Types of studies

We included randomised controlled trials (RCTs), either published or unpublished, that evaluated the effects of any type of hydrogel wound dressing in the treatment of venous leg ulcers, irrespective of language of publication.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

Types of participants

We included RCTs of people of any age, managed in any care setting with a diagnosed venous leg ulcer determined either by clinical evaluation, or complementary laboratory tests (e.g. duplex ultrasonography, plethysmography and venography), or both (Collins 2010), using the definition of a positive diagnosis given by the authors. We included trials that had people with wounds of other aetiology (e.g. pressure ulcers), or trials of mixed populations (venous ulcers along with arterial or diabetic ulcers) that presented the results for the subgroup of people with venous leg ulcers separately, or if the majority of participants (75% or greater in each group) had leg ulcers of venous aetiology. We attempted to contact trial authors to obtain the relevant data, if data from subgroups of people with venous leg ulcers were not reported separately. We excluded studies of people with infected wounds, because hydrogel dressings are not indicated (prescribed) for this type of wound. Trials evaluating skin grafting are covered elsewhere and were excluded from this review (Jones 2007).

Types of interventions

The primary intervention of interest was hydrogel dressings used as a treatment for venous leg ulcers. We included any RCT in which the presence or absence of a hydrogel dressing was the only systematic difference between treatment groups; and in which a hydrogel dressing was compared with other wound dressings, non‐dressing treatments (e.g. topical applications) or another hydrogel dressing. We included RCTs of hydrogel dressings, irrespective of whether compression therapy was reported as a concurrent therapy. For ease of comparison, we categorised dressings according to the Nurse Prescribers' Formulary (BNF 2018). We 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 excluded trials evaluating hydrogel dressings impregnated with antimicrobial, antiseptic or analgesic agents as these interventions are evaluated in other Cochrane Reviews (Briggs 2012; O'Meara 2010). We excluded trials that use larval therapy.

Types of outcome measures

Electronic searches

We searched the following electronic databases to identify reports of relevant clinical trials on 10 May 2021:

• the Cochrane Wounds Specialised Register;

• the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 4) in the Cochrane Library;

• Ovid MEDLINE including In‐Process & Other Non‐Indexed Citations (from 1946);

• Ovid Embase (from 1974);

• EBSCO CINAHL Plus (Cumulative Index to Nursing and Allied Health Literature; from 1937).

The search strategies can be found in 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 2022). We combined the Embase search with the Ovid Embase filter developed by the UK Cochrane Centre (Lefebvre 2022). We combined the CINAHL Plus searches with the trial filters developed by Glanville 2019. There were no restrictions with respect to language, date of publication or study setting.

We searched the following clinical trial registries:

• US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov  (www.clinicaltrials.gov; searched 10 May 2021);

• World Health Organization International Clinical Trials Registry Platform (WHO ICTRP; trialsearch.who.int/; searched 10 May 2021);

• ISRCTN registry (www.isrctn.com/; searched 14 Sep 2021).

Search strategies for clinical trial registries can be found in Appendix 3.

Searching other resources

Selection of studies

Two review authors (CR and FD) independently assessed the titles and abstracts of the studies identified from the search strategy against the inclusion criteria. We obtained full versions of articles that appeared to fulfil the inclusion criteria for further assessment. Two review authors then independently checked the full papers for eligibility, with all disagreements resolved by discussion with another review author (GF). We recorded all reasons for exclusion.

We presented our study selection process as a PRISMA flow diagram (Liberati 2009).

Data extraction and management

We extracted and summarised details of the eligible RCTs using a standardised data extraction form. Two review authors (CR and FD) 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 contacted study authors to obtain the missing information. Data from studies that were published in duplicate were only included once. According to methods described in the Cochrane Handbook for Systematic Reviews of Interventions, we extracted the following information (Lefebvre 2022; Li 2022):

• country of origin;

• study authors and year of publication;

• care setting;

• type of ulcer;

• unit of investigation (per participant) – single ulcer or foot or participant, or multiple ulcers on the same participant;

• number of participants randomised to each treatment group;

• eligibility criteria and key baseline participant data (gender, age, ethnicity, baseline ulcer area, ulcer duration, prevalence of comorbidities such as diabetes);

• details of the dressing/treatment regimen received by each group;

• details of any co‐interventions;

• primary and secondary outcome(s) (with definitions);

• outcome data for primary and secondary outcomes (by group);

• 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 trial to detect this difference);

• duration of treatment;

• duration of follow‐up;

• number of withdrawals (by group with reasons);

• statistical methods used for data analysis;

• risk of bias criteria (sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting);

• source of funding.

