study population was patients with a chronic venous ulcer who were eligible for either compression therapy or an interventional procedure. Data were obtained from systematic review and meta‐analysis of RCTs. Results Surgery gained 0·112 (95 per cent c.i. −0·011 to 0·213) QALYs compared with compression therapy alone, with a difference in lifetime costs of €−1330 (−3570 to 1262). Given the expected savings in community care, the procedure would pay for itself within 4 years. There was insufficient evidence regarding endothermal ablation and UGFS to draw conclusions. Discussion This modelling study found surgery to be more effective and less costly than compression therapy alone. Further RCT evidence is required for both endothermal ablation and UGFS

UK primary care survey of venous leg ulceration management and referral - Post-EVRA trial

Objective Determine standards of referral and management of patients with venous leg ulceration in primary care after the release of the EVRA (A Randomized Trial of Early Endovenous Ablation in Venous Ulceration) study results. Methods An online questionnaire was disseminated over four months to professionals working within primary care. Results The survey received 643 responses. Of respondents, 90 (14%) had heard of the EVRA trial and 51 (8%) were familiar with the results. Of those who answered the following questions, 410 (69.1%) stated that referral to a vascular specialist must be made by the General Practitioner and 13 (2.2%) reported that they would always refer patients for secondary care assessment before the publication of EVRA. Considering the EVRA results, 128 (29%) reported that they would change practice regarding referral and would experience no barriers and 198 (45%) reported that they would like to refer earlier but is not their decision. Barriers to changing practice included local referral policies, training and time restrictions, 266 (59%) had heard of the NICE guideline (CG168) and 194 (43%) were aware of the recommendations for referral to a vascular service within two weeks for patients with an open or healed ulcer. Conclusion There is a considerable variation in local referral pathways for venous leg ulceration, and despite clinicians wanting to refer promptly, many primary care professionals are unable to. Unfortunately, the EVRA study alone may not change the overall practice, and work is needed to overcome barriers faced by primary care professionals

Neuromuscular Electrical Stimulation for Intermittent Claudication (NESIC): multicentre, randomized controlled trial

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. METHODS: This was an open, multicentre, randomized controlled trial. Patients with intermittent claudication attending vascular surgery outpatient clinics were randomized (1:1) to receive either neuromuscular electrical stimulation (NMES) or not in addition to local standard care available at study centres (best medical therapy alone or plus supervised exercise therapy (SET)). The objective of this trial was to investigate the clinical efficacy of an NMES device in addition to local standard care in improving walking distances in patients with claudication. The primary outcome was change in absolute walking distance, measured by a standardized treadmill test at 3 months. Secondary outcomes included intermittent claudication (IC) distance, adherence, quality of life, and haemodynamic changes. RESULTS: Of 200 participants randomized, 160 were included in the primary analysis (intention to treat, Tobit regression model). The square root of absolute walking distance was analysed (due to a right-skewed distribution) and, although adjunctive NMES improved it at 3 months, no statistically significant effect was observed. SET as local standard care seemed to improve distance compared to best medical therapy at 3 months (3.29 units; 95 per cent c.i., 1.77 to 4.82; P < 0.001). Adjunctive NMES improved distance in mild claudication (2.88 units; 95 per cent c.i., 0.51 to 5.25; P = 0.02) compared to local standard care at 3 months. No serious adverse events relating to the device were reported. CONCLUSION: Supervised exercise therapy is effective and NMES may provide further benefit in mild IC.This trial was supported by a grant from the Efficacy and Mechanism Evaluation Program, a Medical Research Council and National Institute for Health and Care Research partnership. Trial registration: ISRCTN18242823.Patients with intermittent claudication experience pain in their legs during walking or exercise which ends with rest. This severely impairs physical activity and quality of life. Treatment for such patients typically involves best medical therapy, which includes exercise advice. This study aimed to determine whether a neuromuscular electrical stimulation device improved the walking distance of patients with intermittent claudication compared to local standard care available (which may include supervised exercise therapy) in a trial. Supervised exercise improved walking distances but there was no difference in those that received a device in this patient group

