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Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline

Linked opinion.

Grasping the nettle of narrative synthesis

• Related content
• Peer review
• Joanne E McKenzie , associate professor 2 ,
• Amanda Sowden , professor 3 ,
• Srinivasa Vittal Katikireddi , clinical senior research fellow 1 ,
• Sue E Brennan , research fellow 2 ,
• Simon Ellis , associate director 4 ,
• Jamie Hartmann-Boyce , senior researcher 5 ,
• Rebecca Ryan , senior esearch fellow 6 ,
• Sasha Shepperd , professor 7 ,
• James Thomas , professor 8 ,
• Vivian Welch , associate professor 9 ,
• Hilary Thomson , senior research fellow 1
• 1 MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, UK
• 2 School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
• 3 Centre for Reviews and Dissemination, University of York, York, UK
• 4 Centre for Guidelines, National Institute for Health and Care Excellence, London, UK
• 5 Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
• 6 School of Psychology and Public Health, La Trobe University, Melbourne, Australia
• 7 Nuffield Department of Population Health, University of Oxford, Oxford, UK
• 8 Evidence for Policy and Practice Information and Coordinating Centre, University College London, London, UK
• 9 Bruyere Research Institute, Ottawa, Canada
• Correspondence to: M Campbell Mhairi.Campbell{at}glasgow.ac.uk
• Accepted 8 October 2019

In systematic reviews that lack data amenable to meta-analysis, alternative synthesis methods are commonly used, but these methods are rarely reported. This lack of transparency in the methods can cast doubt on the validity of the review findings. The Synthesis Without Meta-analysis (SWiM) guideline has been developed to guide clear reporting in reviews of interventions in which alternative synthesis methods to meta-analysis of effect estimates are used. This article describes the development of the SWiM guideline for the synthesis of quantitative data of intervention effects and presents the nine SWiM reporting items with accompanying explanations and examples.

Summary points

Systematic reviews of health related interventions often use alternative methods of synthesis to meta-analysis of effect estimates, methods often described as “narrative synthesis”

Serious shortcomings in reviews that use “narrative synthesis” have been identified, including a lack of description of the methods used; unclear links between the included data, the synthesis, and the conclusions; and inadequate reporting of the limitations of the synthesis

The Synthesis Without Meta-analysis (SWiM) guideline is a nine item checklist to promote transparent reporting for reviews of interventions that use alternative synthesis methods

The SWiM items prompt users to report how studies are grouped, the standardised metric used for the synthesis, the synthesis method, how data are presented, a summary of the synthesis findings, and limitations of the synthesis

The SWiM guideline has been developed using a best practice approach, involving extensive consultation and formal consensus

Decision makers consider systematic reviews to be an essential source of evidence. 1 Complete and transparent reporting of the methods and results of reviews allows users to assess the validity of review findings. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA; http://www.prisma-statement.org/ ) statement, consisting of a 27 item checklist, was developed to facilitate improved reporting of systematic reviews. 2 Extensions are available for different approaches to conducting reviews (for example, scoping reviews 3 ), reviews with a particular focus (for example, harms 4 ), and reviews that use specific methods (for example, network meta-analysis. 5 ) However, PRISMA provides limited guidance on reporting certain aspects of the review, such as the methods for presentation and synthesis, and no reporting guideline exists for synthesis without meta-analysis of effect estimates. We estimate that 32% of health related systematic reviews of interventions do not do meta-analysis, 6 7 8 instead using alternative approaches to synthesis that typically rely on textual description of effects and are often referred to as narrative synthesis. 9 Recent work highlights serious shortcomings in the reporting of narrative synthesis, including a lack of description of the methods used, lack of transparent links between study level data and the text reporting the synthesis and its conclusions, and inadequate reporting of the limitations of the synthesis. 7 This suggests widespread lack of familiarity and misunderstanding around the requirements for transparent reporting of synthesis when meta-analysis is not used and indicates the need for a reporting guideline.

Scope of SWiM reporting guideline

This paper presents the Synthesis Without Meta-analysis (SWiM) reporting guideline. The SWiM guideline is intended for use in systematic reviews examining the quantitative effects of interventions for which meta-analysis of effect estimates is not possible, or not appropriate, for a least some outcomes. 10 Such situations may arise when effect estimates are incompletely reported or because characteristics of studies (such as study designs, intervention types, or outcomes) are too diverse to yield a meaningful summary estimate of effect. 11 In these reviews, alternative presentation and synthesis methods may be adopted, (for example, calculating summary statistics of intervention effect estimates, vote counting based on direction of effect, and combining P values), and SWiM provides guidance for reporting these methods and results. 11 Specifically, the SWiM guideline expands guidance on “synthesis of results” items currently available, such as PRISMA (items 14 and 21) and RAMESES (items 11, 14, and 15). 2 12 13 SWiM covers reporting of the key features of synthesis including how studies are grouped, synthesis methods used, presentation of data and summary text, and limitations of the synthesis.

SWiM is not intended for use in reviews that synthesise qualitative data, for which reporting guidelines are already available, including ENTREQ for qualitative evidence synthesis and eMERGe for meta-ethnography. 14 15

Development of SWiM reporting guideline

A protocol for the project is available, 10 and the guideline development was registered with the EQUATOR Network, after confirmation that no similar guideline was in development. All of the SWiM project team are experienced systematic reviewers, and one was a co-author on guidance on the conduct of narrative synthesis (AS). 9 A project advisory group was convened to provide greater diversity in expertise. The project advisory group included representatives from collaborating Cochrane review groups, the Campbell Collaboration, and the UK National Institute for Health and Care Excellence (see supplementary file 1).

The project was informed by recommendations for developing guidelines for reporting of health research. 16 We assessed current practice in reporting synthesis of effect estimates without meta-analysis and used the findings to devise an initial checklist of reporting items in consultation with the project advisory group. We invited 91 people, all systematic review methodologists or authors of reviews that synthesised results from studies without using meta-analysis, to participate in a three round Delphi exercise, with a response rate of 48% (n=44/91) in round one, 54% (n=37/68) in round two, and 82% (n=32/39) in round three. The results were discussed at a consensus meeting of an expert panel (the project advisory group plus one additional methodological expert) (see supplementary file 1). After the meeting, we piloted the revised guideline to assess ease of use and face validity. Eight systematic reviewers with varying levels of experience, who had not been involved in the Delphi exercise, were asked to read and apply the guideline. We conducted short interviews with the pilot participants to identify any clarification needed in the items or their explanations. We subsequently revised the items and circulated them for comment among the expert panel, before finalising them. Full methodological details of the SWiM guideline development process are provided in supplementary file 1.

Synthesis without meta-analysis reporting items

We identified nine items to guide the reporting of synthesis without meta-analysis. Table 1 shows these SWiM reporting items. An online version is available at www.equator-network.org/reporting-guidelines . An explanation and elaboration for each of the reporting items is provided below. Examples to illustrate the reporting items and explanations are provided in supplementary file 2.

Synthesis Without Meta-analysis (SWiM) items: SWiM is intended to complement and be used as an extension to PRISMA

• View inline

Item 1: grouping studies for synthesis

1a) description.

Provide a description of, and rationale for, the groups used in the synthesis (for example, groupings of interventions, population, outcomes, study design).

1a) Explanation

Methodological and clinical or conceptual diversity may occur (for example, owing to inclusion of diverse study designs, outcomes, interventions, contexts, populations), and it is necessary to clearly report how these study characteristics are grouped for the synthesis, along with the rationale for the groups (see Cochrane Handbook Chapter 3 17 ). Although reporting the grouping of study characteristics in all reviews is important, it is particularly important in reviews without meta-analysis, as the groupings may be less evident than when meta-analysis is used.

Providing the rationale, or theory of change, for how the intervention is expected to work and affect the outcome(s) will inform authors’ and review users’ decisions about the appropriateness and usefulness of the groupings. A diagram, or logic model, 18 19 can be used to visually articulate the underlying theory of change used in the review. If the theory of change for the intervention is provided in full elsewhere (for example, in the protocol), this should be referenced. In Cochrane reviews, the rationale for the groups can be outlined in the section “How the intervention is expected to work.”

1b) Description

Detail and provide rationale for any changes made subsequent to the protocol in the groups used in the synthesis.

1b) Explanation

Decisions about the planned groups for the syntheses may need to be changed following study selection and data extraction. This may occur as a result of important variations in the population, intervention, comparison, and/or outcomes identified after the data are collected, or where limited data are available for the pre-specified groupings, and the groupings may need to be modified to facilitate synthesis (Cochrane Handbook Chapter 2 20 ). Reporting changes to the planned groups, and the reason(s) for these, is important for transparency, as this allows readers to assess whether the changes may have been influenced by study findings. Furthermore, grouping at a broader level of (any or multiple) intervention, population, or outcome will have implications for the interpretation of the synthesis findings (see item 8).

Item 2: describe the standardised metric and transformation method used

Description.

Describe the standardised metric for each outcome. Explain why the metric(s) was chosen, and describe any methods used to transform the intervention effects, as reported in the study, to the standardised metric, citing any methodological guidance used.

Explanation

The term “standardised metric” refers to the metric that is used to present intervention effects across the studies for the purpose of synthesis or interpretation, or both. Examples of standardised metrics include measures of intervention effect (for example, risk ratios, odds ratios, risk differences, mean differences, standardised mean differences, ratio of means), direction of effect, or P values. An example of a statistical method to convert an odds ratio to a standardised mean difference is that proposed by Chinn (2000). 21 For other methods and metrics, see Cochrane Handbook Chapter 6. 22

Item 3: describe the synthesis methods

Describe and justify the methods used to synthesise the effects for each outcome when it was not possible to undertake a meta-analysis of effect estimates.

For various reasons, it may not be possible to do a meta-analysis of effect estimates. In these circumstances, other synthesis methods need to be considered and specified. Examples include combining P values, calculating summary statistics of intervention effect estimates (for example, median, interquartile range) or vote counting based on direction of effect. See table 2 for a summary of possible synthesis methods (for further details, see McKenzie and Brennan 2019 11 ). Justification should be provided for the chosen synthesis method.

Questions answered according to types of synthesis methods and types of data used

Item 4: criteria used to prioritise results for summary and synthesis

Where applicable, provide the criteria used, with supporting justification, to select particular studies, or a particular study, for the main synthesis or to draw conclusions from the synthesis (for example, based on study design, risk of bias assessments, directness in relation to the review question).

Criteria may be used to prioritise the reporting of some study findings over others or to restrict the synthesis to a subset of studies. Examples of criteria include the type of study design (for example, only randomised trials), risk of bias assessment (for example, only studies at a low risk of bias), sample size, the relevance of the evidence (outcome, population/context, or intervention) pertaining to the review question, or the certainty of the evidence. Pre-specification of these criteria provides transparency as to why certain studies are prioritised and limits the risk of selective reporting of study findings.

Item 5: investigation of heterogeneity in reported effects

State the method(s) used to examine heterogeneity in reported effects when it is not possible to do a meta-analysis of effect estimates and its extensions to investigate heterogeneity.

Informal methods to investigate heterogeneity in the findings may be considered when a formal statistical investigation using methods such as subgroup analysis and meta-regression is not possible. Informal methods could involve ordering tables or structuring figures by hypothesised modifiers such as methodological characteristics (for example, study design), subpopulations (for example, sex, age), intervention components, and/or contextual/setting factors (see Cochrane Handbook Chapter 12 11 ). The methods used and justification for the chosen methods should be reported. Investigations of heterogeneity should be limited, as they are rarely definitive; this is more likely to be the case when informal methods are used. It should also be noted if the investigation of heterogeneity was not pre-specified.

Item 6: certainty of evidence

Describe the methods used to assess the certainty of the synthesis findings.

The assessment of the certainty of the evidence should aim to take into consideration the precision of the synthesis finding (confidence interval if available), the number of studies and participants, the consistency of effects across studies, the risk of bias of the studies, how directly the included studies address the planned question (directness), and the risk of publication bias. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) is the most widely used framework for assessing certainty (Cochrane Handbook Chapter 14 23 ). However, depending on the synthesis method used, assessing some domains (for example, consistency of effects when vote counting is undertaken) may be difficult.

Item 7: data presentation methods

Describe the graphical and tabular methods used to present the effects (for example, tables, forest plots, harvest plots).

Specify key study characteristics (for example, study design, risk of bias) used to order the studies, in the text and any tables or graphs, clearly referencing the studies included

Study findings presented in tables or graphs should be ordered in the same way as the syntheses are reported in the narrative text to facilitate the comparison of findings from each included study. Key characteristics, such as study design, sample size, and risk of bias, which may affect interpretation of the data, should also be presented. Examples of visual displays include forest plots, 24 harvest plots, 25 effect direction plots, 26 albatross plots, 27 bubble plots, 28 and box and whisker plots. 29 McKenzie and Brennan (2019) provide a description of these plots, when they should be used, and their pros and cons. 11

Item 8: reporting results

For each comparison and outcome, provide a description of the synthesised findings and the certainty of the findings. Describe the result in language that is consistent with the question the synthesis addresses and indicate which studies contribute to the synthesis.

For each comparison and outcome, a description of the synthesis findings should be provided, making clear which studies contribute to each synthesis (for example, listing in the text or tabulated). In describing these findings, authors should be clear about the nature of the question(s) addressed (see table 2 , column 1), the metric and synthesis method used, the number of studies and participants, and the key characteristics of the included studies (population/settings, interventions, outcomes). When possible, the synthesis finding should be accompanied by a confidence interval.An assessment of the certainty of the effect should be reported.

Results of any investigation of heterogeneity should be described, noting if it was not pre-planned and avoiding over-interpretation of the findings.

If a pre-specified logic model was used, authors may report any changes made to the logic model during the review or as a result of the review findings. 30

Item 9: limitations of the synthesis

Report the limitations of the synthesis methods used and/or the groupings used in the synthesis and how these affect the conclusions that can be drawn in relation to the original review question.

When reporting limitations of the synthesis, factors to consider are the standardised metric(s) used, the synthesis method used, and any reconfiguration of the groups used to structure the synthesis (comparison, intervention, population, outcome).

The choice of metric and synthesis method will affect the question addressed (see table 2 ). For example, if the standardised metric is direction of effect, and vote counting is used, the question will ask “is there any evidence of an effect?” rather than “what is the average intervention effect?” had a random effects meta-analysis been used.

Limitations of the synthesis might arise from post-protocol changes in how the synthesis was structured and the synthesis method selected. These changes may occur because of limited evidence, or incompletely reported outcome or effect estimates, or if different effect measures are used across the included studies. These limitations may affect the ability of the synthesis to answer the planned review question—for example, when a meta-analysis of effect estimates was planned but was not possible.

The SWiM reporting guideline is intended to facilitate transparent reporting of the synthesis of effect estimates when meta-analysis is not used. The guideline relates specifically to transparently reporting synthesis and presentation methods and results, and it is likely to be of greatest relevance to reviews that incorporate diverse sources of data that are not amenable to meta-analysis. The SWiM guideline should be used in conjunction with other reporting guidelines that cover other aspects of the conduct of reviews, such as PRISMA. 31 We intend SWiM to be a resource for authors of reviews and to support journal editors and readers in assessing the conduct of a review and the validity of its findings.

The SWiM reporting items are intended to cover aspects of presentation and synthesis of study findings that are often left unreported when methods other than meta-analysis have been used. 7 These include reporting of the synthesis structure and comparison groupings (items 1, 4, 5, and 6), the standardised metric used for the synthesis (item 2), the synthesis method (items 3 and 9), presentation of data (item 7), and a summary of the synthesis findings that is clearly linked to supporting data (item 8). Although the SWiM items have been developed specifically for the many reviews that do not include meta-analysis, SWiM promotes the core principles needed for transparent reporting of all synthesis methods including meta-analysis. Therefore, the SWiM items are relevant when reporting synthesis of quantitative effect data regardless of the method used.

Reporting guidelines are sometimes interpreted as providing guidance on conduct or used to assess the quality of a study or review; this is not an appropriate application of a reporting guideline, and SWiM should not be used to guide the conduct of the synthesis. For guidance on how to conduct synthesis using the methods referred to in SWiM, we direct readers to the second edition of the Cochrane Handbook for Systematic Reviews of Interventions, specifically chapter 12. 11 Although an overlap inevitably exists between reporting and conduct, the SWiM reporting guideline is not intended to be prescriptive about choice of methods, and the level of detail for each item should be appropriate. For example, investigation of heterogeneity (item 5) may not always be necessary or useful. In relation to SWiM, we anticipate that the forthcoming update of PRISMA will include new items covering a broader range of synthesis methods, 32 but it will not provide detailed guidance and examples on synthesis without meta-analysis.

The SWiM reporting guideline emerged from a project aiming to improve the transparency and conduct of narrative synthesis (ICONS-Quant: Improving the CONduct and reporting of Narrative Synthesis). 10 Avoidance of the term “narrative synthesis” in SWiM is a deliberate move to promote clarity in the methods used in reviews in which the synthesis does not rely on meta-analysis. The use of narrative is ubiquitous across all research and can serve a valuable purpose in the development of a coherent story from diverse data. 33 34 However, within the field of evidence synthesis, narrative approaches to synthesis of quantitative effect estimates are characterised by a lack of transparency, making assessment of the validity of their findings difficult. 7 Together with the recently published guidance on conduct of alternative methods of synthesis, 11 the SWiM guideline aims to improve the transparency of, and subsequently trust in, the many reviews that synthesise quantitative data without meta-analysis, particularly for reviews of intervention effects.

Acknowledgments

We thank the participants of the Delphi survey and colleagues who informally piloted the guideline.

Contributors: All authors contributed to the development of SWiM. HT had the idea for the study. HT, SVK, AS, JEM, and MC designed the study methods. JT, JHB, RR, SB, SE, SS, and VW contributed to the consensus meeting and finalising the guideline items. MC prepared the first draft of the manuscript, and all authors critically reviewed and approved the final manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. HT is the guarantor.

Project advisory group members: Simon Ellis, Jamie Hartmann-Boyce, Mark Petticrew, Rebecca Ryan, Sasha Shepperd, James Thomas, Vivian Welch.

Expert panel members: Sue Brennan, Simon Ellis, Jamie Hartmann-Boyce, Rebecca Ryan, Sasha Shepperd, James Thomas, Vivian Welch.

Funding: This project was supported by funds provided by the Cochrane Methods Innovation Fund. MC, HT, and SVK receive funding from the UK Medical Research Council (MC_UU_12017-13 and MC_UU_12017-15) and the Scottish Government Chief Scientist Office (SPHSU13 and SPHSU15). SVK is supported by an NHS Research Scotland senior clinical fellowship (SCAF/15/02). JEM is supported by an NHMRC career development fellowship (1143429). RR’s position is funded by the NHMRC Cochrane Collaboration Funding Program (2017-2010). The views expressed in this article are those of the authors and not necessarily those of their employer/host organisations or of Cochrane or its registered entities, committees, or working groups.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: funding for the project as described above; HT is co-ordinating editor for Cochrane Public Health; SVK, SE, JHB, RR, and SS are Cochrane editors; JEM is co-convenor of the Cochrane Statistical Methods Group; JT is a senior editor of the second edition of the Cochrane Handbook; VW is editor in chief of the Campbell Collaboration and an associate scientific editor of the second edition of the Cochrane Handbook; SB is a research fellow at Cochrane Australia; no other relationships or activities that could appear to have influenced the submitted work.

Ethical approval: Ethical approval was obtained from the University of Glasgow College of Social Sciences Ethics Committee (reference number 400170060).

Transparency: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Patient and public involvement: This research was done without patient involvement. Patients were not invited to comment on the study design and were not consulted to develop outcomes or interpret the results.

Dissemination to participants and related patient and public communities: The authors plan to disseminate the research through peer reviewed publications, national and international conferences, webinars, and an online training module and by establishing an email discussion group.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/ .

