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The Cochrane Methodology Review Group is the Cochrane Review Group responsible for Cochrane Methodology Reviews, which provide evidence on various methods for conducting and using health and social care research. The Group's unofficial Impact Factor for 2022 was 9.5 , higher than the Impact Factor for all Cochrane Reviews of 8.4

Cochrane methodology reviews are a special type of Cochrane review, examining the evidence on methodological aspects of systematic reviews, randomised trials and other evaluations of health and social care. They are published in the Cochrane Database of Systematic Reviews in the Cochrane Library, alongside Cochrane reviews of the effects of interventions, diagnostic test accuracy, prognosis and overviews of Cochrane reviews. Cochrane invites prospective authors to propose new Cochrane Reviews by submitting a proposal in Editorial Manager . Please see the Cochrane Library information for authors for further details.

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Research resilience and growth: The Cochrane Methodology Review Group has several reviews that might be relevant to making health and social care research become more resilient and grow. These include our reviews on the effects of strategies to improve recruitment and retention in randomised trials.

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Strategies designed to help healthcare professionals to recruit participants to research studies

Factors that impact on recruitment to randomised trials in health care: a qualitative evidence synthesis  Podcast available here

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Cochrane handbook for systematic reviews of interventions, june 2017: handbook editors' update  .

The Handbook editorial team is currently updating Handbook versions 5.0, 5.1 and 5.2 for a planned release of Version 6 in 2018. This is a major update. Senior Scientific Editors Julian Higgins and James Thomas have reorganized some material to include recent developments. There are also several new chapters including writing a protocol, equity and specific populations, complex interventions, network meta-analysis, and synthesizing findings using non-statistical methods. Please note following the introduction of the Methodological Expectations for Cochrane Intervention Review (MECIR) standards, we set out to produce a minor Handbook update, version 5.2 to include these standards. Due to limited editorial capacity, we only produced a limited number of chapters. These   chapters are 1, 8, 9, 10, 11, 12, and 21 and are available as pdf versions for Cochrane members. These chapters only include minor edits to improve clarity, some limited new material and updating. There are currently no substantive changes to methods in these chapters, we expect to include these in Version 6. For more details see the What's new? page.

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The Cochrane Handbook for Systematic Reviews of Interventions is the official guide that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions. The current complete version of the Handbook is 5.1 (updated March 2011), edited by Julian Higgins and Sally Green.

All authors should consult the Handbook for guidance on the methods used in Cochrane systematic reviews. The Handbook includes guidance on the standard methods applicable to every review (planning a review, searching and selecting studies, data collection, risk of bias assessment, statistical analysis, GRADE and intepreting results), as well as more specialised topics (non-randomized studies, adverse effects, economics, patient-reported outcomes, individual patient data, prospective meta-analysis, qualitative research, reviews in public health and overviews of reviews).

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How to cite the Handbook

Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from http://handbook.cochrane.org.

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1.2.2  What is a systematic review?

A systematic review attempts to collate all empirical evidence that fits pre-specified eligibility criteria in order to answer a specific research question.  It  uses explicit, systematic methods that are selected with a view to minimizing bias, thus providing more reliable findings from which conclusions can be drawn and decisions made (Antman 1992, Oxman 1993) . The key characteristics of a systematic review are:

a clearly stated set of objectives with pre-defined eligibility criteria for studies;

an explicit, reproducible methodology;

a systematic search that attempts to identify all studies that would meet the eligibility criteria;

an assessment of the validity of the findings of the included studies, for example through the assessment of risk of bias; and

a systematic presentation, and synthesis, of the characteristics and findings of the included studies.

Many systematic reviews contain meta-analyses. Meta-analysis is the use of statistical methods to summarize the results of independent studies (Glass 1976). By combining information from all relevant studies, meta-analyses can provide more precise estimates of the effects of health care than those derived from the individual studies included within a review (see Chapter 9, Section 9.1.3 ). They also facilitate investigations of the consistency of evidence across studies, and the exploration of differences across studies.

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An overview of methodological approaches in systematic reviews

Prabhakar veginadu.

1 Department of Rural Clinical Sciences, La Trobe Rural Health School, La Trobe University, Bendigo Victoria, Australia

Hanny Calache

2 Lincoln International Institute for Rural Health, University of Lincoln, Brayford Pool, Lincoln UK

Akshaya Pandian

3 Department of Orthodontics, Saveetha Dental College, Chennai Tamil Nadu, India

Mohd Masood

Associated data.

APPENDIX B: List of excluded studies with detailed reasons for exclusion

APPENDIX C: Quality assessment of included reviews using AMSTAR 2

The aim of this overview is to identify and collate evidence from existing published systematic review (SR) articles evaluating various methodological approaches used at each stage of an SR.

The search was conducted in five electronic databases from inception to November 2020 and updated in February 2022: MEDLINE, Embase, Web of Science Core Collection, Cochrane Database of Systematic Reviews, and APA PsycINFO. Title and abstract screening were performed in two stages by one reviewer, supported by a second reviewer. Full‐text screening, data extraction, and quality appraisal were performed by two reviewers independently. The quality of the included SRs was assessed using the AMSTAR 2 checklist.

The search retrieved 41,556 unique citations, of which 9 SRs were deemed eligible for inclusion in final synthesis. Included SRs evaluated 24 unique methodological approaches used for defining the review scope and eligibility, literature search, screening, data extraction, and quality appraisal in the SR process. Limited evidence supports the following (a) searching multiple resources (electronic databases, handsearching, and reference lists) to identify relevant literature; (b) excluding non‐English, gray, and unpublished literature, and (c) use of text‐mining approaches during title and abstract screening.

The overview identified limited SR‐level evidence on various methodological approaches currently employed during five of the seven fundamental steps in the SR process, as well as some methodological modifications currently used in expedited SRs. Overall, findings of this overview highlight the dearth of published SRs focused on SR methodologies and this warrants future work in this area.

1. INTRODUCTION

Evidence synthesis is a prerequisite for knowledge translation. 1 A well conducted systematic review (SR), often in conjunction with meta‐analyses (MA) when appropriate, is considered the “gold standard” of methods for synthesizing evidence related to a topic of interest. 2 The central strength of an SR is the transparency of the methods used to systematically search, appraise, and synthesize the available evidence. 3 Several guidelines, developed by various organizations, are available for the conduct of an SR; 4 , 5 , 6 , 7 among these, Cochrane is considered a pioneer in developing rigorous and highly structured methodology for the conduct of SRs. 8 The guidelines developed by these organizations outline seven fundamental steps required in SR process: defining the scope of the review and eligibility criteria, literature searching and retrieval, selecting eligible studies, extracting relevant data, assessing risk of bias (RoB) in included studies, synthesizing results, and assessing certainty of evidence (CoE) and presenting findings. 4 , 5 , 6 , 7

The methodological rigor involved in an SR can require a significant amount of time and resource, which may not always be available. 9 As a result, there has been a proliferation of modifications made to the traditional SR process, such as refining, shortening, bypassing, or omitting one or more steps, 10 , 11 for example, limits on the number and type of databases searched, limits on publication date, language, and types of studies included, and limiting to one reviewer for screening and selection of studies, as opposed to two or more reviewers. 10 , 11 These methodological modifications are made to accommodate the needs of and resource constraints of the reviewers and stakeholders (e.g., organizations, policymakers, health care professionals, and other knowledge users). While such modifications are considered time and resource efficient, they may introduce bias in the review process reducing their usefulness. 5

Substantial research has been conducted examining various approaches used in the standardized SR methodology and their impact on the validity of SR results. There are a number of published reviews examining the approaches or modifications corresponding to single 12 , 13 or multiple steps 14 involved in an SR. However, there is yet to be a comprehensive summary of the SR‐level evidence for all the seven fundamental steps in an SR. Such a holistic evidence synthesis will provide an empirical basis to confirm the validity of current accepted practices in the conduct of SRs. Furthermore, sometimes there is a balance that needs to be achieved between the resource availability and the need to synthesize the evidence in the best way possible, given the constraints. This evidence base will also inform the choice of modifications to be made to the SR methods, as well as the potential impact of these modifications on the SR results. An overview is considered the choice of approach for summarizing existing evidence on a broad topic, directing the reader to evidence, or highlighting the gaps in evidence, where the evidence is derived exclusively from SRs. 15 Therefore, for this review, an overview approach was used to (a) identify and collate evidence from existing published SR articles evaluating various methodological approaches employed in each of the seven fundamental steps of an SR and (b) highlight both the gaps in the current research and the potential areas for future research on the methods employed in SRs.

An a priori protocol was developed for this overview but was not registered with the International Prospective Register of Systematic Reviews (PROSPERO), as the review was primarily methodological in nature and did not meet PROSPERO eligibility criteria for registration. The protocol is available from the corresponding author upon reasonable request. This overview was conducted based on the guidelines for the conduct of overviews as outlined in The Cochrane Handbook. 15 Reporting followed the Preferred Reporting Items for Systematic reviews and Meta‐analyses (PRISMA) statement. 3

2.1. Eligibility criteria

Only published SRs, with or without associated MA, were included in this overview. We adopted the defining characteristics of SRs from The Cochrane Handbook. 5 According to The Cochrane Handbook, a review was considered systematic if it satisfied the following criteria: (a) clearly states the objectives and eligibility criteria for study inclusion; (b) provides reproducible methodology; (c) includes a systematic search to identify all eligible studies; (d) reports assessment of validity of findings of included studies (e.g., RoB assessment of the included studies); (e) systematically presents all the characteristics or findings of the included studies. 5 Reviews that did not meet all of the above criteria were not considered a SR for this study and were excluded. MA‐only articles were included if it was mentioned that the MA was based on an SR.

SRs and/or MA of primary studies evaluating methodological approaches used in defining review scope and study eligibility, literature search, study selection, data extraction, RoB assessment, data synthesis, and CoE assessment and reporting were included. The methodological approaches examined in these SRs and/or MA can also be related to the substeps or elements of these steps; for example, applying limits on date or type of publication are the elements of literature search. Included SRs examined or compared various aspects of a method or methods, and the associated factors, including but not limited to: precision or effectiveness; accuracy or reliability; impact on the SR and/or MA results; reproducibility of an SR steps or bias occurred; time and/or resource efficiency. SRs assessing the methodological quality of SRs (e.g., adherence to reporting guidelines), evaluating techniques for building search strategies or the use of specific database filters (e.g., use of Boolean operators or search filters for randomized controlled trials), examining various tools used for RoB or CoE assessment (e.g., ROBINS vs. Cochrane RoB tool), or evaluating statistical techniques used in meta‐analyses were excluded. 14

2.2. Search

The search for published SRs was performed on the following scientific databases initially from inception to third week of November 2020 and updated in the last week of February 2022: MEDLINE (via Ovid), Embase (via Ovid), Web of Science Core Collection, Cochrane Database of Systematic Reviews, and American Psychological Association (APA) PsycINFO. Search was restricted to English language publications. Following the objectives of this study, study design filters within databases were used to restrict the search to SRs and MA, where available. The reference lists of included SRs were also searched for potentially relevant publications.

The search terms included keywords, truncations, and subject headings for the key concepts in the review question: SRs and/or MA, methods, and evaluation. Some of the terms were adopted from the search strategy used in a previous review by Robson et al., which reviewed primary studies on methodological approaches used in study selection, data extraction, and quality appraisal steps of SR process. 14 Individual search strategies were developed for respective databases by combining the search terms using appropriate proximity and Boolean operators, along with the related subject headings in order to identify SRs and/or MA. 16 , 17 A senior librarian was consulted in the design of the search terms and strategy. Appendix A presents the detailed search strategies for all five databases.

2.3. Study selection and data extraction

Title and abstract screening of references were performed in three steps. First, one reviewer (PV) screened all the titles and excluded obviously irrelevant citations, for example, articles on topics not related to SRs, non‐SR publications (such as randomized controlled trials, observational studies, scoping reviews, etc.). Next, from the remaining citations, a random sample of 200 titles and abstracts were screened against the predefined eligibility criteria by two reviewers (PV and MM), independently, in duplicate. Discrepancies were discussed and resolved by consensus. This step ensured that the responses of the two reviewers were calibrated for consistency in the application of the eligibility criteria in the screening process. Finally, all the remaining titles and abstracts were reviewed by a single “calibrated” reviewer (PV) to identify potential full‐text records. Full‐text screening was performed by at least two authors independently (PV screened all the records, and duplicate assessment was conducted by MM, HC, or MG), with discrepancies resolved via discussions or by consulting a third reviewer.

Data related to review characteristics, results, key findings, and conclusions were extracted by at least two reviewers independently (PV performed data extraction for all the reviews and duplicate extraction was performed by AP, HC, or MG).

2.4. Quality assessment of included reviews

The quality assessment of the included SRs was performed using the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews). The tool consists of a 16‐item checklist addressing critical and noncritical domains. 18 For the purpose of this study, the domain related to MA was reclassified from critical to noncritical, as SRs with and without MA were included. The other six critical domains were used according to the tool guidelines. 18 Two reviewers (PV and AP) independently responded to each of the 16 items in the checklist with either “yes,” “partial yes,” or “no.” Based on the interpretations of the critical and noncritical domains, the overall quality of the review was rated as high, moderate, low, or critically low. 18 Disagreements were resolved through discussion or by consulting a third reviewer.

2.5. Data synthesis

To provide an understandable summary of existing evidence syntheses, characteristics of the methods evaluated in the included SRs were examined and key findings were categorized and presented based on the corresponding step in the SR process. The categories of key elements within each step were discussed and agreed by the authors. Results of the included reviews were tabulated and summarized descriptively, along with a discussion on any overlap in the primary studies. 15 No quantitative analyses of the data were performed.

From 41,556 unique citations identified through literature search, 50 full‐text records were reviewed, and nine systematic reviews 14 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 were deemed eligible for inclusion. The flow of studies through the screening process is presented in Figure  1 . A list of excluded studies with reasons can be found in Appendix B .

Study selection flowchart

3.1. Characteristics of included reviews

Table  1 summarizes the characteristics of included SRs. The majority of the included reviews (six of nine) were published after 2010. 14 , 22 , 23 , 24 , 25 , 26 Four of the nine included SRs were Cochrane reviews. 20 , 21 , 22 , 23 The number of databases searched in the reviews ranged from 2 to 14, 2 reviews searched gray literature sources, 24 , 25 and 7 reviews included a supplementary search strategy to identify relevant literature. 14 , 19 , 20 , 21 , 22 , 23 , 26 Three of the included SRs (all Cochrane reviews) included an integrated MA. 20 , 21 , 23

Characteristics of included studies

SR = systematic review; MA = meta‐analysis; RCT = randomized controlled trial; CCT = controlled clinical trial; N/R = not reported.

The included SRs evaluated 24 unique methodological approaches (26 in total) used across five steps in the SR process; 8 SRs evaluated 6 approaches, 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 while 1 review evaluated 18 approaches. 14 Exclusion of gray or unpublished literature 21 , 26 and blinding of reviewers for RoB assessment 14 , 23 were evaluated in two reviews each. Included SRs evaluated methods used in five different steps in the SR process, including methods used in defining the scope of review ( n  = 3), literature search ( n  = 3), study selection ( n  = 2), data extraction ( n  = 1), and RoB assessment ( n  = 2) (Table  2 ).

Summary of findings from review evaluating systematic review methods

There was some overlap in the primary studies evaluated in the included SRs on the same topics: Schmucker et al. 26 and Hopewell et al. 21 ( n  = 4), Hopewell et al. 20 and Crumley et al. 19 ( n  = 30), and Robson et al. 14 and Morissette et al. 23 ( n  = 4). There were no conflicting results between any of the identified SRs on the same topic.

3.2. Methodological quality of included reviews

Overall, the quality of the included reviews was assessed as moderate at best (Table  2 ). The most common critical weakness in the reviews was failure to provide justification for excluding individual studies (four reviews). Detailed quality assessment is provided in Appendix C .

3.3. Evidence on systematic review methods

3.3.1. methods for defining review scope and eligibility.

Two SRs investigated the effect of excluding data obtained from gray or unpublished sources on the pooled effect estimates of MA. 21 , 26 Hopewell et al. 21 reviewed five studies that compared the impact of gray literature on the results of a cohort of MA of RCTs in health care interventions. Gray literature was defined as information published in “print or electronic sources not controlled by commercial or academic publishers.” Findings showed an overall greater treatment effect for published trials than trials reported in gray literature. In a more recent review, Schmucker et al. 26 addressed similar objectives, by investigating gray and unpublished data in medicine. In addition to gray literature, defined similar to the previous review by Hopewell et al., the authors also evaluated unpublished data—defined as “supplemental unpublished data related to published trials, data obtained from the Food and Drug Administration  or other regulatory websites or postmarketing analyses hidden from the public.” The review found that in majority of the MA, excluding gray literature had little or no effect on the pooled effect estimates. The evidence was limited to conclude if the data from gray and unpublished literature had an impact on the conclusions of MA. 26

Morrison et al. 24 examined five studies measuring the effect of excluding non‐English language RCTs on the summary treatment effects of SR‐based MA in various fields of conventional medicine. Although none of the included studies reported major difference in the treatment effect estimates between English only and non‐English inclusive MA, the review found inconsistent evidence regarding the methodological and reporting quality of English and non‐English trials. 24 As such, there might be a risk of introducing “language bias” when excluding non‐English language RCTs. The authors also noted that the numbers of non‐English trials vary across medical specialties, as does the impact of these trials on MA results. Based on these findings, Morrison et al. 24 conclude that literature searches must include non‐English studies when resources and time are available to minimize the risk of introducing “language bias.”

3.3.2. Methods for searching studies

Crumley et al. 19 analyzed recall (also referred to as “sensitivity” by some researchers; defined as “percentage of relevant studies identified by the search”) and precision (defined as “percentage of studies identified by the search that were relevant”) when searching a single resource to identify randomized controlled trials and controlled clinical trials, as opposed to searching multiple resources. The studies included in their review frequently compared a MEDLINE only search with the search involving a combination of other resources. The review found low median recall estimates (median values between 24% and 92%) and very low median precisions (median values between 0% and 49%) for most of the electronic databases when searched singularly. 19 A between‐database comparison, based on the type of search strategy used, showed better recall and precision for complex and Cochrane Highly Sensitive search strategies (CHSSS). In conclusion, the authors emphasize that literature searches for trials in SRs must include multiple sources. 19

In an SR comparing handsearching and electronic database searching, Hopewell et al. 20 found that handsearching retrieved more relevant RCTs (retrieval rate of 92%−100%) than searching in a single electronic database (retrieval rates of 67% for PsycINFO/PsycLIT, 55% for MEDLINE, and 49% for Embase). The retrieval rates varied depending on the quality of handsearching, type of electronic search strategy used (e.g., simple, complex or CHSSS), and type of trial reports searched (e.g., full reports, conference abstracts, etc.). The authors concluded that handsearching was particularly important in identifying full trials published in nonindexed journals and in languages other than English, as well as those published as abstracts and letters. 20

The effectiveness of checking reference lists to retrieve additional relevant studies for an SR was investigated by Horsley et al. 22 The review reported that checking reference lists yielded 2.5%–40% more studies depending on the quality and comprehensiveness of the electronic search used. The authors conclude that there is some evidence, although from poor quality studies, to support use of checking reference lists to supplement database searching. 22

3.3.3. Methods for selecting studies

Three approaches relevant to reviewer characteristics, including number, experience, and blinding of reviewers involved in the screening process were highlighted in an SR by Robson et al. 14 Based on the retrieved evidence, the authors recommended that two independent, experienced, and unblinded reviewers be involved in study selection. 14 A modified approach has also been suggested by the review authors, where one reviewer screens and the other reviewer verifies the list of excluded studies, when the resources are limited. It should be noted however this suggestion is likely based on the authors’ opinion, as there was no evidence related to this from the studies included in the review.

