Types of studies

Prospective randomised controlled trials (RCTs) comparing endothermal ablative techniques with conservative management which may include compression therapy.

Types of participants

Studies recruiting people of any age undergoing treatment for venous ulcer disease (C5 ‐ healed venous ulcer and C6 ‐ active venous ulcer) (Khilnani 2010) in which venous reflux was demonstrated in the superficial venous system pre‐operatively using duplex ultrasound. We will exclude studies of people with ulceration thought to be of a mixed or non‐venous aetiology (e.g. arterial, vasculitis). We will exclude studies involving participants with an Ankle Brachial Pressure Index (ABPI) of less than 0.8 or people requiring interventions for peripheral arterial disease.

Types of interventions

Studies comparing (an) endovenous thermal ablative technique(s) with conservative management. We will include evaluations of any endovenous thermal ablative technique including endovenous laser and endovenous radiofrequency ablation in all its applications. In the future, we will expand this review to include evidence regarding any new endovenous technologies which are not currently available or are in evolution, for example endovenous steam.

In trials involving people with active ulceration (C6 disease), patients may also receive compression therapy in addition to either endovenous thermal ablation or conservative management. Compression can be achieved using any form of compression bandage (including both single and multi‐component systems) or stockings. The requirement for compression in C5 disease will be more relaxed, providing both arms receive the same form of compression. We will aim to perform subgroup analyses for C5 and C6 disease. Trials where compression is not delivered as part of either the intervention or control will also be eligible for inclusion.

Types of outcome measures

Electronic searches

We will search the following electronic sources to identify reports of relevant RCTs: 

• the Cochrane Wounds Group Specialised Register;

• the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (latest issue);

• Ovid MEDLINE (1998 to present);

• Ovid EMBASE (1998 to present); and

• EBSCO CINAHL (1998 to present).

We will search the Cochrane Central Register of Controlled Trials (CENTRAL) using the following exploded MeSH headings and keywords: 

#1 MeSH descriptor Laser Therapy explode all trees
#2 "endovenous laser" or EVL or EVLA or EVLO or EVLT: ti,ab,kw
#3 MeSH descriptor Catheter Ablation explode all trees
#4 "radiofrequency ablation" or RFA or RFO:ti,ab,kw
#5 VNUS or ClosureFAST or Closure:ti,ab,kw
#6 VCF or "bipolar radiofrequency induced thermotherapy" or RFITT:ti,ab,kw
#7 (#1 OR #2 OR #3 OR #4 OR #5 OR #6)
#8 MeSH descriptor Leg Ulcer explode all trees
#9 (varicose NEXT ulcer*) or (venous NEXT ulcer*) or (leg NEXT ulcer*) or (stasis NEXT ulcer*) or ((lower NEXTextremit*) NEAR/2 ulcer*) or (crural NEXT ulcer*) or ulcus cruris:ti,ab,kw
#10 MeSH descriptor Venous Insufficiency explode all trees
#11 "chronic venous insufficiency" or CVI:ti,ab,kw
#12 (#8 OR #9 OR #10 OR #11)
#13 (#7 AND #12)

We will adapt this strategy to search Ovid MEDLINE, Ovid EMBASE and EBSCO CINAHL. We will combine the Ovid MEDLINE search with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity‐ and precision‐maximising version (2008 revision) (Lefebvre 2011). We will combine the EMBASE and CINAHL searches with the trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN 2011). We will not restrict on the basis of language of publication, however we will limit searches to 1998 onwards as this was when these technologies were introduced.

We will also search the following trial registries:

• the Australian New Zealand Clinical Trials Registry: http://www.anzctr.org.au/;

• ClinicalTrials.gov register: http://www.clinicaltrials.gov/;

• the WHO International Clinical Trials Registry Platform Search Portal: http://www.who.int/trialsearch; and

• the Current Controlled Trials meta‐search engine: http://www.controlled‐trials.com/.

Searching other resources

We will search the bibliographies of all studies eligible for inclusion identified by the above strategies for further studies. We will contact relevant companies to see if they have any unpublished data that we could include in this review.

Selection of studies

Two review authors will independently assess the titles and available abstracts of all studies identified by the initial search and exclude any clearly irrelevant studies. Two review authors will independently assess full paper copies of reports of potentially eligible studies using the inclusion criteria. The authors will resolve disagreements on inclusion by consensus and, if this fails, by the arbitration of a third review author.

Data extraction and management

Two review authors will independently extract data from the included studies, including source of funding, study population, interventions, analyses and outcomes, using standardised data extraction forms. We will contact the authors of recent original studies to obtain more information as needed.

We will extract raw data for outcomes of interest (means and standard deviations for continuous outcomes, number of events for dichotomous outcomes, and hazard ratio and 95% confidence intervals for time‐to‐event data) where available in the published reports. We will record whether data is converted or imputed in the notes section of the table of 'Characteristics of included studies'. We will include studies that are published in duplicate only once (but will extract data maximally).