• Donnelly CA ,
• Campbell P ,
• Liberati A ,
• Altman DG ,
• Tetzlaff J ,
• Tricco AC ,
• Zorzela L ,
• Ioannidis JP ,
• PRISMAHarms Group
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• Caldwell DM ,
• Shamseer L ,
• Campbell M ,
• Katikireddi SV ,
• Katikireddi S ,
• Roberts H ,
• Higgins J ,
• Chandler J ,
• McKenzie J ,
• Greenhalgh T ,
• Westhorp G ,
• Buckingham J ,
• Flemming K ,
• McInnes E ,
• France EF ,
• Cunningham M ,
• Schulz KF ,
• Higgins JPT ,
• McKenzie JE ,
• Brennan SE ,
• Anderson LM ,
• Petticrew M ,
• Rehfuess E ,
• Schünemann HJ ,
• Ogilvie D ,
• Thomson HJ ,
• Harrison S ,
• Martin RM ,
• Higgins JPT
• Schriger DL ,
• Schroter S ,
• Rehfuess EA ,
• Brereton L ,
• PRISMA Group
• ↵ Page M, McKenzie J, Bossuyt P, et al. Updating the PRISMA reporting guideline for systematic reviews and meta-analyses: study protocol. 2018. https://osf.io/xfg5n .
• Melendez-Torres GJ ,
• O’Mara-Eves A ,
• Petticrew M

Which review is that? A guide to review types

• Which review is that?
• Review Comparison Chart
• Decision Tool
• Critical Review
• Integrative Review
• Narrative Review
• State of the Art Review
• Narrative Summary
• Systematic Review
• Meta-analysis
• Comparative Effectiveness Review
• Diagnostic Systematic Review
• Network Meta-analysis
• Prognostic Review
• Psychometric Review
• Review of Economic Evaluations
• Systematic Review of Epidemiology Studies
• Living Systematic Reviews
• Umbrella Review
• Review of Reviews
• Rapid Review
• Rapid Evidence Assessment
• Rapid Realist Review
• Qualitative Evidence Synthesis
• Qualitative Interpretive Meta-synthesis
• Qualitative Meta-synthesis
• Qualitative Research Synthesis
• Framework Synthesis - Best-fit Framework Synthesis
• Meta-aggregation
• Meta-ethnography
• Meta-interpretation
• Meta-narrative Review
• Meta-summary
• Thematic Synthesis
• Mixed Methods Synthesis

Narrative Synthesis

• Bayesian Meta-analysis
• EPPI-Centre Review
• Critical Interpretive Synthesis
• Realist Synthesis - Realist Review
• Scoping Review
• Mapping Review
• Systematised Review
• Concept Synthesis
• Expert Opinion - Policy Review
• Technology Assessment Review
• Methodological Review
• Systematic Search and Review

Narrative’ synthesis’ refers to an approach to the systematic review and synthesis of findings from multiple studies that relies primarily on the use of words and text to summarise and explain the findings of the synthesis. Whilst narrative synthesis can involve the manipulation of statistical data, the defining characteristic is that it adopts a textual approach to the process of synthesis to ‘tell the story’ of the findings from the included studies. As used here ‘narrative synthesis’ refers to a process of synthesis that can be used in systematic reviews focusing on a wide range of questions, not only those relating to the effectiveness of a particular intervention. (Popay et al. 2006)

Further Reading/Resources

Guidelines Campbell, M., McKenzie, J. E., Sowden, A., Katikireddi, S. V., Brennan, S. E., Ellis, S., ... & Thomson, H. (2020). Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. bmj , 368 . Full Text Other

Popay, J., Roberts, H., Sowden, A., Petticrew, M., Arai, L., Rodgers, M., ... & Duffy, S. (2006). Guidance on the conduct of narrative synthesis in systematic reviews.  A product from the ESRC methods programme Version ,  1 (1), b92. Full Text

Thomson H, Campbell M. “Narrative synthesis” of quantitative effect data in Cochrane reviews: Current issues and ways forward [Internet]. Cochrane Learning Live Webinar Series 2020 Feb. Full Text   

Morley, G., Ives, J., Bradbury-Jones, C., & Irvine, F. (2019). What is 'moral distress'? A narrative synthesis of the literature.  Nursing ethics ,  26 (3), 646–662. https://doi.org/10.1177/0969733017724354 Link

References Popay, J., Roberts, H., Sowden, A., Petticrew, M., Arai, L., Rodgers, M., ... & Duffy, S. (2006). Guidance on the conduct of narrative synthesis in systematic reviews.  A product from the ESRC methods programme Version ,  1 (1), b92. Full Text

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Doing a Systematic Review: A Student’s Guide

Saul McLeod, PhD

Editor-in-Chief for Simply Psychology

BSc (Hons) Psychology, MRes, PhD, University of Manchester

Saul McLeod, PhD., is a qualified psychology teacher with over 18 years of experience in further and higher education. He has been published in peer-reviewed journals, including the Journal of Clinical Psychology.

Learn about our Editorial Process

Olivia Guy-Evans, MSc

Associate Editor for Simply Psychology

BSc (Hons) Psychology, MSc Psychology of Education

Olivia Guy-Evans is a writer and associate editor for Simply Psychology. She has previously worked in healthcare and educational sectors.

What is Systematic Review?

A systematic review is a comprehensive, structured analysis of existing research on a specific topic. It uses predefined criteria to identify, evaluate, and synthesize relevant studies, aiming to provide an unbiased summary of the current evidence.

The explicit and systematic approach of a systematic review distinguishes it from traditional reviews and commentaries.

How systematic reviews differ from narrative reviews:

• Goals: Narrative reviews provide a summary or overview of a topic, while systematic reviews answer a focused review question.
• Sources of Literature: Narrative reviews often use a non-exhaustive and unstated body of literature, which can lead to publication bias. Systematic reviews consider a list of databases, grey literature, and other sources.
• Selection Criteria: Narrative reviews usually use subjective or no selection criteria, which can lead to selection bias. Systematic reviews have a clear and explicit selection process.
• Appraisal of Study Quality: Narrative reviews vary in their evaluation of study quality. Systematic reviews use standard checklists for a rigorous appraisal of study quality.

Systematic reviews are time-intensive and need a research team with multiple skills and contributions. There are some cases where systematic reviews are unable to meet the necessary objectives of the review question.

In these cases, scoping reviews (which are sometimes called scoping exercises/scoping studies) may be more useful to consider.

Scoping reviews are different from systematic reviews because they may not include a mandatory critical appraisal of the included studies or synthesize the findings from individual studies.

Assessing The Need For A Systematic Review

When assessing the need for a systematic review, one must first check if any existing or ongoing reviews already exist and determine if a new review is justified.

Scoping reviews frequently serve as preliminary steps before conducting full systematic reviews. They help assess the available literature’s breadth, identify key concepts, and determine the feasibility of a more comprehensive review.

This initial exploration guides researchers in refining their approach for subsequent in-depth analyses.

This process should begin by searching relevant databases.

Resources to consider searching include:

• NICE : National Institute for Health and Clinical Excellence
• Campbell Library of Systematic Reviews for reviews in education, crime and justice, and social welfare
• EPPI : Evidence for Policy and Practice Information Centre, particularly their database of systematic and non-systematic reviews of public health interventions (DoPHER)
• MEDLINE : Primarily covers the medical domain, making it a primary resource for systematic reviews concerning healthcare interventions
• PsycINFO : For research in psychology, psychiatry, behavioral sciences, and social sciences
• Cochrane Library (specifically CDSR) : Focuses on systematic reviews of health care interventions, providing regularly updated and critically appraised reviews

If an existing review addressing the question of interest is found, its quality should be assessed to determine its suitability for guiding policy and practice.

If a high-quality, relevant review is located, but its completion date is some time ago, updating the review might be warranted.

Assessing current relevance is vital, especially in rapidly evolving research fields. Collaboration with the original research team might be beneficial during the update process, as they could provide access to their data.

If the review is deemed to be of adequate quality and remains relevant, undertaking another systematic review may not be necessary.

When a new systematic review or an update is deemed necessary, the subsequent step involves establishing a review team and potentially an advisory group, who will then develop the review protocol.

How To Conduct A Systematic Review

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) is a reporting guideline designed to improve the transparency and completeness of systematic review reporting.

PRISMA was created to tackle the issue of inadequate reporting often found in systematic reviews:

• Checklist : PRISMA features a 27-item checklist covering all aspects of a systematic review, from the rationale and objectives to the synthesis of findings and discussion of limitations. Each checklist item is accompanied by detailed reporting recommendations in an Explanation and Elaboration document .
• Flow Diagram : PRISMA also includes a flow diagram to visually represent the study selection process, offering a clear, standardized way to illustrate how researchers arrived at the final set of included studies.

Step 1: write a research protocol

A protocol in the context of systematic reviews is a detailed plan that outlines the methodology to be employed throughout the review process.

The protocol serves as a roadmap, guiding researchers through each stage of the review in a transparent and replicable manner.

This document should provide specific details about every stage of the research process, including the methodology for identifying, selecting, and analyzing relevant studies.

For example, the protocol should specify search strategies for relevant studies, including whether the search will encompass unpublished works.

The protocol should be created before beginning the research process to ensure transparency and reproducibility.

This pre-determined plan ensures that decisions made during the review are objective and free from bias, as they are based on pre-established criteria.

Protocol modifications are sometimes necessary during systematic reviews. While adhering to the protocol is crucial for minimizing bias, there are instances where modifications are justified. For instance, a deeper understanding of the research question that emerges from examining primary research might necessitate changes to the protocol.

Systematic reviews should be registered at inception (at the protocol stage) for these reasons:

• To help avoid unplanned duplication
• To enable the comparison of reported review methods with what was planned in the protocol

This registration prevents duplication (research waste) and makes the process easy when the full systematic review is sent for publication.

PROSPERO is an international database of prospectively registered systematic reviews in health and social care. Non-Cochrane protocols should be registered on PROSPERO.

Research Protocol

Rasika Jayasekara, Nicholas Procter. The effects of cognitive behaviour therapy for major depression in older adults: a systematic review. PROSPERO 2012 CRD42012003151 Available from:  https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42012003151

Review question

How effective is CBT compared with other interventions, placebo or standard treatment in achieving relapse prevention and improving mental status for older adults with major depression?

The search strategy aims to find both published and unpublished studies and publications. The search will be limited to English language papers published from 2002 to 2012.

A three-step search strategy will be developed using MeSH terminology and keywords to ensure that all materials relevant to the review are captured.

An initial limited search of MEDLINE and CINAHL will be undertaken followed by an analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms will then be undertaken.

Thirdly, the reference list of all identified reports and articles will be searched for additional studies.

The databases to be searched included:

• Cochrane Central Register of Controlled Trials
• Controlled Trials
• Current Contents

The search for unpublished studies will include:

• Digital Dissertations (Proquest)
• Conference Proceedings

Experts in the field will be contacted for ongoing and unpublished trials. Experts will be identified through journal publications.

Types of study to be included

All randomised controlled trials (RCTs) assessing the effectiveness of CBT as a treatment for older adults with major depression when compared to standard care, specific medication, other therapies and no intervention will be considered.

In the absence of RCTs, other research designs such as quasi-experimental studies, case-controlled studies and cohort studies will be examined. However, descriptive studies and expert opinion will be excluded.

Condition or domain being studied

Major depression is diagnosed according to DSM IV or ICD 10 criteria.

Where trials fail to employ diagnostic criteria, the severity of depression will be described by the use of standardised rating scales, including the Hamilton Depression Rating Scale, Montgomery and Asberg Rating Scale and the Geriatric Depression Rating Scale.

The trials including participants with an explicit diagnosis of dementia or Parkinson’s disease and other mental illnesses will be excluded.

The review will include trials conducted in primary, secondary, community, nursing homes and in-patient settings.

Participants/population

The review will include trials in which patients are described as elderly, geriatric, or older adults, or in which all patients will be aged 55 or over (many North American trials of older adult populations use a cut-off of 55 years).

The review will include trials with subjects of either sex. Where possible, participants will be categorised as community or long term care residents.

Intervention(s), exposure(s)

The review will focus on interventions designed to assess the effects of CBT for older adults with major depression.

The label cognitive behavioural therapy has been applied to a variety of interventions and, accordingly, it is difficult to provide a single, unambiguous definition.

In order to be classified as CBT the intervention must clearly demonstrate the following components:

• the intervention involves the recipient establishing links between their thoughts, feelings and actions with respect to the target symptom;
• the intervention involves the correction of the person’s misperceptions, irrational beliefs and reasoning biases related to the target symptom.
• – the recipient monitoring his or her own thoughts, feelings and behaviours with respect to the target symptom; and
• – the promotion of alternative ways of coping with the target symptom.

In addition, all therapies that do not meet these criteria (or that provide insufficient information) but are labelled as ‘CBT’ or ‘Cognitive Therapy’ will be included as ‘less well defined’ CBT.

Comparator(s)/control

other interventions, placebo or standard treatment

Main outcome(s)

Primary outcomes

• Depression level as assessed by Hamilton Depression Rating Scale, Montgomery or Asberg Rating Scale or the Geriatric Depression Rating Scale.
• Relapse (as defined in the individual studies)
• Death (sudden, unexpected death or suicide).
• Psychological well being (as defined in the individual studies)

Measures of effect

The review will categorise outcomes into those measured in the shorter term (within 12 weeks of the onset of therapy), medium term (within 13 to 26 weeks of the onset of therapy) and longer term (over 26 weeks since the onset of therapy).

Additional outcome(s)

Secondary outcomes

• Mental state
• Quality of life
• Social functioning
• Hospital readmission
• Unexpected or unwanted effect (adverse effects), such as anxiety, depression and dependence on the relationship with the therapist

Data extraction (selection and coding)

Data will be extracted from papers included in the review using JBI-MAStARI. In this stage, any relevant studies will be extracted in relation to their population, interventions, study methods and outcomes.

Where data are missing or unclear, authors will be contacted to obtain information.

Risk of bias (quality) assessment

All papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review.

Since the review will evaluate the experimental studies only, The Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) will be used to evaluate each study’s methodological validity.

If there is a disagreement between the two reviewers, there will be a discussion with the third reviewer to solve the dissimilarity.

Strategy for data synthesis

Where possible quantitative research study results will be pooled in statistical meta-analysis using Review Manager Software from the Cochrane Collaboration.

Odds ratio (for categorical outcome data) or standardised mean differences (for continuous data) and their 95% confidence intervals will be calculated for each study.

Heterogeneity will be assessed using the standard Chi-square. Where statistical pooling is not possible the findings will be presented in narrative form.

Step 2: formulate a research question 

Developing a focused research question is crucial for a systematic review, as it underpins every stage of the review process.

The question defines the review’s nature and scope, guides the identification of relevant studies, and shapes the data extraction and synthesis processes.

It’s essential that the research question is answerable and clearly stated in the review protocol, ensuring that the review’s boundaries are well-defined.

A narrow question may limit the number of relevant studies and generalizability, while a broad question can make it challenging to reach specific conclusions.

PICO Framework

The PICO framework is a model for creating focused clinical research questions. The acronym PICO stands for:

• P opulation/Patient/Problem: This element defines the specific group of people the research question pertains to.
• I ntervention: This is the treatment, test, or exposure being considered for the population.
• C omparison: This is the alternative intervention or control group against which the intervention is being compared.
• O utcome: This element specifies the results or effects of the interventions being investigated

Using the PICO format when designing research helps to minimize bias because the questions and methods of the review are formulated before reviewing any literature.

The PICO elements are also helpful in defining the inclusion criteria used to select sources for the systematic review.

The PICO framework is commonly employed in systematic reviews that primarily analyze data from randomized controlled trials .

Not every element of PICO is required for every research question. For instance, it is not always necessary to have a comparison

Types of questions that can be answered using PICO:

“In patients with a recent acute stroke (less than 6 weeks) with reduced mobility ( P ), is any specific physiotherapy approach ( I ) more beneficial than no physiotherapy ( C ) at improving independence in activities of daily living and gait speed ( O )?

“For women who have experienced domestic violence ( P ), how effective are advocacy programmes ( I ) compared to other treatments ( C ) on improving the quality of life ( O )?”

Etiology/Harm

Are women with a history of pelvic inflammatory disease (PID) ( P ) at higher risk for gynecological cancers ( O ) than women with no history of PID ( C )?

Among asymptomatic adults at low risk of colon cancer ( P ), is fecal immunochemical testing (FIT) ( I ) as sensitive and specific for diagnosing colon cancer ( O ) as colonoscopy ( C )?

Among adults with pneumonia ( P ), do those with chronic kidney disease (CKD) ( I ) have a higher mortality rate ( O ) than those without CKD ( C )?

Alternative Frameworks

• PICOCS : This framework, used in public health research, adds a “ C ontext” element to the PICO framework. This is useful for examining how the environment or setting in which an intervention is delivered might influence its effectiveness.
• PICOC : This framework expands on PICO by incorporating “ C osts” as an element of the research question. It is particularly relevant to research questions involving economic evaluations of interventions.
• ECLIPSE : E xpectations, C lient group, L ocation, I mpact, P rofessionals involved, S ervice, and E valuation. It is a mnemonic device designed to aid in searching for health policy and management information.
• PEO : This acronym, standing for P atient, E xposure, and O utcome, is a variation of PICO used when the research question focuses on the relationship between exposure to a risk factor and a specific outcome.
• PIRD : This acronym stands for P opulation, I ndex Test, R eference Test, and D iagnosis of Interest, guiding research questions that focus on evaluating the diagnostic accuracy of a particular test.
• PFO : This acronym, representing P opulation, P rognostic F actors, and O utcome, is tailored for research questions that aim to investigate the relationship between specific prognostic factors and a particular health outcome.
• SDMO : This framework, which stands for S tudies, D ata, M ethods, and O utcomes, assists in structuring research questions focused on methodological aspects of research, examining the impact of different research methods or designs on the quality of research findings.

Step 3: Search Strategy

PRISMA  (Preferred Reporting Items for Systematic reviews and Meta-Analyses) provide appropriate guidance for reporting quantitative literature searches.

Present the full search strategies for all databases, registers and websites, including any filters and limits used. PRISMA 2020 Checklist

A search strategy is a comprehensive and reproducible plan for identifying all relevant research studies that address a specific research question.

This systematic approach to searching helps minimize bias and distinguishes systematic reviews from other types of literature reviews.

It’s important to be transparent about the search strategy and document all decisions for auditability. The goal is to identify all potentially relevant studies for consideration.

Here’s a breakdown of a search strategy:

Search String Construction

It is recommended to consult topic experts on the review team and advisory board in order to create as complete a list of search terms as possible for each concept.

To retrieve the most relevant results, a search string is used. This string is made up of:

• Keywords:  Search terms should be relevant to the subject areas of the research question and should be identified for all components of the research question (e.g., Population, Intervention, Comparator, and Outcomes – PICO). Using relevant keywords helps minimize irrelevant search returns. Sources such as dictionaries, textbooks, and published articles can help identify appropriate keywords.
• Synonyms: These are words or phrases with similar meanings to the keywords, as authors may use different terms to describe the same concepts. Including synonyms helps cover variations in terminology and increases the chances of finding all relevant studies. For example, a drug intervention may be referred to by its generic name or by one of its several proprietary names.
• Truncation symbols : These broaden the search by capturing variations of a keyword. They function by locating every word that begins with a specific root. For example, if a user was researching interventions for smoking, they might use a truncation symbol to search for “smok*” to retrieve records with the words “smoke,” “smoker,” “smoking,” or “smokes.” This can save time and effort by eliminating the need to input every variation of a word into a database.
• Boolean operators: The use of Boolean operators (AND/OR/NEAR/NOT) helps to combine these terms effectively, ensuring that the search strategy is both sensitive and specific. For instance, using “AND” narrows the search to include only results containing both terms, while “OR” expands it to include results containing either term.

Information Sources

The primary goal is to find all published and unpublished studies that meet the predefined criteria of the research question. This includes considering various sources beyond typical databases

Information sources for systematic reviews can include a wide range of resources like scholarly databases, unpublished literature, conference papers, books, and even expert consultations.

Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted. PRISMA 2020 Checklist

An exhaustive, systematic search strategy is developed with the assistance of an expert librarian.

• Electronic Databases : Searches should include seven key databases: CINAHL, Medline, APA PsycArticles, Psychology and Behavioral Sciences Collection, APA PsycInfo, SocINDEX with Full Text, and Web of Science: Core Collections.
• Grey Literature : In addition to databases, forensic or ‘expansive’ searches can be conducted. This includes: grey literature database searches (e.g.  OpenGrey , WorldCat , Ethos ),  conference proceedings, unpublished reports, theses  , clinical trial databases , searches by names of authors of relevant publications. Independent research bodies may also be good sources of material, e.g. Centre for Research in Ethnic Relations , Joseph Rowntree Foundation , Carers UK .
• Citation Searching : Reference lists often lead to highly cited and influential papers in the field, providing valuable context and background information for the review.
• Handsearching : Manually searching through specific journals or conference proceedings page-by-page is another way to ensure all relevant studies are captured, particularly those not yet indexed in databases.
• Contacting Experts : Reaching out to researchers or experts in the field can provide access to unpublished data or ongoing research not yet publicly available.

It is important to note that this may not be an exhaustive list of all potential databases.

A systematic computerized search was performed for publications that appeared between 1974 and 2018 in English language journals. Four databases were searched including PsychINFO, Embase, OVOID MEDLINE, and AMED. The databases were searched with combinations of search terms relating to attachment (“attachment” OR “working model” OR “safe haven” OR “secure base” OR “felt security”) AND romantic couples (“dyad” OR “couple” OR “spous” OR “partner” OR “romantic” OR “wife” OR “husband” OR “close relationship” OR “interpersonal” OR “intimate” OR “mari”) AND social support (“support prov” OR “caregiving” OR “support giv” OR “social support” OR “enacted support” OR “support received” OR “receiv* support” OR “prov support” OR “dyadic coping” OR “interpersonal coping” OR “collaborative coping” OR “help‐seeking” OR “emotional support” OR “tangible support” OR “instrumental support” OR “perceived support” OR “responsive” OR “buffer” OR “partner support” OR “Support avail*” OR “available support”). The reference lists of the retrieved studies were checked to find other relevant publications, which were not identified in the computerized database searches.

Inclusion Criteria

Specify the inclusion and exclusion criteria for the review. PRISMA 2020 Checklist

Before beginning the literature search, researchers should establish clear eligibility criteria for study inclusion.