Robson et al. 14 also reported two methods describing the use of technology for screening studies: use of Google Translate for translating languages (for example, German language articles to English) to facilitate screening was considered a viable method, while using two computer monitors for screening did not increase the screening efficiency in SR. Title‐first screening was found to be more efficient than simultaneous screening of titles and abstracts, although the gain in time with the former method was lesser than the latter. Therefore, considering that the search results are routinely exported as titles and abstracts, Robson et al. 14 recommend screening titles and abstracts simultaneously. However, the authors note that these conclusions were based on very limited number (in most instances one study per method) of low‐quality studies. 14

3.3.4. Methods for data extraction

Robson et al. 14 examined three approaches for data extraction relevant to reviewer characteristics, including number, experience, and blinding of reviewers (similar to the study selection step). Although based on limited evidence from a small number of studies, the authors recommended use of two experienced and unblinded reviewers for data extraction. The experience of the reviewers was suggested to be especially important when extracting continuous outcomes (or quantitative) data. However, when the resources are limited, data extraction by one reviewer and a verification of the outcomes data by a second reviewer was recommended.

As for the methods involving use of technology, Robson et al. 14 identified limited evidence on the use of two monitors to improve the data extraction efficiency and computer‐assisted programs for graphical data extraction. However, use of Google Translate for data extraction in non‐English articles was not considered to be viable. 14 In the same review, Robson et al. 14 identified evidence supporting contacting authors for obtaining additional relevant data.

3.3.5. Methods for RoB assessment

Two SRs examined the impact of blinding of reviewers for RoB assessments. 14 , 23 Morissette et al. 23 investigated the mean differences between the blinded and unblinded RoB assessment scores and found inconsistent differences among the included studies providing no definitive conclusions. Similar conclusions were drawn in a more recent review by Robson et al., 14 which included four studies on reviewer blinding for RoB assessment that completely overlapped with Morissette et al. 23

Use of experienced reviewers and provision of additional guidance for RoB assessment were examined by Robson et al. 14 The review concluded that providing intensive training and guidance on assessing studies reporting insufficient data to the reviewers improves RoB assessments. 14 Obtaining additional data related to quality assessment by contacting study authors was also found to help the RoB assessments, although based on limited evidence. When assessing the qualitative or mixed method reviews, Robson et al. 14 recommends the use of a structured RoB tool as opposed to an unstructured tool. No SRs were identified on data synthesis and CoE assessment and reporting steps.

4. DISCUSSION

4.1. summary of findings.

Nine SRs examining 24 unique methods used across five steps in the SR process were identified in this overview. The collective evidence supports some current traditional and modified SR practices, while challenging other approaches. However, the quality of the included reviews was assessed to be moderate at best and in the majority of the included SRs, evidence related to the evaluated methods was obtained from very limited numbers of primary studies. As such, the interpretations from these SRs should be made cautiously.

The evidence gathered from the included SRs corroborate a few current SR approaches. 5 For example, it is important to search multiple resources for identifying relevant trials (RCTs and/or CCTs). The resources must include a combination of electronic database searching, handsearching, and reference lists of retrieved articles. 5 However, no SRs have been identified that evaluated the impact of the number of electronic databases searched. A recent study by Halladay et al. 27 found that articles on therapeutic intervention, retrieved by searching databases other than PubMed (including Embase), contributed only a small amount of information to the MA and also had a minimal impact on the MA results. The authors concluded that when the resources are limited and when large number of studies are expected to be retrieved for the SR or MA, PubMed‐only search can yield reliable results. 27

Findings from the included SRs also reiterate some methodological modifications currently employed to “expedite” the SR process. 10 , 11 For example, excluding non‐English language trials and gray/unpublished trials from MA have been shown to have minimal or no impact on the results of MA. 24 , 26 However, the efficiency of these SR methods, in terms of time and the resources used, have not been evaluated in the included SRs. 24 , 26 Of the SRs included, only two have focused on the aspect of efficiency 14 , 25 ; O'Mara‐Eves et al. 25 report some evidence to support the use of text‐mining approaches for title and abstract screening in order to increase the rate of screening. Moreover, only one included SR 14 considered primary studies that evaluated reliability (inter‐ or intra‐reviewer consistency) and accuracy (validity when compared against a “gold standard” method) of the SR methods. This can be attributed to the limited number of primary studies that evaluated these outcomes when evaluating the SR methods. 14 Lack of outcome measures related to reliability, accuracy, and efficiency precludes making definitive recommendations on the use of these methods/modifications. Future research studies must focus on these outcomes.

Some evaluated methods may be relevant to multiple steps; for example, exclusions based on publication status (gray/unpublished literature) and language of publication (non‐English language studies) can be outlined in the a priori eligibility criteria or can be incorporated as search limits in the search strategy. SRs included in this overview focused on the effect of study exclusions on pooled treatment effect estimates or MA conclusions. Excluding studies from the search results, after conducting a comprehensive search, based on different eligibility criteria may yield different results when compared to the results obtained when limiting the search itself. 28 Further studies are required to examine this aspect.

Although we acknowledge the lack of standardized quality assessment tools for methodological study designs, we adhered to the Cochrane criteria for identifying SRs in this overview. This was done to ensure consistency in the quality of the included evidence. As a result, we excluded three reviews that did not provide any form of discussion on the quality of the included studies. The methods investigated in these reviews concern supplementary search, 29 data extraction, 12 and screening. 13 However, methods reported in two of these three reviews, by Mathes et al. 12 and Waffenschmidt et al., 13 have also been examined in the SR by Robson et al., 14 which was included in this overview; in most instances (with the exception of one study included in Mathes et al. 12 and Waffenschmidt et al. 13 each), the studies examined in these excluded reviews overlapped with those in the SR by Robson et al. 14

One of the key gaps in the knowledge observed in this overview was the dearth of SRs on the methods used in the data synthesis component of SR. Narrative and quantitative syntheses are the two most commonly used approaches for synthesizing data in evidence synthesis. 5 There are some published studies on the proposed indications and implications of these two approaches. 30 , 31 These studies found that both data synthesis methods produced comparable results and have their own advantages, suggesting that the choice of the method must be based on the purpose of the review. 31 With increasing number of “expedited” SR approaches (so called “rapid reviews”) avoiding MA, 10 , 11 further research studies are warranted in this area to determine the impact of the type of data synthesis on the results of the SR.

4.2. Implications for future research

The findings of this overview highlight several areas of paucity in primary research and evidence synthesis on SR methods. First, no SRs were identified on methods used in two important components of the SR process, including data synthesis and CoE and reporting. As for the included SRs, a limited number of evaluation studies have been identified for several methods. This indicates that further research is required to corroborate many of the methods recommended in current SR guidelines. 4 , 5 , 6 , 7 Second, some SRs evaluated the impact of methods on the results of quantitative synthesis and MA conclusions. Future research studies must also focus on the interpretations of SR results. 28 , 32 Finally, most of the included SRs were conducted on specific topics related to the field of health care, limiting the generalizability of the findings to other areas. It is important that future research studies evaluating evidence syntheses broaden the objectives and include studies on different topics within the field of health care.

4.3. Strengths and limitations

To our knowledge, this is the first overview summarizing current evidence from SRs and MA on different methodological approaches used in several fundamental steps in SR conduct. The overview methodology followed well established guidelines and strict criteria defined for the inclusion of SRs.

There are several limitations related to the nature of the included reviews. Evidence for most of the methods investigated in the included reviews was derived from a limited number of primary studies. Also, the majority of the included SRs may be considered outdated as they were published (or last updated) more than 5 years ago 33 ; only three of the nine SRs have been published in the last 5 years. 14 , 25 , 26 Therefore, important and recent evidence related to these topics may not have been included. Substantial numbers of included SRs were conducted in the field of health, which may limit the generalizability of the findings. Some method evaluations in the included SRs focused on quantitative analyses components and MA conclusions only. As such, the applicability of these findings to SR more broadly is still unclear. 28 Considering the methodological nature of our overview, limiting the inclusion of SRs according to the Cochrane criteria might have resulted in missing some relevant evidence from those reviews without a quality assessment component. 12 , 13 , 29 Although the included SRs performed some form of quality appraisal of the included studies, most of them did not use a standardized RoB tool, which may impact the confidence in their conclusions. Due to the type of outcome measures used for the method evaluations in the primary studies and the included SRs, some of the identified methods have not been validated against a reference standard.

Some limitations in the overview process must be noted. While our literature search was exhaustive covering five bibliographic databases and supplementary search of reference lists, no gray sources or other evidence resources were searched. Also, the search was primarily conducted in health databases, which might have resulted in missing SRs published in other fields. Moreover, only English language SRs were included for feasibility. As the literature search retrieved large number of citations (i.e., 41,556), the title and abstract screening was performed by a single reviewer, calibrated for consistency in the screening process by another reviewer, owing to time and resource limitations. These might have potentially resulted in some errors when retrieving and selecting relevant SRs. The SR methods were grouped based on key elements of each recommended SR step, as agreed by the authors. This categorization pertains to the identified set of methods and should be considered subjective.

5. CONCLUSIONS

This overview identified limited SR‐level evidence on various methodological approaches currently employed during five of the seven fundamental steps in the SR process. Limited evidence was also identified on some methodological modifications currently used to expedite the SR process. Overall, findings highlight the dearth of SRs on SR methodologies, warranting further work to confirm several current recommendations on conventional and expedited SR processes.

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

Supporting information

APPENDIX A: Detailed search strategies

ACKNOWLEDGMENTS

The first author is supported by a La Trobe University Full Fee Research Scholarship and a Graduate Research Scholarship.

Open Access Funding provided by La Trobe University.

Veginadu P, Calache H, Gussy M, Pandian A, Masood M. An overview of methodological approaches in systematic reviews . J Evid Based Med . 2022; 15 :39–54. 10.1111/jebm.12468 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]

Cochrane Consumer Network

Cochrane and systematic reviews, about the cochrane library, systematic reviews.

• How do I know an intervention works
• What consumers can and cannot get from a review
• Levels of evidence
• Cochrane groups

  Top of page       

The Cochrane Library is an electronic collection of databases published on the internet and also available on CD-Rom. It is updated quarterly in an effort to add to and keep the information current. The Library is made up of a number of parts.

The Cochrane Database of Systematic Reviews (CDSR) contains the published Cochrane reviews and protocols.

The Cochrane Central Register of Controlled Trials (CENTRAL) collates references to controlled trials in health care. These healthcare trial references are entered by Cochrane groups. The main way of finding health care studies is by looking in electronic databases (such as MEDLINE, EMBASE, CINAHL) using special search terms. Other ways are by asking experts in a particular health field and through hand searching journals.

The Database of Abstracts of Reviews of Effects (DARE) is a collection of structured abstracts and bibliographic references of systematic reviews of the effects of health care. It is developed by the Centre for Research and Dissemination, University of York, UK.

Methodological reviews and articles are also presented in The Cochrane Library.

In addition, each Cochrane group (termed an entity) has a section (module) in the Library that gives information on the group’s organisation, contact details, function, reviews, and other general information.

Accessing The Cochrane Library

Abstracts of reviews are readily accessible at www.cochrane.org/reviews . In countries such as Australia, Denmark, Finland, Ireland, Latin America, Norway and UK the full reviews are freely available as the governments of these countries have subscriptions to The Cochrane Library . Consumers who live in other countries and who wish to read a full review may need to access The Cochrane Library through a university, hospital or large public library.

A Cochrane Library Users Guide is available ( https://www.cochrane.org.au/libraryguide/ ) to help you find the information you want from The Cochrane Library.

Brief summaries (plain language summaries) of Cochrane reviews are written for consumers and others to highlight the information in a review. A What’s New Digest summarises the newest reviews.

If you would like to make comments on any existing review in The Cochrane Library, you will find a special section for 'Comments and Criticisms' with the review.

If someone decides to look critically at articles that have appeared in the medical or health literature on a particular topic they are said to be ‘reviewing the literature’. The authors may review, say, all the drug treatments available for one type of heart disease. A review is very clearly defined and sets out to find what evidence there is for prescribing one particular intervention or drug in a specific health condition, often in a certain group of people.

Examples of review topics are: Single dose celecoxib for acute postoperative pain; Artichoke leaf extract for treating hypercholesterolaemia; Chocolate avoidance for preventing migraine; Etidronate for treating and preventing postmenopausal osteoporosis.

What is a systematic review?

A systematic review summarises the results of available carefully designed healthcare studies (controlled trials) and provides a high level of evidence on the effectiveness of healthcare interventions.

The review authors set about their task very methodically following, step by step, an advance plan that covers:

• the way existing studies are found;
• how the relevant studies are judged in terms of their usefulness in answering the review question;
• how the results of the separate studies are brought together to give an overall measure of effectiveness (benefits and harms) – statistical techniques used to combine the results are called meta-analysis.

What is a protocol?

A protocol is the plan or set of steps to be followed in preparing a review. A protocol for a systematic review clearly describes why the review is needed (the review question), what the review is about (the healthcare context of the review), and how the reviewer authors will go about developing the review. It details how they will seek, select as relevant, critically appraise studies, and collect and analyse data (combine data and check for significance to the healthcare situation) from the included studies.

Cochrane protocols are published in the Cochrane Database of Systematic Reviews so that people can comment on them before the actual review has been carried out.

How do I know a healthcare intervention works?

The aim of a systematic review is to thoroughly assess, by means of a set procedure, the best possible evidence about the effects of a healthcare intervention or treatment in a particular healthcare situation.

Healthcare studies are generally designed to assess the benefits, rather than the harms, of an intervention. Studies generally have a relatively short designated time period. Any possible harms of an intervention may be expected to occur less frequently and over a longer period of time than the studies cover.

The process of a review is clearly defined, before starting the actual review of the literature, to minimise associations of expectations of effects and other sources of bias. Bias is a systematic ‘error’ or mistake in the judgments and decisions made that influence the results of a study or a review. Bias differs from a ‘placebo effect’, which is where participants of a study (or assessors of the outcomes) perceive a beneficial effect, or harm, with an inactive treatment.

Synthesising evidence

The specific methods used in a review are carefully set out by The Cochrane Collaboration and are described in each review.

A Cochrane review is prepared and maintained using specific methodologies described in the Cochrane Handbook .

Systematic reviews of randomised controlled trials provide the clearest evidence for the benefits of a healthcare intervention.

This is because the best way to assess the effects of a health care treatment is to use procedures that reduce the influence of chance effects and associations of cause and effect. Individual expectations on the part of a service provider, assessor and the person receiving an intervention can all contribute to modifying observed findings from a healthcare study. Randomised controlled trials where none of these people know the exact intervention a study participant is receiving (intervention under investigation, a placebo, or a comparator) may be expected to provide the best evidence.

Comparing groups can be misleading

By assessing the health of the two comparative groups in a study after their treatments, we can tell which intervention is more successful – but only if the two groups of people were very similar before treatment began. Otherwise we might be misled. For instance, one group may become healthier not because their treatment was better but because they were younger, not so ill, at less risk of ill health before treatment began, or even self selected to a particular intervention because of a particular personality trait, for example, people who chose to take a hormone may have wanted to stay younger and be more active.

Randomised controlled trials

Randomised controlled trials are studies that are rigorously designed. People are allocated to intervention groups in a way that minimises the chances of predicting which treatment group a study participant is in. The intervention under investigation is compared against a well-known intervention or an inactive treatment (placebo). Studies are controlled so that participants have similar associated care in all ways other than the intervention. Ideally, depending on the type of intervention, the service provider is unaware of which group a participant is in and those assessing outcomes are also unaware – this is termed ’ blinding ’.

The strength of evidence for a particular intervention can be increased further by systematically looking at (reviewing) all available randomized controlled trials that have been reported relevant to a particular healthcare situation.

It is important to search thoroughly for all studies

Many people are needed to properly test an intervention. This is more than can be recruited into a single trial; it is also important to investigate the intervention in different populations. Furthermore, the technical aspects of a particular randomised controlled trial may nothave been implemented properly, for one reason or another. The effects of these shortcomings can be minimised by grouping results of a number of studies.

The results of randomised controlled trials may be published in any one of thousands of journals world wide. Indeed some studies are not published at all. In reality the studies found most easily tend to have over-optimistic results and finding reliable information about the effects of care is particularly difficult when there are negative results (the intervention is no better than placebo or another treatment). Sometimes published trials are too small to provide a conclusive result in their own right - as to whether a treatment really does work. Consequently, to find out about a healthcare intervention it is worth searching research literature thoroughly to see if the answer is already known. This may require considerable work over many months, but it will be much less work than conducting a new randomised controlled trial. This process also will not unnecessarily exclude people from effective interventions because of allocation to a placebo (or inactive treatment) group.Discussions are underway in The Cochrane Collaboration as to how qualitative studies can be used to add to the information obtained from controlled studies - those that consider outcomes measured in numerical terms (and so are termed quantitative studies). Qualitative measures include ‘quality of life’ and lifestyle changes obtained from detailed questionnaires. Qualitative studies may also use narrative interviews where participants are asked to talk about their experiences around sets of semi-structured questions and prompts to explore particular issues that information is needed on for a study.

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What consumers can, and cannot, get from systematic reviews

Systematic reviews ask a very specific research question about a particular intervention in a clearly defined group of people who have a clear health condition or problem. Reviews provide powerful information on the state of knowledge about a healthcare intervention and whether that intervention is an effective treatment of a healthcare condition.Reviews:

• cannot offer a guideline for treatment, especially if a person differs from those defined in the review. Individuals may have accompanying health problems, be in a different healthcare setting, or receive more than one intervention, for example;
• follow stringent guidelines as to what types of studies are included and how healthcare measures of effectiveness can be expressed and combined;
• may consider outcomes other than the one you are interested in and may not look at long term effects of an intervention;
• may only find studies that are limited in the healthcare setting in which they take place;
• may provide conclusions that are limited because of the question asked and/or the studies that were found.

