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Systematic reviews Dr Susan D Shenkin 1 Systematic reviews Dr Susan D Shenkin 1

Outline • What is a systematic review? • Introduction to some useful resources • Outline • What is a systematic review? • Introduction to some useful resources • RCTs v observational studies • How to do a systematic review • • • Define question Search the literature Assess the studies Combine the results Put findings in context (write the paper)

What is a systematic review? What is a systematic review?

What is a systematic review? • “collates all empirical evidence that fits prespecified eligibility What is a systematic review? • “collates all empirical evidence that fits prespecified eligibility criteria in order to answer a specific research question ” http: //www. cochrane-handbook. org/

What is a systematic review? • clearly stated objectives with pre-defined eligibility criteria for What is a systematic review? • clearly stated objectives with pre-defined eligibility criteria for studies • explicit, reproducible methodology • a systematic search that attempts to identify all studies • assessment of the validity of the findings of the included studies (e. g. risk of bias) • systematic presentation, and synthesis, of the characteristics and findings of the included studies http: //www. cochrane-handbook. org/

What is a meta-analysis? What is a meta-analysis?

What is a meta-analysis? • “the use of statistical methods to summarize the results What is a meta-analysis? • “the use of statistical methods to summarize the results of independent studies ” • i. e. A specific type of systematic review

Why are reviews needed? Why are reviews needed?

Why are reviews needed? • Massive numbers of publications • Both print, and electronic Why are reviews needed? • Massive numbers of publications • Both print, and electronic media • Diverse languages • Different countries • Primary studies can appear contradictory • Psychology and social sciences predated medical systematic reviews (1930 s)

Why are systematic reviews needed? Why are systematic reviews needed?

Why are systematic reviews needed? • Literature/narrative/critical review –Often not replicable/updated –May be biased Why are systematic reviews needed? • Literature/narrative/critical review –Often not replicable/updated –May be biased by prior beliefs –May be commissioned due to published opinion –Often miss small but important effects –Different reviewers reached different conclusions –Affected by subspecialty of reviewer –Little attempt to discuss heterogeneity

Why are systematic reviews needed? • Benefits of therapy not brought into clinical practice Why are systematic reviews needed? • Benefits of therapy not brought into clinical practice –e. g. Clot-busters/beta blockers for heart attacks –SR would have identified benefit in mid-1970 s –Not in clinical practice till 1990 s • Inadequate summaries of current knowledge –Omitted mention of effective treatment, or suggested only as part of trials Antman et al, JAMA 1992; 268: 240 -248

Why are systematic reviews needed? • • • As part of student dissertation/PG thesis Why are systematic reviews needed? • • • As part of student dissertation/PG thesis To secure grant funding for research To propose future research agenda To establish clinical or cost-effectiveness To establish feasibility of an intervention To allow information to be assimilated quickly and easily • To reduce delay of research to clinical practice • Note this is as substantial a piece of work as original research

Problems with systematic reviews • Vary in quality • Require updating (often by time Problems with systematic reviews • Vary in quality • Require updating (often by time of publication) • May not include all studies – Non-English – Grey literature – Early literature • Quality assessment can still be subjective • Now rapid expansion – 3 x increase in 10 years (7, 579 2006, 24, 517 2015) • Duplication (with similar/different results)

Why are systematic reviews needed? • Mostly –A substantive question –Several primary studies –Uncertainty Why are systematic reviews needed? • Mostly –A substantive question –Several primary studies –Uncertainty • Can be of –RCTs (randomised controlled trials) of intervention (vaccine, drug, behaviour) • e. g. MMR, clot busters, exercise after stroke –Observational studies • e. g. Birth weight and IQ, IQ and mortality, WMH and morbidity/mortality

‘Hierarchy of evidence’ ‘Hierarchy of evidence’

RCTs or observational studies • RCTs –‘gold standard’ for interventions –Minimise bias –Exposed/unexposed groups RCTs or observational studies • RCTs –‘gold standard’ for interventions –Minimise bias –Exposed/unexposed groups are comparable –‘Bigger is better’ http: //www. cochrane-handbook. org/

RCTs or observational studies • Observational studies –The majority of studies –When RCTs are RCTs or observational studies • Observational studies –The majority of studies –When RCTs are not ethical/feasible/done –Need clarity about design ? filter by method –What search techniques are appropriate? –Concern about bias, confounding (bigger not always better) –Difficult to combine different study designs –May require original data –Meta-analysis can be spuriously precise and misleading http: //www. cochrane-handbook. org/

SRs of observational studies • Do not ‘sanctify results from poor studies’ • MOOSE SRs of observational studies • Do not ‘sanctify results from poor studies’ • MOOSE guidelines –SR of observational studies • STROBE guidelines –Reporting of epidemiology studies Shenkin et al 2017 https: //academic. oup. com/ageing/article/46/5/722/3887244 http: //www. equator-network. org/

Introduction to Cochrane • Archie Cochrane (1909 -88) –British epidemiologist –Advocated RCTs to inform Introduction to Cochrane • Archie Cochrane (1909 -88) –British epidemiologist –Advocated RCTs to inform healthcare practice Cardiff University Library, Cochrane Archive, University Hospital Llandough • Cochrane collaboration –Cochrane Reviews (>10, 000) registered –Identify, appraise and synthesise researchbased evidence and present it in accessible format; regularly updated –Focus on interventions –Outstanding general resource http: //www. cochrane-handbook. org/

