1. Systematic Review and Meta-Analysis
Presented by:
Aarushi singh
Roll No: 04/Mph/16

2. Contents Systematic review Characteristics of systematic review
Meta-analysis
Advantages of meta-analysis
Pyramid of evidence
Steps of systematic review
Determining the research question for systematic review
Systematic review search protocol
Literature search
Sources of searching
Critical appraisal
Critical appraisal website and tools
References

3. SYSTEMATIC REVIEW
 A review of a clearly formulated question which uses systematic and explicit methods to identify, select and critically appraise relevant research, and collect and analyze data from the studies that are included in the review.
 They are designed to provide a complete, exhaustive summary of current literature relevant to a research question.

4. Characteristics of Systematic Review
The key characteristics of a systematic review are:
a clearly stated set of objectives with pre-defined eligibility
criteria for studies;
an explicit, reproducible methodology;
a systematic search that attempts to identify all studies that would meet the eligibility criteria;
an assessment of the validity of the findings of the included studies, for example through the assessment of risk of bias; and
a systematic presentation, and synthesis, of the characteristics and findings of the included studies.

5. Meta - Analysis A meta-analysis is a statistical analysis that
combines the results of
multiple scientific studies.  
A meta-analysis may be
conducted on several
clinical trials of a medical
treatment, in an effort to
obtain a better understanding
of how well the treatment
works.

6. Meta analysis The rationale for a meta-analysis is that, by combining
the samples of the individual studies, the overall
Sample size is increased, thereby improving the
Statistical power of the analysis as well as the precision
of the estimates of treatment effects.
The typical graph for displaying the results of a meta
analysis is called a “forest plot”.

7. Advantages of Meta-Analysis
A meta-analysis is a statistical overview of the results from one
or more systematic review. Basically, it produces a weighted
average of the included study results and this approach has
several advantages:
Results can be generalized to a larger population,
The precision and accuracy of estimates can be improved as more data is used. This, in turn, may increase the statistical power to detect an effect.

8. Contd..
Inconsistency of results across studies can be quantified and analyzed. For instance, does inconsistency arise from sampling error, or are study results (partially) influenced by between-study heterogeneity.
Hypothesis testing can be applied on summary estimates,
Moderators can be included to explain variation between studies,
The presence of publication bias can be investigated

9. Pyramid of evidence

10. Why on top Systematic reviews are at the top of pyramid of
evidence because of :
Rigorous methodology
Peer reviewed
Relatively large sample size
Ensures the highest quality evidence

11. Steps in Systematic Review
Five basic steps to conduct systematic review :
Step One
Formulate your question(s). Questions should always be :-
Clear
Unambiguous
Structured
Usually, a protocol for a systematic review (plan or set of steps to
be followed in a study) will only be modified if it becomes clear that
there are alternative ways of defining your population ,
intervention, outcomes or study designs.

12. Contd..
Step Two
Identify relevant studies. This will require extensive searching a wide range of online resource, e.g., Medline, pubmed and print resources.
How to identify what studies to keep and what to reject?
Your study selection criteria should derive directly from your review questions.
Record all reasons for inclusion and exclusion.

13. Contd..
Step Three
Assess the quality of the studies retrieved during the search. 
To assess the quality of your selected studies make use of general critical appraisal guides and design-based quality checklists (refer to the Manuals & Standards tab). Quality assessment is used to:
Explore heterogeneity
Inform decisions regarding suitability of meta-analysis
Help in assessing the strength of inferences and making recommendations for future research

14. Contd.. Step Four Summarize the evidence.
Tabulation of study characteristics, quality and effects
Statistical methods for exploring differences between studies and combining their effects (meta-analysis)

15. Contd.. Step Five Interpret your findings.
Check for any possible risk of bias
Check heterogeneity to help you determine if your overall summary can be trusted. If you have doubts, then check the effects observed in high-quality studies to help generate inferences.
Grade recommendations by reference to the strengths and weaknesses of the evidence

