Estimating & Comparing the Performance, Clinical Effectiveness, and Cost-effectiveness of Current Diagnostic Options for Patients That Present to Primary Care With Suspected Venous Ulcers
Conditions: Venous Leg Ulcer
Sponsor: Imperial College London

 
Research Governance 
           and Integrity Team 
 
 
 
 
IRAS Project ID: 326810 
Protocol V6.0 05Oct2023 IRAS: 326810 
 
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Template Protocol for non-CTIMPs 
 
 
 
Estimating & comparing the performance, clinical effectiveness, and cost-
effectiveness of current diagnostic options for patients that present to primary 
care with suspected venous ulcers. 
 
 
 
Version 7.0, 18/02/2025 
 
 
 
 
MAIN SPONSOR: Imperial College London  
FUNDERS: N/A 
STUDY COORDINATION CENTRE: N/A 
 
IRAS Project ID: 326810 
REC reference: N/A 
NCT: 06181708 
 
 
 
Protocol authorised by: 
 
 
 
 
 
 
 
 
 
 
 
 
Name & Role 
Date 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Study Management Group 
 
Chief Investigator: Professor Alun Davies 
 
Co-investigators: Emma Flint PhD student  
 
 
 
Clinical Queries 
 
Clinical queries should be directed to Emma Flint, e.flint1@nhs.net who will direct 
the query to the appropriate person 
 
 
Sponsor 
 
Imperial College London is the main research Sponsor for this study.  For further 
information regarding the sponsorship conditions, please contact the Head of 
Regulatory Compliance at: 
 
 
 
Research Governance and Integrity Team 
Imperial College London and Imperial College Healthcare NHS Trust 
Room 215, Level 2, Medical School Building 
Norfolk Place 
London, W2 1PG 
Tel: 0207 594 1862 
Imperial College - Research Governance and Integrity Team (RGIT) Website 
 
 
 

 
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IRAS Project ID: 326810 
Protocol V6.0 05Oct2023 IRAS: 326810 
 
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Funder 
 
This study is unfunded.  
This protocol describes the Estimating & comparing the performance, clinical effectiveness, and cost-
effectiveness of current diagnostic options for patients that present to primary care with suspected 
venous ulcers study and provides information about procedures for entering participants.  Every care 
was taken in its drafting, but corrections or amendments may be necessary. These will be circulated to 
investigators in the study.  Problems relating to this study should be referred, in the first instance, to the 
Chief Investigator.  
 
This study will adhere to the principles outlined in the UK Policy Frame Work for Health and Social Care 
Research. It will be conducted in compliance with the protocol, the Data Protection Act and other 
regulatory requirements as appropriate.  
 
Table of Contents                                                             Page No 
1. 
INTRODUCTION 
6 
1.1. BACKGROUND 
6 
1.2. RATIONALE FOR CURRENT STUDY 
7 
2. 
STUDY OBJECTIVES 
7 
3. 
STUDY DESIGN 
8 
3.1. STUDY OUTCOME MEASURES 
9 
4. 
PARTICIPANT ENTRY 
9 
4.1. PRE-REGISTRATION EVALUATIONS 
9 
4.2. INCLUSION CRITERIA 
9 
4.3. EXCLUSION CRITERIA 
9 
4.4. WITHDRAWAL CRITERIA 
9 
6. 
ASSESSMENT AND FOLLOW-UP 
9 
7. 
STATISTICS AND DATA ANALYSIS 
10 
8. 
REGULATORY ISSUES 
10 
8.1. ETHICS APPROVAL 
10 
8.2. CONSENT 
10 
8.3. CONFIDENTIALITY 
10 
8.4. INDEMNITY 
10 
8.5. SPONSOR 
11 
8.6. FUNDING 
11 
8.7. AUDITS 
11 
9. 
STUDY MANAGEMENT 
11 
10. PUBLICATION POLICY 
11 
11. REFERENCES 
11 
 
 
 
 
 
 

 
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GLOSSARY OF ABBREVIATIONS 
CVD 
Chronic venous disease  
CVI 
Chronic venous insufficiency  
VLU 
Venous leg ulcer 
ABPI 
Ankle brachial pressure indices  
NICE  
National Institute of Care and Excellence  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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IRAS Project ID: 326810 
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KEYWORDS 
Chronic venous disease 
Chronic venous insufficiency  
Venous leg ulcers  
Diagnostics  
Vascular Scientists  
Delphi 
Cost effectiveness  
 
