Navigate the links below to jump to a specific section of the page:

• Definition
• How do I know when an Intervention is Complex?
• Outline of Stages
• Methods and Guidance
• Examples of Reviews of Complex Interventions
• Supplementary Resources

Review questions are harder to define when they involve complex interventions. To date, there is no single agreed on definition of complex interventions. 

Characteristics

Guise et al. (2017) put forth that all complex interventions have two common characteristics:

• they have multiple components (intervention complexity)
• and complicated/multiple causal pathways, feedback loops, synergies, and/or mediators and moderators of effect (pathway complexity).

Complex interventions may also have one or more of the following characteristics:

• target multiple participants, groups, or organizational levels (population complexity);
• require multifaceted adoption, uptake, or integration strategies (implementation complexity);
• or work in a dynamic multi-dimensional environment (contextual complexity).

According to Guise et al. (2017): To judge whether an intervention is simple or complex, what the intervention is should be clearly specified. Depending on how the intervention is framed, the same core component could potentially be reviewed as a simple or complex intervention. A complex intervention involves, at minimum, multiple components and a complex pathway. 

For example, if the focus of the review is the efficacy of taking aspirin after a myocardial infarction compared with another pill, placebo, or no treatment, this would not be a complex intervention. Although aspirin may act through complex biologic pathways, biologic or physiologic complexity is not considered sufficient to categorize an intervention as complex for the purposes of a systematic review. 

Commonly, public and population health, community and system-level interventions, and those aimed at behavior change are more likely to be complex than simple.

Example of a complex intervention

Behavioral interventions for medication compliance is an example of a complex intervention. A review question about how to increase adherence with daily aspirin after a myocardial infarction would be complex. Because behavioral interventions often use multiple approaches and target systems or multiple agents (e.g., providers, patients, family members, etc), require multifaceted training and/or adoption, and/or require special consideration about the environment/context and available resources, they are commonly considered complex.

The following stages of conducting a review of complex interventions are derived from the AHRQ Series on Complex Intervention Systematic Reviews (AHRQ CI), Noyes et al. (2016), and Anderson et al. (2011).

This is an outline for a systematic review of complex interventions. If you are planning to do another review of complex interventions that is not a systematic review, please also refer to the stages of that particular review type. 

Timeframe: 12+ months, considering the complexity of the intervention. 

*Varies beyond the type of review. Depends on many factors such as but not limited to: resources available, the quantity and quality of the literature, and the expertise or experience of reviewers" (Grant & Booth, 2009).

Question: Focused PICO question, specifying the complexity of the intervention and the sources of complexity of primary interest (See Definition of Complex Interventions). A priori review protocol is recommended, however question may be expanded iteratively as complexity is explored. May incorporate social theory or logic models to develop the question.

Review should also address the following:

(1) How effective is the intervention? (2) For whom does the intervention work and in what contexts? (3) What happens when the intervention is implemented? and (4) What decisions are possible given the results of the synthesis?

Sources and searches: Comprehensive, exhaustive search, aims to be transparent, thorough and repeatable. Includes database, grey literature/clinical trial registry and handsearching of the literature. Must include a PRISMA flow diagram.   

Selection: Based on inclusion/exclusion criteria, may be more iterative.

Appraisal: Includes a quality assessment of study bias/validity.

Synthesis: Narrative and/or meta-analysis or an alternative (see Table 1 within Tanner-Smith paper).

The following resources are considered to be the best in the field of systematic reviews in terms of guidance and reporting.

Methods & Guidance

Reporting Guideline

• Blakemore, A., Dickens, C., Anderson, R., Tomenson, B., Woodcock, A., & Guthrie, E. (2015). Complex interventions reduce use of urgent healthcare in adults with asthma: systematic review with meta-regression. Respiratory medicine, 109(2), 147–156. doi: 10.1016/j.rmed.2014.11.002
• Jonkman, N. H., Schuurmans, M. J., Groenwold, R., Hoes, A. W., & Trappenburg, J. (2016). Identifying components of self-management interventions that improve health-related quality of life in chronically ill patients: Systematic review and meta-regression analysis. Patient education and counseling, 99(7), 1087–1098. doi: 10.1016/j.pec.2016.01.022
• Reedman, S., Boyd, R. N., & Sakzewski, L. (2017). The efficacy of interventions to increase physical activity participation of children with cerebral palsy: a systematic review and meta-analysis. Developmental medicine and child neurology, 59(10), 1011–1018. doi: 10.1111/dmcn.13413