16. Determining the Research Question for systematic review
Formulation of a research question in systematic review follows the concept of “PICO” which is a useful tool for asking focused clinical questions and to translate the search question in search Concept. P :- Population I :- Intervention C :- Comparison O :- Outcome
PICO

17. P I C O Contd.. Patient, Population or Problem
Intervention or exposure
Comparison ( if appropriate)
Outcome
What are the characteristics of the patient or population?
What is the condition or disease you are interested in?
What do you want to do with this patient (e.g. treat, diagnose, observe)?
What is the alternative to the intervention (e.g. placebo, different drug, surgery, gold standard)
What are the relevant outcomes?  What you are trying to accomplish, measure, improve, affect
 (e.g. morbidity, death, complications, timely diagnosis)?

18. Research Question Example :-
In post cardiac arrest patients with return of
spontaneous circulation (P), does therapeutic
hypothermia (I) compared with usual care (C),
improve morbidity or mortality (O) ?

19. Contd..
Developing a research question for a systematic review requires understanding of the existing literature, including gaps and uncertainities, definitions, and terminologies.

20. Systematic Review search Protocol
Steps for a Protocol
Check existing reviews/protocols - to decide if  the review is doable or not or of the question has to be amended.
Formulate a specific question -  using PICO
Inclusion criteria – puts the question into operation (population, intervention or comparison, outcome, study design, language, publication)
Exclusion criteria for not including certain studies e.g. specific populations, language, setting

21. Contd.. 5. Eligibility criteria for including studies– qualitative
and quantitative (study design, language, date of
publication, duplicate data)
6. Search strategy - explicit and reproducible (must
include grey literature)
7. Critical appraisal - Assess risk of bias in individual
studies
8. Synthesis of results (interpret/analyze
results/determining the applicability of results
9. Report - comprehensive report on all steps of the
systematic review and presents results

22. Literature Search The literature search is the most important part
of a systematic review.
The literature search is how you obtain your data for your study.
The goal of the literature search is to find all
Relevant studies including :-
Traditional peer reviewed literature
Grey literature

23. Contd.. The literature search must be comprehensive and Systematic.
The systematic review literature search must :-
Be well documented
Be transparent and reproducible
Include a diversity of resources
Be iterative

24. Contd.. Search strategy Key concept to be searched ( PICOS if using )
How are these terms represented in different disciplines?
What are related terms / synonyms ? Be as comprehensive as possible
What are the subject heading in each database?
Review known relevant articles to determine keywords and
subject headings.
Review previous relevant systematic reviews for possible
Strategy.

25. Contd.. Save your searches in each database
Create an account within database interface
Label the search clearly ( is it a draft, final, date, database name)
Keep detailed record of all searches conducted :
Month, date, year of search
Database searched
Exact search strategy
Any limits used (year of publication, language etc)
The goal is to search strategy in a transparent manner
so that it can be replicated

26. Sources of searching Databases
Below is a list of some of the most important
databases in Health:
Database of Abstracts of Reviews of Effects (DARE) :
Database of Abstracts of Reviews of Effects seeks to identify the
best quality systematic reviews being published. It complements
the Cochrane Database of Systematic Reviews by offering a
selection of quality-assessed reviews in those subjects where
there is currently no Cochrane Review.

27. Contd.. Cochrane Database of Systematic Reviews
(CDSR)Cochrane Review :
Includes all Cochrane Reviews (and protocols) prepared by
Cochrane Review Groups. Each Cochrane Review is a peer
reviewed systematic review that has been prepared and
supervised by a Cochrane Review Group according to the
Cochrane Handbook for Systematic Reviews of
Interventions or Cochrane Handbook for Diagnostic Test
Accuracy Reviews.

28. Contd.. EMBASE : Medline :
A comprehensive source of online biomedical answers, Embase
helps you track adverse drug events, compare drug therapies for
disease, and search for evidence-based medicine research.
Medline :
Provides authoritative medical information on medicine, nursing,
dentistry, veterinary medicine, the health care system, pre
clinical sciences, and much more. Created by the National Library of
Medicine, MEDLINE uses MeSH (Medical Subject Headings) indexing
with tree numbers, tree hierarchy and explosion capabilities to search
abstracts from over 4,600 current biomedical journals.