A cost-effectiveness analysis of a hydration response technology dressing in the treatment of venous leg ulcers in the UK

Introduction: Venous leg ulceration causes significant pain and suffering for patients, additionally it places considerable financial and service burden on the National Health Service (NHS). A large proportion of venous leg ulceration do not heal within the standard time frames of 16 – 24 weeks, resulting in static wounds which commonly have issues with increasing exudate production. Static wounds can have significant negative impact on the patients quality of life, the wound bed and periwound skin, increased risk of infection all of which results in delayed wound healing and increased health service costs. As the NHS continues to face times of austerity, services need to find solutions to be able to reduce cost and release nursing time whilst maintaining standards of care. Cutimed® Sorbion® Sachet S is a treatment option for the management of patients with a venous leg ulceration. The objective of this study was to provide an update of the health economic analysis of Cutimed® Sorbion® Sachet S in comparison to relevant comparators in the UK with current cost data. Methods: Cutimed® Sorbion® Sachet S was compared against Zetuvit Plus, DryMax extra, KerraMax Care and Eclypse from a cost effectiveness perspective. Clinical data were derived from literature and expert opinion. Cost input was utilized based on publicly available data and literature. The average patient in the model is assumed to be 65 years with a diagnosed venous leg ulcer. It is assumed that patients in the different treatment arms have the same background mortality, hence the endpoint mortality is not included in the model. The analysis is based on a deterministic Markov model derived from Harding et al. with weekly cycles. The following assumptions are made: First, all patients start in a static health state with a non-healed but non-progressing venous leg ulcer. It is assumed in the model that patients can transition to a deteriorating health state where a wound is improving or the wound could progress. Additionally, venous leg ulcers could be healed from a progressed wound (i.e. improved wound), they could develop into a severe wound with complications (infections) to be treated in hospitals. The time frame for the analysis was fixed for one year and no re-occurence after healing was assumed to happen. Results: The cost-effectiveness analysis demonstrates health economic dominance of Cutimed® Sorbion® Sachet S being more effective and cost-saving against all analysed comparators. When using literature-based input values the incrementally higher healing rates for Cutimed® Sorbion® Sachet S are 11.04 months (versus Zetuvit Plus), 29.04 months (versus DryMax extra), 1.68 months (versus KerraMax Care) and 11.04 months (versus Eclypse). Cost savings per patient were 37.60£ (versus Zetuvit Plus), 171.68£ (versus DryMax extra), 3.13£ (versus KerraMax Care) and 43.63£ (versus Eclypse). Clinical benefits and cost savings are increasing when real life practice assumptions based on expert opinion are included. Conclusions: Based on the underlying health economic model, Cutimed® Sorbion® Sachet S is more effective and less costly than other comparative products in venous leg ulcers in the UK

Metabolic profiling reveals changes in serum predictive of venous ulcer healing

Objective: The aim of this study was to identify potential biomarkers predictive of healing or failure to heal in a population with venous leg ulceration. Summary Background Data: Venous leg ulceration presents important physical, psychological, social and financial burdens. Compression therapy is the main treatment, but it can be painful and time-consuming, with significant recurrence rates. The identification of a reliable biochemical signature with the ability to identify nonhealing ulcers has important translational applications for disease prognostication, personalized health care and the development of novel therapies. Methods: Twenty-eight patients were assessed at baseline and at 20 weeks. Untargeted metabolic profiling was performed on urine, serum, and ulcer fluid, using mass spectrometry and nuclear magnetic resonance spectroscopy. Results: A differential metabolic phenotype was identified in healing (n = 15) compared to nonhealing (n = 13) venous leg ulcer patients. Analysis of the assigned metabolites found ceramide and carnitine metabolism to be relevant pathways. In this pilot study, only serum biofluids could differentiate between healing and nonhealing patients. The ratio of carnitine to ceramide was able to differentiate between healing phenotypes with 100% sensitivity, 79% specificity, and 91% accuracy. Conclusions: This study reports a metabolic signature predictive of healing in venous leg ulceration and presents potential translational applications for disease prognostication and development of targeted therapies