Data analysis was performed according to Cochrane guidelines. One review author entered quantitative data into Review Manager Web (Review Manager Web 2020), another checked it, and the data were then analysed.

Assessment of risk of bias in included studies

Two review authors independently assessed each included RCT using the Cochrane RoB 1 tool. This tool addresses six specific domains, namely sequence generation, allocation concealment, blinding of participants and care providers; blinding of outcome assessors, incomplete outcome data, selective outcome reporting and other issues that may potentially bias the study (Appendix 5). For this review, we considered other risk of bias issues as follows: comparability of treatment groups in relation to baseline ulcer surface area; choice of analysis where multiple ulcers on the same individual(s) are studied and choice of analysis in cluster randomised trials. We completed a risk of bias table for each eligible study and classified each study at overall high, low or unclear risk of bias, according to the methods described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2017). We discussed any disagreement among all review authors to achieve a consensus. We presented narrative discussion of the risk of bias, in addition to a risk of bias summary figure, which presents all the judgements in a cross‐tabulation of study by risk of bias domain. We classified trials at high risk of bias overall if they were rated high for any of three key criteria, namely, allocation concealment, blinding of outcome assessors and completeness of outcome data. For trials that had at least one of the three key domains rated as 'unclear' but none of these were at high risk of bias, we classified the trial at overall unclear risk of bias. Trials could only be classified at low risk of bias overall if all three key domains were rated as low risk individually.

Measures of treatment effect

We presented a narrative overview of all included RCTs, with results grouped according to the comparator intervention. We planned to combine trials when sufficiently alike in terms of population and comparison interventions, but this was not possible for this review. We reported mean differences (MD) and 95% confidence intervals (CI) for continuous outcomes (such as absolute or relative changes in ulcer area), and risk ratio (RR) and 95% CI for dichotomous variables (e.g. ulcers healed during time period, number of infected ulcers). We planned to pool standardised mean differences (SMD) estimates where studies measured the same outcome using different methods. In future updates, for time‐to‐event data, we plan to plot estimates of hazard ratios with associated 95% CIs where available from trial reports. In a trial that did not present data for change in ulcer healing but presented data for ulcer area at baseline and at the end of treatment, we estimated the change in ulcer area calculating the MD between these time points and therefore comparing treatment groups; however, caution should be used interpreting the results because samples were treated as independent. 

Unit of analysis issues

We treated the number of ulcers as the unit of analysis in this review; however, we recorded whether outcomes in relation to an ulcer were measured on a per‐participant or per‐ulcer basis, and, in studies where multiple ulcers on a person were treated as being independent, we recorded that as part of our risk of bias assessment. We planned to include data from cluster‐randomised trials; however, we identified no studies with this characteristic. For future updates, we will adjust results when the unit of analysis in the trial is presented as the total number of individual participants instead of the number of clusters. Results will be adjusted using the mean cluster size and intracluster correlation coefficient (ICC) (Deeks 2022). For meta‐analysis, data would have been combined from individually randomised trials using the generic inverse‐variance method as described in Chapter 10 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2022); however, meta‐analysis was not possible in this review.

Dealing with missing data

In the case of missing data, we contacted the original investigators to request these data whenever possible. No additional data were provided by study authors and therefore no data inclusions are reported. If trials had reported complete healing outcomes for only those participants who completed the trial (i.e. participants withdrawing and lost to follow‐up were excluded from the analysis), we planned to treat the participants who were not included in the analysis as if their wound had not healed. Where results were reported for participants who completed the trial without specifying the numbers initially randomised per group, we presented complete‐case data. The trials included in the review either had no dropouts, or analysed data on an intention‐to‐treat basis, excepting one that had withdrawals, but did not fully report data or withdrawals per group; therefore, we presented complete‐case data for this. 

Assessment of heterogeneity

If, for future updates, we are able to include a sufficient number of studies, we will pool data for meta‐analysis using Review Manager Web (Review Manager Web 2020). We will consider clinical heterogeneity (i.e. where trials appear similar in terms of level of participants, intervention type and duration, and outcome type) and statistical heterogeneity. We will assess statistical heterogeneity using the Chi² test (a significance level of P < 0.10 is considered to indicate significant heterogeneity) in conjunction with the I² measure (Deeks 2022). The I² measure examines the percentage of total variation across trials due to heterogeneity rather than variation due to chance (Deeks 2022). Heterogeneity will be categorised as follows: I² values of 40% or less indicate a low level of heterogeneity and 75% or greater to represent substantial heterogeneity (Deeks 2022).