Reviews are dependent on the availability of studies and the information these studies sought or obtained.

Healthcare studies differ dramatically in what they look for and how well they are carried out and, therefore, how much weight one canput on their conclusions. Part of the reason for performing systematic reviews is to reduce the effects of these shortcomings. Issues of conflict of interest and corporate funding of healthcare studies are also important considerations in drawing conclusions from any study.

Reviews are better suited to assess benefits rather than harms.

Well-designed healthcare studies generally set out to determine the efficacy of a healthcare intervention. Information on potential harms is less well investigated.

Carefully controlled studies take place over a limited period of time so that the researchers can account for all people who entered the study from beginning to the end of the study. Harms are generally less common than benefits and may be apparent over a different time period. This may be, for example, only in the long term so that the intervention would have to be given to more people for a long time period for adverse effects to be studied effectively.

Participants of studies are selected to reduce the risk of other problems interfering with the efficacy of an intervention. How selective thisprocess is needs to be carefully considered when assessing the relevance of a study to an individual.

Randomised controlled trials are expensive to run. They are very time consuming and multiple factors may limit how many participants are involved, the outcomes measured and the length of the trial. How many people complete the study is also very important.

Levels of evidence for healthcare interventions

The National Health and Medical Research Council of Australia (1999) defines the ‘dimensions of evidence’ using three main areas.

1. Strength of the evidence

Level of evidence: the study design used – a systematic review of all relevant randomised controlled trials is the highest level, followed by at least one randomised controlled trial, then a pseudo-randomised trial Quality of evidence: the methods used to minimise bias within a study design Statistical precision: the degree of certainty about the existence of a true effect

2. Size of effect

How much the determined intervention effect is above a ‘no apparent effect’ value for clinically relevant effects

3. Relevance of the evidence

How appropriate the outcome measure is for the healthcare problem, and its usefulness in measuring effectiveness of treatment

Using a measure of the variability of results – confidence intervals

Adapted from AD.Oxman Checklists for review articles. BMJ 1994;309:648-51

Level I. For a randomised controlled trial, the lower limit of the confidence interval (expressed as a range) for a measure of effect is still above a meaningful benefit in healthcare terms

Level II. For a randomised controlled trial, the lower limit of the confidence interval (expressed as a range) for a measure of effect is less than a meaningful beneficial effect in healthcare terms; but the point estimate of effect still shows effectiveness of the intervention

Lower levels of evidence

Level III. Measures of effectiveness are taken from non-randomised studies of groups of people where a control group has run concurrently with the group receiving the intervention being assessed

Level IV. Measures of effectiveness are taken from non-randomised studies of groups of people where intervention effects are compared with previous or historical information

Level V. Evidence is from single case studies

Confidence interval (CI):

Even studies perfectly designed and carried out may show variable results because of the play of chance. CI covers the likely range of the true effect. For example, the result of a study may be that 40 per cent (95% CI 30% to 50%) of people are helped by a treatment. That means that we can be 95 per cent certain the true effect is between 30 and 50 per cent. ( Smart Health Choices How to make informed health decisions by Judy Irwig, Les Irwig and Melissa Sweet, Allen and Unwin 1999)

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Cochrane Groups

Cochrane review groups.

Different groups exist for different health conditions: International Cochrane review groups cover important areas of health care diseases and conditions. Review groups are responsible for producing and maintaining Cochrane reviews on specific health care questions. You will see in The Cochrane Library, for example, a Cochrane Consumers and Communication Group, Cochrane Epilepsy Group, Cochrane Heart Group and a Cochrane Pregnancy and Childbirth Group.

The activities of each group (or entity in Cochrane language) are monitored and co-ordinated by one person for each group, known as the managing editor (review group co-ordinator). This person manages the day to day running of the group and is usually the contact person. The co-ordinating editor leads the group and is responsible for the quality and subject of reviews.

Each group attracts members with a variety of backgrounds, experience and expertise, who contribute to the process of developing systematic reviews. They may be doctors, nurses, researchers, health advisers, consumers and caregivers.

Cochrane Fields

Fields cover health care in a broader sense than do review groups. These may include a major section of health care such as cancer, the setting of care (e.g. primary care), the type of patient/consumer (e.g. older persons), the type of provider (e.g. nurses), or the type of intervention (e.g. vaccines). The role of fields is to facilitate the work of collaborative review groups and to ensure that Cochrane reviews appropriate to an area of interest are both relevant and accessible to service providers and consumers.

Each field works to:

• identify relevant healthcare trials and make them accessible in a specialised register;
• ensure the proper representation of its specialist area of health care in review groups;
• act as a liaison point between the entities within The Cochrane Collaboration and the specialist area of health care;
• promote the accessibility of Cochrane reviews.

The principal contact person in a field is its field co-ordinator.

Cochrane Centres

Cochrane centres provide a range of services designed to support collaborative review groups in their area and to facilitate the review process. They serve as a regional source of information about The Cochrane Collaboration, provide support to Cochrane contributors within a defined geographical area and promote access to The Cochrane Library. Each centre has a director.

The Cochrane Consumer Network (CCNet)

The Consumer Network supports consumer participation within The Cochrane Collaboration, internationally. The Network is available to any active consumer. Its mission is to enable and support consumers in contributing to the function of collaborative reviews groups and other Cochrane entities. The Network enables communication with other consumers, provides a sense of belonging within The Cochrane Collaboration, links and dissemination of information from Cochrane reviews.

© The Cochrane Collaboration Comments about this page to: [email protected]

Systematic Reviews

• The Research Question
• Inclusion and Exclusion Criteria
• Original Studies
• Translating
• Deduplication
• Project Management Tools
• Useful Resources
• What is not a systematic review?

Cochrane resources

Cochrane Handbook for Systematic Reviews of Interventions

• Introduction to Systematic Reviews

Here is a PowerPoint presentation that provides a brief overview of Systematic Reviews   Texas Medical Center Library

What is a systematic review?

A systematic review attempts to collate all empirical evidence that fits pre-specified eligibility criteria in order to answer a research question. 1  Systematic Reviews are research projects that provide new insight on a topic and are designed to minimize bias. The project creates accessible research that examines relevant literature, which aids decision makers by aggregating information in a systematic way. Methodological transparency, along with its systematic approach and project reproducibility, are key elements of a systematic review.

1. Taken from Lasserson TJ, Thomas J, Higgins JPT. Chapter 1: Starting a review. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors).  Cochrane Handbook for Systematic Reviews of Interventions  version 6.1 (updated September 2020). Cochrane, 2020. Available from  www.training.cochrane.org/handbook

Components of a Systematic Review

Key elements of a systematic review include :.

• A specific and well-formulated question
• A reproducible methodology intended to avoid bias 
• Multiple databases searched for the review's data
• Specified and predefined inclusion and exclusion criteria 
• Multiple reviewers of the literature 
• Study assessments conducted in a standardized way with definitive methodology
• Adherence to a standardized reporting guideline, such as PRISMA

Systematic reviews can have an impact on the development of public health policies and on resource allocation decisions. They can inform clinical practices and implement evidence-based interventions for diseases and illnesses. Moreover, systematic reviews can compare benefits and harms of treatment options.

The systematic review process has been developed to minimize bias   and ensure transparency. Methods should be adequately documented so that they can be replicated. The integrity of a systematic review is based on its transparency and reproducibility of the methods used for the review. 

There are many resources on how to conduct, organize, and publish a systematic review. This guide is by no means exhaustive; its aim is to provide a starting place for understanding the core of what a systematic review is and how to conduct one.

What does it take to do a systematic review?

Time :  On average, systematic reviews can require up to 18 months of preparation. 

A team:  A systematic review can't be done alone! You need to work with subject experts to clarify issues related to the topic; librarians to develop comprehensive search strategies and identify appropriate databases; reviewers to screen abstracts and read the full text; a statistician who can assist with data analysis; and a project leader to coordinate the team and movement of data.

A clearly defined question : A clearly defined research question can help clarify the key concepts of a systematic review and explain the rationale for the review. It is recommended to use a framework (e.g. the PICO framework) to identify key concepts of the question.

A written protocol :  The protocol should outline the study methodology. The protocol should include the rationale for the systematic review; the research question broken into PICO components; explicit inclusion/exclusion criteria; relevant known literature on the research question; preliminary search terms and databases to be used; intended data abstraction/data management tools; and other components that may be unique to register the protocol. 

A registered protocol :   A few recommendations are  PROSPERO , an International Prospective Register of Systematic Reviews; Cochrane; and the Agency for Healthcare Research and Quality. Registering a protocol is important because it reduces duplication of effort and promotes transparency. 

Inclusion/exclusion criteria: Inclusion/exclusion criteria can help researchers define the terms of the investigation. These will include  the predefined question; study types; study-analysis criteria (i.e. criteria for reporting bias within studies); and quantitative methods to be used for any statistical analysis. 

Comprehensive literature searches :  Identify appropriate databases and conduct comprehensive and detailed literature searches that can be documented and duplicated. Cochrane recommends that 3+ different databases be used to conduct the searches. A strategy must be developed and then translated across the multiple pre-specified databases, preferably by an information specialist.  

Citation management:  You should have working knowledge of EndNote or another citation management system that will be accessible to the research team to help manage citations retrieved from literature searches.

Follow reporting guidelines :  Use appropriate guidelines for reporting your review for publication.

Time -  requires about 18 months of preparation .

  The suggested timeline for a Cochrane review is: 

• Preparation of protocol  1 – 2 months
• Searches for published and unpublished studies  3-8 months
• Pilot test of eligibility criteria  2-3 months
• Inclusion assessments  3-8 months
• Pilot test of ‘Risk of bias’ assessment  3 months
• Validity assessments  3-10 months
• Pilot test of data collection  3 months
• Data collection  3-10 months
• Data entry  3-10 months
• Follow up of missing information  5-11 months
• Analysis  8-10 months
• Preparation of review report  1-11 months
• Keeping the review up-to-date  12 months
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• Last Updated: Jul 29, 2024 2:41 PM
• URL: https://libguides.sph.uth.tmc.edu/SystematicReviews

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Scolaris content display scolaris content display, updated guidance for trusted systematic reviews: a new edition of the cochrane handbook for systematic reviews of interventions.

• Miranda Cumpston
• Tianjing Li
• Matthew J Page
• Jacqueline Chandler
• Vivian A Welch
• Julian PT Higgins
• James Thomas

Version published: 03 October 2019

On a shelf in the sunny, open‐plan office of Cochrane Australia in Melbourne, there's a large, white ring‐binder that, it's fair to say, hasn't been opened in a while. It's a printed copy of the original, 1994 edition of the Cochrane Collaboration Handbook, edited by Dave Sackett, [ 1 ] and within it the original guidance on the methods to be used. The section on preparing and maintaining systematic reviews, edited by Andy Oxman, weighs in at a total of 76 pages. [ 2 ]

From those fairly humble beginnings ‘the Handbook’ has become the go‐to resource for those wanting a guide to current best practice in conducting systematic reviews of interventions. It has grown in depth and breadth over the years, drawing on many dozens of contributors, and it receives tens of thousands of citations.

Now we have a new edition of the Handbook, [ 3 ] its second edition in print and sixth overall, more than a decade after the last major revision. [ 4 ] The new edition has been extensively rewritten and its new guidance reflects a decade of development by experts in research synthesis methodology.

Much has changed since 1994. In the original Handbook, the term ‘forest plot’ does not appear (although two early variations on the plot are presented) and no empirical evidence was available to inform assessments of risk of bias. The challenge of updating reviews was addressed in only four lines of text, and apparently many Cochrane Reviews were “not much longer than a structured abstract.” [ 2 ] A further chapter, edited by Kay Dickersin, focused on a program to establish specialized registers (now a mainstay of Cochrane Review Groups), given the very real difficulty of identifying randomized trials in Medline at the time. [ 5 ]

The 1994 Handbook acknowledged that development of systematic reviews was in its early stages, and that in many areas only general guidance could be given. It also noted that merely by including an explicit methods section, Cochrane Reviews would be “more useful to users than the vast majority of reviews that are currently available”. [ 2 ] Since Cochrane's initial steps 25 years ago, the Handbook has supported the organization's drive towards innovative methods and its commitment to quality, and it still aims to assist authors to produce reviews that are “more useful to users”, whether policy decision makers, consumers, or health professionals.

Cochrane Reviews should answer important questions that are relevant to decision‐making. Reflecting the breadth of these questions, guidance for meta‐analysis is now supplemented by new guidance on intervention complexity and equity, and the guidance on the use of non‐randomized studies has been extensively expanded. Decision makers often need to decide among multiple intervention options, so a major new chapter addresses network meta‐analysis to support such decisions, and Cochrane is actively encouraging the appropriate use of this methodology.

Not all challenges are new, and many of the Handbook's chapters reflect detailed reconsideration of some of the most familiar challenges. New guidance provides in‐depth support for planning the review, constructing good review questions, and grouping included studies according to their populations, interventions, and outcomes for synthesis. This planning ahead will provide more support to authors at the analysis stages of the review and is of particular assistance for reviews with high levels of heterogeneity or multiplicity of outcome measures. In addition, updated guidance on meta‐analysis and new statistical methods are supplemented by an all‐new chapter on alternatives to traditional meta‐analysis for synthesis of results across studies.

There is also revised guidance on the basics, refreshing those core methods that underpin every review. Updated guidance on identifying sources of evidence includes information on sources other than published trials (such as clinical study reports), an extended technical supplement on sources to search, an introduction to the role of technical advances such as text mining and machine learning, and prospective approaches such as living systematic reviews. Substantial developments in guidance on risk of bias assessment are reflected, with an updated overview of key concepts supported by dedicated chapters on the RoB 2 tool for assessing bias in randomized trials, the ROBINS‐I tool for assessing bias in non‐randomized studies of interventions, and a new framework for considering reporting biases and bias due to missing results in a synthesis.

The main sections of the Handbook will be relevant to all authors of systematic reviews. For authors working with Cochrane, new online‐only chapters will provide guidance specific to Cochrane Reviews, covering the planning and logistics stages of Cochrane Reviews as well as guidance on reporting and updating reviews. The new Handbook is available in book form, and is also publicly available, free of charge, at handbook.cochrane.org . Recognizing that recommending a course of action is not the same as implementing it, Cochrane also provides a range of training and other guidance for authors, editors and other contributors to systematic reviews to assist them in meeting the high standards expected ( training.cochrane.org ).

The new Handbook draws on the expertise of over 100 contributing methodologists and editors located around the world, and in particular the efforts of the members of Cochrane's Methods Groups over many years. [ 6 ] These international leaders in their fields conduct research to develop the evidence base that underpins the methodological guidance in the Handbook, ensuring that the findings of Cochrane Reviews rest on strong foundations. [ 7 ] A wide group of peer reviewers also contributed their expertise. Working with this global community over the past few years has been an immense privilege, and a labour of love for many people. We are grateful for their insights as well as their exemplary patience and dogged persistence throughout this process.

While much has changed since that 1994 edition of the Handbook, there is much in its guiding principles that we recognize and continue to emphasize today. Its advice that “whatever is done, reviewers should clearly explain what was done, and why” and that “these guidelines are not a substitute for good judgement” continues to ring true. [ 2 ] It also remains true that, alongside the hard work, “…the rewards are great. This opportunity to remain at the cutting edge of one's field is unparalleled. The fun and learning that accompany working with a world‐wide group of like‐minded colleagues are exceptional.” [ 1 ]

We believe this most recent revision of the Handbook will be of use to all authors, no matter how experienced in their endeavours, in meeting the ongoing challenges of providing trusted evidence to support healthcare decision making.

Information

• Cochrane Database of Systematic Reviews
• 03 October 2019

Article Metrics

Monash University, Australia

[email protected]

The University of Newcastle, Australia

Johns Hopkins University, USA

University Hospital Southampton, UK

Campbell Collaboration, Canada

Bruyère Research Institute, Canada

University of Ottawa, Canada

University of Bristol, UK

University College London, UK

Declarations of interest

The authors have completed the ICMJE form for disclosure of potential conflicts of interest . JPTH and JT co‐edited the Cochrane Handbook for Systematic Reviews of Interventions and received honoraria for that work. JC, MC, TL, MJP, and VW served as associate editors for the Cochrane Handbook for Systematic Reviews of Interventions . JC was an employee of Cochrane until September 2018. TL also reports grants from the National Eye Institute, National Institutes of Health, not related to this Editorial. MJP also reports grants from a National Health and Medical Research Council Early Career Fellowship, not related to this Editorial.

Provenance and peer review

This editorial was commissioned and was not peer reviewed.

• Sackett DL, editor. The Cochrane Collaboration Handbook . Oxford (UK): The Cochrane Collaboration, 1994.
• Oxman A, editor. Preparing and maintaining systematic reviews . In: Sackett DL, editor. The Cochrane Collaboration Handbook . Oxford (UK): The Cochrane Collaboration, 1994.
• Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane Handbook for Systematic Reviews of Interventions . 2nd Edition. Chichester (UK): John Wiley & Sons, 2019.
• Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions . Chichester (UK): John Wiley & Sons, 2008.
• Dickersin K. Establishing and maintaining registers of RCTs . In: Sackett DL, editor. The Cochrane Collaboration Handbook . Oxford (UK): The Cochrane Collaboration, 1994.
• Chandler J, Hopewell S. Cochrane methods ‐ twenty years experience in developing systematic review methods . Systematic Reviews 2013;2:76. https://doi.org/10.1186/2046-4053-2-76
• McKenzie JE, Clarke MJ, Chandler J. Why do we need evidence‐based methods in Cochrane? Cochrane Database of Systematic Reviews 2015;(7):ED000102. https://doi.org/10.1002/14651858.ED000102

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Cochrane Methods Rapid Reviews

Welcome to the Cochrane Rapid Reviews Methods Group (RRMG)  website. The RRMG is  one of 17  Cochrane Method Groups  world-wide comprised of individuals with an interest and expertise in the science of systematic reviews.

While the concept of rapid evidence synthesis, or rapid review (RR) , is not novel, it remains a poorly understood and as yet ill-defined set of diverse methodologies supported by a paucity of published, available scientific literature. The speed with which RRs are gaining prominence and are being incorporated into urgent decision-making underscores the need to explore their characteristics and use further. While rapid review producers must answer the time-sensitive needs of the health decision makers they serve, they must simultaneously ensure that the scientific imperative of methodological rigor is satisfied. In order to a dequately address this inherent tension, a need for methodological research and standard development has been identified.   For these reasons, we have established the  Cochrane Rapid Reviews Methods Group (RRMG)  to better inform ‘rapid review’ methodology. 

Scope of the RRMG  will be serve to inform rapid reviews in general, both within the Cochrane Collaboration and beyond. Including a scope that is beyond the current purview of Cochrane’s work is an opportunity for Cochrane to position itself as a leader in rapid review methodology, just as it has been influential for systematic reviews, in general. 