Inclusion criteria are used to select studies for a systematic review and should be based on the study’s research method and PICO elements.

To maintain transparency and minimize bias, eligibility criteria for study inclusion should be established a priori. Ideally, researchers should aim to include only high-quality randomized controlled trials that adhere to the intention-to-treat principle.

The selection of studies should not be arbitrary, and the rationale behind inclusion and exclusion criteria should be clearly articulated in the research protocol.

When specifying the inclusion and exclusion criteria, consider the following aspects:

• Intervention Characteristics: Researchers might decide that, in order to be included in the review, an intervention must have specific characteristics. They might require the intervention to last for a certain length of time, or they might determine that only interventions with a specific theoretical basis are appropriate for their review.
• Population Characteristics: A systematic review might focus on the effects of an intervention for a specific population. For instance, researchers might choose to focus on studies that included only nurses or physicians.
• Outcome Measures: Researchers might choose to include only studies that used outcome measures that met a specific standard.
• Age of Participants: If a systematic review is examining the effects of a treatment or intervention for children, the authors of the review will likely choose to exclude any studies that did not include children in the target age range.
• Diagnostic Status of Participants: Researchers conducting a systematic review of treatments for anxiety will likely exclude any studies where the participants were not diagnosed with an anxiety disorder.
• Study Design: Researchers might determine that only studies that used a particular research design, such as a randomized controlled trial, will be included in the review.
• Control Group: In a systematic review of an intervention, researchers might choose to include only studies that included certain types of control groups, such as a waiting list control or another type of intervention.
• Publication status : Decide whether only published studies will be included or if unpublished works, such as dissertations or conference proceedings, will also be considered.

Studies that met the following criteria were included: (a) empirical studies of couples (of any gender) who are in a committed romantic relationship, whether married or not; (b) measurement of the association between adult attachment and support in the context of this relationship; (c) the article was a full report published in English; and (d) the articles were reports of empirical studies published in peer‐reviewed journals, dissertations, review papers, and conference presentations.

Iterative Process

The iterative nature of developing a search strategy for systematic reviews stems from the need to refine and adapt the search process based on the information encountered at each stage.

A single attempt rarely yields the perfect final strategy. Instead, it is an evolving process involving a series of test searches, analysis of results, and discussions among the review team.

Here’s how the iterative process unfolds:

• Initial Strategy Formulation: Based on the research question, the team develops a preliminary search strategy, including identifying relevant keywords, synonyms, databases, and search limits.
• Test Searches and Refinement: The initial search strategy is then tested on chosen databases. The results are reviewed for relevance, and the search strategy is refined accordingly. This might involve adding or modifying keywords, adjusting Boolean operators, or reconsidering the databases used.
• Discussions and Iteration: The search results and proposed refinements are discussed within the review team. The team collaboratively decides on the best modifications to improve the search’s comprehensiveness and relevance.
• Repeating the Cycle: This cycle of test searches, analysis, discussions, and refinements is repeated until the team is satisfied with the strategy’s ability to capture all relevant studies while minimizing irrelevant results.

The iterative nature of developing a search strategy is crucial for ensuring that the systematic review is comprehensive and unbiased.

By constantly refining the search strategy based on the results and feedback, researchers can be more confident that they have identified all relevant studies.

This iterative process ensures that the applied search strategy is sensitive enough to capture all relevant studies while maintaining a manageable scope.

Throughout this process, meticulous documentation of the search strategy, including any modifications, is crucial for transparency and future replication of the systematic review.

Step 4: Search the Literature

Conduct a systematic search of the literature using clearly defined search terms and databases.

Applying the search strategy involves entering the constructed search strings into the respective databases’ search interfaces. These search strings, crafted using Boolean operators, truncation symbols, wildcards, and database-specific syntax, aim to retrieve all potentially relevant studies addressing the research question.

The researcher, during this stage, interacts with the database’s features to refine the search and manage the retrieved results.

This might involve employing search filters provided by the database to focus on specific study designs, publication types, or other relevant parameters.

Applying the search strategy is not merely a mechanical process of inputting terms; it demands a thorough understanding of database functionalities and a discerning eye to adjust the search based on the nature of retrieved results.

Step 5: screening and selecting research articles

Once the search strategy is finalized, it is applied to the selected databases, yielding a set of search results.

These search results are then screened against pre-defined inclusion criteria to determine their eligibility for inclusion in the review.

The goal is to identify studies that are both relevant to the research question and of sufficient quality to contribute to a meaningful synthesis.

Studies meeting the inclusion criteria are usually saved into electronic databases, such as Endnote or Mendeley , and include title, authors, date and publication journal along with an abstract (if available).

Study Selection

Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process. PRISMA 2020 Checklist

The selection process in a systematic review involves multiple reviewers to ensure rigor and reliability.

To minimize bias and enhance the reliability of the study selection process, it is recommended that at least two reviewers independently assess the eligibility of each study. This independent assessment helps reduce the impact of individual biases or errors in judgment.

• Initial screening of titles and abstracts: After applying a strategy to search the literature, the next step involves screening the titles and abstracts of the identified articles against the predefined inclusion and exclusion criteria. During this initial screening, reviewers aim to identify potentially relevant studies while excluding those clearly outside the scope of the review. It is crucial to prioritize over-inclusion at this stage, meaning that reviewers should err on the side of keeping studies even if there is uncertainty about their relevance. This cautious approach helps minimize the risk of inadvertently excluding potentially valuable studies.
• Retrieving and assessing full texts: For studies which a definitive decision cannot be made based on the title and abstract alone, reviewers need to obtain the full text of the articles for a comprehensive assessment against the predefined inclusion and exclusion criteria. This stage involves meticulously reviewing the full text of each potentially relevant study to determine its eligibility definitively.
• Resolution of disagreements : In cases of disagreement between reviewers regarding a study’s eligibility, a predefined strategy involving consensus-building discussions or arbitration by a third reviewer should be in place to reach a final decision. This collaborative approach ensures a fair and impartial selection process, further strengthening the review’s reliability.

First, the search results from separate databases were combined, and any duplicates were removed. The lead author (S. M.) and a postgraduate researcher (F. N.) applied the described inclusion criteria in a standardized manner. First, both the titles and abstracts of the articles were evaluated for relevance. If, on the basis of the title and/or abstract, the study looked likely to meet inclusion criteria hard copies of the manuscripts were obtained. If there was doubt about the suitability of an article, then the manuscript was included in the next step. The remaining articles were obtained for full‐text review, and the method and results sections were read to examine whether the article fitted the inclusion criteria. If there was doubt about the suitability of the manuscripts during this phase, then this article was discussed with another author (C. H.). Finally, the reference lists of the eligible articles were checked for additional relevant articles not identified during the computerized search. For the selected articles (n = 43), the results regarding the relationship between attachment and support were included in this review (see Figure 1, for PRISMA flowchart).

PRISMA Flowchart

The PRISMA flowchart is a visual representation of the study selection process within a systematic review.

The flowchart illustrates the step-by-step process of screening, filtering, and selecting studies based on predefined inclusion and exclusion criteria.

The flowchart visually depicts the following stages:

• Identification: The initial number of titles and abstracts identified through database searches.
• Screening: The screening process, based on titles and abstracts.
• Eligibility: Full-text copies of the remaining records are retrieved and assessed for eligibility.
• Inclusion: Applying the predefined inclusion criteria resulted in the inclusion of publications that met all the criteria for the review.
• Exclusion: The flowchart details the reasons for excluding the remaining records.

This systematic and transparent approach, as visualized in the PRISMA flowchart, ensures a robust and unbiased selection process, enhancing the reliability of the systematic review’s findings.

The flowchart serves as a visual record of the decisions made during the study selection process, allowing readers to assess the rigor and comprehensiveness of the review.

• How to fill a PRISMA flow diagram

Step 6: Criticallay Appraising the Quality of Included Studies

Quality assessment provides a measure of the strength of the evidence presented in a review.

High-quality studies with rigorous methodologies contribute to a more robust and reliable evidence base, increasing confidence in the review’s conclusions.

Conversely, including low-quality studies with methodological weaknesses can undermine the review’s findings and potentially lead to inaccurate recommendations.

To judge the quality of studies included in a systematic review, standardized instruments, such as checklists and scales, are commonly used. These tools help to ensure a transparent and reproducible assessment process.

The choice of tool should be justified and aligned with the study design and the level of detail required. Using quality scores alone is discouraged; instead, individual aspects of methodological quality should be considered.

Here are some specific tools mentioned in the sources:

• Jadad score
• Cochrane Risk of Bias tool
• Cochrane Effective Practice and Organisation of Care (EPOC) Group Risk of Bias Tool
• Quality Assessment of Diagnostic Accuracy Studies (QUADAS)
• Newcastle – Ottawa Quality Assessment Scale for case-control and cohort studies
• EPHPP Assessment Tool
• Critical Appraisal Skills Programme (CASP) Appraisal Checklist
• Cochrane Public Health Group (CPHG)

The quality of the study was not an inclusion criterion; however, a study quality check was carried out. Two independent reviewers (S. M. and C. H.) rated studies that met the inclusion criteria to determine the strength of the evidence. The Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies was adapted to assess the methodological quality of each study (Thomas, Ciliska, Dobbins, & Micucci, 2004). The tool was adjusted to include domains relevant to the method of each study. For example, blinding was removed for nonexperimental studies. Following recommendations by Thomas et al. (2004) each domain was rated as either weak (3 points), moderate (2 points), or strong (1 point). The mean score across questions was used as an indicator of overall quality, and studies were assigned an overall quality rating of strong (1.00–1.50), moderate (1.51–2.50),

Evidence Tables

Aspects of the appraisal of studies included in the review should be recorded as evidence tables (NICE 2009): simple text tables where the design and scope of studies are summarised.

The reader of the review can use the evidence tables to check the details, and assess the credibility and generalisability of findings, of particular studies.

Critical appraisal of the quality of included studies may be combined with data extraction tables.

Step 7: extracting data from studies

To effectively extract data from studies that meet your systematic review’s inclusion criteria, you should follow a structured process that ensures accuracy, consistency, and minimizes bias.

1. Develop a data extraction form:

• Design a standardized form (paper or electronic) to guide the data extraction process : This form should be tailored to your specific review question and the types of studies included.
• Pilot test the form : Test the form on a small sample of included studies (e.g., 3-5). Assess for clarity, completeness, and usability. Refine the form based on feedback and initial experiences.
• Reliability : Ensure all team members understand how to use the form consistently.

2. Extract the data:

• General Information: This includes basic bibliographic details (journal, title, author, volume, page numbers), study objective as stated by the authors, study design, and funding source.
• Study Characteristics: Capture details about the study population (demographics, inclusion/exclusion criteria, recruitment procedures), interventions (description, delivery methods), and comparators (description if applicable).
• Outcome Data: Record the results of the intervention and how they were measured, including specific statistics used. Clearly define all outcomes for which data are being extracted.
• Risk of Bias Assessment: Document the methods used to assess the quality of the included studies and any potential sources of bias. This might involve using standardized checklists or scales.
• Additional Information: Depending on your review, you may need to extract data on other variables like adverse effects, economic evaluations, or specific methodological details.

3. Dual independent review:

• Ensure that at least two reviewers independently extract data from each study using the standardized form. Cross-check extracted data for accuracy to minimize bias and helps identify any discrepancies.
• Have a predefined strategy for resolving disagreements: This might involve discussion, consensus, or arbitration by a third reviewer.
• Record the reasons for excluding any studies during the data extraction phase. :This enhances the transparency and reproducibility of your review.
• If necessary, contact study authors to obtain missing or clarify unclear information : This is particularly important for data critical to your review’s outcomes.
• Clearly document your entire data extraction process, including any challenges encountered and decisions made. This enhances the transparency and rigor of your systematic review.

By following these steps, you can effectively extract data from studies that meet your inclusion criteria, forming a solid foundation for the analysis and synthesis phases of your systematic review.

Step 8: synthesize the extracted data

The key element of a systematic review is the synthesis: that is the process that brings together the findings from the set of included studies in order to draw conclusions based on the body of evidence.

Data synthesis in a systematic review involves collating, combining, and summarizing findings from the included studies.

This process aims to provide a reliable and comprehensive answer to the review question by considering the strength of the evidence, examining the consistency of observed effects, and investigating any inconsistencies.

The data synthesis will be presented in the results section of the systematic review.

• Develop a clear text narrative that explains the key findings
• Use a logical heading structure to guide readers through your results synthesis
• Ensure your text narrative addresses the review’s research questions
• Use tables to summarise findings (can be same table as data extraction)

Identifying patterns, trends, and differences across studies

Narrative synthesis uses a textual approach to analyze relationships within and between studies to provide an overall assessment of the evidence’s robustness. All systematic reviews should incorporate elements of narrative synthesis, such as tables and text.

Remember, the goal of a narrative synthesis is to go beyond simply summarizing individual studies. You’re aiming to create a new understanding by integrating and interpreting the available evidence in a systematic and transparent way.

Organize your data:

• Group studies by themes, interventions, or outcomes
• Create summary tables to display key information across studies
• Use visual aids like concept maps to show relationships between studies

Describe the studies:

• Summarize the characteristics of included studies (e.g., designs, sample sizes, settings)
• Highlight similarities and differences across studies
• Discuss the overall quality of the evidence

Develop a preliminary synthesis:

• Start by describing the results of individual studies
• Group similar findings together
• Identify overarching themes or trends

Explore relationships:

• Look for patterns in the data
• Identify factors that might explain differences in results across studies
• Consider how study characteristics relate to outcomes

Address contradictions:

• Consider differences in study populations, interventions, or contexts
• Look at methodological differences that might explain discrepancies
• Consider the implications of inconsistent results
• Don’t ignore conflicting findings
• Discuss possible reasons for contradictions

Avoid vote counting:

• Don’t simply tally positive versus negative results
• Instead, consider the strength and quality of evidence for each finding

Assess the robustness of the synthesis:

• Reflect on the strength of evidence for each finding
• Consider how gaps or limitations in the primary studies affect your conclusions
• Discuss any potential biases in the synthesis process

Step 9: discussion section and conclusion

Summarize key findings:.

• Summarize key findings in relation to your research questions
• Highlight main themes or patterns across studies
• Explain the nuances and complexities in the evidence
• Discuss the overall strength and consistency of the evidence
• This provides a clear takeaway message for readers

Consider study quality and context:

• Assess whether higher quality studies tend to show different results
• Examine if findings differ based on study setting or participant characteristics
• This helps readers weigh the relative importance of conflicting findings

Discuss implications:

• For practice: How might professionals apply these findings?
• For policy: What policy changes might be supported by the evidence?
• Consider both positive and negative implications
• This helps translate your findings into real-world applications

Identify gaps and future research:

• Point out areas where evidence is lacking or inconsistent
• Suggest specific research questions or study designs to address these gaps
• This helps guide future research efforts in the field

State strengths and limitations:

• Discuss the strengths of your review (e.g., comprehensive search, rigorous methodology)
• Acknowledge limitations (e.g., language restrictions, potential for publication bias)
• This balanced approach demonstrates critical thinking and helps readers interpret your findings

Minimizing Bias

To reduce bias in a systematic review, it is crucial to establish a systematic and transparent review process that minimizes bias at every stage. Sources provide insights into strategies and methods to achieve this goal.

• Protocol development and publication: Developing a comprehensive protocol before starting the review is essential. Publishing the protocol in repositories like PROSPERO or Cochrane Library promotes transparency and helps avoid deviations from the planned approach, thereby minimizing the risk of bias.
• Transparent reporting: Adhering to reporting guidelines, such as PRISMA, ensures that all essential aspects of the review are adequately documented, increasing the reader’s confidence in the transparency and completeness of systematic review reporting.
• Dual independent review: Employing two or more reviewers independently at multiple stages of the review process (study selection, data extraction, quality assessment) minimizes bias. Any disagreements between reviewers should be resolved through discussion or by consulting a third reviewer. This approach reduces the impact of individual reviewers’ subjective interpretations or errors.
• Rigorous quality assessment: Assessing the methodological quality of included studies is crucial for minimizing bias in the review findings. Using standardized critical appraisal tools and checklists helps identify potential biases within individual studies, such as selection bias, performance bias, attrition bias, and detection bias.
• Searching beyond published literature: Explore sources of “grey literature” such as conference proceedings, unpublished reports, theses, and ongoing clinical trial databases.
• Contacting experts in the field : Researchers can reach out to authors and investigators to inquire about unpublished or ongoing studies
• Considering language bias : Expanding the search to include studies published in languages other than English can help reduce language bias, although this may increase the complexity and cost of the review.

Reading List

• Galante, J., Galante, I., Bekkers, M. J., & Gallacher, J. (2014). Effect of kindness-based meditation on health and well-being: a systematic review and meta-analysis .  Journal of consulting and clinical psychology ,  82 (6), 1101.
• Schneider, M., & Preckel, F. (2017). Variables associated with achievement in higher education: A systematic review of meta-analyses .  Psychological bulletin ,  143 (6), 565.
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A Systematic Review and Narrative Synthesis: Determinants of the Effectiveness and Sustainability of Measurement-Focused Quality Improvement Trainings

Zuneera khurshid , bba (hons), mba, aoife de brún , ba(hons) psychology, phd, jennifer martin , mb bao bch(medicine), eilish mcauliffe , bsc psychology, msc, mba, phd.

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Correspondence: Zuneera Khurshid, BBA (HONS), MBA, School for Nursing, Midwifery and Health Systems, University College Dublin, Room B111, Health Sciences Centre, Belfield, Dublin 4, Ireland; e-mail: [email protected]

Corresponding author.

Issue date 2021 Summer.

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Supplemental Digital Content is Available in the Text.

Keywords: quality measurement, program evaluation, measurement for improvement, data skills, continuing professional development

Introduction:

The ability of health care professionals to measure change is critical for successful quality improvement (QI) efforts. Currently, there are no systematic reviews focusing on continuing education for health care professionals in data skills for QI. The purpose of this systematic review is to define effectiveness and sustainability of QI programs for health care professionals containing a measurement skills component and to identify barriers and facilitators to effectiveness and sustainability.

The systematic review involved study identification, screening, full text review, and data extraction. Four electronics databases and grey literature sources were searched to identify studies published between 2009 and 2019 (11 years). A customized data extraction form was developed. Mixed methods appraisal tool was used for quality assessment and a thematic analysis was conducted for narrative synthesis.

Fifty-three studies from 11 countries were included. Most study designs were quantitative descriptive (17/53) and used a blended learning approach (25/53) combining face-to face and distance learning modes. The programs included basic, intermediate, and advanced data skills concepts. Overall, studies reported positive outcomes for participant reaction, learning, and behavior, but reported variable success in sustainability and spread of QI.

Discussion:

Studies discussed measurement as a key competency for clinical QI. Effectiveness definitions focused on the short-term impact of the programs, whereas sustainability definitions emphasized maintenance of outcomes and skills in the long-term. Factors that influenced effectiveness and sustainability of the included studies were strategic approach to QI, organizational support, intervention design, communication, accountability, leadership support, and learning networks.

Health care organizations worldwide continue to test new systems and ways to enhance health care quality and patient safety. 1 Organizations are using continuing education programs in quality improvement (QI) methodologies to transform care and improve patient safety, reduce variations in care outcomes, and deliver sustainable changes in the health care system. 2 The use of such programs to improve health care has also gained considerable popularity in the health care system. 3 However, the health care system is complex and professional knowledge alone is not enough to engage in QI work to bring about change. 4 Numerous QI training programs have been developed to train health care staff in QI methodology and application.

QI training can improve processes, staff knowledge, and health outcomes. 5 Measurement is an important construct in all QI efforts because unless we measure, it is impossible to demonstrate whether the change has resulted in an improvement or not. 6 For health care staff today, collecting, processing, and understanding data is a part of routine practice. 7 This makes a strong case to train health care staff in quality measurement and to develop their expertise in the use of data. 8

Although there are several systematic reviews evaluating QI training and curricula, 9 – 11 none have focused on the evaluation of measurement for improvement training components. This systematic review differs from previous reviews by focusing on QI curricula and training programs containing a significant data skills component. The concepts of effectiveness and sustainability are critical to assessing the impact of teaching measurement skills to health care staff, but these concepts are underexplored in the QI literature. Effectiveness is a micro concept and refers to the assessment of the usefulness of an output at a certain point, with little reference to context. On the other hand, sustainability is a macro concept which extends over a longer period as the new ways of working or improved outcomes become the norm, with context being an essential element. 12 The purpose of this systematic review is to address this gap in literature and define effectiveness and sustainability of QI programs for health care professionals that have a data for improvement component and to identify the associated barriers and enablers.

Protocol and Registration

Review protocol for this systematic review is registered on PROSPERO (ID: CRD42019122997). This study was approved by the IRB of our institution.

Eligibility Criteria

Studies were included if:

Conducted in health care setting

Intervention was QI-based training and included a measurement component.