 
 
STUDY SUMMARY 
 
TITLE Estimating & comparing the performance, clinical effectiveness, and cost-
effectiveness of current diagnostic options for patients that present to 
primary care with suspected venous ulcers. 
DESIGN Online questionnaire . survey study 
AIMS The main objective of this project is to determine the role/position of diagnostic 
imaging in the patient journey for a patient with active or healed ulceration.   
OUTCOME MEASURES To determine the minimum diagnostics that any patient that presents to 
primary care with a suspected venous ulcer should receive. Assess the cost 
effectiveness of implementing these established diagnostics into different care 
models. 
POPULATION  Primary care health professionals and vascular scientists. 
ELIGIBILITY Primary care practitioners working in the UK and vascular scientists working 
in secondary care in the UK.  
DURATION 20 months  
 
 
 
 
 
 
 
 
 
 
 
 

 
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IRAS Project ID: 326810 
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1. INTRODUCTION  
 
1.1. 
BACKGROUND 
Chronic venous disease (CVD) encompasses a broad spectrum of venous abnormalities in 
which there is a significant compromise in the return of blood to the heart. CVD is both 
prevalent and progressive in nature (Ortega et al. 2021). CVD refers to complications that 
arise in the lower extremity due to retrograde (reverse) venous flow, also known as chronic 
venous insufficiency (CVI) which is caused by a persistent elevation in venous pressures, 
commonly referred to as venous hypertension (Millan et al. 2019). There are multiple 
potential causes of venous insufficiency and fundamentally venous hypertension. The 
clinical presentation of CVI can vary depending on the severity of the disease, with the most 
severe cases presenting with leg ulceration (Escudero Rodriguez et al. 2014). NICE define a 
venous leg ulcer (VLU) as a loss of skin that take more than 2 weeks to heal due to 
sustained venous hypertension (NICE 2021). Other definitions include a breach in the 
epithelial integrity of the skin occurring between the knee and malleoli (Poskitt and Gohel 
2019). The typical location and most common presentation of VLUs is the medial gaiter area 
of the leg, however lateral and foot ulceration may also occur and be associated with venous 
insufficiency and or hypertension (Poskitt and Gohel 2019). 
Leg ulcers contribute to a huge socio-economic impact on the NHS annually, with over an 
excess of 100,000 active leg ulcers in the UK at any one time (Cunliffe 2021). They have 
been documented to be a significant burden on healthcare systems internationally and 
particularly in association with primary and community care. In addition to the associated 
extreme cost burden, they are associated with detrimental effects on patients quality of life, 
causing pain, discomfort and overall distress to the patients (Alguire and Mathews 1997; 
Barwell et al. 2000). 
Currently there is a wide variation in practice of leg ulcer management leading to a 
discrepancy in treatment that patients are receiving. Data collated from the Health 
Improvement Network database has shown that more than 90% ulcers remained unhealed 
at 6 months (Guest et al. 2012). This, alongside other supporting reviews, leads to questions 
of these alarmingly low healing rates (White et al. 2013). Evidence suggests that this cohort 
of patients are being managed sub optimally in primary care and a more standardized 
approach needs to be taken to improve overall ulcer healing rates and ulcer prevent 
recurrence. Dressings alone will not heal these ulcers and prevent recurrence, the 
underlying cause of these ulcers must be determined and this cause treated (Cunliffe 2021). 
Diagnostics play an important role in the management of venous leg ulceration with multiple 
literature sources emphasising the importance of diagnostic testing to confirm a diagnosis of 
venous insufficiency, to determine the aetiology, localise the anatomical site and level / 
source of disease (O’Donnell et al. 2014; DeMaeseneer et al. 2022). Duplex ultrasound is a 
non-invasive, cost effective and a reproducible imaging modality commonly used determine 
the source of venous insufficiency and to map the venous system (Alguire and Mathews 
1997). It is believed that to perform the correct and necessary venous interventions 
procedures, a venous duplex ultrasound scan should be performed to delineate the source 
or reflux and all potential reflux targets (O’Donnell et al. 2014). To further support this, early 
endovenous ablation of superficial vein reflux has been shown to result in faster healing of 