Presently, the RRMG is comprised of seven co-convenors and two associate convenors from Canada, the United States, Ireland and Austria, with virtual co-administration by the Ottawa Methods Centre based at the   Ottawa Hospital Research Institute (OHRI) and Cochrane Austria .

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The efficacy and safety of neoadjuvant immunochemotherapy in resectable stage I-III non-small cell lung cancer: a systematic review and network meta-analysis

• RESEARCH ARTICLE
• Published: 09 September 2024

Cite this article

• Yujia Gu 1 ,
• Weixing Zhao 1 ,
• Zirui Li 1 ,
• Wanjing Guo 1 ,
• Xinxin Lu 1 &
• Jun Jiang   ORCID: orcid.org/0000-0002-6248-6179 2  

Neoadjuvant immunochemotherapy (NICT) is a new treatment method for resectable non-small-cell lung cancer (NSCLC). Network meta-analysis assessed efficacy, safety, and optimal treatment.

We searched for randomized controlled trials (RCTs) comparing NICT with neoadjuvant chemotherapy (NCT) in PubMed, Embase, Web of Science, Cochrane Library, and international conferences. Outcomes were surgical resection rate, pathological complete response(pCR),event-free survival (EFS), and Grade 3–5 treatment-related adverse events (TRAEs).

RCTs of 3,387 patients, six treatment combinations, and two modalities were included. Meta-analysis showed that NICT yielded higher pCR and EFS rates than NCT. The toripalimab-chemotherapy combination had the highest surgical resection rate (OR = 1.68, 95% CI: 1.05–2.73), pCR (OR = 38.84, 95% CI: 11.05–268.19) and EFS (HR = 0.40, 95% CI: 0.28–0.58).This regimen worked well for patients with low programmed death-ligand 1 (PD-L1) expression or squamous cell pathology. For high PD-L1 expression and patients with NSCLC, neoadjuvant nivolumab with chemotherapy had the most efficacy. The incidence of treatment-related adverse events increased with longer treatment cycles, with perioperative nivolumab combined with chemotherapy showing the worst safety profile (RR = 1.32, 95% CI: 1.00–1.76), while neoadjuvant nivolumab combined with chemotherapy alone had the best safety profile (RR = 0.91, 95% CI: 0.68–1.21). Indirect comparison showed no survival benefit for neoadjuvant-adjuvant immunotherapy (HR = 0.93, 95% CI: 0.65–1.35). In the indirect comparison between the two immune checkpoint inhibitors(ICIs), although there was no significant difference in EFS (HR = 0.81, 95% CI: 0.61–1.08), PD-1 inhibitors may still be the most effective treatment option.

Conclusions

NICT effectively and safely treats resectable NSCLC. The optimal treatment combination is typically toripalimab and chemotherapy. Treatment based on PD-L1 expression and pathological type is recommended.

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Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of Incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. https://doi.org/10.3322/caac.21660 .

Article   CAS   PubMed   Google Scholar  

Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48. https://doi.org/10.3322/caac.21763 .

Article   PubMed   Google Scholar  

Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (Eighth) Edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11:39–51. https://doi.org/10.1016/j.jtho.2015.09.009 .

Daly ME, Singh N, Ismaila N, et al. Management of Stage III non-small-cell lung cancer: ASCO guideline. J Clin Oncol. 2022;40:1356–84. https://doi.org/10.1200/jco.21.02528 .

Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017. https://doi.org/10.1093/annonc/mdx222 .

Bagchi S, Yuan R, E. G. Engleman immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annu Rev Pathol. 2021;16:223–49. https://doi.org/10.1146/annurev-pathol-042020-042741 .

Chaft JE, Rimner A, Weder W, et al. Evolution of systemic therapy for stages I-III non-metastatic non-small-cell lung cancer. Nat Rev Clin Oncol. 2021;18:547–57. https://doi.org/10.1038/s41571-021-00501-4 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Desai AP, Adashek JJ, Reuss JE, et al. Perioperative immune checkpoint inhibition in early-stage non-small cell lung cancer: a review. JAMA Oncol. 2023;9:135–42. https://doi.org/10.1001/jamaoncol.2022.5389 .

Uprety D, Mandrekar SJ, Wigle D, et al. Neoadjuvant Immunotherapy for NSCLC: current concepts and future approaches. J Thorac Oncol. 2020;15:1281–97. https://doi.org/10.1016/j.jtho.2020.05.020 .

Chen Y, Qin J, Wu Y, et al. Does major pathological response after neoadjuvant Immunotherapy in resectable nonsmall-cell lung cancers predict prognosis? A systematic review and meta-analysis. Int J Surg. 2023;109:2794–807. https://doi.org/10.1097/js9.0000000000000496 .

Article   PubMed   PubMed Central   Google Scholar  

Liu L, Bai H, Wang C, et al. Efficacy and safety of first-line immunotherapy combinations for advanced NSCLC: a systematic review and network meta-analysis. J Thorac Oncol. 2021;16:1099–117. https://doi.org/10.1016/j.jtho.2021.03.016 .

Meng LF, Huang JF, Luo PH, et al. The efficacy and safety of immune checkpoint inhibitor plus chemotherapy in patients with advanced non-small-cell lung cancer: a meta-analysis. Invest New Drugs. 2022;40:810–7. https://doi.org/10.1007/s10637-022-01232-8 .

Reck M, Rodríguez-Abreu D, Robinson AG, et al. Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥ 50. J Clin Oncol. 2021;39:2339–49. https://doi.org/10.1200/jco.21.00174 .

Zhao D, Xu L, Wu J, et al. Comparison of perioperative outcomes among non-small cell lung cancer patients with neoadjuvant immune checkpoint inhibitor plus chemotherapy, EGFR-TKI, and chemotherapy alone: a real-world evidence study. Transl Lung Cancer Res. 2022;11:1468–78. https://doi.org/10.21037/tlcr-22-476 .

Hou X, Shi X, J. Luo Efficacy and safety of camrelizumab (a PD-1 inhibitor) combined with chemotherapy as a neoadjuvant regimen in patients with locally advanced non-small cell lung cancer. Oncol Lett. 2022;24:215. https://doi.org/10.3892/ol.2022.13336 .

Cascone T, Leung CH, Weissferdt A, et al. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial. Nat Med. 2023;29:593–604. https://doi.org/10.1038/s41591-022-02189-0 .

Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386:1973–85. https://doi.org/10.1056/NEJMoa2202170 .

Ospina AV, Bolufer Nadal S, Campo-Cañaveral de la Cruz JL, et al. Multidisciplinary approach for locally advanced non-small cell lung cancer (NSCLC): 2023 expert consensus of the Spanish Lung Cancer Group GECP. Clin Transl Oncol. 2024;2024(26):1647–63. https://doi.org/10.1007/s12094-024-03382-y .

Article   Google Scholar  

Spicer JD, Cascone T, Wynes MW, et al. Neoadjuvant and adjuvant treatments for early stage resectable NSCLC: consensus recommendations from the international association for the study of lung cancer. J Thorac Oncol. 2024. https://doi.org/10.1016/j.jtho.2024.06.010 .

Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;350:g7647. https://doi.org/10.1136/bmj.g7647 .

Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol. 2011;64:163–71. https://doi.org/10.1016/j.jclinepi.2010.03.016 .

Demaria S, Santori FR, Ng B, et al. Select forms of tumor cell apoptosis induce dendritic cell maturation. J Leukoc Biol. 2005;77:361–8. https://doi.org/10.1189/jlb.0804478 .

Shim SR, Kim SJ, Lee J, et al. Network meta-analysis: application and practice using R software. Epidemiol Health. 2019;41:e2019013. https://doi.org/10.4178/epih.e2019013 .

Law M, Jackson D, Turner R, et al. Two new methods to fit models for network meta-analysis with random inconsistency effects. BMC Med Res Methodol. 2016;16:87. https://doi.org/10.1186/s12874-016-0184-5 .

Chaimani A, Higgins JP, Mavridis D, et al. Graphical tools for network meta-analysis in STATA. PLoS ONE. 2013;8: e76654. https://doi.org/10.1371/journal.pone.0076654 .

Wakelee H, Liberman M, Kato T, et al. Perioperative pembrolizumab for early-stage non-small-cell lung cancer. N Engl J Med. 2023;389:491–503. https://doi.org/10.1056/NEJMoa2302983 .

Heymach JV, Harpole D, Mitsudomi T, et al. Perioperative durvalumab for resectable non-small-cell lung cancer. N Engl J Med. 2023;389:1672–84. https://doi.org/10.1056/NEJMoa2304875 .

Lu S, Zhang W, Wu L, et al. Perioperative toripalimab plus chemotherapy for patients with resectable non-small cell lung cancer: the neotorch randomized clinical trial. JAMA. 2024;331:201–11. https://doi.org/10.1001/jama.2023.24735 .

Cascone T, Awad MM, Spicer JD, et al. LBA1 CheckMate 77T: Phase III study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant NIVO or placebo for previously untreated, resectable stage II–IIIb NSCLC. Ann Oncol. 2023;34:S1295. https://doi.org/10.1016/j.annonc.2023.10.050 .

Provencio M, Nadal E, González-Larriba JL, et al. Perioperative nivolumab and chemotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2023;389:504–13. https://doi.org/10.1056/NEJMoa2215530 .

Yue D, Wang W, Liu H, et al. VP1-2024: RATIONALE-315: Event-free survival (EFS) and overall survival (OS) of neoadjuvant tislelizumab (TIS) plus chemotherapy (CT) with adjuvant TIS in resectable non-small cell lung cancer (NSCLC). Ann Oncol. 2024;35:332–3. https://doi.org/10.1016/j.annonc.2024.01.005 .

Lei J, Zhao J, Gong L, et al. Neoadjuvant camrelizumab plus platinum-based chemotherapy vs chemotherapy alone for chinese patients With resectable stage IIIA or IIIB (T3N2) non-small cell lung cancer: the TD-FOREKNOW randomized clinical trial. JAMA Oncol. 2023;9:1348–55. https://doi.org/10.1001/jamaoncol.2023.2751 .

Mountzios G, Remon J, Hendriks LEL, et al. Immune-checkpoint inhibition for resectable non-small-cell lung cancer - opportunities and challenges. Nat Rev Clin Oncol. 2023;20:664–77. https://doi.org/10.1038/s41571-023-00794-7 .

Bakos O, Lawson C, Rouleau S, et al. Combining surgery and immunotherapy: turning an immunosuppressive effect into a therapeutic opportunity. J Immunother Cancer. 2018;6:86. https://doi.org/10.1186/s40425-018-0398-7 .

Matzner P, Sandbank E, Neeman E, et al. Harnessing cancer immunotherapy during the unexploited immediate perioperative period. Nat Rev Clin Oncol. 2020;17:313–26. https://doi.org/10.1038/s41571-019-0319-9 .

Mei T, Zhou Q, Gong Y. Comparison of the efficacy and safety of perioperative immunochemotherapeutic strategies for resectable non-small cell lung cancer: a systematic review and network meta-analysis. Clin Oncol (R Coll Radiol). 2024;36:107–18. https://doi.org/10.1016/j.clon.2023.12.006 .

Zhou Y, Li A, Yu H, et al. Neoadjuvant-adjuvant vs neoadjuvant-only PD-1 and PD-L1 inhibitors for patients with resectable NSCLC: an indirect meta-analysis. JAMA Netw Open. 2024;7:e241285. https://doi.org/10.1001/jamanetworkopen.2024.1285 .

Li Y, Liang X, Li H, et al. Efficacy and safety of immune checkpoint inhibitors for advanced non-small cell lung cancer with or without PD-L1 selection: a systematic review and network meta-analysis. Chin Med J (Engl). 2023;136:2156–65. https://doi.org/10.1097/cm9.0000000000002750 .

Duan J, Cui L, Zhao X, et al. Use of immunotherapy with programmed cell death 1 vs programmed cell death ligand 1 inhibitors in patients with cancer: a systematic review and meta-analysis. JAMA Oncol. 2020;6:375–84. https://doi.org/10.1001/jamaoncol.2019.5367 .

Tang Q, Chen Y, Li X, et al. The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers. Front Immunol. 2022;13:964442. https://doi.org/10.3389/fimmu.2022.964442 .

Miao YR, Thakkar KN, Qian J, et al. Neutralization of PD-L2 is essential for overcoming immune checkpoint blockade resistance in ovarian cancer. Clin Cancer Res. 2021;27:4435–48. https://doi.org/10.1158/1078-0432.Ccr-20-0482 .

Khunger M, Rakshit S, Pasupuleti V, et al. Incidence of pneumonitis with use of programmed death 1 and programmed death-ligand 1 inhibitors in non-small cell lung cancer: a systematic review and meta-analysis of trials. Chest. 2017;152:271–81. https://doi.org/10.1016/j.chest.2017.04.177 .

Xiao Y, Yu S, Zhu B, et al. RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance. J Exp Med. 2014;211:943–59. https://doi.org/10.1084/jem.20130790 .

Berner F, Bomze D, Diem S, et al. Association of checkpoint inhibitor-induced toxic effects with shared cancer and tissue antigens in non-small cell lung cancer. JAMA Oncol. 2019;5:1043–7. https://doi.org/10.1001/jamaoncol.2019.0402 .

Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158–68. https://doi.org/10.1056/NEJMra1703481 .

Mudad R, Patel MB, Margunato-Debay S, et al. Comparative effectiveness and safety of nab-paclitaxel plus carboplatin vs gemcitabine plus carboplatin in first-line treatment of advanced squamous cell non-small cell lung cancer in a US community oncology setting. Lung Cancer (Auckl). 2017;8:179–90. https://doi.org/10.2147/lctt.S139647 .

Lin X, Deng H, Li S, et al. Sintilimab with chemotherapy as first-line treatment for locally advanced or metastatic squamous non-small-cell lung cancer: a real-world data study. J Cancer Res Clin Oncol. 2023;149:757–64. https://doi.org/10.1007/s00432-021-03903-0 .

Ni J, Huang M, Zhang L, et al. Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer. Thorac Cancer. 2021;12:1469–88. https://doi.org/10.1111/1759-7714.13942 .

Owen CN, Bai X, Quah T, et al. Delayed immune-related adverse events with anti-PD-1-based immunotherapy in melanoma. Ann Oncol. 2021;32:917–25. https://doi.org/10.1016/j.annonc.2021.03.204 .

Ahern E, Solomon BJ, Hui R, et al. Neoadjuvant immunotherapy for non-small cell lung cancer: right drugs, right patient, right time? J Immunother Cancer. 2021. https://doi.org/10.1136/jitc-2020-002248 .

Deng H, Liang H, Chen J, et al. Preoperative immunochemotherapy for locally advanced non-small cell lung cancer: an analysis of the clinical outcomes, optimal number of cycles, and peripheral immune markers. Transl Lung Cancer Res. 2022;11:2364–81. https://doi.org/10.21037/tlcr-22-439 .

Shao M, Yao J, Wang Y, et al. Two vs three cycles of neoadjuvant sintilimab plus chemotherapy for resectable non-small-cell lung cancer: neoSCORE trial. Signal Transduct Target Ther. 2023;8:146. https://doi.org/10.1038/s41392-023-01355-1 .

Tian W, Niu L, Wang Z, et al. Cost-effectiveness of neoadjuvant pembrolizumab plus chemotherapy with adjuvant pembrolizumab for early-stage non-small cell lung cancer in the United States. Front Immunol. 2023;14:1268070. https://doi.org/10.3389/fimmu.2023.1268070 .

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This study was supported by a grant from the Science and Technology Agency of Qinghai Province (2022-ZJ-719).

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Bo li, Yujia Gu, Weixing Zhao, Zirui Li, Wanjing Guo & Xinxin Lu

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li, B., Gu, Y., Zhao, W. et al. The efficacy and safety of neoadjuvant immunochemotherapy in resectable stage I-III non-small cell lung cancer: a systematic review and network meta-analysis. Clin Transl Oncol (2024). https://doi.org/10.1007/s12094-024-03704-0

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Received : 11 June 2024

Accepted : 28 August 2024

Published : 09 September 2024

DOI : https://doi.org/10.1007/s12094-024-03704-0

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Efficacy of different analgesic strategies combined with conventional physiotherapy program for treating chronic shoulder pain: a systematic review and network meta-analysis

• Fangjie Yang 1 ,
• Xinmin Li 2   na1 ,
• Jing Wang 1 ,
• Qian Gao 1 ,
• Mengyang Pan 1 ,
• Zhenfei Duan 1 ,
• Chunlin Ren 1 ,
• Pengxue Guo 1 &
• Yasu Zhang 1  

Journal of Orthopaedic Surgery and Research volume  19 , Article number:  544 ( 2024 ) Cite this article

Metrics details

This study aims to investigate the efficacy of five analgesic strategies combined with conventional physiotherapy program (CPT) in managing chronic shoulder pain.

Two authors independently screened studies, extracted data using a pre-formatted chart, and assessed bias using the Cochrane Risk of Bias tool. A network meta-analysis was performed by the Stata 17.0 and R 4.3.2 software.

A total of 14 studies with 862 subjects were identified. These analgesic strategies included extracorporeal shock wave therapy (ESWT), suprascapular nerve block (SSNB), corticosteroid injection (CSI), hyaluronic acid injection (HAI), and kinesio taping (KT). ESWT plus CPT was the most efficient intervention in alleviating pain intensity and improving physical function. SSNB plus CPT was the optimal intervention in improving shoulder mobility. Compared to CPT alone, CSI + CPT only significantly improved the SPADI total score, but showed no difference in pain intensity or shoulder mobility. HAI + CPT showed no significant difference in improving pain intensity, physical function, or shoulder mobility compared to CPT alone. Adding KT to CPT did not yield additional benefits in improving shoulder mobility.

Overall, in managing chronic shoulder pain, ESWT + CPT was the most effective intervention for reducing pain intensity and improving physical function. SSNB + CPT was optimal for enhancing shoulder mobility. Future rigorous clinical trials with larger sample sizes and higher methodological rigor are strongly required to confirm the current results.

Introduction

Shoulder pain is the third most common musculoskeletal complaint, with a lifetime incidence of up to 67%, significantly impacting patients’ quality of life and posing a massive socio-economic burden on the healthcare system [ 1 , 2 ]. Chronic shoulder pain, defined as shoulder pain persisting for more than three months, has a significant impact on functional ability, psychosocial well-being, and metabolic stress [ 3 ]. Chronic shoulder pain is caused by multiple shoulder conditions including subacromial impingement syndrome, tendinopathy, rotator cuff tears, and adhesive capsulitis [ 2 ]. Subacromial impingement syndrome, primarily caused by subacromial pathology, is a leading contributor to shoulder pain [ 4 ]. Tendinopathy may arise due to repeated shoulder movements, particularly during overhead activities or heavy lifting [ 5 ]. Rotator cuff tears often lead to shoulder pain and functional impairment, necessitating treatment tailored to the severity, including conservative management or surgical repair [ 6 ]. Adhesive capsulitis is characterized by pain and stiffness, commonly associated with synovitis and contracture of the synovial capsule [ 7 ]. These shoulder conditions can cause chronic shoulder pain and are typically accompanied by stiffness, reduced range of motion, and limited participation [ 8 ].