This is an example of a mapping review of complex interventions:

• Lorenc, T., Clayton, S., Neary, D., Whitehead, M., Petticrew, M., Thomson, H., Cummins, S., Sowden, A., & Renton, A. (2012). Crime, fear of crime, environment, and mental health and wellbeing: mapping review of theories and causal pathways. Health & place, 18(4), 757–765. doi: 10.1016/j.healthplace.2012.04.001

• Grimshaw, J., & Danko, K. (2018, February). Making sense in systematic reviews of complex interventions. Cochrane Training. https://training.cochrane.org/resource/making-sense-systematic-reviews-complex-interventions
• Booth, A., Noyes, J., Flemming, K., Gerhardus, A., Wahlster, P., van der Wilt, G. J., Mozygemba, K., Refolo, P., Sacchini, D., Tummers, M., & Rehfuess, E. (2016). Guidance on choosing qualitative evidence synthesis methods for use in health technology assessments of complex interventions. INTEGRATE-HTA. http://www.integrate-hta.eu/downloads/
• AHRQ series on complex intervention systematic reviews. Journal of clinical epidemiology.
• Agency for Healthcare Research and Quality. (2017, November). Overview: Practical Tools and Guidance for Systematic Review of Complex Interventions. https://effectivehealthcare.ahrq.gov/products/interventions-tools-guidance/overview
• Anderson, L. M., Petticrew, M., Rehfuess, E., Armstrong, R., Ueffing, E., Baker, P., Francis, D., & Tugwell, P. (2011). Using logic models to capture complexity in systematic reviews. Research synthesis methods, 2(1), 33–42. doi: 10.1002/jrsm.32
• Aromataris, E., & Munn, Z. (Eds.). (2020). JBI Manual for Evidence Synthesis. Joanna Briggs Institute. doi: 10.46658/JBIMES-20-01
• Booth, A., Noyes, J., Flemming, K., Moore, G., Tunçalp, Ö., & Shakibazadeh, E. (2019). Formulating questions to explore complex interventions within qualitative evidence synthesis. BMJ global health, 4(Suppl 1), e001107. doi: 10.1136/bmjgh-2018-001107
• Booth, A., Sutton, A., & Papaioannou, D. (2016). Systematic approaches to systematic reviews (2nd ed.). Sage.
• Grant, M. J., & Booth, A. (2009). A typology of reviews: an analysis of 14 review types and associated methodologies. Health information and libraries journal, 26(2), 91–108. doi: 10.1111/j.1471-1842.2009.00848.x

• Guise, J. M., Chang, C., Butler, M., Viswanathan, M., & Tugwell, P. (2017). AHRQ series on complex intervention systematic reviews-paper 1: an introduction to a series of articles that provide guidance and tools for reviews of complex interventions. Journal of clinical epidemiology, 90, 6–10. doi: 10.1016/j.jclinepi.2017.06.011

• Higgins, J., López-López, J. A., Becker, B. J., Davies, S. R., Dawson, S., Grimshaw, J. M., McGuinness, L. A., Moore, T., Rehfuess, E. A., Thomas, J., & Caldwell, D. M. (2019). Synthesising quantitative evidence in systematic reviews of complex health interventions. BMJ global health, 4(Suppl 1), e000858. doi: 10.1136/bmjgh-2018-000858

• Noyes, J., Hendry, M., Booth, A., Chandler, J., Lewin, S., Glenton, C., & Garside, R. (2016). Current use was established and Cochrane guidance on selection of social theories for systematic reviews of complex interventions was developed. Journal of clinical epidemiology, 75, 78–92. doi: 10.1016/j.jclinepi.2015.12.009

• Petticrew, M., Rehfuess, E., Noyes, J., Higgins, J. P., Mayhew, A., Pantoja, T., Shemilt, I., & Sowden, A. (2013). Synthesizing evidence on complex interventions: how meta-analytical, qualitative, and mixed-method approaches can contribute. Journal of clinical epidemiology, 66(11), 1230–1243. doi: 10.1016/j.jclinepi.2013.06.005

• Squires, J. E., Valentine, J. C., & Grimshaw, J. M. (2013). Systematic reviews of complex interventions: framing the review question. Journal of clinical epidemiology, 66(11), 1215–1222. doi: 10.1016/j.jclinepi.2013.05.013

• Tanner-Smith, E. E., & Grant, S. (2018). Meta-Analysis of Complex Interventions. Annual review of public health, 39, 135–151. doi: 10.1146/annurev-publhealth-040617-014112