Study was about development, evaluation, or implementation of the program

Population was health care staff or postgraduate students

Based on primary research

Studies were excluded if:

There was no measurement for improvement component in intervention

Conference proceedings

Population was undergraduate students

Information Sources

Systematic review protocols were scanned in Prospero and Cochrane library to ensure novelty of the review question. A scoping search of databases was conducted to inform the development of the search strategy. Databases were purposively selected to include health care and education sources. The databases were: PubMed, CINAHL Plus, ERIC (via Pro-Quest), and Web of Science. Grey literature sources included two databases: OAIster and OpenGrey along with websites of leading organizations (see Supplemental File 1, Supplemental Digital Content 1, http://links.lww.com/JCEHP/A103 ). The reference lists of eligible studies were scanned to identify additional papers.

The search strategy (see Supplemental File 2, Supplemental Digital Content 2, http://links.lww.com/JCEHP/A104 ) was optimized toward sensitivity rather than specificity because the scoping search revealed that measurement for improvement was integrated into QI studies rather than being delivered as a standalone training. 13 The authors finalized the search strategy and databases iteratively. The systematic search of the literature was conducted in January 2019 and updated in June 2020. The search was restricted to papers published in last 11 years (Search date: January 1, 2009–December 31, 2019). Foreign language papers with English abstracts were considered at the initial stage but only included in full text review if a complete translation was available.

Study Selection

The systematic review consisted of four stages: study identification, title and abstract screening, full text review, and data extraction. Study screening was completed using Covidence tool. 14 Two reviewers independently conducted title and abstract screening. The reviewers met regularly to resolve disputes. The full text review was also conducted independently by two reviewers and discrepancies resolved via discussion. The two reviewers consulted a third reviewer to assist in making the decision on one paper at the full text review stage. Because the studies were heterogenous, a narrative synthesis was performed.

The database search returned 6184 articles, which were imported into Covidence. The 2499 duplicates were removed, leaving 3685 studies eligible for screening. After screening, 110 studies were shortlisted for full text review. A total of 53 studies were included in the review. The PRISMA flow diagram is presented in Figure 1 and the checklist is attached in Supplemental Digital Content 3 (see Supplemental File 3, http://links.lww.com/JCEHP/A105 ). 15

PRISMA Statement. An overview of the study selection process. The 6184 records identified through database searching were screened by 2 reviewers. Nineteen records were identified and included from grey literature sources. Exclusion reasons at each stage are shown.

Assessment of Methodological Quality

The Mixed Methods Appraisal Tool (MMAT) was used to evaluate methodological quality. 16 The validity and reliability of the MMAT has been established and is suitable for appraising mixed method studies. 17 Two reviewers assessed quality independently and results were compared. Studies meeting the screening questions of the MMAT on clarity of research questions and appropriateness of collected data were considered appropriate quality for inclusion. All 53 studies met these criteria and were included in the review. The quality assessment is presented in Table 1 .

Assessment of Methodological Quality Using MMAT *

Y, yes; N, No; C, Cannot tell.

Data Extraction

Two reviewers completed the data extraction independently. A customized data extraction form was developed (see Supplemental File 4, Supplemental Digital Content 4, http://links.lww.com/JCEHP/A106 ). One reviewer compared the data extraction forms and discrepancies were resolved through discussion between reviewers.

The 53 included studies were published between 2009 and 2019 and set in 11 countries. Most studies (35/53) were based in the United States. Most Study designs were quantitative descriptive (17/53) followed by mixed methods studies (16/53). The population varied widely, ranging from frontline staff, clinical and nonclinical staff, and leaders. A summary of studies is presented in Supplemental File 5, Supplemental Digital Content 5, http://links.lww.com/JCEHP/A131 .

Training Description

Less than half (14/53) of the studies were based on a collaborative approach. Duration of the collaboratives was variable, ranging from 2 months to 72 months. Half of the studies used a blended learning approach (25/53) combining face-to face and distance learning modes, whereas 21 studies relied solely on face-to-face learning modes. Four trainings were delivered online, whereas three studies did not state training modality used. Interventions included multiple training methods; the most common (39/53) one being face-to-face learning sessions. Other methods included teleconferencing (12/53), online modules (10/53), workshops (9/53), webinars (6/53), and emails (6/53).

Curriculum Description

The curricula were summarized into categories of basic, intermediate, and advanced data skills based on complexity of data concepts taught. Figure 2 summarizes the three categories and highlights the data concepts part of the training and curricula in the included studies. Basic data skills include concepts of measurement and QI knowledge, which are important for all health care staff. Intermediate data skills concepts are useful for staff working in improvement teams, whereas advanced data skills concepts are useful for improvement team leads and advisors.

Measurement for Improvement Concepts. Summary of basic, intermediate, and advanced measurement and data skills taught in the QI programs.

Study Outcomes

Study outcomes are categorized as participant reaction, participant learning, participant behavior, sustainability, spread, and course design elements (see Supplemental File 6, Supplemental Digital Content 6, http://links.lww.com/JCEHP/A107 ). All studies measuring participation reaction to training and improved learning reported positive outcomes regardless of the study design. Studies measuring participant behavior also reported positive results except two quantitative descriptive studies. 63 , 65 Two randomized control trial studies 24 , 53 and a controlled interrupted time series study 50 reported not achieving the clinical outcomes being measured. A cohort study also reported not achieving the outcome of developing a culture of QI. 42 In spread, one quantitative descriptive study 49 reported no spread of QI methods. For sustainability outcomes, Glasgow et al 37 (Interrupted time series), Doyle et al 30 (Quantitative descriptive), and Cranley et al 26 (Mixed methods) reported a lack of sustainability of QI.

The Role of Measurement

The included studies reported on the role of measurement in QI for tracking progress toward goals and offering a systematic way to test changes to close performance gaps. 20 , 61 Measurement was identified as a key competency for clinical QI 21 to understand variation and improve the design health care. 4 Measurement was used to view data over time and draw conclusions regarding variations. 54 Measurement also played a role in implementation of QI methods 19 and contributed to the success of QI. 49

Knowledge about statistics and statistical process control 4 and additional support for measurement skills was reported by studies as critical. 2 , 33 , 39 Defining clear aims and measuring progress toward them was described as essential for QI. 62 Measurement was used to demonstrate patient outcomes to the host organizations 30 and provide guidance to decision makers. 49 Continuous measurement followed the processes through the project period into daily operations. 4 One study labelled measurement as one of the crucial elements of strategy for QI spread and sustainability. 31 Timely data and measurement are important for assessing progress and evaluation. 30

Challenges in identifying, collecting, and displaying appropriate measures of care impact QI program success. 4 , 18 , 63 Studies cited measurement challenges such as difficulty in obtaining measurable data 34 , 64 and presenting data in run/control chart formats. 35 Many participating hospitals were not equipped for systematic data collection. 31 Data collection and measurement was valued, 29 but perceived to be time consuming by participants. 52 , 53

Defining Effectiveness and Sustainability

The purpose of the review is to define effectiveness and sustainability and identify the barriers and enablers to success, in the context of QI programs with a focus on data and measurement for improvement. There is variability in how effectiveness and sustainability is defined in the studies. Another related concept that emerged was that of spread. It is therefore important to distinguish between effectiveness, spread, and sustainability. Effectiveness and sustainability definitions were extracted as part of the data extraction tool and summarized in Supplemental Digital Content 7 (see Supplemental file 7, http://links.lww.com/JCEHP/A108 ). The aspects addressed by these extracted definitions were then used to synthesize definitions. This was completed via consultation between three reviewers.

Effectiveness definitions focused on the short-term impact of the QI programs and were measured using participant reaction to the program, improved knowledge and skill application of participants, program participation and completion of QI projects by participants, and improvement in clinical outcomes at the end of the intervention period. Sustainability on the other hand, is defined not only as long-term outcomes beyond the intervention period, but also as a continuous process. Spread definitions focused on the diffusion of QI methods, processes, and skills from the intervention setting to nonintervention settings. We synthesized the following definitions of effectiveness, sustainability, and spread for measurement for improvement programs:

Effectiveness

Demonstrating improvement in key process, outcome, or quality measures being tracked, accompanied with an improvement in measurement knowledge, skills, and behaviors of learners during the intervention period.

Sustainability

Ongoing measurement, and development of processes and policies to maintain and improve the achieved gains in outcomes and participant skills and integration of measurement practices into routine after the intervention period, without further support from the trainers.

Active and passive diffusion of measurement skills and practices to areas and staff within and outside the organization that were not exposed to the training intervention.

Barriers and Enablers

A six-phased thematic analysis methodology (familiarization with data, initial coding, identifying themes, reviewing themes, naming themes, and reporting) was used to identify the barriers and enablers of sustainability 66 (see Supplemental file 8, Supplemental Digital Content 8, http://links.lww.com/JCEHP/A109 ). The definitions of effectiveness and sustainability synthesized were used as reference. The coding process was done manually by one reviewer and final themes were discussed and agreed with two other reviewers.

The four themes that emerged in enablers to effectiveness were intervention design, staff engagement, supportive leadership, and organizational support. Intervention design was the most important factor in the effectiveness of the program. Customizing training allows teaching of skills relevant to participant's role. 3 , 31 Considering the implementation context 3 , 39 , 52 , 53 and the challenges and opportunities of the setting 33 , 43 , 62 leads to targeted skill building. 19 A good starting point is to assess the prior knowledge and experience of participants 21 to determine training needs 31 and design a suitable range of resources 57 , 65 corresponding to diversity of experiences and knowledge levels. 64 Offering online modules 44 and online resources 53 also helps bridge this gap.

Intervention effectiveness can be enhanced using multiple learning strategies 21 and evidence-based curricula. 28 An effective intervention is responsive to participant learning styles 65 and improves the training based on feedback. 28 , 64 The best way to learn is by doing 21 and incorporating experiential learning principles 23 through demonstration projects 29 and case studies 65 builds capability. Another aspect of customized content is developing an interdisciplinary and team-based course 46 , 60 , 65 as working in teams prevents participants from becoming overburdened with measurement. 64 Having a participatory, data-driven approach contributes to effectiveness. 19 , 53 Focusing on real-time data increases 20 the program's value as participants can identify gaps in current processes. 23 , 55 Teaching practical data gathering, 21 statistical control charts, 4 data analysis, and comparison contribute to effectiveness. Feedback from fellow participants allows them to learn from each other and adds to effectiveness. 36 , 64 Similarly, informing participants about other team's progress creates healthy competition and prevents redundancy of efforts. 64

Effective coaching also plays an important role. Customized coaching experience through just-in-time coaching 28 and direct onsite, in-person support 33 improves effectiveness. Coaching is more effective when trainers can respond directly to participant concerns. 40 The ability of coaches to provide measurement support 22 in creating data collection processes 27 and data quality troubleshooting 33 adds to effectiveness. Practice facilitation 33 is also an enabler because providing private coaching between learning sessions, 44 ongoing mentorship 21 and tools and resources 39 are valued by participants. Coaches can provide customized feedback and assistance. 29 When participants perceive the training organization to be credible and have a sense of affiliation with it, they consider the training to be more effective. 23

Guiding participants in indicator selection by focusing on establishing clear, realistic, mutually agreed, 18 , 22 and clinically meaningful goals 43 , 47 , 50 is a successful strategy. Encouraging participants to focus on simple solutions 18 , 25 and making small changes 26 , 62 leads to effectiveness. In-person workshops 21 are an effective mode of training as face-to-face contact 33 is preferred by participants. Using technology for designing easy to access, self-paced and self-initiated interventions 57 improves effectiveness.

Successfully engaging health care staff is another important theme in effectiveness. Clinical staff feel empowered when they can identify and address gaps 25 and select relevant QI topics. 41 , 52 Providing dedicated time to participants to attend training sessions 34 , 41 , 42 , 45 , 53 also adds to effectiveness. Demonstrating the value of competency in QI skills 64 and offering maintenance of certification credit 59 also helps in creating enthusiasm among staff. Supportive policies of the organization such as assuring time release recognizes the training as a valued activity. 21 Leadership support is an important factor in the success of such programs. 21

There are four themes in barriers to effectiveness: incompatible intervention design, lack of staff engagement, lack of organizational support, and lack of strategic approach. Fast pace of collaboratives 18 and didactic instruction 30 which did not correspond to learning needs of all participants, especially those in support roles 3 were perceived as barriers. The number of concepts covered in the training made it difficult for participants to keep up and the terminology used was sometimes difficult to understand. 29 A single day of classroom training was an insufficient dose 50 and scheduling a full day training workshop is tiring for participants. 63 When training programs that did not incorporate advice on implementation 53 and leading change, 36 it proved to be a barrier to effectiveness.

Lack of organizational support was visible in cases where participants were not provided protected time and struggled to attend the sessions. 3 , 64 Poor data infrastructure impeded data collection 31 and obtaining baseline measures. 34 , 44 Lack of staff engagement and a negative perception about QI work and training because of previous negative experiences 18 , 45 dampened effectiveness. Some programs failed to incorporate appropriate reward systems to motivate behavior 36 and the lack of interest among participants resulted in low attendance 35 , 50 and in some cases, staff disliked new tools and processes that required learning new methods. 39 Staff struggled with learning measurement skills such as presenting data as run charts/control charts 35 , 36 which decreased collaborative effectiveness. Some did not see any value in investing time in such collaboratives 63 and believed the burdens outweighed the benefits. 29 , 36 Another barrier was the lack of a strategic approach and the participants selected projects that were incompatible with the goals of their institutions. 36 , 51

The themes observed in enablers to sustainability were taking a strategic approach, accountability, communication, learning networks, staff engagement, organizational support, intervention design, and supportive leadership. Taking a strategic approach requires connecting the program to organizational and national priorities, 21 strategic goals, 2 , 27 and teaming up with other departments 64 and organizations 53 with similar agendas. 29 As organizations prioritize and implement QI, 57 they move from sporadic efforts toward performance management systems, 5 which sustains learning. Incorporating strategies to address psychology 20 of change improves sustainability. Using a standard approach to QI ensures a common and clear improvement language. 44

Another aspect of sustainability is to recruit the right people in the project team. 4 , 22 A purposeful participant selection strategy 46 ensures inclusion of individuals who are interested in improvement work. Scale-up plans 18 with a goal of institution-wide diffusion 31 add to sustainability. It is important to integrate QI into programs and services 42 , 53 through updated job descriptions, 33 building QI responsibility into operational responsibilities 47 and continually reinforcing skills. 49 Engaging all stakeholders from an early stage 2 , 18 , 19 , 21 , 53 is also an enabler. In addition, while planning evaluations, it is important to assess learner involvement and QI project outcomes beyond completion of the programme. 52 A strategic approach requires taking a system-level view 20 , 21 of improvements with a blameless culture focusing on systems rather than individuals, 24 , 53 which considers challenges as system issues rather than staff issues. 28

Supportive organizational practices encourage QI by removing barriers, 26 investing in workforce capacity and culture change 28 and providing a conducive environment for teamwork. 38 , 45 It also commits resources 3 , 33 , 46 , 56 and provides opportunities to practice the skills learned. 19 , 22 , 27 Accountability is an important enabler for sustainability. A clear definition of responsibilities, 34 tasks 39 and individual roles 62 is key. Establishing time-bound targets 20 and regular meetings to follow through on action 62 ensures accountability. It is also beneficial to establish measurement guidelines to follow the process through the project period into daily operations. 4 This continuous sharing of numbers leads 53 to motivation and boosts sustainability. 4 The training organization can also provide external accountability 33 and ensure participants see projects to completion. 41

Focus on capacity building also improves sustainability. This includes training staff for specialized QI roles such as QI champion, 28 process coach, 31 and QI advisor. 33 A mentorship framework to support those interested in developing QI skills and encouraging permanent staff to develop coaching skills improves sustainability. 47 Effective communication contributes to sustainability. Recognizing the efforts of QI teams 26 , 34 by showcasing success stories 28 through ongoing promotional activities 56 is a rewarding strategy. Senior leader communication through board letters 31 also supports sustainability. Formal and informal dissemination are vital to communication and sustainability. Formal dissemination can include internal dissemination, 31 dissemination to local, national, and international audiences 2 and toolkits. 55 Informal dissemination can include enthusiastic employees 53 and other informal contacts. 31 Similarly, visual display of data and progress helps in disseminating the message of improvement. 59

Learning networks are an important enabler. 53 Learning from peers by sharing ideas 18 , 21 and building relationships creates a strong learning community for idea exchange. 33 These learning platforms serve as venues for knowledge transfer 57 and repositories for QI. 27 Development of collaborations between organizations leads to networking 56 and solution sharing. 33 Another area in staff engagement is generating awareness about QI 18 beyond the project team 2 , 26 , 42 and its impact on career. 22 Extended support from coaches for implementation sequencing 48 improves sustainability.

Support from leaders is crucial to sustainability. 53 This involves improving leaders' QI skills so they can develop infrastructure for QI in their organizations 28 such as establishing QI teams. 53 Senior leadership support 22 including board executives and chief of the medical staff provide legitimacy to QI. 31 A strong leadership structure championing QI on a daily basis 34 sends a message for sustainability. Leadership support allows staff to try new ideas in a safe environment that does not punish risk-taking. 56 Organizational support plays a role through various strategies such as incentivizing diffusion 48 and providing resources and autonomy to innovate. 3

Themes in barriers to sustainability include lack of accountability, poor communication, lack of leadership support, lack of staff engagement, lack of organizational support, absence of learning networks, and not having a strategic approach. When timelines, roles, and responsibilities are not established, the plan of actions can evaporate leading to slippage in agreed timeframes and a loss of momentum. 50 Because of poor institutional communication, staff lack a shared perception of problems 51 and often lack institutional knowledge to approach the relevant individuals for QI work. 60 Lack of leadership support manifests in the form of a lack of interest from top management 4 and variations in the readiness of senior leaders to engage in QI. 46

Learning networks play a vital role in sustainability; however, they are challenging to establish because few practices reach out to others to learn from them 62 and may also face difficulty in learning from practices with dissimilar QI capacity and patients. 29 Lack of organizational support is a major barrier to sustainability 53 because it represents a culture that is not conducive to making or sustaining change. 33 Presence of administrative red tape 3 , 64 can inhibit innovation and indicate that QI is not a priority for the organization. 55

Poor data infrastructure, 4 , 33 , 53 data quality, and access to data 4 decrease sustainability. Repeated data collection can be cumbersome and labor intensive in the long run. 52 Lack of resource availability 3 , 26 , 46 for QI projects is another barrier. Programs that lack ongoing organizational support are likely to be unsuccessful. 65 Health care staff have competing demands on their time, 46 , 62 , 63 , 63 which interferes with team's ability to meet and work. 3 Because QI teams are a disparate group of staff, 50 a lack of dedicated time for QI work 57 can be a barrier. Failing to engage staff, and leadership effectively and not focusing on motivation and behavior change can be a barrier to sustainability. 53 It is also important to account for the high levels of stress and emotional demands experienced by front-line staff. 1

The purpose of the systematic review is to define effectiveness and sustainability of QI programs with a significant data skills component and to identify the relevant barriers and enablers. Fifty-three studies were included in the review. There was heterogeneity in the content, teaching methods, and program design in the included studies and variability in the way effectiveness, sustainability, and spread were defined and measured in the context of QI programs. The review also highlighted variation in the ability of the programs to achieve desired outcomes. These inconsistencies in program success were attributed to various barriers and enablers to effectiveness and sustainability.

The lack of staff engagement, lack of a strategic approach, and lack of organizational support are barriers common between effectiveness and sustainability, which implies that these factors have implications for the short-term and long-term success of the programs. Poor intervention design affects the effectiveness of the program while poor communication, lack of accountability, and lack of leadership support can plague the ability to sustain the skills and results in the long-term. In enablers, intervention design, supportive leadership, engaged staff, and organizational support can affect positively on both effectiveness and sustainability of programs. Enablers that are relevant to sustainability are learning networks, communication, accountability, and a strategic approach to QI. The barriers and enablers highlight the importance of organizational, 39 learner, teacher, curricular, 35 and contextual factors 3 in the success of QI programs.

The definitions derived for effectiveness and sustainability highlight the importance of measurement. Studies reported measurement as a key competency for clinical QI. 21 Continuous measuring and remeasuring play an important role in maintaining 62 and operationalizing improvements in the long run. Selecting appropriate measures, 18 , 22 data collection 34 and using charts to display data 35 are essential to show effective change. 64 QI programs therefore need to focus on training staff in QI methods and how to measure care and use data to drive change. 62 There is an increasing expectation from health care professionals to measure, report, and continually improve the quality of care. 62 This indicates the need for a cultural shift from traditional academic-focused programs toward programs focusing on measurement and results to develop the capability of health professionals in leading improvement. 44

The findings of this systematic review also advocate for program evaluation to consider impact on participant behavior, patient outcomes, and supporting downstream learning beyond the direct participants of the programme. 43 Instead of solely relying on measuring quantitative outcomes, evaluators should also use qualitative data to assess whether program outcomes are achieved. 29

Measurement emerged as a critical element of QI training programs, which enables health care professionals and organizations to demonstrate effectiveness of improvement efforts and sustain improvements in the long run. Training health care professionals in data skills can have implications for improving health systems. However, health care systems are complex and various actors such as the health care authorities, training organizations, trainers, trainees, and trainee's organization have a collaborative role to play in ensuring effectiveness and sustainability of QI programs. Outputs of the thematic analysis in the form of effectiveness and sustainability barriers and enablers were broken down into inputs, outputs, and short- and long-term outcomes, which were then mapped onto a logic model. This was completed via consultation between three reviewers and presented in Figure 3 .