The complex anatomy of the shoulder joint, the wide range of pathogenic factors, and the absence of standardized diagnostic criteria pose a significant dilemma for diagnose [ 9 , 10 , 11 , 12 ]. Consequently, the term “non-specific shoulder pain” is frequently used in both clinical practice and research studies [ 13 ]. A review has emphasized the need for future research targeting undivided subjects with “general” shoulder pain [ 14 ]. Besides, several such studies already yielding valuable clinical insights [ 15 , 16 , 17 , 18 ]. For example, a recent NMA compared the effectiveness of different exercise therapies in alleviating chronic shoulder pain [ 15 ]. Thus, performing a network meta-analysis based solely on chronic shoulder pain is reasonable.

Several conservative treatments of chronic shoulder pain have been proposed and assessed, such as non-steroidal anti-inflammatory drugs (NSAIDs), conventional physiotherapy program (CPT), and other analgesic strategies. NSAIDs are not always effective and may increase the risk of cardiovascular, gastrointestinal, liver or renal complications [ 9 , 19 ]. CPT, the first line therapy, includes exercise therapy, physical factor therapy, joint mobilization, massage therapy, and stretching [ 20 , 21 ]. It is helpful in alleviating pain, increasing muscle strength and joint stability, and facilitating function recovery [ 22 , 23 ]. Additionally, CPT can rectify biomechanical issues by improving muscle extensibility, increasing range of motion, enhancing stability of the rotator cuff muscles, and correcting scapulohumeral rhythm [ 24 , 25 ]. Recent evidence unveiled that there was no significant difference in reducing pain and improving physical function between physiotherapy and surgery for adults with shoulder pain [ 26 , 27 , 28 ]. These evidence also strengthen the necessity of CPT in the management of shoulder pain. Nevertheless, it also has some limitations. For instance, the efficacy of exercise may be compromised due to inherent challenges such as insufficient self-initiative and inadequate external supervision. Furthermore, manual therapy may transiently exacerbate pain and symptoms of patients with shoulder pain. Therefore, it is crucial to explore alternative treatments to complement or improve the therapeutic efficacy of CPT [ 29 ].

Besides NSAIDs and CPT, various analgesic strategies are widely used in clinical practice for treating chronic shoulder pain, such as extracorporeal shock wave therapy (ESWT), suprascapular nerve block (SSNB), corticosteroid injection (CSI), hyaluronic acid injection (HAI), and kinesio taping (KT). Numerous randomized controlled trials (RCTs) and reviews have demonstrated that these interventions can alleviate pain and improve joint function in individuals with shoulder pain [ 20 , 21 , 26 , 27 , 28 , 30 , 31 , 32 , 33 , 34 , 35 ]. However, these interventions may be limited in their long-term efficacy as they offer only temporary pain relief and anti-inflammatory effects without rectifying fundamental biomechanical issues. Recurrence of symptoms post-intervention is common due to biomechanical issues, such as imbalance in the rotator cuff muscles, postural dysfunction, and changes in shoulder-thoracic kinematics.

Recent well-designed RCTs have proven that combining CPT with analgesic strategies results in better outcomes than CPT alone. Previous network meta-analyses (NMAs) have compared the efficacy of various shoulder joint drug injections for shoulder disorders. However, they have not compared the effectiveness of different analgesic strategies when combined with CPT. This gap hinders the selection and promotion of the optimal treatment protocols in clinical practice. Therefore, this study aims to conduct a systematic review and NMA to evaluate the efficacy of five analgesic strategies combined with CPT in treating chronic shoulder pain. The findings will provide evidence-based clinical recommendations.

Protocol and registration

This study was conducted by Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Network Meta-Analysis (PRISMA-NMA) [ 36 ]. A prospective protocol for the NMA has been reported on PROSPERO (CRD 42024519473).

Search strategy

We systematically searched Pubmed, Web of Science, Embase, and Cochrane Library from their inceptions to April 15, 2024. The search terms used were: “Shoulder Pain”, “Rotator Cuff Injury”, “shoulder impingement syndrome”, “adhesive capsulitis”, “frozen shoulder”, “shoulder girdle”, “physiotherapy”, “physical therapy”, “steroid”, “corticosteroid”, “extracorporeal shock wave therapy”, “kinesio taping”, “kinesiology taping”, “Suprascapular Nerve Block”, “suprascapular nerve blocks”, “hyaluronic acid”, “randomized”, “random”, “randomly”, and “randomised”. Additionally, the references cited in the included articles were traced to identify any further eligible studies. The specific search strategies are given in Table S1 .

Inclusion criteria

Type of study: RCTs with parallel design were included.

Subjects: adults (≥ 18 years) were diagnosed with shoulder pain lasting at least 3 months, including rotator cuff tendinopathy, shoulder impingement syndrome, frozen shoulder, adhesive capsulitis, non-specific shoulder pain, and shoulder myofascial pain.

Types of interventions: acceptable interventions were mainly various analgesic strategies combined with CPT. Analgesic strategies included CSI, HAI, SSNB, ESWT, and KT.

Comparison: CPT alone or intercomparison between interventions.

Outcome measures: outcomes encompassed data on pain intensity assessed by Visual Analogue Scale (VAS) and Shoulder Pain and Disability Index pain (SPADI pain), physical function measured by SPADI disability and SPADI total, and shoulder mobility measured by shoulder range of motion (ROM).

Exclusion criteria

Studies that met any of the following criteria were strictly excluded: (1) studies specifically focused on patients with post-mastectomy shoulder pain; (2) studies published as conference abstracts, trial registry records, animal studies, reviews, meta-analyses, protocols, case reports, or letters; (3) incomplete trial data; (4) irrelevant trial outcome indicators; (5) inappropriate interventions; (6) insufficient patient information; (7) non-English studies.

Screening and data extraction

The retrieved articles were uploaded into Endnote X9 software, and then duplicates were removed. Two authors independently scrutinized the titles and abstracts for an initial screening, and conducted a meticulous full-text reading of selected RCTs for the final decision. The following data were collected and summarized by two authors using a pre-formatted chart: first author, publication year, country, study design, sample size, participant age, disease type, pain duration, intervention protocols (intervention modalities and duration), and outcome assessments (VAS, SPADI pain, SPADI total, SPADI disability, and shoulder ROM). Any discrepancies were resolved through collaboration with other authors. If complete data were not available, we contacted the corresponding author for missing information. When necessary, the mean and standard deviation were calculated using the Cochrane Handbook formulas based on the baseline and outcome data.

Risk of bias

Two authors independently performed quality assessment of the included studies via the Cochrane Collaboration’s tool. Seven items of bias were as follows: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. Any disagreements were resolved by achieving a consensus. The risk of bias for each domain was rated as low, unclear, or high. Studies with low bias risk in three or more domains were rated moderate to high quality. Publication bias was evaluated using a comparison-adjusted funnel plot and Egger’s test.

Data synthesis and analysis

A frequentist NMA using random-effects model was adopted to pool direct and indirect evidence simultaneously. All analyses were achieved using Stata/MP statistical software version 17.0, R statistical software version 4.3.2, and RStudio statistical software version 22023.09.1–494 [ 37 , 38 , 39 ]. Mean difference (MD) with a 95% confidence interval (CI) was used to evaluate the effect size of the continuous variables. If a closed loop was formed, we examined statistical inconsistency between direct and indirect evidence using local (the node-splitting technique) and global (the design-by-treatment interaction technique) models [ 40 ]. If P  > 0.05, it suggested that there was no statistically significant difference between the two kinds of evidence, and a consistency model analysis was used for analysis [ 41 ]. A network plot was created to show the relationships among the different interventions. The size of nodes reflects the sample size of each intervention, and the thickness of lines corresponds to the quantity of RCTs with direct comparisons. Then, a league table was created to present the outcome for all paired comparisons, incorporating both direct and indirect comparisons. Subsequently, the surface under the cumulative ranking surve (SUCRA) probabilities were computed to compare the efficacy of different treatment approaches for each outcome. And a larger SUCRA value suggests a better effect of the intervention. Then, cumulative probability line charts were created. Finally, the potential publication bias in NMA was examined using a comparison-adjusted funnel plot and Egger’s test. Egger’s test was performed using Rstudio, and if P  > 0.05, it indicated that there was no significant publication bias.

Study selection

The preliminary search identified 1248 records, of which 527 duplicate records were removed. After reviewing titles and abstracts, 48 studies remained. After excluding 1 unavailable studies, the full texts of the reserved 47 studies were further evaluated for their eligibility. Following the screening criteria, 14 studies were selected for our NMA with a total of 862 patients [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The process of literature screening is shown in Fig.  1 .

Flow diagram of studies selection

Study characteristics

A total of 14 eligible studies [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ] and 6 interventions fulfilled the inclusion criteria and were included for analysis. The different interventions of included studies were defined in Table  1 . The characteristics of the included RCTs are presented in Table  2 . They were carried out in 6 different countries and published from 2011 to 2024. Egypt has contributed four articles, the highest number among all countries. The sample sizes spanned from 30 to 97. The average age of patients ranged from 30.47 to 71.3 years old. Participants in the included studies were diagnosed with chronic shoulder pain. Multiple studies reported the effectiveness of different interventions: 5 studies for “CSI + CPT” [ 42 , 44 , 51 , 52 , 53 ], 5 studies for “HAI + CPT” [ 43 , 45 , 46 , 49 , 55 ], 2 studies for “SSNB + CPT” [ 42 , 51 ], 4 studies for “ESWT + CPT” [ 47 , 50 , 52 , 54 ], 1 studies for “KT + CPT” [ 48 ], and 14 studies for “CPT” [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The duration of intervention in the included studies varied from 4 weeks to 12 weeks, including 4 weeks for 4 studies [ 47 , 50 , 52 , 54 ], 6 weeks for 2 studies [ 44 , 48 ], 8 weeks for 1 studies [ 53 ], and 12 weeks for 7 studies [ 42 , 43 , 45 , 46 , 49 , 51 , 55 ]. The indicators of pain intensity encompassed VAS score and SPADI pain score. VAS score was reported in 5 studies [ 47 , 50 , 51 , 53 , 55 ], and SPADI pain score was reported in 6 studies [ 42 , 43 , 44 , 53 , 54 , 55 ]. The indicators of physical function encompassed SPADI disability score and SPADI total score. The SPADI disability score was reported in 6 studies [ 42 , 43 , 44 , 53 , 54 , 55 ], while the SPADI total score was reported in 8 studies [ 42 , 43 , 44 , 51 , 52 , 53 , 54 , 55 ]. The indicators of shoulder mobility included flexion, abduction, and external rotation ROM. The flexion ROM was measured in 8 studies [ 42 , 47 , 48 , 50 , 51 , 52 , 53 , 55 ]; the abduction ROM was reported in 8 studies [ 42 , 47 , 48 , 50 , 51 , 52 , 53 , 55 ], and the external rotation ROM was reported in 9 studies [ 42 , 45 , 46 , 47 , 49 , 50 , 51 , 53 , 55 ].

Quality assessment

Among all the included studies, eight (57.1%) studies [ 43 , 47 , 48 , 50 , 52 , 53 , 54 , 55 ] used a computer or a random number table and were rated as low risk in random sequence generation. Five studies [ 42 , 44 , 45 , 46 , 51 ] lacked a clear description of the random allocation method and were assessed as unclear risk. Five (35.7%) studies [ 48 , 50 , 52 , 53 , 55 ] used a sealed envelope to conceal assignment scheme and were judged as low risk in allocation concealment. The remaining nine studies [ 42 , 43 , 44 , 45 , 46 , 47 , 49 , 51 , 54 ] presented uncertain risk due to a lack of clear description of the allocation concealment. In blinding participants and personnel, ten studies had unclear risk [ 42 , 43 , 44 , 46 , 47 , 48 , 50 , 52 , 53 , 54 ], and four studies had high risk [ 45 , 49 , 51 , 55 ]. Five RCTs [ 50 , 52 , 53 , 54 , 55 ] blinded the outcome evaluators. One study [ 44 ] was rated as high attrition bias owing to a dropout rate exceeding 20%, while three studies had unclear risk, and ten studies [ 42 , 43 , 46 , 48 , 50 , 51 , 52 , 53 , 54 , 55 ] had low risk in this aspect. All included studies were assessed as low risk in reporting bias. Other bias were evaluated as unclear risk in all studies. In summary, six studies were rated as high quality [ 48 , 50 , 52 , 53 , 54 , 55 ], one studies [ 43 ] were rated as moderate quality, and seven studies were rated as low quality [ 42 , 44 , 45 , 46 , 47 , 49 , 51 ]. The funnel plots were symmetrical, and the P values of Egger’s test were exceeding 0.05, suggesting the absence of publication bias among the studies. Risk of bias assessment of the studies is illustrated in Fig.  2 .

Risk of bias. ( A ) Risk of bias summary; ( B ) Risk of bias graph

• Network meta-analysis

Pain intensity

Five studies with 362 subjects assessed the efficacy of 5 interventions in reducing VAS score, and the network plot is depicted in Fig.  3 A. The VAS score is commonly used to measure pain intensity, and a higher score signifies greater pain intensity. Both the design-by-treatment interaction model and the node-splitting method did not detect any inconsistency (global: P  = 0.15; local: P  > 0.05) (Table S2 ). Figure  4 A is the league table of VAS, presenting the two-by-two comparison matrix for reducing VAS score. Compared with CPT, SSNB + CPT (MD: -0.56; 95% CI: -0.96 to -0.16) and ESWT + CPT (MD: -1.06; 95% CI: -1.40 to -0.71) had significant effects on reducing VAS score. ESWT + CPT was significantly more effective than CSI + CPT (MD: 0.84; 95% CI: 0.24 to 1.43). As shown in Fig.  4 B, results of SUCRA analysis unveiled that ESWT + CPT had the highest probability of being best (95.1%), followed by SSNB + CPT (61.5%), HAI + CPT (57.8%), CSI + CPT (27.8%), and CPT (7.8%). We were unable to identify publication bias using a funnel plot or Egger’s test because the number of included studies in this outcome was less than 10.

The network plots. ( A ) VAS; ( B ) SPADI pain/SPADI disability; ( C ) SPADI total; ( D ) Flexion; ( E ) Abduction; ( F ) External rotation

Visual Analogue Scale score (VAS). ( A ) The league table of VAS. MD with a 95% CI was used to evaluate the effect size. The comparisons in the lower left triangle should be read in a left-to-right manner. MD < 0 suggests that this intervention is more effective in reducing VAS score compared to other interventions. Data marked with an asterisk (*) indicates significant group differences ( P  < 0.05); ( B ) Cumulative probability line chart of VAS

A total of 6 with 316 patients were included to compare the effects of 5 interventions on SPADI pain score in subjects with shoulder pain, and the network plot is shown in Fig.  3 B. The SPADI questionnaire is a standardized tool used to assess pain and functional limitations in individuals with shoulder problems. It consists of two subscales: the Pain subscale and the Disability subscale. A higher SPADI pain score signifies more severe pain intensity. Both the design-by-treatment interaction model and the node-splitting method did not detect any inconsistency (global: P  = 0.84; local: P  > 0.05) (Table S2 ). Figure  5 A is the league table of SPADI pain, presenting the two-by-two comparison matrix for reducing SPADI pain score. Compared with CPT, SSNB + CPT (MD: -12.60; 95% CI: -19.79 to -5.41) and ESWT + CPT (MD: -30.53; 95% CI: -36.94 to -24.12) had significant effects on reducing SPADI pain score. ESWT + CPT was significantly more effective than CSI + CPT (MD: 27.61; 95% CI: 19.32 to 35.90), HAI + CPT (MD: 29.84; 95% CI: 20.21 to 39.46), and SSNB + CPT (MD: 17.93; 95% CI: 8.30 to 27.56). As shown in Fig.  5 B, the findings of SUCRA analysis indicated that ESWT + CPT had the highest probability of being best (100.0%), followed by SSNB + CPT (74.6%), CSI + CPT (38.8%), HAI + CPT (22.3%), and CPT (14.3%). We were unable to identify publication bias using a funnel plot or Egger’s test because the number of included studies in this outcome was less than 10.

SPADI pain. ( A ) The league table of SPADI pain. MD with a 95% CI was used to evaluate the effect size. The comparisons in the lower left triangle should be read in a left-to-right manner. MD < 0 suggests that this intervention is more effective in reducing SPADI pain score compared to other interventions. Data marked with an asterisk (*) indicates significant group differences ( P  < 0.05); ( B ) Cumulative probability line chart of SPADI pain

Physical function

A total of 6 with 316 subjects were included to compare the effects of 5 interventions on SPADI disability score in patients with shoulder pain, and the network plot is shown in Fig.  3 B. A higher SPADI disability score indicates more severe disabilities. Both the design-by-treatment interaction model and the node-splitting method did not detect any inconsistency (global: P  = 0.14; local: P  > 0.05) (Table S2 ). Figure  6 A is the league table of SPADI disability, presenting the two-by-two comparison matrix for reducing SPADI disability score. ESWT + CPT was significantly more effective than HAI + CPT (MD: 23.87; 95% CI: 1.03 to 46.71) and CPT (MD: -25.25; 95% CI: -42.96 to -7.54). As shown in Fig.  6 B, outcomes of SUCRA analysis unveiled that ESWT + CPT had the highest probability of being best (96.2%), followed by SSNB + CPT (55.6%), CSI + CPT (52.4%), HAI + CPT (28.1%), and CPT (17.6%). Funnel plot and Egger’s test were not performed because the number of included studies in this outcome was less than 10.

SPADI disability. ( A ) The league table of SPADI disability. MD with a 95% CI was used to evaluate the effect size. The comparisons in the lower left triangle should be read in a left-to-right manner. MD < 0 suggests that this intervention is more effective in reducing SPADI disability score compared to other interventions. Data marked with an asterisk (*) indicates significant group differences ( P  < 0.05); ( B ) Cumulative probability line chart of SPADI disability

Eight studies with 473 subjects assessed the efficacy of 5 interventions in reducing SPADI total score, and the network plot is shown in Fig.  3 C. A higher total SPADI score indicates poorer shoulder function. The design-by-treatment interaction model did not detect any inconsistency ( P  = 0.32). However, small percentages of local inconsistency were observed between some comparisons in SPADI total (1/6 loops) (Table S2 ). The league table of SPADI total is shown in Fig.  7 A which exhibits the two-by-two comparison matrix for reducing SPADI total score. Compared with CPT, CSI + CPT (MD: -8.50; 95% CI: -16.21 to -0.78) and ESWT + CPT (MD: -17.07; 95% CI: -28.32 to -5.82) had significant effects on reducing SPADI total score. As shown in Fig.  7 B, results of SUCRA analysis unveiled that ESWT + CPT had the highest probability of being best (94.6%), followed by CSI + CPT (62.6%), SSNB + CPT (54.6%), HAI + CPT (24.0%), and CPT (14.2%). The symmetrical funnel plot and Egger’s test ( P  = 0.61) indicated that there was no significant publication bias (Fig.  7 C).