 
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IRAS Project ID: 326810 
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venous leg ulcers and a longer period of ulcer free time, compared to those that received 
delayed endovenous ablation (Gohel et al. 2019). 
Primary care has limited resources for performing diagnostic investigations for suspected 
venous leg ulcers and limited appropriately trained staff to manage these patients. 
Additionally, the pathway for onward referral to a specialist ulcer service are variable and 
vary by geographical location (NHS England 2018).  
In the UK, currently the only diagnostic test mentioned in the NICE guidelines with regards to 
managing these patients is an ABPI. This test is to determine the state of a patients arterial 
blood supply and therefore the suitability of these patients to go into compression bandaging 
(NICE 2021). Patients presenting with leg ulcers are therefore receiving different diagnostic, 
management, and treatment pathways and most importantly, they are al receiving this care 
at different time intervals depending on where they present.  
 
 
1.2. 
RATIONALE FOR CURRENT STUDY 
The pathway of current practice from the patient first presenting to receiving this treatment, 
including vascular diagnostics, has not been investigated in detail, and is therefore not 
optimised. There is a lack of evidence and written documentation regarding diagnostics in 
the available guidelines. This means that there is a lack of standardised care for this cohort 
of patients across the UK.  
 
It is hypothesised that by understanding how primary care currently refer onto specialist 
centres and establishing a consensus on what diagnostic tests should be performed on this 
cohort of patients, a conclusion on the most cost and clinical effective method of delivering 
diagnostics and care to this cohort of patients can be established. It is hypothesised that this 
will involve generating clearer guidelines and standardised pathways based on up-to-date 
literature for when VLU patients initially present into primary care, including when they 
should be referred onto specialist vascular centres, what specific diagnostic tests should be 
performed upon initial presentation and an outline of treatment options. The most cost-
effective method may also suggest the initiation of specialist leg ulcer clinics involving a 
multidisciplinary team.  
 
 
2. STUDY OBJECTIVES 
 
The aim of this project is to determine the minimum diagnostics that any patient that 
presents to primary care with a suspected venous ulcer should receive and look at the 
most effective way to implement this.  
 
Primary Objective 
1) To determine the role/position of diagnostic imaging in the patient journey for a 
patient with active or healed ulceration. 
 
 
Secondary Objective 

 
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1) To determine the current practice in primary care for venous ulcer management. 
2) To determine the current practice for diagnosis and management of suspected 
venous leg ulcers in vascular scientist departments across the UK  
3) To establish what the minimum diagnostics should be for this cohort of patients 
including what scans should be performed and can a set criterion be applied to this 
cohort of patients. 
4)  To determine the cost effectiveness of implementing this in both primary and 
secondary care settings.  
 
 
3. STUDY DESIGN 
 
1) To determine the current practice of primary care, a questionnaire will be designed 
using Qualtrics management platform (Qualtrics, UT, USA) to assess various aspects 
of the national management and diagnostics for venous leg ulceration. A similar 
methodology will be utilised to that of a previous primary care questionnaire that was 
disseminated to primary care practitioners pre and post the EVRA trial (Heatley et al. 
2020). Key areas to be investigated will be whether there are one main set of 
guidelines that primary care practitioners follow, the availability of services they have 
in their centre and if they have any major barriers to onward referrals. The 
questionnaire is attached, it has been tested and optimised after engagement with 
key stakeholders.  
2) To determine the current diagnostic pathways for this cohort of patients in vascular 
departments across the UK and to try and establish a uniform standardised 
diagnostic pathway, a Delphi consensus will be performed amongst vascular 
scientists. Responses will be summarised between each round and fed back to the 
participants.  This will be used to determine a consensus on the best and most 
realistic diagnostic management of these patients. For the purpose of this study, a 
consensus has been defined at a ≥70% agreement. The hope is that by involving 
those that could be directly implicated by any changes to the guidelines, it will initiate 
interest and engagement both during the consensus itself and implementing the 
findings of the consensus. The first round of the Delphi questionnaire is attached, it 
has been tested and optimised after engagement with key stakeholders.  
3) To investigate whether there is a minimum diagnostic that can be recommended for 
this cohort of patients the current literature regarding typical pattern of reflux and 
anatomical location of ulcers will be reviewed. This may involve details on who 
should perform and where these investigations should or could be performed. To 
determine whether there is a minimum number of diagnostic investigations that 
needs to be carried for these patients, in conjunction with the results from the Delphi 
consensus, a detailed literature review will be carried out looking into the location of 
venous ulcer and source of reflux. This will be done by initially identifying PICOS 
criteria. I will then develop a search strategy and input this into Ovid. From the 
papers identified in this search, I will perform abstract screening against the pre-
defined PICOS criteria, complete full text screening, data and information extraction, 
analysis, and synthesis. This is to determine whether all patients require a full venous 