Intervention success factors. Summary of QI program inputs contributing to achievement of short-term and long-term outcomes.

Limitations

A limitation of this review is that there were no stand-alone measurement for improvement training studies. The reviewers overcame this by establishing the presence of measurement component in the QI programs as an inclusion criterion. Because no search strategy is perfect, there is a risk of missing relevant studies; however, we mitigated this risk using a search strategy focused on sensitivity and iteratively testing the search strategy in selected databases.

The review highlighted that measuring the improvement in outcomes and participant knowledge establishes effectiveness while remeasuring continuously helps in sustaining outcomes in the long-term for QI programs with a significant measurement skills component. The review identified staff engagement, strategic approach to QI, organizational support, intervention design, communication, accountability, leadership support, and learning networks as factors that affect effectiveness and sustainability. The review expands current knowledge about the importance of measurement in QI training programs. Ensuring effectiveness and sustainability of measurement for improvement programs requires a collective effort from trainers, trainees, the organizations in which the interventions are implemented and policy makers.

Lessons for Practice

■ Measurement has a central role in demonstrating improvements and maintaining desired improvement outcomes of QI programs in the short- and long-term.

■ Staff engagement, strategic approach to QI, organizational support, intervention design, communication, accountability, leadership support, and learning networks influence effectiveness and sustainability of QI programs.

■ Effectiveness, sustainability, and spread of QI programs with a measurement component requires a collective effort from trainers, trainees, the organizations in which the interventions are implemented, and policy makers.

Supplementary Material

The corresponding author receives a PhD funding from the Health Service Executive Ireland (Project reference 57399). The study is also supported by the Irish Health Research Board (RL-2015-1588).

Disclosures: The authors declare no conflict of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site ( www.jcehp.org ).

Contributor Information

Aoife De Brún, Email: [email protected].

Jennifer Martin, Email: [email protected].

Eilish McAuliffe, Email: [email protected].

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• Published: 12 March 2019

A systematic literature review and narrative synthesis on the risks of medical discharge letters for patients’ safety

• Christine Maria Schwarz 1 ,
• Magdalena Hoffmann   ORCID: orcid.org/0000-0003-1668-4294 1 , 2 ,
• Petra Schwarz 3 ,
• Lars-Peter Kamolz 1 ,
• Gernot Brunner 1 &
• Gerald Sendlhofer 1 , 2  

BMC Health Services Research volume  19 , Article number:  158 ( 2019 ) Cite this article

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The medical discharge letter is an important communication tool between hospitals and other healthcare providers. Despite its high status, it often does not meet the desired requirements in everyday clinical practice. Occurring risks create barriers for patients and doctors. This present review summarizes risks of the medical discharge letter.

The research question was answered with a systematic literature research and results were summarized narratively. A literature search in the databases PubMed and Cochrane Library for Studies between January 2008 and May 2018 was performed. Two authors reviewed the full texts of potentially relevant studies to determine eligibility for inclusion. Literature on possible risks associated with the medical discharge letter was discussed.

In total, 29 studies were included in this review. The major identified risk factors are the delayed sending of the discharge letter to doctors for further treatments, unintelligible (not patient-centered) medical discharge letters, low quality of the discharge letter, and lack of information as well as absence of training in writing medical discharge letters during medical education.

Conclusions

Multiple risks factors are associated with the medical discharge letter. There is a need for further research to improve the quality of the medical discharge letter to minimize risks and increase patients’ safety.

Peer Review reports

The medical discharge letter is an important communication medium between hospitals and general practitioners (GPs) and an important legal document for any queries from insurance carriers, health insurance companies, and lawyers [ 1 ]. Furthermore, the medical discharge letter is an important document for the patient itself.

A timely transmission of the letter, a clear documentation of findings, an adequate assessment of the disease as well as understandable recommendations for follow-up care are essential aspects of the medical discharge letter [ 2 ]. Despite this importance, medical discharge letters are often insufficient in content and form [ 3 ]. It is also remarkable that writing of medical discharge letters is often not a particular subject in the medical education [ 4 ]. Nevertheless, the medical discharge letter is an important medical document as it contains a summary of the patient’s hospital admission, diagnosis and therapy, information on the patient’s medical history, medication, as well as recommendations for continuity of treatment. A rapid transmission of essential findings and recommendations for further treatment is of great interest to the patient (as well as relatives and other persons that are involved in the patients’ caring) and their current and future physicians. In most acute care hospitals, patients receive a preliminary medical discharge letter (short discharge letter) with diagnoses and treatment recommendations on the day of discharge [ 5 ]. Unfortunately, though, the full hospital medical discharge letter, which is often received with great delay, is an area of constant conflict between GPs and hospital doctors [ 1 ]. Thus the medical discharge letter does not only represent a feature of process and outcome quality of a clinic, but also influences confidence building and binding of resident physicians to the hospital [ 6 ].

Beside the transmission of patients’ findings from physician to physician, the delivery of essential information to the patient is an underestimated purpose of the medical discharge letter [ 7 ]. The medical discharge letter is often characterized by a complex medical language that is often not understood by the patients. In recent years, patient-centered/patient-directed medical discharge letters are more in discussion [ 8 ]. Thus, the medical discharge letter points out risks for patients and physicians while simultaneously creating barriers between them.

A systematic review of the literature was undertaken to identify patient safety risks associated with the medical discharge letter.

Search strategy

A systematic literature search was conducted using the electronic databases PubMed and Cochrane Database. Additionally, we scanned the reference lists of selected articles (snowballing). The following search terms were used: “discharge summary AND risks”, “discharge summary AND risks AND patient safety” and “discharge letter AND risks” and “discharge letter AND risks AND patient safety”. We reviewed relevant titles and abstracts on English and German literature published between January 2008 and May 2018 and started the search at the beginning of February 2018 and finished it at the end of May 2018.

Eligibility criteria

In this systematic review, articles were included if the title and/or abstract indicated the report of results of original research studies using quantitative, qualitative, or mixed method approaches. Studies in paediatric settings or studies that do not handle possible risks of the medical discharge letter were excluded, as well as reports, commentaries and letters. Electronic citations, including available abstracts of all articles retrieved from the search, were screened by two authors to select reports for full-text review. Duplicates were removed from the initial search. Nevertheless, during the search of articles the selection, publication as well as language bias must be considered. Thereafter, full-texts of potentially relevant studies were reviewed to determine eligibility for inclusion. In the following Table  1 inclusion and exclusion criteria for the studies are listed. Afterwards, key outcomes and main results were summarized. Differences were resolved by consensus. Finally, a narrative synthesis of studies meeting the inclusion criteria was conducted. Reference management software MENDELEY (Version 1.19.3) was used to organise and store the literature.

Data extraction

The data extraction in form of a table was used to summarize study results. The two authors extracted the data relating to author, country, year, study design, and outcome measure as well as potential risk factors to patient safety directly into a pre-formatted data collection form. After data extraction, the literature was discussed and synthesized into themes. The evaluation of the single studies was done using checklists [STROBE (combined) and the Cochrane Data collection form for intervention reviews (RCTs and non-RCTs)]. Meta-analysis was not considered appropriate for this body of literature because of the wide variability of studies in relation to research design, study population, types of interventions and outcomes.

Then a narrative synthesis was performed to synthesize the findings of the different studies. Because of the range of very different studies that were included in this systematic review, we have decided that a narrative synthesis constitutes the best instrument to synthesise the findings of the studies. First, a preliminary synthesis was undertaken in form of a thematic analysis involving searching of studies, listing and presenting results in tabular form. Then the results were discussed again and structured into themes. Afterwards, summarizing of included studies in a narrative synthesis within a framework was performed by one author.

This framework consisted of the following factors: the individuals and the environment involved in the studies (doctors, hospitals), the tools and technology (such as discharge letter delivery systems), the content of the medical discharge letter (such as missing content, quality of content), the accuracy and timeliness of transfer. These themes were discussed in relation to potential risks for patient’s safety. All articles that were included in this review were published before. The framework of this study was chosen following a previously published systematic review dealing with patient risks associated with telecare [ 9 ].

The initial literature search in the two online databases identified 940 records. From these records, 65 full text articles were screened for eligibility. Then 36 full-text articles were excluded because they pertained to patient transfer within the hospital or to another hospital, or to patient hand-over situations. Finally, 29 studies were included in this review. Included studies are listed in Table  2 . All document types were searched with a focus on primary research studies. The results of the search strategy are shown in Fig.  1 .

Flow chart literature search strategy

From these 29 studies, 13 studies dealt with the quality analysis of discharge letters, 12 studies with delayed transmission of medical discharge letters and just as many with the lack of information in medical discharge letters. Only few studies dealt with training on writing medical discharge letters and with understanding of patients of their medical discharge letters. The descriptive information of the included articles is presented in Table 2 . Overall quality of the articles was found to be acceptable, with clearly stated research questions and appropriate used methods.

Risk factors

In the following the identified major risk factors concerning the medical discharge letter are presented in a narrative summary.

Delayed delivery

The medical discharge letters should arrive at the GP soon after hospital discharge to ensure the quickest possible further treatment [ 4 ]. If letters are delivered weeks after the hospital stay, a continuous treatment of the patient cannot be ensured. Furthermore, the author of the medical discharge letter will no longer have current data after the discharge of the patient, which may result in a loss of important information [ 10 ]. Interfaces between different treatment areas and organizational units are known to cause a loss of information and a lack of quality in patient handling [ 11 ]. The improvement of information transfer between different healthcare providers during the transition of patients has been recommended to improve patient care [ 12 , 13 ]. Delayed communication of findings may lead to a lack of continuity of care and suboptimal outcomes, as well as decreased satisfaction levels for both patients and GPs [ 14 , 15 , 16 ]. In a review of Kripalani et al., it was shown that 25% of discharge summaries were never received by GPs [ 17 ]. This has several negative consequences for patients. Li et al. [ 18 ] found that a delayed transmission or absence of the medical discharge summary is related to patient readmission, and a study by Gilmore-Bykovskyi [ 19 ] found a strong relationship between patients whose discharge summaries omitted designation of a responsible clinician/clinic for follow-up care and re-hospitalisation and/or death. A Swedish study by Carlsson et al. [ 20 ] points out that a lack of accuracy and continuity in discharge information on eating difficulties may increase risk of undernutrition and related complications. A study of Were et al. [ 18 ] investigated pending lab results in medical discharge summaries and found that only 16% of tests with pending results were mentioned in the discharge summaries, and Walz et al. [ 21 ] found that approximately one third of the sub-acute care patients had pending lab results at discharge, but only 11% of these were documented in the medical discharge summaries.

Quality, lack of information

Medical discharge letters are a key communication tool for patient safety issues [ 17 ]. Incomplete and insufficient medical discharge letters increase the risks of readmission and myriad other complications [ 22 ]. Langelaan et al. (2017) evaluated more than 2000 medical discharge letters and found that in about 60% of the letters essential information was missing, such as a change of the existing medication, laboratory data, and even data on the patients themselves [ 23 ]. Accurate and complete medical discharge summaries are essential for patient safety [ 17 , 24 , 25 ]. Addresses; patient data, including duration of stay; diagnoses; procedures; operations; epicrisis and therapy recommendations; as well as findings in the appendix; are minimum requirements that are supposed to be included in the medical discharge letter [ 4 ]. However, it was found that key components are often lacking in medical discharge letters, including information about follow-up and management plans [ 23 , 26 ], test results [ 27 , 28 , 29 ], and medication adjustments [ 30 , 31 , 32 , 33 , 34 , 35 ]. In a review of Wimsett et al. [ 36 ] key components of a high-quality medical discharge summary were identified in 32 studies. These important components were discharge diagnosis, the received treatment, results of investigations as well as follow-up plans.

Accuracy of patients’ medication information is important to ensure patient safety. Hospital doctors expect GPs to continue with the prescribed (or modified) drug therapy. However, the selection of certain drugs is not always transparent for the GPs. A study by Grimes et al. [ 30 ] found that a discrepancy in medication documentation at discharge occurred in 10.8% of patients. From these patients nearly 65.5% were affected by discrepancies in medication documentation. The most prevalent inconsistency was drug omission (20.9%). Only 2% of patients were contacted, although general patient harm was assessed. A Swedish study of 2009 [ 37 ] investigated the quality improvement of medical discharge summaries. A higher quality of discharge letter led to an average of 45% fewer medication errors per patient.

A recent study by Tong et al. [ 38 ] revealed a reduced rate of medication errors in medical discharge summaries that were completed by a hospital pharmacist. Hospital pharmacists play a key role in preparing the discharge medication information transferred to GPs upon patient discharge and should work closely with hospital doctors to ensure accurate medication information that is quickly communicated to GPs at transitions of care [ 39 ]. Most hospitals have introduced electronic systems to improve the discharge communication, and many studies found a significant overall improvement in electronic transfer systems due to better documentation of information about follow-up care, pending test results, and information provided to patients and relatives [ 40 , 41 , 42 ]. Mehta et al. [ 43 ] found that the changeover to a new electronic system resulted in an increased completeness of discharge summaries from 60.7 to 75.0% and significant improvements in levels of completeness in certain categories.

Writing of medical discharge letter is missing in medical education

Both junior doctors as well as medical students reported that they received inadequate guidance and training on how to write medical discharge summaries [ 44 , 45 ] and recognized that higher priority is often given to pressing clinical tasks [ 46 ]. Research into the causes of prescribing errors by junior doctors at hospitals in the UK has revealed that latent conditions like organizational processes, busy environments, and medical care for complex patients can lead to medication errors in the medical discharge summary [ 47 ].

Fortunately, some study results demonstrate that information and education on writing medical discharge letters would enhance communication to the GPs and prevent errors during the patient discharge process [ 37 ]. Minimal formal teaching about writing medical discharge summaries is common in most medical schools [ 39 , 46 ]; however, a study by Shivji et al. has shown that simple, intensive educational sessions can lead to an improvement in the writing process of medical discharge summaries and communication with primary care [ 48 ].

Since the medical discharge letter should meet specific quality criteria, senior physicians and/or the head physician correct(s) and validate(s) the letter. The medical discharge letter therefore represents an essential learning target [ 8 ]. Training activities and workshops are necessary for junior doctors to improve writing medical discharge letters [ 44 , 49 ]. It might be also useful for young doctors to use checklists or other structured procedures to improve writing [ 4 ]. Maher et al. showed that the use of a checklist enhanced the quality (content, structure, and clarity) of medical discharge letters written by medical students [ 50 ].

In the following Table  3 main risk factors of the medical discharge letter are summarized.

The results of this systematic literature research indicate notable risk factors relating to the medical discharge letter. In a study by Sendlhofer et al., 360 risks were identified in hospital settings [ 51 ]. From these, 176 risks were scored as strategic and clustered into “top risks”. Top risks included medication errors, information errors, and lack of communication, among others. During this review, these potential risk factors were also identified in terms of the medical discharge letter.

Delayed sending and low quality of medical discharge letters to the referring physicians, may adversely affect the further course of treatment. However, a study of Spencer et al. has determined rates of failures in processing actions requested in hospital discharge summaries in general practice. It was found that requested medication changes were not made in 17% and patient harm occurred in 8% in relation to failures [ 52 ].

Despite the existence of reliable standards [ 53 ] many physicians are not adequately trained for writing medical discharge letters during their studies. Regular trainings and workshops and standardized checklists may optimize the quality of the medical discharge letter. Furthermore, electronic discharge letters have the potential to easily and quickly extract important information such as diagnoses, medication, and test results into a structured discharge document, and offer important advantages such as reliability, speed of information transfer, and standardization of content. Comprehensive discharge letters reduce the readmission rate and increase safety and quality by discharging of the patient. A missing structure, as well as a complex language, illegible handwriting, and unknown abbreviations, make reading medical discharge letters more complicated [ 4 ]. At least, poor patient understanding of their diagnosis and treatment plans and incomprehensible recommendations can adversely impact clinical outcome following hospital discharge. Many studies confirm that inadequate communication of findings [ 3 , 39 , 54 ] is an important risk factor in patients’ safety [ 51 ].

Most medical information in the discharge letter is not understood by patients (as well as relatives and other persons that are involved in the patients’ caring) and patients themselves do not receive a comprehensible medical discharge letter. The content of the medical discharge letter is often useless for the patient due to its medical terminology and content that is not matching with the patient’s level of knowledge or health literacy [ 55 , 56 , 57 ]. Poor understanding of diagnoses and related discharge plans are common among patients and family members and often accompanied by unplanned hospital readmissions [ 58 , 59 , 60 , 61 ]. In a study by Lin et al., it was shown that a patient-directed discharge letter enhanced understanding for hospitalization and for recommendations. Furthermore, verbal communication of the letter contents, explanation of every section of the medical discharge letter, and the opportunity for discussion and asking questions improved patient comprehension [ 7 ]. A study by O’Leary et al. showed that roughly 80–95% of patients with breast tumours want to be informed and educated about their illness, treatment, and prognosis [ 62 ].

High quality of care is characterized by a patient-centered communication, where the patient’s personal needs are also in focus [ 63 ]. Translation of medical terms in reports and letters leads to a better understanding of the disease and, interestingly, the avoidance of medical terms did not lead to deterioration in the transmission of information between the treating physicians. Moreover, it was found that the minimisation of medical terminology in medical discharge letters improved understanding and perception of patients’ ability to manage chronic health conditions [ 64 ]. In effect, it is clear that patient-centered communication improves outcome, mental health, patient satisfaction and reduces the use of health services [ 65 ].

Strengths and limitations

We have identified key problems with the medical discharge summaries that negatively impact patients’ safety and wellbeing. However, there is a heterogeneous nature of the included studies in terms of study design, sample size, outcomes, and language. Only two reviewers screened the studies for eligibility and only full-text articles were included in the literature review; furthermore, only the databases Pubmed and Cochrane library were screened for appropriate studies. Due to these constraints, there is a chance that other relevant studies may have been missed.

High-quality medical discharge letters are essential to ensure patient safety. To address this, the current review identified the major risk factors as delayed sending and low quality of medical discharge letters, lack of information and patient understanding, and inadequate training in writing medical discharge letters. In future, research studies should focus on improving the communication of pending test results and findings at discharge, and on evaluating the impact that this improved communication has on patient outcomes. Moreover, a simple patient-centered medical discharge letter may improve the patient’s (as well as family members’ and other caregivers’) understanding of disease, treatment and post-discharge recommendations.

Abbreviations

General practitioner

Randomized Controlled Trial

STrengthening the Reporting of OBservational studies in Epidemiology

United Kingdom

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Acknowledgements

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This research project was part of a project funded by the Gesundheitsfonds Steiermark. The funders had no role in study design, data collection and analyses, decision to publish, or preparation of the manuscript.

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CS wrote the manuscript; CS, MH and PS performed the literature search; LK contributed to the conception of this work; GB contributed to the interpretation of data and GS supervised the project. All authors were critically revising the manuscript and all authors have read and approved the final manuscript.

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Schwarz, C.M., Hoffmann, M., Schwarz, P. et al. A systematic literature review and narrative synthesis on the risks of medical discharge letters for patients’ safety. BMC Health Serv Res 19 , 158 (2019). https://doi.org/10.1186/s12913-019-3989-1

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“narrative synthesis” of quantitative effect data in cochrane reviews: current issues and ways forward.

In these videos, the presenters give an overview of current use of, and reasons for using narrative approaches to synthesis. They describe use of the term “narrative synthesis” and common issues in narrative synthesis including transparency in reporting and ambiguity about narrative synthesis as a method. They also provide an overview of how transparency can be improved and finish by introducing the Synthesis Without Meta-analysis (SWiM) reporting guideline, which is the focus of the second webinar. The work presented is from the ICONS-Quant (Improving the Conduct and reporting of Narrative Synthesis of Quantitative data) project which is funded by the Cochrane Strategic Methods Fund (May 2017-May 2019).

The webinar was delivered in February 2020 and below you will find the videos from the webinar, together with accompanying slides to download [PDF].

Part 1: Definition and use of ‘narrative synthesis’ Part 2: Reasons for using ‘narrative synthesis’ Part 3: Common issues in ‘narrative synthesis’ Part 4: Improving transparency in synthesis without meta-analysis; moving from ‘narrative synthesis’ to SWiM Part 5: Questions and answers

Presenter bios.

Dr Hilary Thomson , co-ordinating editor of Cochrane Public Health, Senior Research Fellow, University of Glasgow. Hilary Thomson has extensive experience in conducting large complex reviews of questions about the health impacts of social policy interventions such as housing, transport, and welfare. Her work focusses on ways to improve the reliability and utility of systematic reviews that address public health policy relevant questions.

Mhairi Campbell , Systematic Reviewer, University of Glasgow. Mhairi Campbell has broad experience of conducting complex systematic reviews, including: qualitative evidence of policy interventions, review of theories linking income and health, and research investigating the reporting of narrative synthesis methods of quantitative data in public health systematic reviews.