Evaluating pharmacological THRomboprophylaxis in Individuals undergoing superficial endoVEnous treatment across NHS and private clinics in the UK: a multi-centre, assessor-blind, randomised controlled trial - THRIVE trial

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.Introduction Endovenous therapy is the first choice management for symptomatic varicose veins in NICE guidelines, with 56-70 000 procedures performed annually in the UK. Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a known complication of endovenous therapy, occurring at a rate of up to 3.4%. Despite 73% of UK practitioners administering pharmacological thromboprophylaxis to reduce VTE, no high-quality evidence supporting this practice exists. Pharmacological thromboprophylaxis may have clinical and cost benefit in preventing VTE; however, further evidence is needed. This study aims to establish whether when endovenous therapy is undertaken: a single dose or course of pharmacological thromboprophylaxis alters the risk of VTE; pharmacological thromboprophylaxis is associated with an increased rate of bleeding events; pharmacological prophylaxis is cost effective. Methods and analysis A multi-centre, assessor-blind, randomised controlled trial (RCT) will recruit 6660 participants from 40 NHS and private sites across the UK. Participants will be randomised to intervention (single dose or extended course of pharmacological thromboprophylaxis plus compression) or control (compression alone). Participants will undergo a lower limb venous duplex ultrasound scan at 21-28 days post-procedure to identify asymptomatic DVT. The duplex scan will be conducted locally by blinded assessors. Participants will be contacted remotely for follow-up at 7 days and 90 days post-procedure. The primary outcome is imaging-confirmed lower limb DVT with or without symptoms or PE with symptoms within 90 days of treatment. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, using a repeated measures analysis of variance, adjusting for any pre-specified strongly prognostic baseline covariates using a mixed effects logistic regression. Ethics and dissemination Ethical approval was granted by Brent Research Ethics Committee (22/LO/0261). Results will be disseminated in a peer-reviewed journal and presented at national and international conferences. Trial registration number ISRCTN18501431

Early versus deferred endovenous ablation of superficial venous reflux in patients with venous ulceration: the EVRA RCT