 
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duplex scan, or whether in some situations, a quicker less detailed ‘spot check’ scan 
can be performed. This in turn will also contribute valuable information regarding the 
setting for the diagnostic testing.  
4) To establish the cost effectiveness of different proposed models, a Markov model will 
be constructed to estimate the health outcomes and costs over 5 years of different 
testing strategies applied to a cohort of VLU patients. Variations of diagnostic tests 
combinations and settings to be investigated may include, ABPI in primary care and 
full venous duplex in secondary care, ABPI and venous duplex in primary care, ABPI 
and venous duplex in secondary care. Health outcomes will be venous ulcer healing 
rates and venous ulcer recurrence rates. Sensitivity analyse will also be performed 
(Normahani et al. 2021; Epstein et al. 2018). 
 
 
3.1. 
STUDY OUTCOME MEASURES 
1) The electronic questionnaire to primary care networks will be shared via various 
social media platforms and will remain open for 1 months for responses. The 
questionnaire will be reposted at regular intervals to promote engagement.  
2) The Delphi consensus will continue until a consensus has been reached, ≥70% 
agreement. Each round of the consensus will be open for one month. Response 
analysis and design and dissemination of the next round will occur within two weeks.  
 
 
4. PARTICIPANT ENTRY 
 
4.1. 
PRE-REGISTRATION EVALUATIONS  
N/A 
 
4.2. 
INCLUSION CRITERIA  
Primary care practitioners working in the UK will be recruited for the primary care 
questionnaire.  
Vascular scientists working in a secondary care hospital in the uk will be recruited for 
the online delphi consensus. 
 
4.3. 
EXCLUSION CRITERIA 
Participants not meeting the inclusion criteria.  
 
4.4. 
WITHDRAWAL CRITERIA  
A participant may withdraw at any time by notifying the researcher Via email: 
e.flint1@nhs.net 
If a participant wishes to withdraw from the primary care study, any data collected up until 
that time will be kept for analysis.   
If a participant wishes to withdraw from the Delphi consensus, they will no longer receive 
further questionnaires, however any data collected up until that time will be kept for analysis. 
 
 
5. ASSESSMENT AND FOLLOW-UP  
 

 
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There will be no formal assessment or follow-up in this study.  
 
Definition of end of study: 
The study will end when he primary care questionnaire has been live for one month and 
when a consensus has been reached amongst vascular scientists, defined as a >70% 
agreement. 
 
 
6. STATISTICS AND DATA ANALYSIS 
 
A series of descriptive statistics will be carried out on the results obtained from the 
questionnaire and consensus. Advice will be sought from John Norry, The University of 
Edinburgh.  
 
Data and all appropriate documentation will be stored for a minimum of 10 years after the 
completion of the study  
 
 
7. REGULATORY ISSUES  
 
7.1. 
ETHICS APPROVAL  
The Study Coordination Centre has obtained approval from the xxx Research Ethics 
Committee (REC) and Health Research Authority (HRA). The study must also receive 
confirmation of capacity and capability from each participating NHS Trust before accepting 
participants into the study or any research activity is carried out. The study will be conducted 
in accordance with the recommendations for physicians involved in research on human 
subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions. 
 
 
7.2. 
CONSENT   
 
Consent will be taken online via Qualtrics. All participants will have access to an online 
participant information sheet before agreeing to the online consent.  The right of the participant 
to refuse to participate without giving reasons must be respected.  All participants are free to 
withdraw at any time from the protocol without giving reasons. 
 
7.3. 
CONFIDENTIALITY  
The Chief Investigator will preserve the confidentiality of participants taking part in the study 
and is registered under the Data Protection Act. 
 
Data from the primary care and Delphi questionnaires will be pseudonymised.  
 
 
7.4. 
INDEMNITY 
Imperial College London holds negligent harm and non-negligent harm insurance policies 
which apply to this study 
 

 
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7.5. 
SPONSOR  
Imperial College London will act as the main Sponsor for this study.  Delegated responsibilities 
will be assigned to the NHS trusts taking part in this study.   
 