29. Contd.. Literature that is NOT published in traditional
Grey Literature
Literature that is NOT published in traditional
sources such as books and journals is referred to as
“Grey literature”.
Conference proceedings and theses are the most
common types of Grey literature in the academic
context, but examples also include technical and
research reports, government publications, policy
papers, annual reports, fact sheets, maps,
geological surveys and statistics.

30. Contd.. Sources of grey Literature Dissertations and Theses:
ProQuest Dissertations and Theses Global
Trove : Australian Theses
Conference abstracts & proceedings:
Directory of published papers : contains material from more than 40,000 conferences & symposia, across Science/Technology, Medical/Life Sciences, Pollution Control/Ecology, Social Sciences/Humanities.
Australian sources of grey literature:
Australian Institute of Health and Welfare
State Health Departments
National Health and Medical Research Council
Australian Indigenous HealthInfoNet

31. Contd.. International sources of grey literature:
World Health Organization
The Grey Literature Report : The report is a bimonthly publication of The New York Academy of Medicine Library alerting readers to new grey literature publications in health services research and selected public health topics.
Grey Matters: a practical search tool for evidence-based medicine: Published by The Canadian Agency for Drugs and Technologies in Health (CADTH). Provides details on where to locate grey literature in Australia and other countries.
OpenGrey: System for Information on Grey Literature in Europe, is your open access to bibliographical references of grey literature (paper) produced in Europe and allows you to export records and locate the documents.

32. Contd.. Hand Searching : Hand searching is the manual examination of
resources which are not indexed electronically,
such as special issues of journals or conference
proceedings.
Study Registers :
Australian New Zealand Clinical Trials Registry Covers trials being undertaken in Australia, New Zealand on the therapeutic areas of pharmaceuticals, surgical procedures, preventive measures, lifestyle, devices, treatment and rehabilitation strategies and complementary therapies.
Clinicaltrials.gov  Database of federally and privately supported clinical trials conducted in the United States and around the world.
UK CRN Study Portfolio
EU Clinical Trials Register

33. Critical Appraisal Critical appraisal is the process of carefully and
systematically examining research to judge its
trustworthiness, and its value and relevance in a
particular context.
We critically appraise the literature in order to:
Weigh up the evidence for usefulness
Assess benefits and strengths for research against flaws and weaknesses
Assess if findings are reliable and useful in our own context for decision-making

34. Contd.. There are several tools and checklist available to
critically appraise studies. Some commonly asked
questions include:
What is the research question and why was the study needed? 
Does the study have new findings? Is the work original and important?
Does the research question address the following components? ( PICO)
The group or population of patients
The intervention or therapy
The outcome

35. Contd..
4. Did the authors use the right type of study design for the research question? 
Therapy questions > Randomized controlled trials
Experiences > Qualitative studies
5. Did the chosen study design minimize bias? 
6. Was the study designed in line with the original protocol i.e. stated methods? Eg., were there changes to the inclusion or exclusion criteria?

36. Contd..
7. Has the study's hypothesis (expected outcome) been tested? 8. Is the analysis of the data accurate? Eg., Are the conclusions based on the data and analysis? 9. Does the study contribute to the understanding of the problem being investigated? 10. What are the strengths and limitations of the study? 11. Are the findings of the study useful for clinical practice?

37. Critical Appraisal website and tool
Center for Evidence Based Medicine (CEBM) :
The Centre for Evidence-Based Medicine in Oxford (UK) provides tools
To develop, teach and promote evidence-based health care. Has useful
tools and downloads for the critical appraisal of medical evidence.
Example appraisal sheets are provided together with several helpful
examples.
Critical Appraisal Skills Program (CASP) :
The Critical Appraisal Skills Program (CASP) helps people to find and
interpret the best available evidence from health research.

47. References http://libguides.nus.edu.sg
Google images

48. Thank you