Part 1: Definition and use of ‘narrative synthesis’

Part 2: Reasons for using ‘narrative synthesis’

Part 3: Common issues in ‘narrative synthesis’

Part 4: Improving transparency in synthesis without meta-analysis; moving from ‘narrative synthesis’ to SWiM

Part 5: Questions and answers

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Strengths and limitations of early warning scores: A systematic review and narrative synthesis

Affiliations.

• 1 Leeds Institute of Biomedical & Clinical Sciences, Clinical Sciences Building St. James's University Hospital, University of Leeds, Leeds, LS9 7TF, United Kingdom. Electronic address: [email protected].
• 2 Leeds Institute of Biomedical & Clinical Sciences, Clinical Sciences Building St. James's University Hospital, University of Leeds, Leeds, LS9 7TF, United Kingdom.
• 3 School of Healthcare, Baines Wing, University of Leeds, Leeds LS2 9JT, United Kingdom.
• 4 Leeds Institute of Clinical Trials Research, Worsley Building, University of Leeds, Leeds LS2 9NL, United Kingdom.
• PMID: 28950188
• DOI: 10.1016/j.ijnurstu.2017.09.003

Background: Early warning scores are widely used to identify deteriorating patients. Whilst their ability to predict clinical outcomes has been extensively reviewed, there has been no attempt to summarise the overall strengths and limitations of these scores for patients, staff and systems. This review aims to address this gap in the literature to guide improvements for the optimization of patient safety.

Methods: A systematic review was conducted of MEDLINE ® , PubMed, CINAHL and The Cochrane Library in September 2016. The citations and reference lists of selected studies were reviewed for completeness. Studies were included if they evaluated vital signs monitoring in adult human subjects. Studies regarding the paediatric population were excluded, as were studies describing the development or validation of monitoring models. A narrative synthesis of qualitative, quantitative and mixed- methods studies was undertaken.

Findings: 232 studies met the inclusion criteria. Twelve themes were identified from synthesis of the data: Strengths of early warning scores included their prediction value, influence on clinical outcomes, cross-specialty application, international relevance, interaction with other variables, impact on communication and opportunity for automation. Limitations included their sensitivity, the need for practitioner engagement, the need for reaction to escalation and the need for clinical judgment, and the intermittent nature of recording. Early warning scores are known to have good predictive value for patient deterioration and have been shown to improve patient outcomes across a variety of specialties and international settings. This is partly due to their facilitation of communication between healthcare workers. There is evidence that the prediction value of generic early warning scores suffers in comparison to specialty-specific scores, and that their sensitivity can be improved by the addition of other variables. They are also prone to inaccurate recording and user error, which can be partly overcome by automation.

Conclusions: Early warning scores provide the right language and environment for the timely escalation of patient care. They are limited by their intermittent and user-dependent nature, which can be partially overcome by automation and new continuous monitoring technologies, although clinical judgment remains paramount.

Keywords: Early warning scores; Limitations; Strengths; Systematic review; Vital signs.

Copyright © 2017 Elsevier Ltd. All rights reserved.

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• Volume 14, Issue 9
• Health impact of urban green spaces: a systematic review of heat-related morbidity and mortality
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• http://orcid.org/0000-0002-9778-4811 Ahsana Nazish 1 , 2 ,
• Kiran Abbas 2 ,
• Emmama Sattar 3
• 1 London School of Hygiene & Tropical Medicine , London , UK
• 2 The Aga Khan University , Karachi , Pakistan
• 3 Ziauddin Medical University , Karachi , Pakistan
• Correspondence to Dr Ahsana Nazish; ahsana.nazish{at}lshtm.ac.uk

Objectives The objective of this review was to scrutinise the impact of urban green spaces on heat-related morbidity and mortality.

Design This systematic review was meticulously carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines

Data sources A comprehensive search was conducted across PubMed, Scopus and Google Scholar including studies from January 2000 to December 2022.

Eligibility criteria Studies that examined the influence of urban green spaces on heat-related morbidity and mortality, including randomised controlled trials, observational and modelling studies, were included.

Data extraction and synthesis A total of 3301 publications were initially identified, out of which 12 studies met the inclusion criteria and were selected for analysis. The selected studies were predominantly from high-income and upper-middle-income nations (95%).

Results The research points towards a pattern where regions abundant in green spaces report lower rates of heat-related morbidity and mortality in contrast to those with sparse greenery. Additionally, urban vegetation appears to exert a positive influence on mental health and well-being, potentially aiding in offsetting the adverse health repercussions of high temperatures.

Conclusion Urban green spaces play a vital role in mitigating heat-related health risks, offering a potential strategy for urban planning to address climate change and enhance public health. Additional research is required to thoroughly comprehend the magnitude of urban greenery’s impact on heat-related morbidity and mortality, as well as its interplay with other variables, including air pollution, socioeconomic status, among others.

• PUBLIC HEALTH
• PREVENTIVE MEDICINE
• Health policy

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Data are available on reasonable request.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/ .

https://doi.org/10.1136/bmjopen-2023-081632

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STRENGTHS AND LIMITATIONS OF THIS STUDY

The study conducted a rigorous and comprehensive literature review, drawing from multiple well-established databases, ensuring a comprehensive and representative overview of the existing research.

The study employed well-defined inclusion and exclusion criteria to select relevant research, enhancing the precision and quality of the included studies.

Prior to selection, each paper underwent a systematic quality assessment using the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies checklist, ensuring a rigorous approach to data inclusion.

While the study evaluates associations between green spaces and health outcomes, it does not establish causal relationships. Causality between these variables may require further research using experimental methods.

The study may be susceptible to publication bias, as it relies on published research. Unpublished studies or those with negative results may not be represented in the review, potentially affecting the comprehensiveness of the findings.

Introduction

As consequences of urbanisation and climate change, environmental alterations such as the urban heat island effect and other extreme weather phenomena are increasingly evident. Compounding these issues are escalating temperatures, primarily fuelled by rapid urbanisation. 1 Counteracting these global challenges—encompassing climate change, health inequity and sustainable urbanisation—green areas or urban vegetation are deemed critical. In this vein, the United Nations Sustainable Development Goal 11 target 7 stipulates the provision of universal access to secure, inclusive, and accessible green and public spaces, especially for vulnerable populations, by 2030. 2

The health implications of high temperatures are profound, posing substantial risks to individuals across all age groups. If untreated, persistent exposure to elevated temperatures can escalate into heat exhaustion and potentially prove lethal. A multitude of studies have endeavoured to comprehend the toll exerted by high temperatures on human health. 3 Vulnerable demographics, including children, the elderly and individuals with pre-existing medical conditions, are especially at risk from the adverse effects of high temperatures. Children’s developing bodies, older adults’ decreased physiological resilience and compromised health status of those with chronic conditions make these groups particularly susceptible to heat stress and heat-related illnesses. The exacerbated vulnerability of these populations highlights the critical need for targeted urban planning and public health strategies. Urban green spaces, by mitigating urban heat, offer a protective buffer that can reduce the incidence of heat-related morbidity and mortality among these sensitive groups, underscoring the importance of accessible and well-maintained green infrastructure as part of comprehensive climate adaptation and health equity efforts. 4

Urban green areas have emerged as a potential counter to heat, demonstrated by research evidencing their critical role in thermal mitigation. 1 5 For instance, a study in China underscored the efficient cooling effect of green spaces. 1 Vegetation, through its added shading effect, significantly cools night-time temperatures in urban regions while trees contribute to daytime temperature regulation. 6 Green spaces have also been linked to mental well-being, with their health advantages attributed to community cohesion, physical activity enhancement and mental well-being improvement. 6 Furthermore, they offer environmental benefits such as reductions in environmental exposures (air and noise pollution), cooling effects and flood risk reduction. Such evidence is invaluable in informing public health policy and providing recommendations for safeguarding public health during periods of extreme heat. 7

Despite ample research elucidating the overall health impacts of green spaces, their effect on heat-related health risks remains inadequately understood. This review, therefore, seeks to investigate the impact of vegetation or green areas within urban settings on heat-related mortality and morbidity.

Review question

What is the effect (positive, negative or none) of green zones on health-related mortality and morbidity in urban areas across the globe?

This systematic review has been duly registered at Figshare ( https://doi.org/10.6084/m9.figshare.23744553.v1 ) and access to protocol can be requested from the corresponding author. This review aims to explore the worldwide influence of urban green spaces on heat-related morbidity and mortality. This systematic review was meticulously carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. 8

In this study, ‘morbidity’ refers to the incidence or levels of health conditions and illnesses related to or exacerbated by exposure to heat stress within urban environments, particularly focusing on how urban green spaces can mitigate these health impacts.

Study selection criteria

All studies that examined the influence of urban green spaces on heat-related morbidity and mortality including randomised controlled trials, observational and modelling studies were included to encapsulate the entirety of the available evidence. We included peer-reviewed journal articles in English, published from January 2000 to December 2022. We have specifically chosen articles focused on urban settings, as the impact of green spaces can vary across urban, rural and other contexts. We have excluded commentaries, conference abstracts, book reviews, conference and editorial articles, and those articles that do not delve into heat-related health outcomes.

Search strategy

To identify the relevant literature, three databases including PubMed, Scopus and Google Scholar were searched from 2000 to 2022 using the search terms and strings provided in online supplemental table S1 .

Supplemental material

Screening and data extraction.

Microsoft Excel and Rayyan Software for Systematic Reviews were used to perform screening and extraction of data. All results from each database were exported to Rayyan and screening for duplicated articles was performed. After the duplicates were removed, two researchers (AN and KA) independently screened all titles and abstracts as per the eligibility criteria. Any conflicts were resolved on the basis of detailed discussion and mutual consensus. Articles that fulfilled the eligibility criteria were undertaken for full-text screening, independently by the two researchers (AN and KA), for final inclusion in the review.

Once the list of eligible articles was finalised, data extraction for descriptive parameters was independently performed by the two researchers (AN and KA) who undertook screening procedures. A standardised charting form was developed for data extraction and categorisation. The form included sections on author details, publication details, and year of study, study design, participants/population, health outcomes, results, and interpretations. Both extraction files were compared, and any conflicts were resolved through mutual discussion.

Risk of bias assessment

The rigorous evaluation of the quality of selected studies is an integral part of this systematic review, ensuring the robustness and reliability of the findings. This was performed by using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) Checklist. 9 The following items of CHARMS checklist were handled: study participants and characteristics, outcome to be predicted, sample size, missing data, model development and evaluation and result interpretation. Each study was scored for the risk of bias as low if bias is unlikely, moderate if there are no essential shortcomings, but not all criteria were satisfied, and high if bias was likely due to errors in one or more domains. Applicability refers to the extent to which the study matches the review question. Each study was independently assessed by two researchers (AN and KA), and any discrepancies in their evaluations were resolved through discussion until a consensus was reached. Studies were not excluded based on their quality score; instead, the quality assessment was used to critically interpret and discuss the findings of the review.

Data synthesis and analysis

Measures of heat-related diseases, hospital admissions, death rates and other health effects were retrieved from outcome data relating to morbidity and mortality brought on by the summer heat. Data were taken from all relevant research, including observational, modelling and randomised controlled trials. We retrieved and synthesised any pertinent data from several heat-related outcome metrics. A quantitative meta-analysis was not possible due to the heterogeneity, complexity and variation in the studies’ variables and results. The results from the included studies were instead critically analysed and synthesised using a narrative synthesis. This narrative synthesis used a thematic method to group data into categories based on important topics including the kind of urban green spaces, geography, population demographics and particular heat-related health outcomes.

The narrative synthesis offered an interpretive analysis of the data, showcasing patterns and discrepancies and bringing together the results from diverse research types. This method made it possible to thoroughly examine many context-specific ways that urban green spaces may affect heat-related illness and death.

Patient and public involvement

No patient is involved.

Study characteristics

A total of 3301 publications were identified from selected databases ( figure 1 ). Title and abstract screening resulted in the inclusion of 28 potentially relevant articles. After full-text screening, 12 articles met the inclusion criteria. Table 1 summarises the characteristics of all 12 studies conducted between 2014 and 2022. 10–21 These studies focused on the impact of green spaces on heat-related mortality and health outcomes across various countries including Hong Kong, 10 Australia, 11 15 16 21 Vietnam, 12 the USA, 13 19 20 South Korea, 14 Portugal 17 and Japan. 18 The research methodologies range from epidemiological studies, 10 12 14 16 17 modelling and simulation, 11 13 experimental research, 18 to quantitative analyses. 19–21 Most studies have used meteorological data, census and mortality data.

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Table 2 provides a critical appraisal of studies related to the impact of green spaces on heat-related mortality and morbidity. The majority of the studies (9 out of 13) were evaluated with a low risk of bias, suggesting a reliable and robust methodology. Four studies were found to have a medium risk of bias. All studies demonstrated applicability to our review question, reflecting relevance to the investigation of urban green spaces and their influence on heat-related mortality and morbidity.

Critical appraisal of included studies

Main findings

Effect on the vulnerable.

As documented in table 3 , green spaces have the potential to improve health of urban residents, particularly of specific vulnerable groups such as the elderly and children. In the study conducted in Hanoi the capital city of Vietnam, researchers examined the protective effect of green space in urban areas heat-treated respiratory hospitalisation of children under 5. 10 They used a two-stage model, including a distributed non-linear model coupled with multivariate meta-analysis. Hospitalisation in the central districts which are hotter and crowded increased significantly at temperatures >34°C. Heat significantly increased the risk of hospitalisation among children under 5. 12 In another study conducted in Lisbon, authors emphasised on the relevance of urban green on heat mitigation. Heat and mortality had a significant association in the elderly. Researchers used remote senses data and geographic information to determine the urban spaces. They conclude that urban green has a mitigation effect on heat-related mortality in elderly population. 17

Comparison of results and interpretation

Positive effect on heat-related mortality /morbidity

Interestingly, three studies included in this review were conducted in Australia. Chen et al used two scale modelling approach to quantify the effect of the urban vegetation schemes on current 2009 and future climates in 2030–2050. Results showed that the average summer temperatures can be reduced in the range of around 0.5 and 2 C. If Melbourne Central Business District (CBD) were replaced by vegetated suburbs and planted parklands, it would result in significant changes to the city's urban landscape, environment, and potentially its socioeconomic structure. 11 Another study found the benefit of urban vegetation in reducing heat-related mortality. Mortality records (2006–2018) were linked with weather observations (1997–2016), census population data and climate change projections to 2100. Heat wave attributable deaths were calculated based on risk estimates from published study of Australia. High-resolution satellite observations of green cover and air temperature excesses were used to determine the associated effects on heat-related mortality. 15 Moreover, the heatwave–mortality relationship was assessed using different study periods in the three largest cities in Australia (Brisbane, Sydney and Melbourne). The study has implications for developing approaches to evaluate heatwave–mortality relationship and setting up heat health warning systems. 16 In Seoul, Korea, a study showed high mortality effect of high temperatures with low vegetation. Poisson generalised liner model was used to assess the effect modification of mortality temperature association by urban vegetation. 14 Another study claims that roughly one in four lives currently lost during heat waves could be saved. They propose a climate change-induced warming could be delayed approximately 40–70 years under business-as-usual and moderate mitigation scenarios, respectively. 13

The research conducted in Japan found that wisteria trellises provided a more effective means of improving thermal comfort and mitigating heat stress compared with tents. 18 These findings are further reinforced by Sinha et al , 19 revealing that existing tree cover significantly contributes to reducing mortality from extreme heat, particularly among the most vulnerable elderly population. Another Australian study revealed that urban greening infrastructure reduced heat-related deaths, highlighting the significant health benefits of implementing greening infrastructure. 21

Interestingly, our review found that increasing urban spaces is not only an effective way to reduce urban ambient temperatures, but it may also be associated with economic value. 20

No significant effect on heat-related mortality/morbidity

The study conducted in Hong Kong did not show any significant effect of green spaces on heat-related mortality for the whole population or any specific gender and age. The findings challenge existing evidence on the role of vegetation in mitigating heat-related mortality risk. 10

There was heterogeneity in studies, this could be due to a variety of reasons such as differences in study design, population characteristics and exposure assessment methods. Some studies focused on a specific subgroup of population, such as children under 5 years and elderly. The study conducted in Hong Kong did not show any significant effect of green and blue spaces on heat-related mortality risk, unlike other studies included in this review. These findings challenge existing evidence on the role of urban green spaces in mitigating heat-related mortality risk. This could perhaps be due to the difference in study design and population.

Interestingly, research conducted in various settings further shed light on the importance of green spaces. For instance, in Japan, experimental study on the usefulness of wisteria trellises found that they offered a more effective means of reducing thermal discomfort and preventing heat stress compared with tents, even demonstrating psychological relaxation effects. 18 In the USA, urban tree canopy has been significantly associated with decreased heat-related mortality, accentuating the significance of maintaining and expanding urban green spaces. 19 20 A study in Australia has also emphasised the health benefits of greening infrastructure, possibly reducing heat-attributable mortality by up to 11.7 per day in the Sydney region. 21 These results accentuate the palpable impact of urban green spaces on temperature control and health outcomes, underpinning the need for targeted efforts in urban planning and infrastructure development.

Almost all studies that are published on assessing the effect of green vegetation on heat-related mortality and morbidity are from high-income countries. However, people living in low-middle-income countries face higher heat-related health issues due to poverty, lack of access to air conditioning and inadequate infrastructure for dealing with extreme heat events. 22 Moreover, people living in low-resource settings are particularly susceptible, as outdoor manual labour is more common and adaptation to climate change is costly. Moreover, they are at a higher risk from heat waves due to shortages of electricity during summer months, this further disadvantage those who cannot afford alternative sources of power. In 2015, Karachi Pakistan, 65 000 people were taken to the hospital with heat related or lack of access to air conditioning symptoms. 23 Heat-related deaths are also reported in countries such as India and Bangladesh where people are exposed to extreme heat from climate change and heat island effects. Furthermore, it is important for countries to generate local evidence to understand the impact of heat on population.

There is a wide range of international commitment and international agreements and support to establish green spaces in urban settings, however, there is a gap in literature on the assessments of green space accessibility and its impact on health. Such data would enable urban planners and local authorities to establish planning decisions. Interventions for urban green space should be planned and designed with the local community and intended green space users. Moreover, such interventions need to be considered as long-term investments and should be integrated in national developmental strategies, for example, housing regulations, urban masterplans, transport policies, etc. This requires a general understanding that urban green go beyond ecological or environmental objectives and deliver health benefits that increase well-being of urban residents and improves quality of life.

It is also important to accurately measure accessibility to green spaces, for this, we propose a multidimensional approach that considers not only the physical proximity but also the quality and usability of these spaces. This includes factors like maintenance, safety and availability of facilities. In economically developed countries, integrating geographical information systems with social demographic data can provide insights into equitable access. We also suggest incorporating community engagement metrics to understand the perceived value and actual use of green spaces, thereby offering a holistic measure of accessibility.

The limitation of this review is that we could not examine studies for the size, location and accessibility of green spaces that can have a significant effect on heat-related health outcomes and the potential to mitigate heat exposure. Second, our analysis acknowledges the diverse time span of studies reviewed, spanning nearly a decade. This range allows for a broader understanding of urban green spaces’ impacts over time, including changing urbanisation patterns and climate change effects. However, it also introduces variability in data due to evolving environmental policies, green space management practices and socioeconomic factors. We discuss the methodological approaches to mitigate these challenges, such as standardising outcome measures and adjusting for confounding factors, providing a comprehensive view of the accumulated evidence.

A review of urban greenery and its effect on heat-related morbidity and mortality suggests that urban green spaces, such as parks and trees, can have a positive impact on reducing the negative health effects associated with high temperatures. Studies have found that areas with more green space have lower rates of heat-related morbidity and mortality compared with areas with less green space. Moreover, urban greenery can also have a positive impact on mental health and well-being, which can also contribute to reducing the negative health effects of high temperatures. However, it is important to note that more research is needed to fully understand the extent of the impact of urban greenery on heat-related morbidity and mortality, and how it interacts with other factors such as air pollution, socioeconomic status and others.

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Supplementary materials

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This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

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Contributors AN conceptualised, planned the study, undertook the screening process, data extraction, draft writing, and proofread the manuscript. KA undertook the data extraction, analysis, interpretation and draft writing. ES did draft writing and proofreading. AN is responsible for the overall content of the manuscript as guarantor.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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A systematic review and narrative synthesis of inclusive health and social care research with people with intellectual disabilities: How are co-researchers involved and what are their experiences?

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Research output : Contribution to journal › Review article › peer-review

Background: Using inclusive research methods with people with intellectual disabilities is increasingly common. A recent consensus statement identified key elements when conducting and reporting inclusive research with people with intellectual disabilities. This review identifies the range of health and social care research topics using inclusive research methodologies, systematically appraises the involvement of researchers with intellectual disabilities, and identifies facilitators and barriers to inclusive research. Researchers' experiences of engaging with inclusive research are synthesised. Method: Seventeen empirical studies focused upon inclusive health and social care research were identified. The associated inclusive research methodologies employed, and the stages in which researchers with intellectual disabilities were involved, along with the experiences of researchers with and without intellectual disabilities were synthesised. Results: Papers focused on a broad range of health and social care topics and largely employed qualitative or mixed-methods designs. Researchers with intellectual disabilities were frequently involved with data collection, analysis and dissemination. Facilitators of inclusive research comprised sharing power, team working, having sufficient resources and making research methodologies accessible. Conclusions: Researchers with intellectual disabilities are involved in a wide range of methodologies and research tasks. How the added value of inclusive research is measured and its impact on outcomes, require consideration.

