Section 2.2: Knowledge Synthesis
Jennifer Tetzlaff, Ottawa Hospital Research Institute
Andrea C. Tricco, PhD, Ottawa Hospital Research Institute
David Moher, PhD, Ottawa Hospital Research Institute
Definitions*
- Knowledge syntheses (KS) consist of a clearly formulated question and use systematic and explicit methods to identify, select, critically appraise, and interpret data from relevant research
 - A meta-analysis is a statistical technique used to quantitatively integrate the results of included studies in a KS
 - A KS does not necessarily include a meta-analysis
 
* From the Cochrane Collaboration
Knowledge Synthesis
- KS is used to interpret individual study results within the context of global evidence
 - KS can be used as a starting point for practice guidelines and new primary research (e.g. trials)
 - KS bridges the gap between research and decision-making
 
Types of Evidence
- Many groups worldwide conduct KS and methods involved usually depends on the question(s) being considered 
- Questions regarding the effectiveness of interventions will usually include quantitative evidence (e.g. odds ratio for a particular drug versus placebo)
 - Contextual questions about why an intervention worked in a particular context will usually include qualitative evidence
 
 
General Methods of a KS
- Incorporating qualitative evidence into KS can be: 
- Challenging
 - Difficult to locate qualitative evidence
 - Difficult to integrate qualitative evidence with quantitative evidence
 - Methods are just emerging
 
 - As such, the focus will be on general methods applicable to most KS
 
Overview
- Assembling the review team
 - Formulating the question, protocol, and eligibility criteria
 - Identifying relevant studies
 - Selecting studies
 - Risk of bias assessment
 - Data extraction
 - Data analysis
 - Presenting results
 - Interpreting results
 
The Review Team
- Determined by the question
 - May include the following people: 
- Clinical experts with knowledge of the topic
 - Methodologists who know the KS process
 - Librarian to help locate relevant studies
 - Researchers who conducted studies on the topic
 - Funder or commissioning agency for context
 - Statistician if meta-analysis is being considered
 - End-users (e.g. policy makers, patients) to increase relevance and uptake
 
 
Formulating the Question
- Most important step because it guides the KS process
 - PICO (S or T): Population, Intervention, Comparators, Outcome, and (Study design or Time period) facilitates question development
 - May not fit all KS (e.g. Intervention sometimes replaced by Exposure) but still useful template to consider
 
Formulating the Protocol
- Pre-specifies the review process
 - Important because it decreases post-hoc changes to methods and selective outcome reporting
 - Elements include primary versus secondary outcomes, search methods, appraisal of the literature, and data abstraction
 - Any changes to the protocol should be transparently reported in the review write-up
 
Formulating the Eligibility Criteria
- Should extend from the question
 - Based on PICO (S or T)
 - Consider language of publication
 - Consider publication status (e.g. published vs. unpublished material)
 - Needs to be thoroughly considered, properly defined, and transparently reported
 
Identifying Relevant Studies
- Based on the question and PICO (S or T)
 - MEDLINE, EMBASE, and The Cochrane Library electronic databases are commonly used for health-related research
 - At least 2 relevant databases should be searched
 - Advisable that a librarian guides this process
 - Should search for unpublished and difficult to locate (i.e. grey) literature (e.g. trial registries, public health agency websites)
 
Selecting Studies
- Based on the eligibility criteria
 - 2 stages: broad screening of titles and abstracts and stricter screening of potentially relevant full-text articles
 - 2 independent reviewers should screen at all levels to ensure relevant studies aren't missed
 - Agreement between reviewers can be assessed using the kappa statistic
 
Risk of Bias Assessment
- Many assessment tools have been developed to asses the risk of bias for different study designs
 - Only reporting a summary score is not advisable; the assessments for each criterion from the quality appraisal should be reported for each study
 - Sensitivity analyses on risk of bias can be conducted versus excluding studies based on risk of bias
 
Data Extraction
- Primary outcomes should be differentiated from secondary outcomes
 - Data extraction form(s) should be developed a priori and pilot-tested to increase reliability
 - Potential errors are decreased if more than one reviewer independently extracts the data
 - Authors of included studies should be contacted for missing or unclear information
 
Data Analysis
- Depends on the question and type of data collected
 - All KS must have a narrative synthesis of results and risk of bias
 - Standard effect measures (e.g. odds ratios, hazard ratio) may be used
 - Meta-analysis may not be possible or advisable if outcomes were assessed inconsistently and clinical, methodological or statistical heterogeneity is observed
 
Presenting Results
- Screening process should be described in the text and/or presented as a flow-chart
 - Characteristics of included studies should be described in the text and/or a table (e.g. participant populations, interventions)
 - Results of risk of bias assessments should be presented in a table and/or text
 - Quantitative data should be presented as summary data (e.g. effect estimates with confidence intervals for each study) and may be presented for each outcome in a table or in a forest plot figure
 - Qualitative data can be presented visually (e.g. conceptual framework)
 
Interpreting Results
- Discuss risk of bias, strength, and applicability of the evidence for each outcome
 - Relevance of the results should be considered for key stakeholders to increase applicability
 - Qualitative evidence can help explain how the intervention worked and whether it will work in a different setting
 - Should consider study and KS limitations
 
Disseminating Results
- Most common form of dissemination is publication in peer-reviewed journals 
- Open access journals will increase dissemination
 
 - Targeted dissemination via media for the public, brief reports for health care providers, policy makers and consumers, and decision-aids for patients
 
Uptake of Results
- Much attention has been paid to enhancing the quality of KS but relatively little has been done regarding the format for presentation to enhance uptake
 - Resources are available to make KS more user-friendly (e.g. Clinical Evidence and Program in Policy Decision-Making/Canadian Cochrane Centre database).
 
Future Research
- Increasing the uptake of KS
 - How best to update KS
 - Comparability between different types of KS (e.g. rapid reviews versus conventional reviews)
 - How to prioritize KS topics
 
Contact Details
- Ottawa Methods Centre, Clinical Epidemiology Program, Ottawa Hospital Research Institute
 - JMT: jtetzlaff@ohri.ca
 - ACT: atric060@uottawa.ca
 - DM: dmoher@ohri.ca
 
Acknowledgments
- We thank CIHR for their funding and Dr Sharon Straus for her funding and useful feedback on our paper
 - ACT: CIHR (Frederick Banting and Charles Best Canada Graduate Scholarship and a Rising Star Award from the Institute of Health Services and Policy Research)
 - DM: University of Ottawa Research Chair
 
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