Types of studies

We included randomised controlled trials (RCTs), either published or unpublished, that evaluated the effects of any type of alginate dressing in the treatment of venous ulcers, irrespective of language of report. RCTs reported in abstract form only were eligible for inclusion, provided adequate information was either presented in the abstract or available from the trial author. Studies using quasi‐randomisation were excluded.

Types of participants

We considered RCTs recruiting people described in the primary report as having venous leg ulcers, managed in any care setting, to be eligible for inclusion. As the method of diagnosis of venous ulceration may vary, we accepted definitions as used in the RCTs. We included RCTs recruiting samples that comprised people with venous leg ulcers and people with other types of wounds (e.g. arterial ulcers, diabetic foot ulcers) if the results for people with venous ulcers were presented separately (or available from the trial authors), or if the majority of participants (75% or more in each arm) had leg ulcers of venous aetiology.

Types of interventions

The primary intervention of interest was alginate wound dressings. For ease of comparison, we grouped included RCTs according to the comparator intervention using categories presented in the British National Formulary (BNF 2015). We have reported generic names for all products where possible, also providing trade names and manufacturers, where available. However, it is important to note that manufacturers and distributors of dressings may vary from country to country, and dressing names may also differ. We have not included RCTs assessing alginate dressings impregnated with antibiotic, antiseptic or analgesic agents as these interventions are evaluated in other Cochrane reviews (Briggs 2012; O'Meara 2014). RCTs evaluating foam dressings, hydrocolloid dressings and hydrogels are covered in other Cochrane reviews (O'Meara 2013; Ribeiro 2013; Ribeiro 2014) and were included in this review only if they involved a comparison with an alginate dressing.

We included any RCT in which the presence or absence of an alginate dressing was the only systematic difference between treatment groups; and in which an alginate dressing was compared with other wound dressings (including alternative alginate dressings), non‐dressing treatments (for example, topical applications) or no dressing. We included RCTs of alginate dressings, irrespective of whether compression was reported as a concurrent therapy.

Types of outcome measures

Electronic searches

In March 2015, for this first update, we searched the following electronic databases for potentially relevant RCTs:

• The Cochrane Wounds Group Specialised Register (searched 4 March 2015);

• The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 2);

• Ovid MEDLINE (1946 to 3 March 2015);

• Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations searched 3 March 2015);

• Ovid EMBASE (1980 to 3 March 2015);

• EBSCO CINAHL (1982 to 4 March 2015)

We used the following search strategy in the Cochrane Central Register of Controlled Trials (CENTRAL):

#1 MeSH descriptor Alginates explode all trees
#2 (alginate* or activheal or algisite or algosteril or curasorb or kaltostat or melgisorb or seasorb or sorbalgon or sorbsan or suprasorb a or tegaderm or tegagel or urgosorb):ti,ab,kw
#3 (#1 OR #2)
#4 MeSH descriptor Leg Ulcer explode all trees
#5 ((varicose NEXT ulcer*) or (venous NEXT ulcer*) or (leg NEXT ulcer*) or (stasis NEXT ulcer*) or (crural NEXT ulcer*) or "ulcus cruris" or "ulcer cruris"):ti,ab,kw
#6 (#4 OR #5)
#7 (#3 AND #6)

We adapted this strategy to search Ovid MEDLINE, Ovid EMBASE and EBSCO CINAHL (Appendix 3). We combined 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 combined the EMBASE search with the Ovid EMBASE filter developed by the UK Cochrane Centre (Lefebvre 2011). We combined the CINAHL searches with the trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN 2014). We did not restrict searches with respect to language or date of publication.

We searched for ongoing RCTs in the following clinical trial registries using the search term 'leg ulcer':

• World Health Organization International Trial Registry Platform (http://www.who.int/ictrp/en/);

• ISRCTN (International Standard Randomised Controlled Trial Number) register (http://www.controlled‐trials.com/);

• ClinicalTrials.gov (http://www.clinicaltrials.gov).

All registries were accessed on 1st August 2012 for the original review and on 17th July 2015 for this update.

Searching other resources

We attempted to contact trial authors to obtain unpublished data and other information as required. For the first version of this review, we contacted manufacturers to request information about ongoing or unpublished RCTs (for a list of manufacturers see Appendix 4). We also examined the reference lists of eligible RCTs and relevant review articles.