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• co-production
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• intellectual disability
• systematic review

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T1 - A systematic review and narrative synthesis of inclusive health and social care research with people with intellectual disabilities

T2 - How are co-researchers involved and what are their experiences?

AU - Hewitt, Olivia

AU - Langdon, Peter E.

AU - Tapp, Katherine

AU - Larkin, Michael

N1 - Publisher Copyright: © 2023 The Authors. Journal of Applied Research in Intellectual Disabilities published by John Wiley & Sons Ltd.

PY - 2023/7

Y1 - 2023/7

N2 - Background: Using inclusive research methods with people with intellectual disabilities is increasingly common. A recent consensus statement identified key elements when conducting and reporting inclusive research with people with intellectual disabilities. This review identifies the range of health and social care research topics using inclusive research methodologies, systematically appraises the involvement of researchers with intellectual disabilities, and identifies facilitators and barriers to inclusive research. Researchers' experiences of engaging with inclusive research are synthesised. Method: Seventeen empirical studies focused upon inclusive health and social care research were identified. The associated inclusive research methodologies employed, and the stages in which researchers with intellectual disabilities were involved, along with the experiences of researchers with and without intellectual disabilities were synthesised. Results: Papers focused on a broad range of health and social care topics and largely employed qualitative or mixed-methods designs. Researchers with intellectual disabilities were frequently involved with data collection, analysis and dissemination. Facilitators of inclusive research comprised sharing power, team working, having sufficient resources and making research methodologies accessible. Conclusions: Researchers with intellectual disabilities are involved in a wide range of methodologies and research tasks. How the added value of inclusive research is measured and its impact on outcomes, require consideration.

AB - Background: Using inclusive research methods with people with intellectual disabilities is increasingly common. A recent consensus statement identified key elements when conducting and reporting inclusive research with people with intellectual disabilities. This review identifies the range of health and social care research topics using inclusive research methodologies, systematically appraises the involvement of researchers with intellectual disabilities, and identifies facilitators and barriers to inclusive research. Researchers' experiences of engaging with inclusive research are synthesised. Method: Seventeen empirical studies focused upon inclusive health and social care research were identified. The associated inclusive research methodologies employed, and the stages in which researchers with intellectual disabilities were involved, along with the experiences of researchers with and without intellectual disabilities were synthesised. Results: Papers focused on a broad range of health and social care topics and largely employed qualitative or mixed-methods designs. Researchers with intellectual disabilities were frequently involved with data collection, analysis and dissemination. Facilitators of inclusive research comprised sharing power, team working, having sufficient resources and making research methodologies accessible. Conclusions: Researchers with intellectual disabilities are involved in a wide range of methodologies and research tasks. How the added value of inclusive research is measured and its impact on outcomes, require consideration.

KW - co-production

KW - health and social care research

KW - inclusive

KW - intellectual disability

KW - research

KW - systematic review

UR - http://www.scopus.com/inward/record.url?scp=85151967378&partnerID=8YFLogxK

U2 - 10.1111/jar.13100

DO - 10.1111/jar.13100

M3 - Review article

AN - SCOPUS:85151967378

SN - 1360-2322

JO - Journal of Applied Research in Intellectual Disabilities

JF - Journal of Applied Research in Intellectual Disabilities

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Topical Diclofenac, an Efficacious Treatment for Osteoarthritis: A Narrative Review

Frédérique bariguian revel, marina fayet, martina hagen.

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Received 2019 Dec 19; Collection date 2020 Jun.

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ .

Multiple head-to-head trials have demonstrated that topical nonsteroidal anti-inflammatory drugs (NSAIDs), including topical diclofenac, provide at least equivalent analgesia, improvement in physical function, and reduction of stiffness compared with oral NSAIDs in osteoarthritis and have fewer systemic adverse events. While efficacy of topical diclofenac in osteoarthritis is well established, understanding of the time to onset of action, duration of effect, and the minimum effective concentration is limited. Factors likely to influence these parameters include drug penetration and localization. Diclofenac concentrations in the joint tissues are likely to be more relevant than plasma concentrations. However, although diclofenac penetrates and is retained in these “effect compartments” at the site of inflammation and drug activity, no specific minimum effective concentration of diclofenac in plasma or synovial tissue has been identified. Recent evidence suggests that a reduction in inflammatory markers may be a better predictor of efficacy than plasma concentrations. This narrative review explores existing evidence in these areas and identifies the gaps where further research is needed. Based on our findings, topical NSAIDs such as diclofenac should be considered as a guideline-supported, generally well-tolerated, and effective first-line treatment option for knee and hand OA, especially for older patients and those who have comorbid conditions and/or risk factors for various systemic (gastrointestinal, hepatic, renal, or cardiovascular) adverse events associated with oral NSAIDs, particularly at high doses and with long-term use.

Electronic supplementary material

The online version of this article (10.1007/s40744-020-00196-6) contains supplementary material, which is available to authorized users.

Keywords: Anti-inflammatory agents, Arthralgia, Chronic pain, Diclofenac, Non-steroidal, Osteoarthritis

Key Summary Points

Introduction.

Osteoarthritis (OA) currently affects approximately 300 million people worldwide [ 1 ]. Because risk factors for OA are known to include older age and obesity, the global prevalence and burden of disease attributable to OA are expected to increase over time [ 2 , 3 ].

OA is a heterogeneous disease with a wide range of underlying pathologies that ultimately lead to joint damage [ 3 – 6 ]. For this reason, OA can be described as a complex syndrome rather than a single disease [ 7 ]. OA involves structural alterations in articular cartilage, subchondral bone, ligaments, joint capsule, synovial membrane, and periarticular muscle [ 8 ]. In addition to mechanical and metabolic factors, inflammation is now understood to be a key mediator of OA that contributes to cartilage loss and progressive degeneration of affected joints [ 9 , 10 ]. Preclinical investigations have demonstrated that abnormal mechanical joint stress is converted into activated intracellular signaling, leading to downstream overexpression of inflammatory mediators such as prostaglandins, chemokines, and cytokines [ 11 – 13 ]. Thus, OA is no longer considered a noninflammatory arthritis or a “wear and tear” disease [ 9 , 10 ].

OA-related joint destruction and inflammation cause pain, which contributes to functional limitations, increased healthcare resource utilization, and reduced quality of life in patients with this condition [ 5 , 14 , 15 ]. National and international English-language guidelines for the treatment of OA uniformly support a role for nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management in patients with OA (described and referenced in Supplementary Table 1). Of 24 such guidelines, 19 endorse the use of topical NSAIDs as a treatment option for OA pain. The most recent such guideline, the 2019 American College of Rheumatology and Arthritis Foundation guideline for management of OA of the hand, hip, and knee, strongly recommends topical NSAIDs for knee OA, conditionally recommends them for hand OA, and further notes that topical NSAIDs should be used prior to oral NSAIDs on the basis that it is preferable to use medications with the least systemic exposure [ 16 ].

Topical diclofenac is absorbed through the skin and penetrates into subdermal tissues, including synovial tissue, to act directly at the site of pain and inflammation [ 17 ]. By inhibiting predominantly cyclooxygenase 2 (COX-2) enzymes (COX-1/COX-2 IC 50 ratio = 29 [ 18 ])—which are responsible for converting arachidonic acid into prostaglandins, thromboxanes, and prostacyclins [ 19 ]—diclofenac reduces prostaglandin production (Fig.  1 [ 19 – 26 ]), thereby limiting prostaglandin-related sensitization of peripheral nociceptors to painful/mechanical stimuli [ 27 ]. In this review, we survey studies of topical diclofenac’s efficacy, tolerability, and pharmacokinetic/pharmacodynamic properties in OA, and identify areas where additional research is needed.

NSAID modulation of COX-2 and NFκB pathways leads to decreases in PGE2 plasma levels and pro-inflammatory cytokines [ 19 – 26 ]. COX-1 and COX-2, cycolooxygenase-1 and -2; EP2 and EP4, two of the four prostanoid receptors for prostaglandin E2; IL-1β, -6, and -8, interleukin-1β, -6, and -8; NF-кB, nuclear factor kappa B; NSAIDs, nonsteroidal anti-inflammatory drugs; TNFα, tumor necrosis factor alpha

For this narrative review, we conducted three literature searches related to the general efficacy of topical diclofenac in OA, the onset and duration of analgesia, and the minimum effective concentration (MEC) of diclofenac in plasma and target tissue.

For the general efficacy search, we included English-language trials containing outcomes pertaining to pain relief or other measures of improvement associated with use of topical diclofenac or other topical NSAIDs as treatment for OA (at any anatomical site) in adults. The search was conducted using PubMed on October 24, 2018 without date restrictions. A comparable search was subsequently conducted to include safety outcomes of topical diclofenac in patients with OA, and both the efficacy and safety searches were broadened to include systematic reviews, meta-analyses, and professional guidelines on OA.

The search related to onset/duration of action was limited to English-language clinical studies of oral or topical diclofenac in adults with various pain states that reported onset of action (time to start of pain relief, some pain relief, clinically relevant pain relief, or other equivalent outcome) or duration of postdose efficacy. The search was conducted using PubMed on October 10, 2018, without date restrictions. The search results were then narrowed to include only studies of topical diclofenac in OA.

The search on the MEC was conducted broadly to include clinical studies of either oral or topical diclofenac in adults with any pain-related condition that reported plasma/serum or tissue concentrations of diclofenac coupled with an efficacy measure of pain relief or an indirect measure such as reduction of biomarkers, published in English. This search was conducted without date restrictions on October 4, 2018 using PubMed and January 29, 2019 using Embase. The search results were subsequently narrowed to include only studies of topical diclofenac in OA.

For all of the search categories, the authors then added publications based on their knowledge of the field, and additional references were identified by cross-referencing publications. This review article is based on previously conducted studies and does not contain any unpublished original data from studies with human participants or animals performed by any of the authors.

Topical Diclofenac Efficacy in Osteoarthritis

Systematic reviews and meta-analyses have confirmed the efficacy of topical diclofenac in chronic pain due to OA [ 28 – 30 ]. A recent network meta-analysis of randomized controlled trials (RCTs) and observational studies, predominantly of knee OA, reported the superiority of topical diclofenac compared with placebo for pain relief as well as functional improvement [ 28 ]. Statistically significant improvements in pain relief were found for diclofenac solution [standardized mean difference (SMD) vs. placebo − 0.29; 95% confidence interval (CI) − 0.40, − 0.18)] and diclofenac gel (SMD − 0.30; 95% CI − 0.39, − 0.20), with diclofenac patches demonstrating the largest effect on pain relief of any topical NSAID studied (diclofenac, ibuprofen, piroxicam, nimesulide, ketoprofen, salicylate, eltenac, etoricoxib, indomethacin) (SMD − 0.94; 95% CI − 1.20, − 0.68). Significant improvements in function also were noted for diclofenac solution (SMD − 0.32; 95% CI − 0.43, − 0.21), gel (SMD − 0.36; 95% CI − 0.46, − 0.27), and patch (SMD − 0.55; 95% CI − 0.81, − 0.30).

Most recently, Wiffen et al. [ 30 ] conducted a systematic review of placebo-controlled studies of topical diclofenac in patients with knee or hand OA. In five 6- to 12-week studies, they reported clinical success (defined as ≥ 50% reduction in pain intensity or Osteoarthritis Research Society International Index response) in 59% of those treated with topical diclofenac gel or solution vs. 48% of those treated with placebo [i.e., carrier alone; risk ratio (RR) 1.2; 95% CI 1.1–1.3). In five 2- to 6-week studies in patients with knee OA, Wiffen et al. reported clinical success (≥ 50% reduction in pain or patient global assessment of very good or excellent) in 43% treated with topical diclofenac plaster, gel, or solution versus 23% with placebo (RR 1.9; 95% CI 1.5–2.3).

Three RCTs have directly compared topical diclofenac with an oral NSAID, and all three found them to provide at least equivalent relief of OA pain and other symptoms (Table  1 ) [ 31 – 33 ]. Two of these trials used oral diclofenac [ 31 , 32 ] as the comparator and the third used ibuprofen [ 33 ]. Both of the head-to-head topical vs. oral diclofenac studies were included in the meta-analysis described above [ 28 ].

Studies comparing topical diclofenac and oral NSAIDs for osteoarthritis pain management

DEA diethylamine, DMSO dimethyl sulfoxide, HAQ Health Assessment Quality of Life (lower score = improvement), NSAID non-steroidal anti-inflammatory drug, OA osteoarthritis, PBO placebo, PGA patient global assessment, POHA patient overall health assessment, QID four times per day, RCT randomized controlled trial, TID three times per day, VAS visual analog scale, WOMAC Western Ontario and McMaster Universities Osteoarthritis Index

One of the two topical vs. oral diclofenac studies was a 12-week double-blind, double-dummy study comparing topical diclofenac solution (1.5% diclofenac sodium in 45.5% dimethyl sulfoxide [DMSO]) with oral diclofenac capsules 50 mg three times daily (the maximum daily dose) in patients with symptomatic primary knee OA (per protocol N  = 492) [ 31 ]. Patients with pain in both knees were allowed to apply the topical solution to both, but only the knee with the most pain at baseline was included in the efficacy evaluation. Topical and oral diclofenac were associated with similar rates ( P  > 0.05) of improvement across all variables of pain (44 vs. 49%), physical function (39 vs. 46%), and stiffness (39 vs. 45%), as well as on a patient global assessment (43 vs. 49%), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at the end of 12-week treatment (or earlier discontinuation). All variables met prespecified criteria for equivalency [ 31 ].

A double-blind, double-dummy, 12-week study compared five treatments in 722 patients with knee OA: (1) topical diclofenac solution (1.5% diclofenac sodium in 45.5% DMSO) plus oral placebo, (2) DMSO solution (45.5% DMSO without diclofenac) plus oral placebo, (3) topical and oral placebos, (4) oral diclofenac 100 mg slow-release tablets plus placebo solution, and (5) topical diclofenac solution plus oral diclofenac tablets [ 32 ]. If both knees were affected by OA, topical treatments were applied only to the knee with more pain at baseline, or to the dominant knee if pain was equivalent in both. Primary efficacy variables were WOMAC pain and physical function and patient overall health assessment (POHA). WOMAC stiffness and patient global assessment (PGA) were secondary outcomes. At the end of treatment, topical diclofenac had efficacy comparable to that of oral diclofenac on all efficacy measures: mean [standard deviation (SD)] change in pain score from baseline to final assessment was − 6.0 (4.5) vs. − 6.4 (4.1), P  = 0.429; change in physical function score was − 15.8 (15.1) vs. − 17.5 (14.3), P  = 0.319; change in POHA was − 0.95 (1.30) vs. − 0.88 (1.31), P  = 0.956; change in stiffness score was − 1.93 (2.01) vs. − 2.07 (2.02), P  = 0.596; and change in PGA was − 1.36 vs. − 1.42 (1.29), P  = 0.439. Topical diclofenac was superior ( P  < 0.05) to vehicle solution on all of those outcomes and superior to oral placebo on all outcomes except stiffness. No additional efficacy was evident by combining topical and oral diclofenac [ 32 ].

The third head-to-head, randomized, double-blind, double-dummy study compared topical diclofenac diethylamine gel (1.16%, 10 cm applied to the affected finger four times daily) with oral ibuprofen (400 mg three times daily, the maximum nonprescription daily dose) for 21 days in 321 patients with OA affecting at least three finger joints (mean, ~ 8) [ 33 ]. Response, defined as a ≥ 40% reduction in general pain on movement rated on 100-mm visual analog scale (VAS) at the end of treatment, occurred in 44% with topical diclofenac and 34% with ibuprofen and met the predefined criterion for equivalency. Topical diclofenac and oral ibuprofen resulted in comparable improvements with regard to morning stiffness [mean (SD) change − 14.5 (24.3) vs. − 16.6 (23.2) min] and grip strength measured using a dynamometer [left hand: + 0.030 (0.085) vs. + 0.020 (0.085); right hand; + 0.023 (0.082) vs. + 0.036 (0.093) bar], as well as equivalent improvements on other measures of pain relief, self-rated and physician-rated disease activity, and quality of life [ 33 ]. One limitation of all three of these head-to-head studies is that comparisons were reported only at the end of treatment, so whether results were consistent throughout the course of treatment is unknown.

Results of the three studies of topical diclofenac are consistent with findings from studies of other topical NSAIDs (ibuprofen, ketoprofen), which were also found to provide relief from chronic knee pain and stiffness as well as improvements in physical function similar to oral NSAIDs [ 34 – 36 ]. A recent systematic review pooled the three topical diclofenac studies in patients with knee OA [ 30 ]. Clinical success (defined as ≥ 50% reduction in pain, very good or excellent global rating, or rating of no or slight pain) was achieved by 55% of patients with OA treated with topical NSAIDs and 56% treated with oral NSAIDs (RR 0.98; 95% CI 0.89–1.08), again supporting the equivalent analgesic effects of topical and oral NSAIDs in OA.

Another recent meta-analysis of RCTs in OA analyzed pain reduction in seven trials of topical NSAIDs (diclofenac or ketoprofen) in knee and hand OA and nine studies of oral NSAIDs (naproxen, ibuprofen, and diclofenac) in knee or hip OA [ 29 ]. (One study [ 32 ] was also analyzed in the two meta-analyses described above [ 28 , 30 ]). For this meta-analysis, authors standardized the WOMAC and VAS pain scores on a 1–100 scale, calculated relative (%) change from baseline, and then pooled the results taking into account the number of participants in each study arm [ 29 ]. Topical NSAIDs were associated with a greater relative reduction in pain (− 40.9%; 95% CI 39.4–42.5) than oral NSAIDs (− 34.3%; 95% CI 32.6–36.0), and this difference was statistically significant ( P  < 0.001). Topical NSAIDs also provided significantly ( P  < 0.001) greater relative reductions in pain (− 40.9%) compared with oral acetaminophen (− 32.5%), COX-2 inhibitors celecoxib and meloxicam (− 36.9%), and opioids tramadol and controlled-release oxycodone (− 35.4%). It should be noted that in this analysis, calculation of relative change from baseline in OA pain intensity was not adjusted for placebo effect [ 29 ]. As a point of comparison, the relative change in pain was − 38.1% with topical placebo and − 31.1% with oral placebo [ 29 ]. Placebo effect, which is typically higher with topical than with oral treatment, may have contributed to the superiority of topical vs. oral NSAIDs in this analysis.

Placebo effect can be considerable and the fact that it is greater with topical than oral administration suggests that the route of administration itself may contribute to perceptions of pain reduction. In one study, WOMAC pain scores were reduced by 38 and 40% with topical placebos (4.4 and 2.2 g gels, respectively) vs. 29% with oral placebo [ 36 ]. The systematic review described above [ 30 ] reported clinical success in 48% of participants treated with topical placebo in the 6- to 12-week studies, whereas a separate pooled analysis of seven trials reported that 25% of participants treated with oral placebo had a ≥ 50% reduction in pain after 12 weeks [ 37 ]. Patient expectation can enhance drug effects, and the two are not simply additive [ 38 , 39 ]. Placebo effects are thought to be influenced by the patient’s expectations of or hopes for a treatment effect, treatment setting, patient–provider relationship, beliefs about medications, and contextual/verbal/social cues coupled with prior conditioning [ 40 – 42 ]. They can also be the result of changes related to the natural history of the disease, unrecognized concomitant medication use, regression to the mean, and experimenter and patient biases [ 42 ]. With topical therapies, the smell, color, and massage during application also may have psychological effects [ 43 ].

Thus, current evidence indicates that topical diclofenac relieves OA pain and stiffness and improves physical function, at least to the same degree as some oral NSAIDs. Notably, two of the three head-to-head studies of topical diclofenac used doses of oral NSAIDs that were lower than maximum prescription doses. However, the results of these two trials were consistent with the trial that used the maximum dose of oral diclofenac as a comparator as well as with studies and meta-analyses that included other topical NSAIDs. It should also be noted that while the studies reviewed here evaluated efficacy in a single target joint, topical diclofenac may be used on multiple joints concurrently by real-world patients with polyarticular arthritis. In such cases, dosing instructions should be carefully followed, particularly with regard to maximum daily doses to be used across all joints. Along with therapeutic effects of the active ingredient, the topical route of administration may positively contribute to the perceived pain reduction in OA.