Introduction to Campbell Collaboration • Systematic reviews of the effects of social interventions • Introduction to Campbell Collaboration • Systematic reviews of the effects of social interventions • Prepare, maintain and disseminate systematic reviews in education, crime and justice, and social welfare • Register relevant reviews • Links to useful methodology sites – Effect sizes – http: //www. campbellcollaboration. org/resources/research/ Methods_Links. php http: //www. campbellcollaboration. org/

Introduction to EPPI-Centre • Evidence for Policy and Practice Information and Co-ordinating Centre • Introduction to EPPI-Centre • Evidence for Policy and Practice Information and Co-ordinating Centre • Systematic reviews of public policy –Education, health promotion, employment, social care, criminal justice • Online evidence library • Methods, tools and databases (quantitative and qualitative) • http: //eppi. ioe. ac. uk/cms/ • EPPI-Centre (March 2007) EPPI-Centre methods for conducting systematic reviews. London: EPPI-Centre, Social Science Research Unit, Institute of Education, University of London. http: //eppi. ioe. ac. uk/

Introduction to PROSPERO • Centre for Reviews and Dissemination, York • Evaluate the effects Introduction to PROSPERO • Centre for Reviews and Dissemination, York • Evaluate the effects of health and social care interventions and the delivery and organisation of health care • Guidance on systematic reviews – http: //www. york. ac. uk/inst/crd/Sys. Rev/!SSL!/Web. Help/Sys. Rev 3. htm • PROSPERO – International prospective register of SRs http: //www. crd. york. ac. uk/PROSPERO/

Introduction to EQUATOR • Enhancing the QUAlity and Transparency Of health Research • Started Introduction to EQUATOR • Enhancing the QUAlity and Transparency Of health Research • Started March 2006 • Grew from guideline development groups (including CONSORT) • Aim to: – Provide resources and education enabling the improvement of health research reporting – Monitor progress in the improvement of health research reporting http: //www. equator-network. org/

Introduction to EQUATOR • Detailed reporting guidelines – PRISMA (reporting of systematic reviews) – Introduction to EQUATOR • Detailed reporting guidelines – PRISMA (reporting of systematic reviews) – CONSORT Statement (reporting of randomized controlled trials) – STARD (reporting of diagnostic accuracy studies) – STROBE (reporting of observational studies in epidemiology) – MOOSE (reporting of meta-analyses of observational studies) • Very useful library / toolkits for writing and reporting http: //www. equator-network. org/resource-centre/library-of-health-research-reporting/

What’s new in systematic reviews? • Reducing research waste www. researchwaste. net – Registration What’s new in systematic reviews? • Reducing research waste www. researchwaste. net – Registration of all clinical trials (and observational studies) www. All. Trials. net • Umbrella reviews – SRs of SRs • Rapid reviews • Crowd sourcing • Realist synthesis – ‘what works for whom in what circumstances and in what respects’ • Individual participant meta-analysis • Network meta-analysis • Prospective meta-analysis

What to expect today: How to do a systematic review? 1. 2. 3. 4. What to expect today: How to do a systematic review? 1. 2. 3. 4. 5. Define a question Search the literature Assess the studies Combine the results Put the findings in context

How to do a systematic review? 1. 2. 3. 4. 5. Define a question: How to do a systematic review? 1. 2. 3. 4. 5. Define a question: Anne Donnelly Search the literature Assess the studies Combine the results Put the findings in context

How to do a systematic review? 1. 2. 3. 4. 5. Define a question: How to do a systematic review? 1. 2. 3. 4. 5. Define a question: Anne Donnelly Search the literature: Anne Donnelly Assess the studies Combine the results Put the findings in context

How to do a systematic review? 1. 2. 3. 4. 5. Define a question: How to do a systematic review? 1. 2. 3. 4. 5. Define a question: Anne Donnelly Search the literature: Anne Donnelly Assess the studies: Rebecca Woodfield Combine the results Put the findings in context

How to do a systematic review? 1. 2. 3. 4. 5. Define a question: How to do a systematic review? 1. 2. 3. 4. 5. Define a question: Anne Donnelly Search the literature: Anne Donnelly Assess the studies: Rebecca Woodfield Combine the results: Mike Allerhand Put the findings in context

How to do a systematic review? 1. 2. 3. 4. 5. Define a question: How to do a systematic review? 1. 2. 3. 4. 5. Define a question: Anne Donnelly Search the literature: Anne Donnelly Assess the studies: Rebecca Woodfield Combine the results: Mike Allerhand Put the findings in context: R Woodfield 6. Some hints and tips: Ellen Backhouse

Acknowledgements CCACE (developing this course) Catherine Calvin Dominika Dykiert Geoff Der Beverly Roberts Anna Acknowledgements CCACE (developing this course) Catherine Calvin Dominika Dykiert Geoff Der Beverly Roberts Anna Sim Contact me: Susan. [email protected] ac. uk www. ccace. ed. ac. uk The work was supported by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G 0700704/84698). Funding from the BBSRC, EPSRC, ESRC and MRC is gratefully acknowledged. 38