Assessment of reporting biases

If, for future updates, we are able to include a sufficient number of studies (10 RCTs or more), we will investigate publication bias using funnel plots as described in the Cochrane Handbook for Systematic Reviews of Interventions (Page 2022). If there is asymmetry, we will explore possible causes including publication bias, risk of bias and true heterogeneity.

Data synthesis

We combined details of included studies in a narrative review according to type of comparator. There were an insufficient number of included studies to pool data for meta‐analysis. Clinical and methodological heterogeneity would have been considered and pooling undertaken when studies appeared appropriately similar in terms of wound type, intervention type, duration of follow‐up and outcome type. We anticipated using a random‐effects approach for meta‐analysis. Conducting meta‐analysis with a fixed‐effect model in the presence of even minor heterogeneity may provide overly narrow CIs. We would only have used a fixed‐effect approach when clinical and methodological heterogeneity was minimal. Chi² and I² would have been used to quantify heterogeneity but would not have been used to guide choice of model for meta‐analysis. For dichotomous outcomes, we presented the summary estimate as an RR with 95% CI. Where continuous outcomes were measured, we presented an MD with 95% CI. We planned to pool SMD estimates where studies measured the same outcome using different methods, such as health‐related quality of life data; however, this outcome was not reported in the included studies. For time‐to‐event data, we planned to plot (and, if appropriate, pool) estimates of hazard ratios and 95% CIs as presented in the study reports using the generic inverse variance method in Review Manager Web (Review Manager Web 2020). Where time‐to‐healing was analysed as a continuous measure, but it was not clear if all wounds healed, use of the outcome in the study would have been documented, but data would not have been summarised or used in any meta‐analysis.

Subgroup analysis and investigation of heterogeneity

If, for future updates, we are able to include sufficient data and identify substantial heterogeneity, we will conduct subgroup analyses (Page 2022). We planned to conduct subgroup analysis according to presence or absence of compression therapy independent of type (elastic or inelastic) or level (moderate or high) compression.

Sensitivity analysis

For future updates, in case there are a sufficient number of included studies, we plan to undertake sensitivity analyses for each comparison that has a meta‐analysis according to the overall risk of bias. RCTs with overall high or unclear risk of bias will be excluded and the difference between estimates of treatment effect from this analysis and the main analysis considered.

Summary of findings and assessment of the certainty of the evidence

Two review authors (CR, FD) graded the certainty of the evidence using GRADE (GRADEpro GDT), using four levels of certainty: high, moderate, low and very low (Schünemann 2022). We carried out a GRADE assessment on all outcomes summarised in this review, rather than limiting this to complete wound healing and incidence of wound infection (as proposed in the published protocol). We presented the main results of the review in summary of findings tables. The review protocol did not specify outcomes for the summary of findings tables. We included the following outcomes: complete wound healing, incidence of wound infection, change in ulcer size, time‐to‐ulcer healing, health‐related quality of life and costs, because we consider them critical or important for decision‐making in health care; these will be prespecified for any future updates. These tables present key information concerning the certainty of evidence, the magnitude of the effects of the interventions examined and the sum of the available data for the main outcomes (Schünemann 2022). The GRADE approach defines the certainty of a body of evidence as the extent to which one can be confident that an estimate of effect or association is close to the true quantity of specific interest. The certainty of a body of evidence involves consideration of within‐trial risk of bias (methodological quality), directness of evidence, heterogeneity, precision of effect estimates and risk of publication bias (Schünemann 2022). When making decisions for the risk of bias domain, we downgraded one level if studies presented unclear risk of bias for all outcomes, and downgraded once or twice when studies were at high risk of bias for one or more domains (Schünemann 2022). We followed the methods described in Guyatt 2011 when downgrading for imprecision: either considering both the optimal information size (OIS) and the 95% CI of each meta‐analysis if they were estimable; or considering the sample size, the number of events and other eIectiveness indicators if the calculation of OIS and undertaking a meta‐analysis were not applicable. We downgraded twice for imprecision when there were very few events and CIs around effects included both appreciable benefit and appreciable harm.