Systematic Reviews: principles and processes MED 264 Mary Linn Bergstrom Nancy Stimson

“A systematic review is a review of a clearly formulated question that uses systematic and explicit methods to identify, select, and critically appraise relevant research, and to collect and analyze data from the studies that are included in the review. Statistical methods (meta-analysis) may or may not be used to analyze and summarize the results of the included studies. Meta-analysis refers to the use of statistical techniques in a systematic review to integrate the results of included studies.” PLOS Medicine v6 issue 7 July 1009 doi: /journal.pmed

Types of reviews narrative or integrative systematic Describes the methodology in detail; includes search strategy, study selection criteria, assessment of study quality, and data synthesis Balancing sensitivity and specificity meta analysis analysis of combined data from quantitative studies with similar methodologies

Sources Cochrane Collaboration EPPI-Centre Campbell Collaboration Cardiff University Library Cochrane Archive University Hospital Llandough

Standards IOM Institute of Medicine of the National Academies – Standards for Systematic Reviews Systematic-Reviews/Standards.aspx PRISMA Preferred Reporting Items for Systematic reviews and Meta-Analyses …an evidence-based minimum set of items for reporting in systematic reviews and meta-analyses

Evidence Based Pyramid

Formulate Question PICO: population, intervention, comparison, outcome Check for recent systematic reviews on topic

Inclusion & Exclusion Criteria Criteria for considering studies for this review Types of studies All randomized controlled trials with parallel or cross-over design, blinded or open-label with a duration of 24 weeks or longer. Reports of which no full publication exists were considered for inclusion in this review only, if the information available would allow for a publication in accordance with all criteria of the CONSORT statement. Types of participants People with type 2 diabetes mellitus. Types of interventions Comparison of long-acting insulin analogues (insulin glargine or insulin detemir) to NPH insulin. In case of a combination therapy (long-acting insulin analogue combined with another antihyperglycaemic drug) the additional antihyperglycaemic agent had to be part of each treatment arm. Only studies reporting on insulin scheme with subcutaneous application were considered for inclusion in this review. Types of outcome measures …. Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus Cochrane Database of Systematic Reviews 2007 DOI: / CD pub3

Select Databases  Reduce bias and improve sensitivity by searching multiple databases  PubMed, Cochrane Library, Scopus (for Embase content)  Consider other sources:  Grey literature  Clinical trial registers  Cited reference searching  Article bibliographies  Hand searching  Experts in the field

Develop Search Terms  Brainstorm  Review controlled / structured vocabulary in selected databases  Harvest keywords and structured vocabulary indexing terms from good database records on topic  Harvest keywords and structured vocabulary indexing terms from good articles on topic  Use a harvest form (spreadsheet, Word doc, etc.)

PubMed Harvesting Process  For each concept, perform a separate “quick and dirty” search in PubMed  Enter a single concept( MeSH, textword, phrase) in the PubMed search box and run the search  Examine records:  Look for MeSH that reflect your major concept  Look in title and abstract for author-generated terms (i.e., text words, phrases) that reflect the concept.  Add any new MeSH and text words/phrases into harvesting form Indicate MeSH with the tag [mh] Indicate text word with the tag [tw] title word or abstract word[tiab] [ti] [ab] Use other tags as appropriate, e.g., [pa]  PubMed search field descriptions & tags:

Create Search Strategy  Strategies will differ in different databases  Document search details & results for each database  Common errors affect results  conceptualization of research question  spelling errors  translation of search strategy to different databases  missed subject headings  missed natural language search terms  spelling variants and truncation  irrelevant subject headings  irrelevant natural language terms  search limits

Run Search  Create a selective test database  Run search  Store search results  Compare search results with test database citations  Revise, re-run

Select and Assess Studies  Select studies for inclusion into SR  Apply your established inclusion/exclusion criteria  Usually conducted in two passes  Review title/abstract  Review full-text  Use two independent reviewers with a third person available as ‘tie breaker’ for conflicts  Keep a log of excluded studies with reasons for exclusion  Assess study quality  Each study meeting the inclusion criteria is assessed for quality  More studies may be excluded in this process  Document decisions

Analyze. Interpret, Report  Extract data from the included articles for qualitative or quantitative (meta-analysis) analysis  Analyze, synthesize results  Interpret results  Comment on  Strength of the evidence  Applicability of the results  Benefits/costs/tradeoffs  Limitations  Implication for future research  Report  “Publish the final report in a manner that ensures free public access” IOM Standards for Systematic Reviews STANDARD 5.3

Meta-analysis

PRISMA

Why document?  Ensure scientific integrity, replicability  Documentation is standard practice for any research project  Meet publication standards  Investigator must have documentation details for final paper  Utilize PRISMA checklist to structure report  Keep your sanity  Searching is a complex iterative process completed over an extended period of time  Track internal decision-making affecting search construction

What to document? The entire process: Define question Formulate search terms and strategies Select databases & sources Run searches Store results in a test database Revise, re-run Collect & compare results Manage data selection Evaluate evidence, conduct qualitative and/or quantitative analysis Prepare and publish final report See PRISMA 2009 Checklist

How to document?  MED264 course website  Confirm documentation practices with entire research team  Citation format, etc.  Back up, back up, back up

Figure 1. Flow of information through the different phases of a systematic review Moher D, Liberati A, Tetzlaff J, Altman DG, et al. (2009) Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e doi: /journal.pmed

Mary Linn Bergstrom Nancy Stimson