SPADI total. ( A ) The league table of SPADI total. MD with a 95% CI was used to evaluate the effect size. The comparisons in the lower left triangle should be read in a left-to-right manner. MD < 0 suggests that this intervention is more effective in reducing SPADI total score compared to other interventions. Data marked with an asterisk (*) indicates significant group differences ( P  < 0.05); ( B ) Cumulative probability line chart of SPADI total; ( C ) The funnel plots of SPADI total

Shoulder mobility

Eight studies with 529 subjects examined the efficacy of 6 interventions in improving flexion ROM, and the network plot is shown in Fig.  3 D. Both the design-by-treatment interaction model and the node-splitting method did not detect any inconsistency (global: P  = 0.56; local: P  > 0.05) (Table S2 ). The league table of flexion is shown in Fig.  8 A, which presents the two-by-two comparison matrix for improving flexion ROM. Compared with CPT, SSNB + CPT (MD: 15.20; 95% CI: 1.56 to 28.85), and ESWT + CPT (MD: 14.37; 95% CI: 3.06 to 25.68) had significant effects on improving flexion ROM. As shown in Fig.  8 B, results of SUCRA analysis indicated that SSNB + CPT had the highest probability of being best (81.2%), followed by ESWT + CPT (78.1%), CSI + CPT (49.4%), HAI + CPT (43.5%), KT + CPT (30.3%), and CPT (17.5%). The symmetrical funnel plot and Egger’s test ( P  = 0.74) indicated that there was no significant publication bias (Fig.  8 C).

Flexion. ( A ) The league table of flexion. MD with a 95% CI was used to evaluate the effect size. The comparisons in the lower left triangle should be read in a left-to-right manner. MD > 0 suggests that this intervention is more effective in reducing flexion ROM compared to other interventions. Data marked with an asterisk (*) indicates significant group differences ( P  < 0.05); ( B ) Cumulative probability line chart of flexion; ( C ) The funnel plots of flexion

Eight studies with 529 subjects assessed the efficacy of 6 interventions in improving abduction ROM, and the network plot is shown in Fig.  3 E. Both the design-by-treatment interaction model and the node-splitting method did not detect any inconsistency (global: P  = 0.67; local: P  > 0.05) (Table S2 ). Figure  9 A is the league table of abduction, showing the two-by-two comparison matrix for improving abduction ROM. Compared with CPT, SSNB + CPT (MD: 22.02; 95% CI: 4.70 to 39.35), and ESWT + CPT (MD: 16.58; 95% CI: 1.69 to 31.46) had significant effects on improving abduction ROM. As shown in Fig.  9 B, outcomes of SUCRA analysis revealed that SSNB + CPT had the highest probability of being best (84.5%), followed by ESWT + CPT (70.2%), HAI + CPT (45.5%), CSI + CPT (44.2%), KT + CPT (40.8%), and CPT (14.9%). The symmetrical funnel plot and Egger’s test ( P  = 0.77) indicated that there was no significant publication bias (Fig.  9 C).

Abduction. ( A ) The league table of abduction. MD with a 95% CI was used to evaluate the effect size. The comparisons in the lower left triangle should be read in a left-to-right manner. MD > 0 suggests that this intervention is more effective in reducing abduction ROM compared to other interventions. Data marked with an asterisk (*) indicates significant group differences ( P  < 0.05); ( B ) Cumulative probability line chart of abduction; ( C ) The funnel plots of abduction

Nine studies with 620 subjects evaluated the efficacy of 5 interventions in improving external rotation ROM, and the network plot is shown in Fig.  3 F. Both the design-by-treatment interaction model and the node-splitting method did not detect any inconsistency (global: P  = 0.71; local: P  > 0.05) (Table S2 ). Figure  10 A is the league table of abduction, displaying the two-by-two comparison matrix for improving external rotation ROM. Compared with CPT, SSNB + CPT (MD: 16.48; 95% CI: 8.08 to 24.88), and ESWT + CPT (MD: 12.46; 95% CI: 4.32 to 20.60) showed significant improvement in external rotation ROM. SSNB + CPT was significantly more effective than CSI + CPT (MD: -11.32; 95% CI: -19.67 to -2.97) and HAI + CPT (MD: -15.41; 95% CI: -25.74 to -5.08). Compared with HAI + CPT, ESWT + CPT (MD: -11.39; 95% CI: -21.48 to -1.31) had significant effects on improving external rotation ROM. As shown in Fig.  10 B, results of SUCRA analysis confirmed that SSNB + CPT had the highest probability of being best (93.5%), followed by ESWT + CPT (78.4%), CSI + CPT (45.0%), HAI + CPT (21.7%), and CPT (11.4%). The symmetrical funnel plot and Egger’s test ( P  = 0.94) indicated that there was no significant publication bias (Fig.  10 C).

External rotation. ( A ) The league table of external rotation. MD with a 95% CI was used to evaluate the effect size. The comparisons in the lower left triangle should be read in a left-to-right manner. MD > 0 suggests that this intervention is more effective in reducing external rotation ROM compared to other interventions. Data marked with an asterisk (*) indicates significant group differences ( P  < 0.05); ( B ) Cumulative probability line chart of external rotation; ( C ) The funnel plots of external rotation

To the best of our knowledge, this is the first systematic review and NMA to examine the therapeutic effects of five analgesic strategies combined with CPT for chronic shoulder pain. NMA can compare multiple treatments by combining direct and indirect evidence and perform relative ranking. According to the results of NMA, ESWT + CPT ranked highest in alleviating pain intensity and improving physical function compared to other interventions + CPT; SSNB + CPT was the best intervention in improving shoulder mobility. Compared to CPT alone, ESWT + CPT significantly improved pain intensity, physical function, and shoulder mobility; SSNB + CPT significantly improved pain intensity and shoulder mobility; CSI + CPT significantly improved the SPADI total score in patients with chronic shoulder pain, but showed no difference in pain intensity or shoulder mobility. HAI + CPT showed no significant difference in improving pain intensity, physical function, or shoulder mobility compared to CPT alone. The addition of KT to CPT had no significant effect on improving shoulder mobility.

Chronic shoulder pain is caused by diverse pathologies like tendon tears, tendinopathy, ligament instability, bursitis, and arthropathy, posing significant challenges for clinical management [ 17 ]. Effective management requires integrating multiple intervention methods, as comprehensive approaches often have more effective and longer-lasting effects than single treatments. CPT is a multimodal approach that includes exercise therapy, physical factor therapy, joint mobilization, massage therapy, and stretching [ 59 ]. Exercise is a central component of CPT and is strongly recommended as the initial approach for alleviating pain, enhancing mobility, and improving function in patients with subacromial shoulder pain [ 24 , 60 ]. Based on surveys, in the rehabilitation of musculoskeletal shoulder issues, the following principles are commonly applied: patients are permitted to experience mild discomfort (rated below 5/10 on a VAS) during exercise sessions, which should include some resistance. Further, the expected duration of exercise spans 12 weeks [ 61 , 62 ]. However, exercise often causes discomfort and hinders patients from fully engaging in the rehabilitation program. Pain relief facilitates patients to engage CPT, consequently enhancing overall effectiveness. Consequently, the combined application of analgesic strategies and CPT is gaining popularity in the management of chronic shoulder pain.

We found that ESWT + CPT ranked highest in alleviating pain intensity and improving physical function compared to other interventions + CPT. The greater effectiveness of the combined approach can be attributed to the fact that physical therapists use ESWT before addressing biomechanical issues with CPT. CPT can increase subacromial space, enhance movement control, restore normal scapulohumeral rhythm, improve proprioception, and ultimately improve shoulder joint function [ 22 , 23 ]. Pain can restrict shoulder joint mobility by inducing arthrogenic muscle inhibition [ 63 ]. Therefore, preemptively addressing pain prior to initiating exercise programs can enhance effectiveness in reducing pain-related functional impairments over the short and medium-term [ 64 ]. There are two main hypotheses explaining the analgesic effect of ESWT. One of the mechanisms, known as the hyper-stimulation theory, suggests that ESWT induces the release of analgesic molecules by activating the descending inhibitory system, thereby alleviating pain [ 65 ]. Secondly, ESWT may lower the concentration of substance P levels in the target tissue and dorsal root ganglia, thereby impairing the pain transmission to the brainstem. Furthermore, the interstitial and extracellular responses caused by the shock wave can produce multiple biological effects, including vascularization, protein biosynthesis, cell proliferation, neuroprotection, and chondroprotection [ 66 ]. These biological effects result in long-term improvements in pain and function. A recent RCT demonstrated that in patients with chronic shoulder pain, ESWT + exercise exhibited greater efficacy in reducing pain intensity compared to rehabilitation alone, which was consistent with our outcome [ 67 ].

Compared to CPT alone, SSNB + CPT significantly improved pain reduction and shoulder mobility, but no significant differences were observed in improving physical function. Recent research has shown that continuous SSNB combined with intensive rehabilitation is an effective treatment for patients with chronic adhesive capsulitis unresponsive to conventional therapies [ 68 ]. Parashar et al. also suggested that combining SSNB with non-invasive rehabilitation was more effective for treating idiopathic frozen shoulder than non-invasive rehabilitation alone, aligning with our findings [ 69 ].The suprascapular nerve supplies sensory fibers to around 70% of the shoulder joint and directly innervates the supraspinatus and infraspinatus muscles [ 70 ]. SSNB can alleviate pain and improve shoulder joint motion by blocking the suprascapular nerve [ 71 ]. Previous research on adhesive capsulitis showed that the effects of SSNB surpassed the pharmacological effects of anesthetics, potentially due to desensitization from reduced peripheral nociceptive input or decreased central sensitivity [ 72 , 73 ]. In terms of improving physical function. researchers found that SSNB significantly improved disability scores in the treatment of chronic shoulder pain compared to placebo [ 72 , 74 , 75 ]. However, our study yielded an opposite result, possibly due to limited evidence from only one included study in the NMA. Thus, more studies are strongly required to confirm the efficacy of SSNB + CPT in improving physical function compared to CPT alone.

Compared to CPT alone, CSI + CPT significantly improved the SPADI total score in patients with chronic shoulder pain, but showed no difference in pain intensity or shoulder mobility. A prior study found that subacromial injection of betamethasone and xylocaine was no more effective than xylocaine alone in improving shoulder mobility or alleviating impingement signs in patients with chronic rotator cuff tendinosis, which was consistent with our finding [ 76 ]. More recently, a meta-analysis indicated that CSI provide only small and transient pain relief for a limited number of patients with rotator cuff tendinopathy, and do not alter the natural progression of the disease [ 77 ]. A systematic review reported that a single CSI in conjunction with home exercise may be beneficial for patients with frozen shoulder lasting less than 6 months [ 78 ]. Therefore, there is currently no conclusive evidence supporting the effectiveness of CSI in managing chronic shoulder pain. Given the potential side effects of CSI, such as the risk of tendon damage with repeated use, caution should be taken when combining with physical therapy [ 79 ].

In our NMA, we found that compared to CPT alone, HAI + CPT had no significant effect on improving pain intensity, physical function, or shoulder mobility in patients with chronic shoulder pain. HA, a non-sulfated glycosaminoglycan, is thought to protect tissues from environmental damage and to promote regeneration and repair in articular cartilage, synovial tissue, and synovial fluid [ 80 ]. A multicenter RCT found no significant difference between HAI and phosphate-buffered saline in treating chronic shoulder pain related to glenohumeral osteoarthritis, which was consistent with our finding [ 81 ]. Similarly, in the management of chronic subacromial bursitis, a previous study also found no difference between the HAI group and the saline group in improving SPADI scores [ 82 ]. However, Blaine et al. found that HAI was both effective and well-tolerated in treating persistent shoulder pain that was unresponsive to other standard nonoperative interventions [ 83 ]. Jiménez et al. indicated that subacromial HAI was notably effective for patients with reduced subacromial space or cuff tears, but showed limited effectiveness in those with acromioclavicular osteoarthritis [ 84 ]. The evidence regarding the effectiveness of HAI for chronic shoulder pain is contradictory, highlighting the need for high-quality basic science studies and RCTs to better assess its efficacy.

Our analysis showed that for patients receiving CPT treatment, the combination of KT did not yield additional benefits in improving shoulder mobility. KT, an elastic therapeutic tape, is widely used for a variety of musculoskeletal disorders. Some researchers believed that KT could increase the non-noxious stimulus through the skin, thereby lessening the input of painful stimulus induced by complex pathogenic factors. KT is also considered to elevate fascia and soft tissues, creating additional space and reducing localized pressure, ultimately improving circulation and lymphatic drainage [ 35 ]. However, two prior systematic reviews indicated that current evidence does not recommend the application of KT in clinical practice [ 35 , 85 ]. Likewise, a recent meta-analysis also suggested that KT for rotator cuff disease has uncertain efficacy in improving active ROM when compared to sham taping [ 86 ]. These evidence all aligned with our findings.

To the best of our knowledge, this is the first study to evaluate the therapeutic effects of five analgesic strategies combined with CPT for patients with chronic shoulder pain. As chronic shoulder pain requires multidisciplinary management, comparing these combined approaches is more in line with clinical practice. We performed a comprehensive ranking of ESWT + CPT, SSNB + CPT, CSI + CPT, HAI + CPT, and KT + CPT to identify the best combined approaches for improving pain intensity, physical function, and shoulder mobility in patients with chronic shoulder pain. There were still several limitations in this study. Firstly, our study aims to compare interventions from a broad perspective, thus omitting detailed specific interventions such as CPT. Likewise, several factors such as injection site, injection dose, energy levels, and intervention durations are also ignored, possibly inducing some bias. Secondly, the methodological quality of these included studies is not high. Pain and functional improvement, as subjective indicators, may introduce bias in the results. Thirdly, we included only English-language papers, possibly leading to linguistic bias. Finally, the findings should be interpreted cautiously due to the limited number of clinical trials for head-to-head comparisons between these interventions.

Overall, in managing chronic shoulder pain, ESWT + CPT was the most effective intervention for reducing pain intensity and improving physical function. SSNB + CPT was optimal for enhancing shoulder mobility. Compared to CPT alone, CSI + CPT only significantly improved the SPADI total score, but showed no difference in pain intensity or shoulder mobility. HAI + CPT had no significant difference in improving pain intensity, physical function, or shoulder mobility compared to CPT alone. Adding KT to CPT did not yield additional benefits in improving shoulder mobility. Due to the existing limitations of this study, our findings should be interpreted cautiously. Future clinical trials with larger sample sizes and higher methodological rigor are strongly required to confirm the current results.

Data availability

No datasets were generated or analysed during the current study.

Greving K, Dorrestijn O, Winters JC, Groenhof F, van der Meer K, Stevens M, et al. Incidence, prevalence, and consultation rates of shoulder complaints in general practice. Scand J Rheumatol. 2012;41(2):150–5. https://doi.org/10.3109/03009742.2011.605390 .

Article   CAS   PubMed   Google Scholar  

Luime JJ, Koes BW, Hendriksen IJ, Burdorf A, Verhagen AP, Miedema HS, et al. Prevalence and incidence of shoulder pain in the general population; a systematic review. Scand J Rheumatol. 2004;33(2):73–81. https://doi.org/10.1080/03009740310004667 .

Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, et al. Chronic pain as a symptom or a disease: the IASP classification of Chronic Pain for the International classification of diseases (ICD-11). Pain. 2019;160(1):19–27. https://doi.org/10.1097/j.pain.0000000000001384 .

Article   PubMed   Google Scholar  

Diercks R, Bron C, Dorrestijn O, Meskers C, Naber R, de Ruiter T, et al. Guideline for diagnosis and treatment of subacromial pain syndrome: a multidisciplinary review by the Dutch Orthopaedic Association. Acta Orthop. 2014;85(3):314–22. https://doi.org/10.3109/17453674.2014.920991 .

Article   PubMed   PubMed Central   Google Scholar  

Cook JL, Purdam CR. Is tendon pathology a continuum? A pathology model to explain the clinical presentation of load-induced tendinopathy. Br J Sports Med. 2009;43(6):409–16. https://doi.org/10.1136/bjsm.2008.051193 .

Hill JR, Olson JJ, Sefko JA, Steger-May K, Teefey SA, Middleton WD et al. Does Surgical intervention alter the natural history of degenerative rotator cuff tears? Comparative analysis from a prospective longitudinal study. Journal of shoulder and elbow surgery 2024;S1058-2746(24):00509–3. https://doi.org/10.1016/j.jse.2024.05.056

Berner JE, Nicolaides M, Ali S, Pafitanis G, Preece J, Hopewell S, et al. Pharmacological interventions for early-stage frozen shoulder: a systematic review and network meta-analysis. Rheumatology (Oxford). 2024;keae176. https://doi.org/10.1093/rheumatology/keae176 .

Dias D, Neto MG, Sales SDSR, Cavalcante BDS, Torrierri P Jr, Roever L, et al. Effect of mobilization with Movement on Pain, disability, and Range of Motion in patients with Shoulder Pain and Movement Impairment: a systematic review and Meta-analysis. J Clin Med. 2023;12(23):7416. https://doi.org/10.3390/jcm12237416 .

Walker J. Shoulder pain: pathogenesis, diagnosis and management. Nurs Stand. 2014;28(22):51–60. https://doi.org/10.7748/ns2014.01.28.22.51.e8145 .

Schwerla F, Hinse T, Klosterkamp M, Schmitt T, Rütz M, Resch KL. Osteopathic treatment of patients with shoulder pain. A pragmatic randomized controlled trial. J Bodyw Mov Ther. 2020;24(3):21–8. https://doi.org/10.1016/j.jbmt.2020.02.009 .

Gismervik SØ, Drogset JO, Granviken F, Rø M, Leivseth G. Physical examination tests of the shoulder: a systematic review and meta-analysis of diagnostic test performance. BMC Musculoskelet Disord. 2017;18(1):41. https://doi.org/10.1186/s12891-017-1400-0 .

Hanchard NC, Lenza M, Handoll HH, Takwoingi Y. Physical tests for shoulder impingements and local lesions of bursa, tendon or labrum that may accompany impingement. Cochrane Database Syst Rev. 2013;2013(4):CD007427. https://doi.org/10.1002/14651858.cd007427.pub2 .

Peek AL, Miller C, Heneghan NR. Thoracic manual therapy in the management of non-specific shoulder pain: a systematic review. J Man Manip Ther. 2015;23(4):176–87. https://doi.org/10.1179/2042618615y.0000000003 .