7.6. 
FUNDING  
This study is not funded.  
 
7.7. 
AUDITS   
The study may be subject to audit by Imperial College London under their remit as sponsor 
and other regulatory bodies to ensure adherence to GCP and the UK Policy Frame Work for 
Health and Social Care Research.  
 
 
8. STUDY MANAGEMENT  
 
The day-to-day management of the study will be co-ordinated through Emma Flint, 
e.flint1@nhs.net.  
 
 
9. PUBLICATION POLICY  
 
The results will be included in the final clinical doctorate thesis. The results will be published 
in peer reviewed journals, conference papers and research presentations. The anonymity of 
the participants will be ensured when publishing.  
 
 
10. REFERENCES  
Alguire, P. and Mathews, B. (1997). Chronic venous insufficiency and venous ulceration. 
Journal of General Internal Medicine, 12(6), pp.374–383. 
Barwell, J.R. et al. (2000). Risk factors for healing and recurrence of chronic venous leg 
ulcers. Phlebology, 15(2), pp.49–52. 
Cunliffe, T. (2021). Primary care dermatology society - Leg ulcers. [online]. Available from: 
https://www.pcds.org.uk/clinical-guidance/leg-ulcers [Accessed October 1, 2021]. 
DeMaeseneer, M. et al. (2022). Editor’s Choice – European Society for Vascular Surgery 
(ESVS) 2022 Clinical Practice Guidelines on the Management of Chronic Venous Disease of 
the Lower Limbs. European Journal of Vascular and Endovascular Surgery, 63(2), pp.184–
267. [online]. Available from: https://doi.org/10.1016/j.ejvs.2021.12.024. 
Epstein, D. et al. (2018). Cost‐effectiveness of treatments for superficial venous reflux in 
patients with chronic venous ulceration. BJS Open, 2(4), pp.203–212. 
Escudero Rodriguez, J., Fernandez Quesada, F. and Bellmunt Montoya, S. (2014). 
Prevalence and clinical characteristics of chronic venous disease in patients seen in primary 
care in Spain: results of the international study Vein Consult Program. Cirugia espanola, 
92(8), pp.539–546. 
Gohel, M. et al. (2019). A randomized trial of early endovenous ablation in venous 
ulceration: a critical appraisal. British Journal of Dermatology, 180(1), pp.51–55. 
Guest, J. et al. (2012). Relative cost-effectiveness of a skin protectant in managing venous 
leg ulcers in the UK. Journal of wound care, 21(8), pp.389–398. [online]. Available from: 
https://pubmed.ncbi.nlm.nih.gov/22885312/ [Accessed October 1, 2021]. 
Heatley, F. et al. (2020). Primary care survey of venous leg ulceration management and 

 
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referral pre-EVRA trial. British Journal of Community Nursing, 25(December), pp.S6–S10. 
Millan, S.B., Gan, R. and Townsend, P.E. (2019). Venous ulcers: Diagnosis and treatment. 
American Family Physician, 100(5), pp.298–305. 
NHS England. (2018). NHS England » Improving venous leg ulcer healing in the community. 
Leading Change, Adding Value. [online]. Available from: 
https://www.england.nhs.uk/atlas_case_study/improving-venous-leg-ulcer-healing-in-the-
community/ [Accessed October 1, 2021]. 
NICE. (2021). Leg ulcer - venous. [online]. Available from: https://cks.nice.org.uk/topics/leg-
ulcer-venous/ [Accessed October 1, 2021]. 
Normahani, P. et al. (2021). Cost-Effectiveness of Diagnostic Tools to Establish the 
Presence of Peripheral Arterial Disease in People with Diabetes. Annals of Surgery, Volume 
pub. 
O’Donnell, T.F. et al. (2014). Management of venous leg ulcers: Clinical practice guidelines 
of the Society for Vascular Surgery® and the American Venous Forum. Journal of Vascular 
Surgery, 60(2), pp.3S-59S. 
Ortega, M.A. et al. (2021). Understanding chronic venous disease: A critical overview of its 
pathophysiology and medical management. Journal of Clinical Medicine, 10(15), pp.1–42. 
Poskitt, K. and Gohel, M. (2019). Chronic ulceration of the leg. Surgery (United Kingdom), 
37(2), pp.88–92. 
White, R., Brown, A. and Whayman, N. (2013). Nonhealing venous leg ulcers in primary 
care: Clinical significance of training, knowledge, treatment, and healing. Wounds UK, 9(1), 
pp.12–14.