Selection of studies

Two review authors independently assessed the titles and abstracts for relevance. After this initial assessment, we obtained the full text of all RCT reports felt to be potentially relevant. Two review authors then independently checked the full papers for eligibility, with all disagreements resolved by discussion. We recorded all reasons for exclusion.

We have presented our study selection process as a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) flow diagram (Liberati 2009) (Figure 1).

Figure 1

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Flow diagram of the trial selection process.

Data extraction and management

We extracted and summarised details of the eligible RCTs using a standardised data extraction form (Appendix 5). We extracted the data from RCT reports using an Excel spreadsheet designed to capture the RCT information detailed below. Initially, we piloted the spreadsheet with a sample of eligible RCTs, to explore any issues that might arise in relation to the data extraction process. We expanded and amended the spreadsheet as necessary after the piloting process. Two review authors performed independent data extraction of all included RCTs after which both data extractions were compared for agreement. We resolved any disagreements by discussion. If data were missing from reports we attempted to contact the trial authors to obtain the missing information. We included RCTs published as duplicate reports (parallel publications) once, using all associated RCT reports to extract the maximum amount of information, but ensuring that data were not duplicated in the review. We extracted the following information:

• trial authors;

• year of publication;

• country where trial was undertaken;

• setting of care;

• trial design details (e.g. pragmatic, pilot);

• ethical approval;

• participant consent;

• unit of investigation – participant, leg or ulcer;

• overall sample size and methods used to estimate statistical power (relates to the target number of participants to be recruited, the clinical difference to be detected and the ability of the RCT to detect this difference);

• participant selection criteria;

• number of participants randomised to each treatment arm;

• baseline characteristics of participants per treatment arm (gender, age, baseline ulcer area, ulcer duration, prevalence of co‐morbidities such as diabetes, prevalence of clinically infected wounds or colonised wounds, previous history of ulceration, baseline levels of wound exudate, and participant mobility);

• details of the dressing/treatment regimen prescribed for each arm including details of any concomitant therapy, for example, compression;

• duration of treatment;

• duration of follow‐up;

• statistical methods used for data analysis;

• primary and secondary outcomes measured;

• primary and secondary outcome data by treatment arm;

• adverse effects of treatment (per treatment arm with numbers and type);

• withdrawals (per treatment arm with numbers and reasons); and

• source of trial funding.

Assessment of risk of bias in included studies

Two review authors independently assessed each included RCT report using The Cochrane Collaboration tool for assessing risk of bias (Higgins 2011). This tool addresses specific domains, namely: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcome reporting (see Appendix 6 for details of the criteria on which judgements were based). For blinded outcome assessment we made separate judgements for primary and secondary outcomes. As assessment of healing (the primary outcome) is likely to be subject to potential observer/measurement bias, blinding of outcome assessment is important. Similarly we made separate judgements for primary and secondary outcomes for the domain of incomplete outcome data. In order to assess selective outcome reporting, we sought protocols for all included RCTs. Where protocols were unavailable, we made a judgement based on congruence of information in methods and results sections of reports of RCTs. We classified RCTs as being at overall high risk of bias if they were rated as 'high' for any one of three key domains (allocation concealment, blinding of outcome assessors and completeness of outcome data).

We have presented our assessment of risk of bias findings using 'Risk of bias' figures (Figure 2 is a summary of information across all included RCTs and Figure 3 shows a cross‐tabulation of each individual RCT with each risk of bias item). This display of internal validity indicates the weight the reader may give the results of each RCT.

Figure 2

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included trials.

Figure 3

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Risk of bias summary: review authors' judgements about each risk of bias item for each included trial.

Measures of treatment effect

We reported estimates for dichotomous outcomes (e.g. number of ulcers healed) as risk ratio (RR) with associated 95% confidence interval (CI). We reported estimates for continuous data outcomes (e.g. absolute or relative change in ulcer area and healing rate) as mean difference (MD) with 95% CI. We planned to report estimates of time to healing and hazard ratios where available. Where RCTs reported adverse events in sufficient detail (e.g. the number of participants who experienced at least one adverse event) we analysed these data as dichotomous. Where adverse events were reported as dressing‐related we planned to analyse these data separately. We calculated measures of effect using Cochrane RevMan software (version 5.1) (RevMan 2014). We reported data narratively as provided in the RCT reports, without additional estimation of treatment effect, in the following instances:

• where time to healing estimates were based on non‐censored data;

• where count data were provided (e.g. where the denominator was the total number of adverse events or total number of dressing changes per group);

• and where it was unclear whether the denominator was the total number of events (such adverse events or dressing changes) or the number of participants.