Schellingerhout JM, Verhagen AP, Thomas S, Koes BW. Lack of uniformity in diagnostic labeling of shoulder pain: time for a different approach. Man Ther. 2008;13(6):478–83. https://doi.org/10.1016/j.math.2008.04.005 .

Silveira A, Lima C, Beaupre L, Chepeha J, Jones A. Shoulder specific exercise therapy is effective in reducing chronic shoulder pain: a network meta-analysis. PLoS ONE. 2024;19(4):e0294014. https://doi.org/10.1371/journal.pone.0294014 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Smith N, Liew Z, Johnson S, Ellard DR, Underwood M, Kearney R. A systematic review of the methods and drugs used for performing suprascapular nerve block injections for the non-surgical management of chronic shoulder pain. Br J Pain. 2021;15(4):460–73. https://doi.org/10.1177/2049463721992091 .

Chang KV, Hung CY, Wu WT, Han DS, Yang RS, Lin CP. Comparison of the effectiveness of suprascapular nerve Block with Physical Therapy, Placebo, and Intra-articular Injection in Management of Chronic Shoulder Pain: a Meta-analysis of Randomized controlled trials. Arch Phys Med Rehabil. 2016;97(8):1366–80. https://doi.org/10.1016/j.apmr.2015.11.009 .

Jurak I, Delaš K, Erjavec L, Stare J, Locatelli I. Effects of Multidisciplinary Biopsychosocial Rehabilitation on Short-Term Pain and Disability in Chronic Low Back Pain: a systematic review with Network Meta-Analysis. J Clin Med. 2023;12(23):7489. https://doi.org/10.3390/jcm12237489 .

Ejnisman B, Andreoli CV, Soares BG, et al. Interventions for tears of the rotator cuff in adults. Cochrane Database Syst Rev. 2004;1CD002758. https://doi.org/10.1002/14651858.pub2 .

Burbank KM, Stevenson JH, Czarnecki GR, Dorfman J. Chronic shoulder pain: part II. Treat Am Fam Physician. 2008;77(4):493–7.

PubMed   Google Scholar  

Haik MN, Alburquerque-Sendín F, Moreira RF, Pires ED, Camargo PR. Effectiveness of physical therapy treatment of clearly defined subacromial pain: a systematic review of randomised controlled trials. Br J Sports Med. 2016;50(18):1124–34. https://doi.org/10.1136/bjsports-2015-095771 .

McDevitt AW, Young JL, Cleland JA, Hiefield P, Snodgrass SJ. Physical therapy interventions used to treat individuals with biceps tendinopathy: a scoping review. Braz J Phys Ther. 2024;28(1):100586. https://doi.org/10.1016/j.bjpt.2023.100586 .

Marinko LN, Chacko JM, Dalton D, Chacko CC. The effectiveness of therapeutic exercise for painful shoulder conditions: a meta-analysis. J Shoulder Elb Surg. 2011;20(8):135–9. https://doi.org/10.1016/j.jse.2011.05.013 .

Article   Google Scholar  

Pieters L, Lewis J, Kuppens K, Jochems J, Bruijstens T, Joossens L, et al. An update of systematic reviews examining the effectiveness of conservative physical therapy interventions for subacromial shoulder pain. J Orthop Sports Phys Ther. 2020;50(3):131–41. https://doi.org/10.2519/jospt.2020.8498 .

Zhong Z, Zang W, Tang Z, Pan Q, Yang Z, Chen B. Effect of scapular stabilization exercises on subacromial pain (impingement) syndrome: a systematic review and meta-analysis of randomized controlled trials. Front Neurol. 2024;15:1357763. https://doi.org/10.3389/fneur.2024.1357763 .

Holmgren T, Hallgren HB, Oberg B, Adolfsson L, Johansson K. Effect of specific exercise strategy on need for surgery in patients with subacromial impingement syndrome: randomised controlled study. Br J Sports Med. 2014;48(19):1456–7. https://doi.org/10.1136/bjsports-2014-e787rep .

Lähdeoja T, Karjalainen T, Jokihaara J, Salamh P, Kavaja L, Agarwal A, et al. Subacromial decompression surgery for adults with shoulder pain: a systematic review with meta-analysis. Br J Sports Med. 2020;54(11):665–73. https://doi.org/10.1136/bjsports-2018-100486 .

Kukkonen J, Joukainen A, Lehtinen J, Mattila KT, Tuominen EK, Kauko T et al. Treatment of Nontraumatic Rotator Cuff Tears: A Randomized Controlled Trial with Two Years of Clinical and Imaging Follow-up published correction appears in J Bone Joint Surg Am. 2016;98(1):e1. J Bone Joint Surg Am 2015;97(21):1729–1737. https://doi.org/10.2106/JBJS.N.01051

Smith BE, Hendrick P, Smith TO, Bateman M, Moffatt F, Rathleff MS, et al. Should exercises be painful in the management of chronic musculoskeletal pain? A systematic review and meta-analysis. Br J Sports Med. 2017;51(23):1679–87. https://doi.org/10.1136/bjsports-2016-097383 .

Saltychev M, Äärimaa V, Virolainen P, Laimi K. Conservative treatment or surgery for shoulder impingement: systematic review and meta-analysis. Disabil Rehabil. 2015;37(1):1–8. https://doi.org/10.3109/09638288.2014.907364 .

Huang YC, Leong CP, Tso HH, Chen MJ, Liaw MY, Hsieh HC, et al. The long-term effects of hyaluronic acid on hemiplegic shoulder pain and injury in stroke patients: a randomized controlled study. Medicine. vol 2018;97(35):e12078. https://doi.org/10.1097/MD.0000000000012078 .

Dahan TH, Fortin L, Pelletier M, Petit M, Vadeboncoeur R, Suissa S. Double blind randomized clinical trial examining the efficacy of bupivacaine suprascapular nerve blocks in frozen shoulder. J Rheumatol. 2000;27(6):1464–9.

CAS   PubMed   Google Scholar  

Rezasoltani Z, Esmaily H, Dadarkhah A, Rousta M, Mohebbi R, Vashaei F. Low molecular-weight Hyaluronic Acid Versus Physiotherapy for the treatment of Supraspinatus Tendinopathy: a randomized comparative clinical trial. J Am Acad Orthop Surg. 2021;29(19):e979–92. https://doi.org/10.5435/JAAOS-D-20-01014 .

Liao CD, Xie GM, Tsauo JY, Chen HC, Liou TH. Efficacy of extracorporeal shock wave therapy for knee tendinopathies and other soft tissue disorders: a meta-analysis of randomized controlled trials. BMC Musculoskelet Disord. 2018;19(1):278. https://doi.org/10.1186/s12891-018-2204-6 .

Williams S, Whatman C, Hume PA, Sheerin K. Kinesio taping in treatment and prevention of sports injuries: a meta-analysis of the evidence for its effectiveness. Sports Med. 2012;42(2):153–64. https://doi.org/10.2165/11594960-000000000-00000 .

Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160. https://doi.org/10.1136/bmj.n160 .

White IR. Network meta-analysis. STATA J. 2015;15(4):951–85. https://doi.org/10.1177/1536867X1501500403 .

Chaimani A, Salanti G. Visualizing assumptions and results in network metaanalysis: the network graphs package. STATA J. 2015;15(4):905–50. https://doi.org/10.1177/1536867X1501500402 .

Shim SR, Kim SJ. Intervention meta-analysis: application and practice using R software. Epidemiol Health. 2019;41:e2019008. https://doi.org/10.4178/epih.e2019008 .

Higgins JP, Jackson D, Barrett JK, Lu G, Ades AE, White IR. Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res Synth Methods. 2012;3(2):98–110. https://doi.org/10.1002/jrsm.1044 .

Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS ONE. 2013;8(10):e76654. https://doi.org/10.1371/journal.pone.007665 .

Abdelshafi ME, Yosry M, Elmulla AF, Al-Shahawy EA, Adou Aly M, Eliewa EA. Relief of chronic shoulder pain: a comparative study of three approaches. Middle East J Anaesthesiol. 2011;21(1):83–92.

Hsieh LF, Hsu WC, Lin YJ, Chang HL, Chen CC, Huang V. Addition of intra-articular hyaluronate injection to physical therapy program produces no extra benefits in patients with adhesive capsulitis of the shoulder: a randomized controlled trial. Arch Phys Med Rehabil. 2012;93(6):957–64. https://doi.org/10.1016/j.apmr.2012.01.021 .

Maryam M, Zahra K, Adeleh B, Morteza Y. Comparison of corticosteroid injections, physiotherapy, and combination therapy in treatment of frozen shoulder. Pak J Med Sci. 2012;28(4):648–51.

Google Scholar  

Di Giacomo G, De Gasperis N. The role of hyaluronic acid in patients affected by glenohumeral osteoarthritis. J Biol Regul Homeost Agents. 2015;29(4):945–51.

Di Giacomo G, de Gasperis N. Hyaluronic Acid Intra-articular injections in patients affected by moderate to severe glenohumeral osteoarthritis: a prospective Randomized Study. Joints. 2017;5(3):138–42. https://doi.org/10.1055/s-0037-1605389 .

Duymaz T, Sindel D. Comparison of Radial extracorporeal shock Wave Therapy and Traditional Physiotherapy in Rotator Cuff Calcific Tendinitis Treatment. Arch Rheumatol. 2019;34(3):281–7. https://doi.org/10.5606/ArchRheumatol.2019.7081 .

de Oliveira FCL, Pairot de Fontenay B, Bouyer LJ, Desmeules F, Roy JS. Kinesiotaping for the Rehabilitation of Rotator Cuff-Related Shoulder Pain: a Randomized Clinical Trial. Sports Health. 2021;13(2):161–72. https://doi.org/10.1177/1941738120944254 .

Di Giacomo G, de Gasperis N. Glenohumeral osteoarthritis treatment with a single hyaluronic acid administration: clinical outcomes. J Biol Regul Homeost Agents. 2021;35(2):657–61. https://doi.org/10.23812/20-457-L .

Yehia RM, ElMeligie MM. Effectiveness of extracorporeal shockwave therapy for frozen shoulder in perimenopausal diabetic women. Biomed Hum Kinet. 2022;14(1):109–16. https://doi.org/10.2478/bhk-2022-0014 .

Mardani-Kivi M, Nabi BN, Mousavi MH, Shirangi A, Leili EK, Ghadim-Limudahi ZH. Role of suprascapular nerve block in idiopathic frozen shoulder treatment: a clinical trial survey. Clin Shoulder Elb. 2022;25(2):129–39. https://doi.org/10.5397/cise.2021.00661 .

ElGendy MH, Mazen MM, Saied AM, ElMeligie MM, Aneis Y. Extracorporeal shock Wave Therapy vs. Corticosteroid Local Injection in Shoulder Impingement Syndrome: A Three-Arm Randomized Controlled Trial. Am J Phys Med Rehabil. 2023;102(6):533–40. https://doi.org/10.1097/PHM.0000000000002158 .

Hsieh LF, Kuo YC, Huang YH, Liu YF, Hsieh TL. Comparison of corticosteroid injection, physiotherapy and combined treatment for patients with chronic subacromial bursitis - A randomised controlled trial. Clin Rehabil. 2023;37(9):1189–200. https://doi.org/10.1177/02692155231166220 .

Khalifa HA, Darwish MH, El-Tamawy MS, Elazizy HM, Abu Ella IA, Abo-Zaid NA, et al. The influence of radial extracorporeal shock wave therapy on shoulder pain and structural abnormalities in stroke patients. Arch Med Sci. 2022;19(6):1731–8. https://doi.org/10.5114/aoms/151477 .

Wu SY, Hsu PC, Tsai YY, Huang JR, Wang KA, Wang JC. Efficacy of combined ultrasound-guided hydrodilatation with hyaluronic acid and physical therapy in patients with adhesive capsulitis: a randomised controlled trial. Clin Rehabil. 2024;38(2):202–15. https://doi.org/10.1177/02692155231200089 .

Kamel SI, Rosas HG, Gorbachova T. Local and systemic side effects of Corticosteroid injections for Musculoskeletal indications. AJR Am J Roentgenol. 2024;222(3):e2330458. https://doi.org/10.2214/AJR.23.30458 .

Ogden JA, Alvarez RG, Levitt R, Marlow M. Shock wave therapy (Orthotripsy) in musculoskeletal disorders. Clin Orthop Relat Res. 2001;387:22–40. https://doi.org/10.1097/00003086-200106000-00005 .

Moya D, Ramón S, Schaden W, Wang CJ, Guiloff L, Cheng JH. The role of extracorporeal Shockwave Treatment in Musculoskeletal disorders. J Bone Joint Surg Am 2018(3);100:251–63. https://doi.org/10.2106/JBJS.17.00661

Chester R, Shepstone L, Daniell H, Sweeting D, Lewis J, Jerosch-Herold C. Predicting response to physiotherapy treatment for musculoskeletal shoulder pain: a systematic review. BMC Musculoskelet Disord. 2013;14:203. https://doi.org/10.1186/1471-2474-14-203 .

Struyf F, Meeus M. Current evidence on physical therapy in patients with adhesive capsulitis: what are we missing? Clin Rheumatol. 2014;33(5):593–600. https://doi.org/10.1007/s10067-013-2464-3 .

Bury J, Littlewood C. Rotator cuff disorders: a survey of current (2016) UK physiotherapy practice. Shoulder Elb. 2018;10(1):52–61. https://doi.org/10.1177/1758573217717103 .

Struyf F, De Hertogh W, Gulinck J, Nijs J. Evidence-based treatment methods for the management of shoulder impingement syndrome among dutch-speaking physiotherapists: an online, web-based survey. J Manipulative Physiol Ther. 2012;35(9):720–6. https://doi.org/10.1016/j.jmpt.2012.10.009 .

Mao HY, Hu MT, Yen YY, Lan SJ, Lee SD. Kinesio Taping relieves Pain and improves isokinetic not isometric muscle strength in patients with knee Osteoarthritis-A systematic review and Meta-analysis. Int J Environ Res Public Health. 2021;18(19):10440. https://doi.org/10.3390/ijerph181910440 .

Raeesi J, Negahban H, Kachooei AR, Moradi A, Ebrahimzadeh MH, Daghiani M. Comparing the effect of physiotherapy and physiotherapy plus corticosteroid injection on pain intensity, disability, quality of life, and treatment effectiveness in patients with Subacromial Pain Syndrome: a randomized controlled trial. Disabil Rehabil. 2023;45(25):4218–26. https://doi.org/10.1080/09638288.2022.2146215 .

Saggini R, Di Stefano A, Saggini A, Bellomo RG. CLINICAL APPLICATION OF SHOCK WAVE THERAPY IN MUSCULOSKELETAL DISORDERS: PART I. J Biol Regul Homeost Agents. 2015;29(3):533–45.

Simplicio CL, Purita J, Murrell W, Santos GS, Dos Santos RG, Lana JFSD. Extracorporeal shock wave therapy mechanisms in musculoskeletal regenerative medicine. J Clin Orthop Trauma. 2020;11:S309–18. https://doi.org/10.1016/j.jcot.2020.02.004 .

Shao H, Zhang S, Chen J, Wen A, Wu Z, Huang M, et al. Radial extracorporeal shockwave therapy reduces pain and promotes proximal tendon healing after rotator cuff repair: randomized clinical trial. Ann Phys Rehabil Med. 2023;66(4):101730. https://doi.org/10.1016/j.rehab.2023.101730 .

Martens G, Fontaine R, Goffin P, Raaf M, Tasset H, Lecoq JP, et al. Continuous suprascapular nerve blockade to potentiate intensive rehabilitation for refractory adhesive shoulder capsulitis: a cohort study. Int Orthop. 2024;48(2):495–503. https://doi.org/10.1007/s00264-023-05999-0 .

Parashar A, Goni V, Neradi D, Guled U, Rangasamy K, Batra YK. Comparing three modalities of treatment for frozen shoulder: a prospective, Double-Blinded, Randomized Control Trial. Indian J Orthop. 2020;55(2):449–56. https://doi.org/10.1007/s43465-020-00201-8 .

Hou Y, Wang Y, Sun X, Lou Y, Yu Y, Zhang T. Effectiveness of suprascapular nerve block in the treatment of Hemiplegic Shoulder Pain: a systematic review and Meta-analysis. Front Neurol. 2021;12:723664. https://doi.org/10.3389/fneur.2021.723664 .

Sun C, Ji X, Zhang X, Ma Q, Yu P, Cai X, et al. Suprascapular nerve block is a clinically attractive alternative to interscalene nerve block during arthroscopic shoulder surgery: a meta-analysis of randomized controlled trials. J Orthop Surg Res. 2021;16(1):376. https://doi.org/10.1186/s13018-021-02515-1 .

Shanahan EM, Ahern M, Smith M, Wetherall M, Bresnihan B, FitzGerald O. Suprascapular nerve block (using bupivacaine and methylprednisolone acetate) in chronic shoulder pain. Ann Rheum Dis. 2003;62(5):400–6. https://doi.org/10.1136/ard.62.5.400 .

Klç Z, Filiz MB, Çakr T, Toraman NF. Addition of suprascapular nerve block to a physical therapy program produces an Extra Benefit to Adhesive Capsulitis: a Randomized Controlled Trial. Am J Phys Med Rehabil. 2015;94:912–20. https://doi.org/10.1097/PHM.0000000000000336 .

Shanahan EM, Gill TK, Briggs E, Hill CL, Bain G, Morris T. Suprascapular nerve block for the treatment of adhesive capsulitis: a randomised double-blind placebo-controlled trial. RMD Open. 2022;8(2):e002648. https://doi.org/10.1136/rmdopen-2022-002648 .

Shanahan EM, Smith MD, Wetherall M, Lott CW, Slavotinek J, FitzGerald O, et al. Suprascapular nerve block in chronic shoulder pain: are the radiologists better? Ann Rheum Dis. 2004;63(9):1035–40. https://doi.org/10.1136/ard.2003.015909 .

Alvarez CM, Litchfield R, Jackowski D, Griffin S, Kirkley A. A prospective, double-blind, randomized clinical trial comparing subacromial injection of betamethasone and xylocaine to xylocaine alone in chronic rotator cuff tendinosis. Am J Sports Med. 2005;33(2):255–62. https://doi.org/10.1177/0363546504267345 .

Mohamadi A, Chan JJ, Claessen FM, Ring D, Chen NC. Corticosteroid injections give small and transient Pain Relief in Rotator Cuff Tendinosis: a Meta-analysis. Clin Orthop Relat Res. 2017;475(1):232–43. https://doi.org/10.1007/s11999-016-5002-1 .

Maund E, Craig D, Suekarran S, Neilson A, Wright K, Brealey S, et al. Management of frozen shoulder: a systematic review and cost-effectiveness analysis. Health Technol Assess. 2012;16(11):1–264. https://doi.org/10.3310/hta16110 .

