Systematic reviews and Meta-analyses Alison Brettle, Research Fellow (Information) Salford Centre for Nursing, Midwifery and Collaborative Research University of Salford

Aims To discuss the role of the systematic reviews and meta-analyses and cover issues involved in their critical appraisal and interpretation

Systematic Review A review of all the literature on a particular topic, which has been systematically identified, appraised and summarised giving a summary answer.

What is a systematic review? An overview of primary research studies conducted according to explicit and reproducible methodology A rigorous method of summarising research evidence Shows what we know and don’t know about a topic area Provides evidence of effectiveness (or not) by summarising and appraising relevant evidence

Systematic reviews aim To find all relevant research studies (published and unpublished) To assess each study on basis of defined criteria Synthesise the findings in an unbiased way Present a balanced and impartial summary of the findings taking any flaws into consideration

Advantages of systematic reviews Summarise evidence, keep people up to date without reading all published research literature Allow large amounts of data to be assimilated (eg by busy clinicians, policy makers etc) A clearer picture by collating results of research Reduce bias – removes reviewers personal opinions, preferences and specialist knowledge Explicit methods - allow the reader to assess how review has been compiled More reliable conclusions because of methods used

Systematic review models Medical/Health care Cochrane Collaboration, NHS Centre for Reviews and Dissemination Usually includes “high quality” research evidence – RCTs Often includes meta-analysis (mathematical synthesis of results of 2+ studies that addressed same hypothesis in same way) Social care/Social Sciences SCIE, EPPI Centre, Campbell Collaboration Often include wider range of studies including qualitative Often narrative synthesis of evidence

Systematic review process Define/focus the question Develop a protocol Search the literature (possibly 2 stages scoping and actual searches) Refine the inclusion/exclusion criteria Assess the studies (data extraction tools, 2 independent reviewers) Combine the results of the studies to produce conclusion– can be a qualitative or quantitative (meta-analysis) Place findings in context – quality and heterogeniety of studies, applicability of findings

Methodology for a systematic review of randomised controlled trials1 Greenhalgh, T, BMJ 1997;315:672-675

What type of study design? How effective is paracetamol at reducing pain? Does smoking increase the risk of oral cancer?

STRONG Experimental studies/ clinical trials Randomised controlled trials Non-randomised controlled trials Observational studies Cohorts Case-controls Cross-sectional surveys Case series Case reports WEAK Expert opinion, consensus

Experimental studies Randomised controlled trial Non-randomised controlled clinical trial Evaluating the effectiveness of an intervention

Observational studies Measuring the incidence of a disease; looking at the causes of disease; determining prognosis Looking at the causes of disease; identification of risk factors; suitable for examining rare diseases Measuring the prevalence of a disease; examining the association Cohort Case-control Cross-sectional survey

What is a meta-analysis? Optional part of a systematic review Systematic reviews Meta-analyses

Meta-analysis The process of using statistical methods to combine the results of different studies. The aim is to integrate the findings, pool the data, and identify the overall trend of results (Dictionary of Epidemiology, 1995)

Systematic Reviews Understanding the jargon and the blobs!

Odds Ratio, Relative Risk Measures of risk The likelihood of something happening V The likelihood of something not happening Methods that describe/work out if something is causing harm (or having an effect)

Odds Ratio Graph (Blobbogram) LEFT E S M O RIGHT E Line of no significance 2 more than 1 0.5 less than 1 1

Odds Ratio 2 more than 1 0.5 less than 1 1 Best estimate Confidence Interval (wobble factor) 2 more than 1 0.5 less than 1 1

Odds Ratio (Blobbogram) 2 more than 1 0.5 less than 1 1 Less than one is good – causing no harm (having an effect), middle line is no effect and right of line is causing harm/having no effect

Confidence Interval Is the range within which the true size of effect (never exactly known) lies, with a given degree of assurance (95% or 99%).

Confidence Intervals (Wobble factor)

Confidence Interval (CI) = the wobble factor, how sure are we about the results? - the shorter the CI the more certain we are about the results - if it crosses the line of 1 (no treatment effect) the intervention might not be doing any good and could be doing harm

Heterogeneity Clinical heterogeneity – differences in trial characteristics Statistical heterogeneity - the variability in the reported effect sizes between studies how similar are the results? are the differences among the results of the trials greater than could be expected by chance alone?

Number needed to treat (NNT) the number of people you would need to treat with a specific intervention to see one additional occurrence of a specific outcome Another way of describing the benefits of treatment

The p-value in a nutshell How often you would see a similar result by chance, when actually there was no effect by the drug or treatment. 0 1 Impossible Certain Absolutely p=0.001 Very unlikely 1 in 1000 p=0.05 Fairly unlikely 1 in 20 p=0.5 Fairly likely 1 in 2 p=0.75 Very likely 3 in 4 The probability of something happening

Critical appraisal Is the study valid? What are the results? Trustworthy What are the results? Is it useful in practice? Relevant? Generalisable?

Evaluating quality of systematic reviews Is there a clearly defined question? Thorough and comprehensive search Was methodological quality assessed and studies weighted accordingly? (Were studies reliable and valid?) How sensitive are the results to the way the review was done – ie if you changed the inclusion criteria how would this affect results? Interpretation of numerical results Things you are looking for to establish if it is valid

Further reading Greenhalgh T (1997) How to read a paper: papers that summarize other papers (systematic reviews and meta-analyses), BMJ, 315:672-675

Useful resources Cochrane Collaboration http://www.cochrane.org/ http://www.cochrane.org/docs/irmg.htm Centre for Reviews and Dissemination http://www.york.ac.uk/inst/crd/ Finding studies for systematic reviews http://www.york.ac.uk/inst/crd/revs.htm EPPI-Centre – Stages of a review http://eppi.ioe.ac.uk/cms/Default.aspx?tabid=89 SCIE - The conduct of systematic research reviews for SCIE knowledge reviews http://www.scie.org.uk/publications/details.asp?pubID=111