Unit of analysis issues

We recorded whether RCT reports specified participants, limbs or ulcers as the units of allocation and analysis. In cases where multiple limbs or ulcers on the same individual were studied, we planned to note whether the trial authors' analysis was appropriate (i.e. correctly taking account of highly correlated data) or inappropriate (i.e. considering outcomes for multiple ulcers on the same participant as independent). Where the number of wounds appeared to be equal to the number of participants, we have assumed that the ulcer was the unit of analysis, unless otherwise stated.

Dealing with missing data

Missing data are a common problem in RCTs. Excluding randomised participants from the analysis, or ignoring those lost to follow‐up, can compromise the process of randomisation and introduce bias. Where RCTs reported the outcome of complete healing only for participants who completed the RCT (i.e. participants withdrawing and lost to follow‐up were excluded from the analysis), we treated the excluded participants as if their wound did not heal (that is, they were included in the denominator but not the numerator). Where results were reported for participants who completed the RCT without specifying the numbers initially randomised per group, we presented complete case data. For other outcomes we presented data for all participants randomised where reported; otherwise we based our estimates on complete case data.

Assessment of heterogeneity

We considered clinical heterogeneity (that is the degree to which RCTs vary in terms of participant, intervention and outcome characteristics) and statistical heterogeneity. We assessed statistical heterogeneity using the Chi² test (a significance level of P < 0.10 was considered to indicate statistically significant heterogeneity) in conjunction with the I² statistic (Higgins 2003). The I² statistic examines the percentage of total variation across RCTs that is due to heterogeneity rather than chance (Higgins 2003). We considered that I² values of 40%, or less, indicated a low level of heterogeneity, and values of 75%, or more, indicated very high heterogeneity (Deeks 2011).

Assessment of reporting biases

Reporting biases arise when the dissemination of research findings is influenced by the nature and direction of results. Publication bias is one of a number of possible causes of 'small study effects', that is, a tendency for estimates of the intervention effect to be more beneficial in smaller RCTs. Funnel plots allow a visual assessment of whether small study effects may be present in a meta‐analysis. A funnel plot is a simple scatter plot of the intervention effect estimates from individual RCTs against some measure of each trial’s size or precision (Sterne 2011). We planned to present funnel plots for meta‐analyses comprising 10 RCTs or more using RevMan 5.1.

Data synthesis

We have presented a narrative synthesis of all included RCTs, with results grouped according to type of comparator (e.g. foam dressings compared with alginates, hydrocolloids compared with alginates). We undertook statistical pooling of outcome data on groups of RCTs with available data and considered to be sufficiently similar in terms of design and characteristics of participants, interventions and outcomes. The decision to undertake meta‐analysis depended on the availability of outcome data and assessment of heterogeneity. For comparisons where there was no apparent clinical heterogeneity and the I² value was 40%, or less, we applied a fixed‐effect model. Where there was no apparent clinical heterogeneity and the I² value was over 40%, we planned to apply a random‐effects model. However, we planned not to pool data where heterogeneity was very high (I² values of 75% or above).

For dichotomous outcomes we have presented the summary estimate as a risk ratio (RR) with 95% CI. Where continuous outcomes were measured in the same way across RCTs, we planned to present a pooled mean difference (MD) with 95% CI; we planned to pool standardised mean difference (SMD) estimates where RCTs measured the same outcome using different methods. For time to event data, we planned to plot (and, if appropriate, pool) estimates of hazard ratios and 95% CIs as presented in the RCT reports using the generic inverse variance method in RevMan 5.1. Where hazard ratios were not reported we planned to extrapolate estimates, where possible, using other reported data (Parmar 1998). Pooled estimates of treatment effect were obtained using Cochrane RevMan software (version 5.1) (RevMan 2014).

Subgroup analysis and investigation of heterogeneity

We planned to conduct a subgroup analysis for complete healing according to whether compression was used as a concurrent treatment, excluding any RCTs in which use of compression was unclear.

Sensitivity analysis

We planned two sensitivity analyses for the outcome of complete healing: one where RCTs classified as being at overall high risk of bias were excluded; and one where RCTs that possibly, or definitely, reported outcomes only for participants who completed the trial were excluded.