Background Venous ulceration is a common and costly health-care issue worldwide, with poor healing rates greatly affecting patient quality of life. Compression bandaging has been shown to improve healing rates and reduce recurrence, but does not address the underlying cause, which is often superficial venous reflux. Surgical correction of the reflux reduces ulcer recurrence; however, the effect of early endovenous ablation of superficial venous reflux on ulcer healing is unclear. Objectives To determine the clinical effectiveness and cost-effectiveness of compression therapy with early endovenous ablation of superficial venous reflux compared with compression therapy with deferred endovenous ablation in patients with venous ulceration. Design A pragmatic, two-arm, multicentre, parallel-group, open randomised controlled trial with a health economic evaluation. Setting Secondary care vascular centres in England. Participants Patients aged ≥ 18 years with a venous leg ulcer of between 6 weeks’ and 6 months’ duration and an ankle–brachial pressure index of ≥ 0.8 who could tolerate compression and were deemed suitable for endovenous ablation of superficial venous reflux. Interventions Participants were randomised 1 : 1 to either early ablation (compression therapy and superficial endovenous ablation within 2 weeks of randomisation) or deferred ablation (compression therapy followed by endovenous ablation once the ulcer had healed). Main outcome measures The primary outcome measure was time from randomisation to ulcer healing, confirmed by blinded assessment. Secondary outcomes included 24-week ulcer healing rates, ulcer-free time, clinical success (in addition to quality of life), costs and quality-adjusted life-years (QALYs). All analyses were performed on an intention-to-treat basis. Results A total of 450 participants were recruited (224 to early and 226 to deferred superficial endovenous ablation). Baseline characteristics were similar between the two groups. Time to ulcer healing was shorter in participants randomised to early superficial endovenous ablation than in those randomised to deferred ablation [hazard ratio 1.38, 95% confidence interval (CI) 1.13 to 1.68; p = 0.001]. Median time to ulcer healing was 56 (95% CI 49 to 66) days in the early ablation group and 82 (95% CI 69 to 92) days in the deferred ablation group. The ulcer healing rate at 24 weeks was 85.6% in the early ablation group, compared with 76.3% in the deferred ablation group. Median ulcer-free time was 306 [interquartile range (IQR) 240–328] days in the early ablation group and 278 (IQR 175–324) days in the deferred endovenous ablation group (p = 0.002). The most common complications of superficial endovenous ablation were pain and deep-vein thrombosis. Differences in repeated measures of Aberdeen Varicose Vein Questionnaire scores (p < 0.001), EuroQol-5 Dimensions index values (p = 0.03) and Short Form questionnaire-36 items body pain (p = 0.05) over the follow-up period were observed, in favour of early ablation. The mean difference in total costs between the early ablation and deferred ablation groups was £163 [standard error (SE) £318; p = 0.607]; however, there was a substantial and statistically significant gain in QALY over 1 year [mean difference between groups 0.041 (SE 0.017) QALYs; p = 0.017]. The incremental cost-effectiveness ratio of early ablation at 1 year was £3976 per QALY, with a high probability (89%) of being more cost-effective than deferred ablation at conventional UK decision-making thresholds (currently £20,000 per QALY). Sensitivity analyses using alternative statistical models give qualitatively similar results. Limitations Only 7% of screened patients were recruited, treatment regimens varied significantly and technical success was assessed only in the early ablation group. Conclusions Early endovenous ablation of superficial venous reflux, in addition to compression therapy and wound dressings, reduces the time to healing of venous leg ulcers, increases ulcer-free time and is highly likely to be cost-effective. Future work Longer-term follow-up is ongoing and will determine if early ablation will affect recurrence rates in the medium and long term. Trial registration Current Controlled Trials ISRCTN02335796. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 24. See the NIHR Journals Library website for further project information

Comparative costs and activity from a sample of UK clinical trials units

Background: The costs of medical research are a concern. Clinical Trials Units (CTUs) need to better understand variations in the costs of their activities. Methods: Representatives of ten CTUs and two grant-awarding bodies pooled their experiences in discussions over 1.5 years. Five of the CTUs provided estimates of, and written justification for, costs associated with CTU activities required to implement an identical protocol. The protocol described a 5.5-year, nonpharmacological randomized controlled trial (RCT) conducted at 20 centres. Direct and indirect costs, the number of full time equivalents (FTEs) and the FTEs attracting overheads were compared and qualitative methods (unstructured interviews and thematic analysis) were used to interpret the results. Four members of the group (funding-body representatives or award panel members) reviewed the justification statements for transparency and information content. Separately, 163 activities common to trials were assigned to roles used by nine CTUs; the consistency of role delineation was assessed by Cohen's κ. Results: Median full economic cost of CTU activities was £769,637 (range: £661,112 to £1,383,323). Indirect costs varied considerably, accounting for between 15% and 59% (median 35%) of the full economic cost of the grant. Excluding one CTU, which used external statisticians, the total number of FTEs ranged from 2.0 to 3.0; total FTEs attracting overheads ranged from 0.3 to 2.0. Variation in directly incurred staff costs depended on whether CTUs: supported particular roles from core funding rather than grants; opted not to cost certain activities into the grant; assigned clerical or data management tasks to research or administrative staff; employed extensive on-site monitoring strategies (also the main source of variation in non-staff costs). Funders preferred written justifications of costs that described both FTEs and indicative tasks for funded roles, with itemised non-staff costs. Consistency in role delineation was fair (κ = 0.21-0.40) for statisticians/data managers and poor for other roles (κ < 0.20). Conclusions: Some variation in costs is due to factors outside the control of CTUs such as access to core funding and levels of indirect costs levied by host institutions. Research is needed on strategies to control costs appropriately, especially the implementation of risk-based monitoring strategies