Topical Diclofenac Safety and Tolerability in Osteoarthritis

Adverse events associated with topical diclofenac are primarily local reactions at the application site (dry skin, redness/erythema, pruritus) with minimal systemic effects. A meta-analysis of topical NSAIDs found higher rates of overall adverse events (odds ratio [OR] 1.30; 95% CI 1.10–1.53) with topical diclofenac compared with placebo ( N  = 8 studies) in studies of knee or hand OA, driven predominantly by increased skin and subcutaneous tissue disorders (OR 1.73; 95% CI 0.96–3.10) [ 44 ]. However, there was no increase in gastrointestinal adverse events (OR 1.11; 95% CI 0.75–1.64) and no increase in severe events (OR 1.19; 95% CI 0.68–2.07) or serious events (OR 0.94; 95% CI 0.26–3.42) compared with placebo [ 44 ]. Another meta-analysis reported no increase in systemic adverse events (RR 0.89; 95% CI 0.59–1.3) or gastrointestinal adverse events (RR 1.1; 95% CI 0.76–1.6) with topical diclofenac compared with carrier alone in knee and hand OA [ 30 ]. A randomized, placebo-controlled study found no increase in risk of hepatic enzyme elevations with topical diclofenac solution in a DMSO vehicle compared with the vehicle alone in patients with knee OA [ 32 ].

Limited systemic exposure occurs with topical administration (e.g., 6.6% absorption of applied dose of 1.5% diclofenac sodium lotion [ 45 ]; area under the plasma concentration–time curve from 0 to 24 h: mean 233 ng·h/ml with topical administration of 4 g diclofenac sodium gel 1% four times daily vs. 3890 ng·h/ml with oral diclofenac sodium 50 mg three times daily for 7 days [ 46 ]). This is a potential advantage over oral NSAIDs, which have a higher risk of systemic adverse events.

A pooled analysis of two studies directly comparing the safety of topical diclofenac with that of oral diclofenac in patients with knee OA found that the topical solutions resulted in fewer gastrointestinal events (25.4 vs. 39.0% of patients, P  < 0.0001), especially dyspepsia (11.0 vs. 18.4%, P  = 0.001), diarrhea (6.5 vs. 13.4%, P  = 0.0004), abdominal distension (6.0 vs. 10.6%, P  = 0.01), and upper abdominal pain (5.6 vs. 12.1%, P  = 0.0005) [ 47 ]. Topical diclofenac was also associated with a lower incidence of abnormal liver enzyme levels at the end of the study, including alanine aminotransferase levels (10.4 vs. 22.2%, P  < 0.0001), aspartate aminotransferase levels (7.0 vs. 14.6%, P  = 0.0004), and γ-glutamyl transferase (21.1 vs. 33.4%, P  < 0.0001). Topical administration was associated with more dermatologic reactions (29.0 vs. 6.1%, P  < 0.0001), most commonly dry skin (24.1 vs. 1.9%, P  < 0.0001), pruritus (4.9 vs. 1.9%, P  = 0.01) and contact dermatitis (4.3 vs. 0.6%, P  < 0.001) at the application site [ 47 ]. Similarly, pooling the three trials that directly compared topical diclofenac with oral NSAIDs demonstrated that topical diclofenac was associated with a lower risk of gastrointestinal adverse events (RR 0.63; 95% CI 0.53–0.73) and a higher risk of local adverse events (RR 8.31; 95% CI, 4.5–14) than oral NSAIDs [ 30 ].

In the pooled analysis of the two studies comparing topical and oral diclofenac, described above, cardiovascular adverse events were numerically, but not statistically significantly, lower with topical than oral diclofenac (1.5 vs. 3.5%, P  = 0.055). Oral NSAIDs, especially rofecoxib or diclofenac, have been associated with increased risk of myocardial infarction when used at high doses for prolonged periods [ 48 ]. Cardiovascular risk associated with topical vs. oral NSAIDs was also compared in a retrospective cohort study using national claims data from Taiwanese patients with rheumatoid arthritis [ 49 ]. Topical nonselective NSAIDs were associated with a lower risk of composite cardiovascular events (myocardial infarction, unstable angina, heart failure, stroke, and revascularization) than oral nonselective NSAIDs (crude incidence 1.83 vs. 2.14 per 100 person-years; HR 0.54; 95% CI 0.37–0.77 by multivariate Cox model [ 49 ]).

Given that topical diclofenac provides at least equivalent analgesia to some oral NSAIDs and has fewer systemic adverse events, topical diclofenac administration may be preferred, especially for older patients with OA and those who have comorbid conditions and/or risk factors for various systemic (gastrointestinal, hepatic, renal, or cardiovascular) adverse events associated with oral NSAIDs. Adverse events are typically local skin reactions, which are usually minor and transient [ 50 ]. If required, the products should be discontinued (e.g., by removal of patches or by washing off creams or gels) and application of symptomatic treatments could be considered.

Onset of Action in Osteoarthritis

Data on timing of onset of efficacy for topical diclofenac are sparse. Most studies of OA treatment were designed to evaluate efficacy and safety rather than onset of effect. Due to the chronic nature of OA, these studies tend to span a prolonged period of time with emphasis on long-term effects and few assessments capturing short-term effects following treatment application.

Only one study was found that directly assessed onset of action by making hourly assessments during the first few hours after topical diclofenac application. The study was a double-blind RCT of diclofenac epolamine patch containing 180 mg of drug (equivalent to 130 mg of diclofenac) vs. placebo patch in 155 patients with knee OA. Pain intensity was measured using a VAS score hourly for the first 5 h after patch application [ 51 ]. Pain intensity in the diclofenac group was significantly decreased vs. baseline starting at the first assessment, 1-h post treatment (Wilcoxon rank test, P  = 0.0316), with further reductions observed over the following hours. Pain relief was significantly greater with diclofenac than placebo beginning at the third hour ( P  = 0.0034). Thus, the authors observed the pain-relieving effect before diclofenac is thought to be detectable in plasma, which, on average, occurs about 4.5 h after topical application. The authors suggested that during this interval, diclofenac accumulates in the tissue under the patch, permeating the muscles, tendons, and joint capsules in direct contact with the subcutis, thereby explaining this fast onset of local pain relief in the absence of considerable diclofenac concentrations in plasma [ 51 ].

Three other studies collected pain ratings daily after topical diclofenac application in patients with OA [ 52 – 54 ], and two collected pain ratings in patients with OA at 4–7 days [ 55 , 56 ]. While none of these studies included time to onset of effect as a specific study outcome, benefit was consistently observed sometime within or at the first week of treatment. Daily (or longer) assessment does not provide a good indication of true time of onset of effect, which could potentially occur before this first measurement.

While the onset of action in chronic conditions may seem less relevant to clinicians than the overall efficacy and safety, for patients, the onset of pain relief likely carries considerable importance. Being able to accurately advise patients as to when they can expect the medication to start working may be important to avoid unjustified treatment cessation, excessive repeat doses, or concomitant intake of oral pain medications while waiting for the topical medication to work. Additional studies to assess the onset of action, in recognition of its importance in pain management, may be useful, not only in the treatment of acute injuries but also in the treatment of chronic conditions like OA.

Duration of Effect

Duration of pain relief is an important consideration for analgesic medications, because higher dosing frequency is associated with nonadherence among chronic pain patients [ 57 ]. Better adherence to analgesic regimens may reduce suffering and improve physical functioning [ 58 ], and the link between treatment adherence/persistence and patient satisfaction has been well established across a spectrum of diseases including chronic pain states [ 59 ].

One large ( N  = 260) double-blind, vehicle-controlled study of 2% diclofenac sodium topical solution applied twice daily in adults with knee OA found that analgesia as determined by WOMAC pain score was maintained throughout the 12-h dosing interval among responders [ 53 ]. In two (selected) responder groups [≥ 30% and ≥ 50% reduction in numeric rating scale (NRS) score at week 4 vs. baseline], scores on an 11-point NRS during active treatment were not significantly different at midday vs. evening, suggesting that the twice-daily regimen maintained pain relief in these responder groups throughout the 12-h dosing interval at week 4 [ 53 ]. This long-lasting effect may be attributed to the slower clearance of diclofenac from the inflamed tissue compared with plasma [ 60 – 62 ], as discussed in the next section of this review.

Further studies investigating the duration of analgesia with other topical diclofenac formulations may be informative.

Pharmacokinetic Effect Compartments and Minimum Effective Concentration

Plasma and synovial tissue concentrations after topical administration.

It is well established that topical diclofenac penetrates the skin, permeates underlying tissues, and enters the synovium (Fig.  2 ) [ 63 – 66 ]. Analgesic efficacy may be dependent on diclofenac concentration in the synovial compartment, the site of diclofenac’s activity. However, reports of the relative distribution of diclofenac following topical administration in joint tissue (the “effect compartment”) and in plasma (a “side effect compartment”) are variable [ 65 – 68 ], and the minimum concentration needed in plasma or synovial tissue to achieve a meaningful reduction in pain intensity is still poorly defined.

Flow of diclofenac from topical application to the joint capsule showing known steps ( green arrows ) and potential influencers of minimum effective concentration ( red question marks )

The pharmacokinetic profile of diclofenac in the synovium differs from that in the plasma, with a faster rate of elimination in plasma [ 60 – 62 ]. Following oral administration, diclofenac has been found to persist in inflamed tissues for up to 12 h after dosing, potentially accounting for its extended duration of action compared with its short plasma half-life of 1–2 h [ 60 , 62 , 69 ].

There are certain reasons for diclofenac to preferentially accumulate in the inflamed joint tissues. Drugs that are highly protein-bound [e.g., diclofenac (> 99% in plasma [ 70 ])] concentrate wherever albumin concentrates [ 63 ]. Albumin concentrations are increased in inflamed synovial tissue and fluid compared with the joints of healthy persons [ 9 , 71 ]. Diclofenac’s protein-binding and short plasma half-life (1–2 h) creates a high plasma/tissue gradient promoting movement into inflamed joints [ 67 , 72 , 73 ]. Diclofenac has hydrophilic/lipophilic polarity, which also facilitates permeation of and retention in the intracellular spaces and cell membranes in inflamed tissues [ 17 , 67 , 72 – 74 ]. Given the lack of a clear association between diclofenac levels in plasma compared with target tissues, attainment of a specific plasma concentration may be unrelated to therapeutic effect.

The results of a randomized, double-blind, placebo-controlled crossover study suggest that analgesic efficacy may be dependent on diclofenac concentration in the synovial compartment, the site of diclofenac’s activity. This study compared the analgesic efficacy of topical (65 mg) and oral (93 mg) diclofenac acid and placebo in reducing inflammatory hyperalgesia from a “freeze lesion” in ten healthy volunteers [ 75 ]. That study found that topical diclofenac was more effective than oral diclofenac 1 h after dosing (though not at later assessments) and that this efficacy coincided with higher tissue concentrations in the group that received topical administration (46.1 ± 25.8 ng/ml vs. 11.4 ± 2.09 ng/ml, P  < 0.02) at about 1–1.5 h, when no diclofenac was detectable in plasma after topical administration [ 75 ]. No dose–response relationship has been reported for synovial diclofenac concentrations and analgesic efficacy. Data are still lacking on the minimum amount of diclofenac needed in the joint to achieve pain relief.

In summary, diclofenac concentrations in inflamed joint tissue may be more relevant to potential therapeutic effect than plasma concentrations. Diclofenac penetrates these “effect compartments” at the site of inflammation and drug activity. Diclofenac is known to be effective in reducing pain in these target joints; however, a specific MEC in synovial tissue or synovial fluid has not been defined.

Identifying the MEC Based on Prostaglandin E2 (PGE2) Inhibition and Inflammatory Mediators

Because the mechanism of NSAIDs indirectly involves reduction of PGE2 via inhibition of COX-2 enzymes, PGE2 serves as a surrogate marker of COX-2 inhibition. Diclofenac is an effective inhibitor of PGE2 production and has been reported to be 3–1000 times more potent on a molar basis compared with other NSAIDs in its ability to inhibit COX activity [ 76 , 77 ]. Therefore, compared with other NSAIDs, much smaller diclofenac concentrations may be required to achieve the same level of PGE2 reduction and therapeutic effect.

Some investigators have demonstrated relationships between synovial NSAID concentrations and PGE2 reduction. Chlud and Wagner previously suggested that a diclofenac concentration of 100–500 ng/ml in the synovium was consistent with clinical efficacy and in agreement with in vitro studies correlating these concentrations with inhibition of prostaglandin synthesis [ 43 ]. We have previously estimated that a synovial diclofenac concentration of 45 ng/ml would result in a 50% reduction (IC 50 ) in PGE2 [ 63 ]. In another study, Liauw et al. [ 78 ] found that after a single oral 75-mg dose of diclofenac, diclofenac concentrations in synovial fluid peaked at hour 4 (181 ng/ml), coinciding with a 95% reduction in PGE2 levels in synovial fluid. Diclofenac concentrations gradually decreased to 60 ng/ml at hour 12, and PGE2 inhibition remained at about 50% during that interval. After twice-daily dosing for a week, on day 8 the diclofenac concentration in synovial fluid again peaked at hour 4 (227 ng/ml) and declined to 117 ng/ml at hour 12, while PGE2 levels remained suppressed throughout the 12-h dosing interval. Martel-Pelletier et al. [ 79 ] measured PGE2 in ex vivo synovial membrane and cartilage tissue samples from eight patients with OA after addition of diclofenac 125 and 250 ng/ml; this resulted in > 90% inhibition of PGE2 synthesis. However, the relationship between PGE2 reduction and analgesic effect remains poorly elucidated.

After exposure to NSAIDs, inflammatory cytokines that follow PGE2 in the signal transduction pathway [e.g., interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα)] are reduced along with PGE2 [ 20 , 26 , 63 , 80 ] (Fig.  1 [ 19 – 26 ]). Clinical data measuring inflammatory biomarkers after topical diclofenac use are limited. A randomized, open-label study of oral NSAIDs, including slow-release diclofenac 75 mg once or twice daily, ibuprofen 600 mg two or three times daily, or celecoxib 200 mg once or twice daily, in patients with OA reported dose-dependent reductions in IL-6, TNFα, and vascular endothelial growth factor in the synovial fluid, which significantly correlated with improvement in total WOMAC scores [ 25 ]. As a point of reference, an oral 75-mg dose is associated with an estimated synovium diclofenac concentration of 50–175 ng/ml [ 63 ]. There is also evidence that NSAIDs may reduce proinflammatory cytokines like IL-6 at the transcription level through effects on the transcription factor NF-κB (nuclear factor kappa B) and independent of effects on prostaglandins [ 26 ].

Whereas the severity of OA-related pain does not correlate with the degree of structural joint damage [ 81 , 82 ], the presence of synovitis or effusion has been found to predict joint pain in OA [ 4 , 6 , 83 , 84 ]. Furthermore, the presence of pro-inflammatory biomarkers in synovial fluid has been found to correlate with pain, and different inflammatory mediators are associated with different pain manifestations (Table  2 ) [ 85 – 88 ]. Leung et al. [ 85 ] estimated that a change in inflammatory biomarkers (e.g., TNFα, IL-6, IL-8) of two standard deviations might be associated with meaningful pain response; however, it remains unknown what concentration of diclofenac would be needed to produce such a change in these biomarkers.

Cytokines associated with pain, and direct effects on sensory neurons and other downstream inflammatory mediators

(+) positive association, (−) negative (inverse) association, IL interleukin, NA no association identified, NE not evaluated in the articles identified, TNFα tumor necrosis factor alpha, VEGF vascular endothelial growth factor

In summary, existing evidence based largely on studies of oral administration suggest that a diclofenac concentration of 45 ng/ml in synovial tissue is associated with a 50% reduction in PGE2, while concentrations > 100 ng/ml are associated with > 80% reduction in PGE2. Further research is needed before it can be determined whether these concentrations also apply to topical diclofenac and to clarify what degree of reduction in COX-2, PGE2, and downstream inflammatory cytokines is required for clinically meaningful pain relief.

Challenges in Identifying the MEC

Patient- and disease-related factors can lead to variability in individual responses to topical diclofenac, which poses a challenge to identification of an MEC. Such factors include the stage of OA progression, the variable extent and nature of inflammation, and the underlying mechanisms of the patient’s pain (inflammatory, nociceptive, and/or central; Fig.  2 [ 20 , 21 , 63 ]).

Pain phenotypes differ at different stages of OA. Patients with early OA tend to experience predictable bouts of pain triggered by activity. At its middle stages, OA is associated with more constant background pain/achiness, especially at night, and in advanced OA, patients may experience constant background pain accompanied by intermittent bouts of unpredictable severe pain [ 5 , 89 ]. Some patients with OA progress rapidly through these stages whereas others may have more stable disease. The extent of inflammation varies over the course of the disease, with more inflammatory mediators (e.g., TNFα, IL-1β) present in early (< 1 year) knee OA compared with advanced-stage knee OA [ 5 , 85 ].

While bone remodeling, loss of cartilage, and narrowing of the joint space are the characteristic morphological changes observed in OA, pain often is associated with the presence of inflammation (synovitis) [ 4 , 6 , 84 ]. In such cases, peripheral nerves in the various degenerating joint tissues become exposed to the intra-articular environment rich in cytokines, chemokines, proteases, prostaglandins, and neuropeptides, which serve as ligands for nociceptors [ 86 , 90 – 92 ]. Ligand binding lowers the threshold of these receptors and sensitizes the peripheral neurons, such that even normal joint movement triggers a pain response [ 86 , 87 , 93 ]. In addition, based on murine models, serine proteases (e.g., mast cell tryptase and neutrophil elastase) may activate protease-activated receptor-2, thereby serving as signaling molecules for leukocyte trafficking and nociceptive OA joint pain [ 94 , 95 ].

In addition to nociceptive pain, neuropathic pain may result from direct damage to the nerves in the injured joint, dorsal root ganglia, and spinal cord [ 11 , 96 , 97 ]. Neuropathic pain is not responsive to NSAIDs [ 92 ].

Central sensitization can be another major component of OA pain, manifesting as increased sensitivity to noxious stimuli (hyperalgesia) or interpretation of non-noxious stimuli as painful (allodynia) [ 27 , 92 ]. Although there is some evidence that diclofenac crosses the blood–brain barrier [ 98 , 99 ], low concentrations are likely to enter the central nervous system following topical administration given the limited systemic exposure associated with topical use. Therefore, the neuropathic component of OA pain is not expected to be responsive to topical NSAIDs.

Thus, OA pain may have peripheral elements (e.g., inflammation, sensitization of peripheral neurons, direct damage to nerves) as well as central components (e.g., hyperalgesia and allodynia), and these heterogeneous underlying mechanisms may respond differently to treatment [ 5 , 92 , 100 ]. Patients with earlier-stage OA pain related to active inflammation, particularly inflammatory mediators downstream of PGE2, would likely have the best response to topical NSAIDs based on their mechanism of action, but this remains to be confirmed. Given that the magnitude of inflammation, the specific inflammatory mediators present, and the extent to which central pain mechanisms contribute may vary from patient to patient and over the course of OA, it is not surprising that the existing, albeit limited, data related to concentrations achieved in different target areas have been variable/inconsistent, and it may not be possible to identify a single diclofenac MEC that would universally apply to all patients with OA.

Conclusions

The use of topical NSAIDs including diclofenac is endorsed by a majority of treatment guidelines for management of OA-related joint pain. In multiple head-to-head RCTs, topical diclofenac provided pain relief, improvement of physical function, and reduction in stiffness comparable to that of some oral NSAIDs, with fewer systemic side effects, in patients with knee or hand OA. The topical route of administration may further enhance and benefit the analgesic effects, given that topical placebo is more effective than oral placebo. Limited data suggest that pain relief begins within a few hours of topical administration and is generally well sustained throughout the 12-h dosing interval, especially with ongoing use.

Following topical administration, diclofenac accumulates in inflamed joint tissue; however, no specific diclofenac MECs have been identified. While synovial tissue concentrations are likely to be more relevant than plasma concentrations, and have been found to correlate with PGE2 reductions (a measure of COX-2 inhibition), identification of a specific synovial MEC is hampered by the fact that OA is a heterogeneous disease with widely varying pain mechanisms in individual patients and at different stages of the disease. The concentration of different biomarkers varies over the course of OA and the reduction of specific biomarkers seems to impact different aspects of pain sensations.

While efficacy of topical diclofenac in OA is well established, further research is needed to better elucidate what degree of reduction in PGE2 or other downstream inflammatory mediators (e.g., IL-6, TNFα) in synovial tissue is necessary to achieve an analgesic effect. Additional research also is needed to more clearly identify time to onset of action and duration of pain relief to differentiate individual topical formulations of diclofenac.

Below is the link to the electronic supplementary material.

Acknowledgements

This review and the Rapid Service Fee were funded by GSK Consumer Healthcare S.A., Nyon, Switzerland.

Medical Writing Assistance

Medical writing assistance was provided to the authors by Lauren Cerruto of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and funded by GSK Consumer Healthcare S.A., Nyon, Switzerland.

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosures

Frédérique Bariguian Revel, Marina Fayet and Martina Hagen are employees of GSK Consumer Healthcare S.A., Nyon, Switzerland, which produces a wide range of analgesics (e.g., paracetamol, ibuprofen, diclofenac), including both topical and oral formulations.

Compliance with Ethics Guidelines

This review article is based on previously conducted studies and does not contain any unpublished original data from studies with human participants or animals performed by any of the authors.

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To view enhanced digital features for this article go to: 10.6084/m9.figshare.11791470.

Contributor Information

Frédérique Bariguian Revel, Email: [email protected].

Martina Hagen, Email: [email protected].

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