Inclusion criteria for study selection
Types of studies
Randomized controlled trials and controlled clinical trials will be included. Including two arm or 3-arm parallel designed trials, animal experiments will be excluded.
Types of patients
Patients who were diagnosed as DFU according to the diagnostic criteria were included (Ulcers in or below the ankle in diabetic patients and with no other cause shown or suspected), without restrictions on age, race, gender and geographical location or setting. The diagnostic criteria for DFU: Refer to the 2019 IWGDF Guidelines on the prevention and management of diabetic foot disease.
Types of interventions
The intervention must be described as Extracorporeal shockwave therapy.
Control group consisted of standard care or sham ESWT.
Types of outcome measures
The primary outcomes are closure of diabetic foot ulcers and ulcer healing rate.
The secondary outcomes include ulcer healing time, ulcer recurrence rate, pain, Participant health-related quality of life/health score, hospital charges and amputation.
The evaluation of clinical results will be defined as within 6 months after the beginning of treatment. Follow-up time was defined as within 1 year.
Search methods for the identification of studies
Electronic databases including China Science and Technology Journal Database, PubMed, EMBASE, Ovid MEDLINE, Web of Science, Embase, Cochrane Central Registry of Controlled Trials and China National Knowledge Infrastructure Database. Two independent researchers (WF and FX) will search all electronic databases above from inception to June, 2020.
The following search terms will be used to search in PubMed and other English databases: ”extracorporeal shockwave therapy”, ”shockwave therapy”, ”shockwave”, ”diabetic foot”, ”diabetic feet”, ”diabetic foot ulcer”, ”diabetic ulcer”, ”diabetic ulcers”, ”chronic diabetic foot ulcers”, ”Randomized controlled trial”, ”controlled trial”, ”trial”. The search strategy for PubMed is shown in Table 1.
Searching other resources
The following trials registries will be searched: ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform. We will also review the reference lists of all major studies, and contact relevant experts to identify any unpublished research, or publications of a study in non-indexed journals.
We will contact authors of key papers and abstracts to request further information about their trials when necessary.
Selection of studies
All studies will be imported into Endnote software and excluded duplicated studies before the screening. Two authors will independently scan all title and abstract and all irrelevant literatures will be removed. Then, full manuscripts of all remaining studies will be further identified to check if they meet all inclusion criteria. We will note all excluded citations with specific reasons. If there are any different opinions between 2 authors, we will invite another author for consultation and final decision will be made after discussion. The detail of the study selection will be presented in a PRISMA flow diagram (Fig. 1).
Data extraction and management
Two review authors (WF and XY) will extract data independently and collect data on a data extraction form. We will resolve discrepancies in the results by discussion. All data will be entered into the RevMan software (V.5.3) after double cross-checking.
We will collect the following information:
publication details (e.g. year, country, authors);
population data (e.g. age, ethnicity, baseline aspects such as severity, duration,symptoms, history concerning treatments and responses);
details of interventions (e.g. number of treatmentsessions, regimen, fluence, scheme, adjunctive therapies, increasing or decreasing fluence, who delivered the intervention,the location of the intervention);
the duration of follow-up.
types of outcome measures;
timing of outcomes;
Assessment of risk of bias in included studies
Two review authors will independently apply the Cochrane tool for assessing risk of bias to the included studies. This tool assesses six domains: sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, other issues (e.g. source of funding).
Measures of treatment effect
We will calculate risk ratios (RR) and 95% confidence intervals (CIs) for dichotomous variables. We will calculate the mean difference (MD) and 95% CIs for continuous outcomes that have used similar scales for assessments, and will calculate the standardized mean difference (SMD) and 95% CI for continuous outcomes where different scales have been used. In the event that study authors do not make the necessary information available, we will present the results narratively and insert any data into an additional table.
Dealing with missing data
In the case of missing data, we will contact the original trial investigators to request missing data whenever possible. If necessary, we will perform data imputation according to the principles from the Cochrane Handbook. We will explicitly describe our assumptions in case of imputing missing data.
Also, we will address the potential impact of missing data on the findings of the review in the Discussion section.
Assessment of heterogeneity
We will assess statistical heterogeneity using the χ² test (a significance level of P value less than 0.10 will be considered to indicate statistically significant heterogeneity) in conjunction with the I²measure. We will consider that I²values of 25%, or less may not indicate important heterogeneity and values of more than 75% indicate considerable heterogeneity. Where there is no clinical or statistical heterogeneity, we will use a fixed-effect model. In the absence of clinical heterogeneity and in the presence of some statistical heterogeneity (I²over 50%), we will use a random-effects model; however, we will not anticipate pooling data across studies where heterogeneity is considerable (I²over 75%). Where there is evidence of considerable heterogeneity we will explore this further if required.
Assessment of reporting bias
If more than 10 studies are included in the review, we will attempt to identify existence of any reporting bias by constructing a funnel plot. If we detect evidence of asymmetry, we will explore possible explanations such as reporting bias, selective outcome reporting, poor methodological design, inadequate analysis and true heterogeneity.
We will conduct subgroup analysis for the following groups, where data permit:
types of shockwave devices;
different fluences and schemes;
duration of treatment.
If we find substantial heterogeneity (when the I²statistic exceeds 50%), and there are sufficient data, we will investigate the possible causes by exploring the impact of the condition of the individuals and interventions (i.e. participant characteristics, addition of adjuvant therapies) using subgroup analyses.
We will perform a sensitivity analysis to determine whether our results are robust by excluding those studies assessed as having a high risk of bias. The following sensitivity analyses will be performed to test whether critical methodological factors or decisions have affected the main result, where there is a sufficient number of studies in the meta-analyses：
removing unpublished data
changing effects model
Grading the quality of evidence
The evidence quality from each study will be assessed by 2 researchers independently.
The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines will be used and divided into 4 level: Very low, low, moderate or high.
Limitation of study design, imprecision, inconsistency, indirectness and bias of publication will be assessed.
Protocol development and potential amendments
This is an original research protocol, any changes will be stated in the final review manuscript and updated via PROSPERO and INPLASY.