Assessment of risk of bias in included studies

Two review authors will independently assess the risk of bias of each included study against key criteria: random sequence generation; allocation concealment; blinding of participants, personnel and outcomes; incomplete outcome data; selective outcome reporting; and other sources of bias (such as whether groups were similar at baseline for important prognostic indicators ‐ infection, wound size and severity and duration of ulcer; and if co‐interventions were avoided or similar between the treatment and control groups) in accordance with the methods recommended by The Cochrane Collaboration (Higgins 2011a). We will explicitly judge each of these criteria using: low risk of bias, high risk of bias or unclear risk of bias (either lack of information or uncertainty over the potential for bias).

We will resolve disagreements by consensus and consult a third review author to resolve disagreements if necessary.

Measures of treatment effect

If RCTs are identified, we will chart the results of each included study on forest plots as point estimates, i.e. risk ratios (RR) with corresponding 95% confidence interval (CI) for dichotomous outcomes, mean difference (MD) with 95% CI for continuous outcomes, and hazard ratio (HR) with 95% CI for time‐to‐event outcomes (e.g. time to healing). When the results cannot be shown in this way, we will report the results in the text of the review. For continuous measures, we will calculate mean differences if possible as these results are easier for clinicians/readers to interpret. If individual outcome measures vary but the construct being measured is the same (i.e. use of different scales across trials or inability to convert data into the same scale, or both), then we will use standardised mean differences (SMD).

Unit of analysis issues

If we identify RCTs that randomise or allocate clusters but do not account for clustering during analysis (and thus may have potential unit of analysis errors), we will attempt to re‐analyse such studies by calculating effective sample sizes where possible, according to the recommended Cochrane methods (Higgins 2011b). We will incorporate an estimate of the intra‐cluster coefficient (ICC) using external estimates obtained from similar studies if necessary.

Dealing with missing data

If data are missing from the trial reports, we will attempt to contact trial authors. Where it is not possible to ascertain the healed status of patients, we will report data based on assumptions of both healing/ no recurrence and non‐healing/recurrence, performing a sensitivity analysis on the effect of these extreme assumptions.

Assessment of heterogeneity

Prior to meta‐analysis, we will first assess studies for clinical homogeneity with respect to patient demographics, type of therapy, comparator treatment and the nature of the outcomes reported. We will not combine clinically heterogeneous studies in the analysis, but will describe them separately. For studies judged as clinically homogeneous, we will test statistical heterogeneity with the Q test (Chi² and the I² statistic). We will interpret a Chi² test resulting in a P value < 0.10 as indicating significant statistical heterogeneity. In order to assess and quantify the possible magnitude of inconsistency heterogeneity across studies, we will use the I² statistic with a rough guide for interpretation as follows: 0% to 40% will be viewed as indicating low levels of heterogeneity that may not be important; 30% to 60% may represent moderate heterogeneity; 50% to 90% represents substantial heterogeneity; 75% to 100% represents considerable heterogeneity and unsuitability for meta‐analysis (Deeks 2011).

Assessment of reporting biases

As with conduct bias, two review authors will independently assess any evidence of reporting bias and report this as recommended (Higgins 2011a). Where there is any doubt, we will contact the study authors for clarification, and if necessary for unpublished data. We will endeavour to locate and acquire the original study protocols of included studies in order to assess the risk of outcome reporting bias.

Data synthesis

For clinically homogeneous studies with similar participants, comparators and using the same outcome measure, we will pool outcomes in a meta‐analysis. We will use a fixed‐effect model for meta‐analysis, but in the presence of heterogeneity that may be important (I² statistic of 40% or more) we will use a random‐effects model For time‐to‐event data, we will convert estimates of hazard ratio (HR) and 95% CI, if presented in the trial reports, into the log rank observed minus expected events and variance of the log rank, and pool these estimates using a fixed‐effect model (Deeks 2011).

Subgroup analysis and investigation of heterogeneity

If there are sufficient data, we will perform subgroup analyses to determine whether effect size is influenced by the following factors:

• severity of ulcers at baseline, determined by size (> 5 cm or ≤ 5 cm ) or ulcer duration (> 6 months or ≤ 6 months) at baseline;

• different endothermal techniques;

• different forms of compression;

• the presence of infection (determined by clinical features and positive culture); and

• aetiology of the ulcer (occlusive or reflux).

Sensitivity analysis

If there are sufficient data, we will conduct a sensitivity analysis to investigate the robustness of the treatment effect to allocation concealment, by removing the trials that did not report adequate allocation concealment from the meta‐analysis to see if this changes the overall treatment effect. We will also do this for blinded outcome assessment.