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Synthesising quantitative evidence in systematic reviews of complex health interventions
  1. Julian P T Higgins1,
  2. José A López-López1,
  3. Betsy J Becker2,
  4. Sarah R Davies1,
  5. Sarah Dawson1,
  6. Jeremy M Grimshaw3,4,
  7. Luke A McGuinness1,
  8. Theresa H M Moore1,5,
  9. Eva A Rehfuess6,
  10. James Thomas7,
  11. Deborah M Caldwell1
  1. 1Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  2. 2Department of Educational Psychology and Learning Systems, College of Education, Florida State University, Tallahassee, Florida, USA
  3. 3Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada
  4. 4Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  5. 5NIHR Collaboration for Leadership in Applied Health Care (CLAHRC) West, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
  6. 6Institute for Medical Information Processing, Biometry and Epidemiology, Pettenkofer School of Public Health, LMU Munich, Munich, Germany
  7. 7EPPI-Centre, Department of Social Science, University College London, London, UK
  1. Correspondence to Professor Julian P T Higgins; julian.higgins{at}


Public health and health service interventions are typically complex: they are multifaceted, with impacts at multiple levels and on multiple stakeholders. Systematic reviews evaluating the effects of complex health interventions can be challenging to conduct. This paper is part of a special series of papers considering these challenges particularly in the context of WHO guideline development. We outline established and innovative methods for synthesising quantitative evidence within a systematic review of a complex intervention, including considerations of the complexity of the system into which the intervention is introduced. We describe methods in three broad areas: non-quantitative approaches, including tabulation, narrative and graphical approaches; standard meta-analysis methods, including meta-regression to investigate study-level moderators of effect; and advanced synthesis methods, in which models allow exploration of intervention components, investigation of both moderators and mediators, examination of mechanisms, and exploration of complexities of the system. We offer guidance on the choice of approach that might be taken by people collating evidence in support of guideline development, and emphasise that the appropriate methods will depend on the purpose of the synthesis, the similarity of the studies included in the review, the level of detail available from the studies, the nature of the results reported in the studies, the expertise of the synthesis team and the resources available.

  • meta-analysis
  • complex interventions
  • systematic reviews
  • guideline development

Data availability statement

No additional data are available.

This is an open access article distributed under the terms of the Creative Commons Attribution IGO License (CC BY NC 3.0 IGO), which permits use, distribution,and reproduction in any medium, provided the original work is properly cited. In any reproduction of this article there should not be any suggestion that WHO or this article endorse any specific organization or products. The use of the WHO logo is not permitted. This notice should be preserved along with the article’s original URL.Disclaimer: The author is a staff member of the World Health Organization. The author alone is responsible for the views expressed in this publication and they do not necessarily represent the views, decisions or policies of the World Health Organization.

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Data availability statement

No additional data are available.

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  • Handling editor Soumyadeep Bhaumik

  • Contributors JPTH co-led the project, conceived the paper, led discussions and wrote the first draft. JAL-L undertook analyses, contributed to discussions and contributed to writing the manuscript. BJB drafted material on mechanisms, contributed to discussions and contributed extensively to writing the manuscript. SRD screened and categorised the results of the literature searches, collated examples and contributed to discussions. SD undertook searches to identify relevant literature and contributed to discussions. JMG contributed to discussions and commented critically on drafts. LAM undertook analyses, contributed to discussions and commented critically on drafts. THMM contributed examples, contributed to discussions and commented critically on drafts. EAR and JT contributed to discussions and commented critically on drafts. DMC co-led the project, contributed to discussions and drafted extensive parts of the paper. All authors approved the final version of the manuscript.

  • Funding Funding provided by the World Health Organization Department of Maternal, Newborn, Child and Adolescent Health through grants received from the United States Agency for International Development and the Norwegian Agency for Development Cooperation. JPTH was funded in part by Medical Research Council (MRC) grant MR/M025209/1, by the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_12013/9) and by the MRC ConDuCT-II Hub (Collaboration and innovation for Difficult and Complex randomised controlled Trials In Invasive procedures – MR/K025643/1). BJB was funded in part by grant DRL-1252338 from the US National Science Foundation (NSF). JMG holds a Canada Research Chair in Health Knowledge Transfer and Uptake. LAM is funded by a National Institute for Health Research (NIHR) Systematic Review Fellowship (RM-SR-2016-07 26). THMM was funded by the NIHR Collaboration for Leadership in Applied Health Research and Care West (NIHR CLAHRC West). JT is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care North Thames at Bart’s Health NHS Trust. DMC was funded in part by NIHR grant PHR 15/49/08 and by the Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer –MR/KO232331/1).

  • Disclaimer The views expressed are those of the authors and not necessarily those of the CRC program, the MRC, the NSF, the NHS, the NIHR or the UK Department of Health.

  • Competing interests JMG reports personal fees from the Campbell Collaboration. EAR reports being a Methods Editor with Cochrane Public Health.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.