Dean BJ, Franklin SL, Murphy RJ, Javaid MK, Carr AJ. Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator cuff tendon: a mechanism underpinning the ultimately deleterious effect of steroid injection in tendinopathy? Br J Sports Med. 2014;48(22):1620–6. https://doi.org/10.1136/bjsports-2013-093178 .

Liang J, Jiang D, Noble PW. Hyaluronan as a therapeutic target in human diseases. Adv Drug Deliv Rev. 2016;97:186–203. https://doi.org/10.1016/j.addr.2015.10.017 .

Kwon YW, Eisenberg G, Zuckerman JD. Sodium hyaluronate for the treatment of chronic shoulder pain associated with glenohumeral osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled trial. J Shoulder Elb Surg. 2013;22(5):584–94. https://doi.org/10.1016/j.jse.2012.10.040 .

Hsieh LF, Lin YJ, Hsu WC, Kuo YC, Liu YC, Chiang YP, et al. Comparison of the corticosteroid injection and hyaluronate in the treatment of chronic subacromial bursitis: a randomized controlled trial. Clin Rehabil. 2021;35(9):1305–16. https://doi.org/10.1177/02692155211007799 .

Blaine T, Moskowitz R, Udell J, Skyhar M, Levin R, et al. Treatment of persistent shoulder pain with sodium hyaluronate: a randomized, controlled trial. A multicenter study. J Bone Joint Surg Am. 2008;90(5):970–9. https://doi.org/10.2106/jbjs.f.01116 .

Jiménez I, Marcos-García A, Muratore-Moreno G, Romero-Pérez B, Álvarez-León EE, Medina J. [Subacromial sodium hyaluronate injection for the treatment of chronic shoulder pain: a prospective series of eighty patients]. Acta Ortop Mex. 2018;32(2):70–5.

Parreira Pdo C, Costa Lda C, Hespanhol LC Jr, Lopes AD, Costa LO. Current evidence does not support the use of Kinesio Taping in clinical practice: a systematic review. J Physiother. 2014;60(1):31–9. https://doi.org/10.1016/j.jphys.2013.12.008 .

Gianola S, Iannicelli V, Fascio E, Andreano A, Li LC, Valsecchi MG, et al. Kinesio taping for rotator cuff disease. Cochrane Database Syst Rev. 2021;8(8):CD012720. https://doi.org/10.1002/14651858.CD012720.pub2 .

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Acknowledgements

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The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Henan Province Science and Technology Research Project [grant number 242300420107], 2023 Henan Special Research Project of TCM on “Double First-Class” Construction [grant number HSRP-DFCTCM-2023-1-21], Henan Province Science and Technology Research Project [grant number 232102310466], and Campus-level project of Henan University of Chinese Medicine [grant number 2024JX62].

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Fangjie Yang and Xinmin Li contributed equally to this work.

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Rehabilitation Medicine College, Henan University of Chinese Medicine, Zhengzhou, Henan, China

Fangjie Yang, Jing Wang, Qian Gao, Mengyang Pan, Zhenfei Duan, Chunlin Ren, Pengxue Guo & Yasu Zhang

School of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan, China

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All authors contributed to the study conception. Yasu Zhang and Qian Gao designed the search strategies. Fangjie Yang and Mengyang Pan screened eligible studies. Xinmin Li and Jing Wang collected and summarized the data. Fangjie Yang, Zhenfei Duan, Chunlin Ren, and Pengxue Guo analyzed the data. Fangjie Yang and Xinmin Li wrote initial draft of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yasu Zhang .

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Ethical Approval and Consent to participate are not applicable. The study protocol was registered at PROSPERO (CRD 42024519473).

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Yang, F., Li, X., Wang, J. et al. Efficacy of different analgesic strategies combined with conventional physiotherapy program for treating chronic shoulder pain: a systematic review and network meta-analysis. J Orthop Surg Res 19 , 544 (2024). https://doi.org/10.1186/s13018-024-05037-8

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Published : 06 September 2024

DOI : https://doi.org/10.1186/s13018-024-05037-8

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Systemic steroids and bronchopulmonary dysplasia: a systematic review and meta-analysis

• Talkad S. Raghuveer   ORCID: orcid.org/0000-0001-6482-9684 1 ,
• Rosey E. Zackula   ORCID: orcid.org/0000-0003-2439-8714 2 ,
• Richa Lakhotia 1 , 3 &
• Stephanie A. Binder 1 , 3  

Journal of Perinatology ( 2024 ) Cite this article

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It is unclear if systemic steroids decrease the risk of Bronchopulmonary Dysplasia (BPD) while increasing the risk of neurodevelopmental impairment (NDI).

Conduct a systematic review of randomized controlled trials of systemic steroids to evaluate the risk of BPD, mortality, and NDI in premature infants ≤30 weeks.

Data sources

MEDLINE, EBSCOhost, Web of Science, Cochrane Library, Embase, and CINAHL.

Study selection

Randomized clinical trials of Dexamethasone (DEX) or Hydrocortisone (HC) to prevent BPD in premature infants ≤ 30 weeks.

Data extraction and synthesis

Data were extracted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Random-effects meta-analyses and multivariable meta-regression were conducted.

Main outcomes and measures

Primary outcomes were BPD, mortality, and NDI. Secondary outcomes were hypertension, hyperglycemia, sepsis, intestinal perforation, necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP). The a priori hypothesis was that steroids would reduce the risk of BPD without increasing NDI.

There were 6377 preterm infants in the 44 (32 DEX, 13 HC) selected studies. DEX significantly reduced the risk of BPD, RR = 0.66, (95% CI, 0.56–0.78). The most effective DEX regimen was medium cumulative dose (2 to 3 mg/kg), RR = 0.43 (95% CI, 0.29–0.65); day of initiation <8 days: RR = 0.68, (95% CI, 0.59–0.79); and treatment for ≥14 days: RR = 0.67 (95% CI, 0.55–0.80). HC did not significantly decrease the risk of BPD, RR = 0.98, (95% CI, 0.87–1.10). Neither DEX, (RR = 0.92, 95% CI, 0.78–1.09) nor HC (RR = 0.83, 95% CI, 0.68–1.01) decrease the risk of mortality. The risk of CP was not increased by either DEX (RR = 1.09, 95% CI, 0.55–2.17) or HC (RR = 1.18, 95% CI, 0.75–1.87). There were no significant differences between steroids and placebo for MDI/PDI scores. Multivariable meta-regression models showed that DEX significantly reduced the risk of BPD without increased risk of CP. DEX increased the risk of hypertension and hyperglycemia. Studies showed high heterogeneity, differing treatment regimen, missing data and different rates of follow-up.

Conclusion and relevance

DEX, but not HC, significantly decreased the risk of BPD. Neither steroid showed an increased risk of NDI or mortality.

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Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S. et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA. 2015;314:1039–51. https://doi.org/10.1001/jama.2015.10244 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Bell EF, Hintz SR, Hansen NI, Bann CM, Wyckoff MH, DeMauro SB, et al. Mortality, in-hospital morbidity, care practices, and 2-year outcomes for extremely preterm infants in the US, 2013-2018. JAMA. 2022;327:248–63. https://doi.org/10.1001/jama.2021.23580 .

Article   PubMed   Google Scholar  

Jensen EA, Edwards EM, Greenberg LT, Soll RF, Ehret DEY, Horbar JD. Severity of bronchopulmonary dysplasia among very preterm infants in the United States. Pediatrics. 2021;148. https://doi.org/10.1542/peds.2020-030007 .

Hwang JS, Rehan VK. Recent advances in bronchopulmonary dysplasia: pathophysiology, prevention, and treatment. Lung. 2018;196:129–38. https://doi.org/10.1007/s00408-018-0084-z .

Article   PubMed   PubMed Central   Google Scholar  

Levy PT, Dioneda B, Holland MR, Sekarski TJ, Lee CK, Mathur A, et al. Right ventricular function in preterm and term neonates: reference values for right ventricle areas and fractional area of change. J Am Soc Echocardiogr. 2015;28:559–69. https://doi.org/10.1016/j.echo.2015.01.024 .

Bui CB, Pang MA, Sehgal A, Theda C, Lao JC, Berger PJ, et al. Pulmonary hypertension associated with bronchopulmonary dysplasia in preterm infants. J Reprod Immunol. 2017;124:21–29. https://doi.org/10.1016/j.jri.2017.09.013 .

Donda K, Agyemang CO, Adjetey NA, Agyekum A, Princewill N, Ayensu M, et al. Tracheostomy trends in preterm infants with bronchopulmonary dysplasia in the United States: 2008-2017. Pediatr Pulmonol. 2021;56:1008–17. https://doi.org/10.1002/ppul.25273 .

Collaco JM, McGrath-Morrow SA. Respiratory phenotypes for preterm infants, children, and adults: bronchopulmonary dysplasia and more. Ann Am Thorac Soc. 2018;15:530–8. https://doi.org/10.1513/AnnalsATS.201709-756FR .

Manimtim WM, Agarwal A, Alexiou S, Levin JC, Aoyama B, Austin ED, et al. Respiratory outcomes for ventilator-dependent children with bronchopulmonary dysplasia. Pediatrics. 2023;151. https://doi.org/10.1542/peds.2022-060651 .

Cheong JLY, Doyle LW. An update on pulmonary and neurodevelopmental outcomes of bronchopulmonary dysplasia. Semin Perinatol. 2018;42:478–84. https://doi.org/10.1053/j.semperi.2018.09.013 .

Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitefield MF. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA. 2003;289:1124–9. https://doi.org/10.1001/jama.289.9.1124 .

Sriram S, Schreiber MD, Msall ME, Kuban KCK, Joseph RM, O’Shea TM, et al. Cognitive development and quality of life associated with BPD in 10-year-olds born preterm. Pediatrics. 2018;141:e20172719. https://doi.org/10.1542/peds.2017-2719 .

Doyle LW, Ranganathan S, Mainzer RM, Cheong JLY. Victorian infant collaborative study G. Relationships of severity of bronchopulmonary dysplasia with adverse neurodevelopmental outcomes and poor respiratory function at 7-8 years of age. J Pediatr. 2024;269:114005. https://doi.org/10.1016/j.jpeds.2024.114005 .

Jensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, et al. The diagnosis of bronchopulmonary dysplasia in very preterm infants. an evidence-based approach. Am J Respir Crit Care Med. 2019;200:751–9. https://doi.org/10.1164/rccm.201812-2348OC .

Mammel MC, Green TP, Johnson DE, Thompson TR. Controlled trial of dexamethasone therapy in infants with bronchopulmonary dysplasia. Lancet. 1983;1:1356–8. https://doi.org/10.1016/s0140-6736(83)92139-6 .

Article   CAS   PubMed   Google Scholar  

American Academy of Pediatrics. Committee on fetus and newborn. Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants. Pediatrics. 2002;109:330–8. https://doi.org/10.1542/peds.109.2.330 .

Article   Google Scholar  

Walsh MC, Yao Q, Horbar JD, Carpenter JH, Lee SK, Ohlsson A. Changes in the use of postnatal steroids for bronchopulmonary dysplasia in 3 large neonatal networks. Pediatrics. 2006;118:e1328–35. https://doi.org/10.1542/peds.2006-0359 .

Yoder BA, Harrison M, Clark RH. Time-related changes in steroid use and bronchopulmonary dysplasia in preterm infants. Pediatrics. 2009;124:673–9. https://doi.org/10.1542/peds.2008-2793 .

Abiramalatha T, Ramaswamy VV, Bandyopadhyay T, Somanath SH, Shaik NB, Pullattayil AK, et al. Interventions to prevent bronchopulmonary dysplasia in preterm neonates: an umbrella review of systematic reviews and meta-analyses. JAMA Pediatr. 2022;176:502–16. https://doi.org/10.1001/jamapediatrics.2021.6619 .

Ramaswamy VV, Bandyopadhyay T, Nanda D, Bandiya P, Ahmed J, Garg A, et al. Assessment of postnatal corticosteroids for the prevention of bronchopulmonary dysplasia in preterm neonates: a systematic review and network meta-analysis. JAMA Pediatr. 2021;175:e206826. https://doi.org/10.1001/jamapediatrics.2020.6826 .

Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB. Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized, controlled trial. Pediatrics. 2006;117:75–83. https://doi.org/10.1542/peds.2004-2843 .

Job S, Clarke P. Current UK practices in steroid treatment of chronic lung disease. Arch Dis Child Fetal Neonatal Ed. 2015;100:F371. https://doi.org/10.1136/archdischild-2014-308060 .

Cummings JJ, Pramanik AK. Postnatal corticosteroids to prevent or treat chronic lung disease following preterm birth. Pediatrics. 2022;149:e2022057530. https://doi.org/10.1542/peds.2022-057530 .

Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160. https://doi.org/10.1136/bmj.n160 .

Onland W, Cools F, Kroon A, Ramful D, El Moussawi F, Nicaise C, et al. Effect of hydrocortisone therapy initiated 7 to 14 days after birth on mortality or bronchopulmonary dysplasia among very preterm infants receiving mechanical ventilation: a randomized clinical trial. JAMA. 2019;321:354–363. https://doi.org/10.1001/jama.2018.21443 .

Doyle LW, Cheong JL, Ehrenkranz RA, Halliday HL. Late (>7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev. 2017;10:CD001145. https://doi.org/10.1002/14651858.CD001145.pub4 .

Baud O, Biran V, Trousson C, Leroy E, Mohamed D, Alberti C. Two-year outcomes after prophylactic hydrocortisone in extremely preterm neonates. EAPS Congress 2016. Eur J Pediatr. 2016;175:1393–880. https://doi.org/10.1007/s00431-016-2785-8 .

Clauss C, Thomas S, Khodak I, Tack V, Akerman M, Hanna N, et al. Hydrocortisone and bronchopulmonary dysplasia: variables associated with response in premature infants. J Perinatol. 2020;40:1349–57. https://doi.org/10.1038/s41372-020-0680-7 .

Htun ZT, Schulz EV, Desai RK, Marasch JL, McPherson CC, Mastrandrea LD. et al. Postnatal steroid management in preterm infants with evolving bronchopulmonary dysplasia. J Perinatol. 2021;41:1783–96. https://doi.org/10.1038/s41372-021-01083-w .

Sterne J, Savović J, Page M, Elbers R, Blencowe N, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:14898. https://doi.org/10.1136/bmj.14898 .

GRADEpro Guideline Development Tool [Software]. McMaster University and Evidence Prime, 2022. Available from gradepro.org. 2022.

Viechtbauer W. Conducting meta-analyses in R with metafor package. J Stat Softw. 2010;36:1–48.

Harrer M, Cuijpers P, Furukawa TA, Ebert DD. Doing meta-analysis with R: a hands-on guide. 1st ed. Chapman & Hall/CRC Press; 2021.

Borenstein M, Hedges LV, Higgins JP, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1:97–111. https://doi.org/10.1002/jrsm.12 .

Christiansen S, Iverson C, Flanagin A, Livingston EH, Fishcer L, Manno C, et al. AMA manual of style: A guide for authors and editors. American Medical Association manual of style. 11th edition. New York, NY: Oxford University Press; 2020.

Doyle LW, Cheong JL, Hay S, Manley BJ, Halliday HL. Early (< 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev. 2021;10:Cd001146. https://doi.org/10.1002/14651858.CD001146.pub6 .

Doyle LW, Cheong JL, Hay S, Manley BJ, Halliday HL. Late (≥ 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev. 2021;11:Cd001145. https://doi.org/10.1002/14651858.CD001145.pub5 .

Zeng LN, Tian JH, Song FJ, Li WR, Jiang LC, Gui G, et al. Corticosteroids for the prevention of bronchopulmonary dysplasia in preterm infants: a network meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2018;103:F506–11. https://doi.org/10.1136/archdischild-2017-313759 .

Hay S, Ovelman C, Zupancic JA, Doyle LW, Onland W, Konstantinidis M, et al. Systemic corticosteroids for the prevention of bronchopulmonary dysplasia, a network meta-analysis. Cochrane Database Syst Rev. 2023;8:CD013730. https://doi.org/10.1002/14651858.CD013730.pub2 .

van de Loo M, van Kaam A, Offringa M, Doyle LW, Cooper C, Onland W. Corticosteroids for the prevention and treatment of bronchopulmonary dysplasia: an overview of systemic reviews. Cochrane Database Syst Rev. 2024:CD013271. https://doi.org/10.1002/14651858.CD013271.pub2 .

Onland W, Offringa M, Jaegere APD, Van Kaam AH. Finding the optimal postnatal dexamethasone regimen for preterm infants at risk of bronchopulmonary dysplasia: a systematic review of placebo-controlled trials. Pediatrics. 2009;123:367–77. https://doi.org/10.1542/peds.2008-0016 .

Doyle LW, Halliday HL, Ehrenkranz RA, Davis PG, Sinclair JC. An update on the impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: effect modification by risk of bronchopulmonary dysplasia. J Pediatr. 2014;165:1258–60. https://doi.org/10.1016/j.jpeds.2014.07.049 .

Greenberg RG, McDonald SA, Laughon MM, Tanaka D, Jensen E, Van Meurs K, et al. Online clinical tool to estimate risk of bronchopulmonary dysplasia in extremely preterm infants. Arch Dis Child Fetal Neonatal Ed. 2022. https://doi.org/10.1136/archdischild-2021-323573 .

Shimotsuma T, Tomotaki S, Akita M, Araki R, Tomotaki H, Iwanaga K, et al. Severe Bronchopulmonary Dysplasia adversely affects brain growth in preterm infants. Neonatology. 2024. https://doi.org/10.1159/000538527 .

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Acknowledgements

The authors thank the contributions of Hayrettin Okut, PhD, who advised us on statistical aspects of model development, including programming in R.

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Talkad S. Raghuveer, Richa Lakhotia & Stephanie A. Binder

Office of Research, University of Kansas School of Medicine—Wichita, Wichita, KS, USA

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TSR: conceptualized, formulated the research methodology, wrote the original draft, reviewed and edited the manuscript, supervised/administered the whole project and guarantor for the project. REZ: conceptualized, formulated the research methodology, performed formal analysis, curated data and wrote the original draft, reviewed and edited the manuscript. RL: conceptualized, formulated the research methodology, wrote the original draft, reviewed and edited the manuscript. SAB: conceptualized, formulated the research methodology, wrote the original draft, reviewed and edited the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Talkad S. Raghuveer .

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TSR, REZ, RL, and SAB have no relevant conflicts to disclose. This study was not supported by funding from any source.

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Raghuveer, T.S., Zackula, R.E., Lakhotia, R. et al. Systemic steroids and bronchopulmonary dysplasia: a systematic review and meta-analysis. J Perinatol (2024). https://doi.org/10.1038/s41372-024-02097-w

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Accepted : 16 August 2024

Published : 02 September 2024

DOI : https://doi.org/10.1038/s41372-024-02097-w

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