Systematic Review: Beginner's Guide

S
Saee DeshpamdeTeacher at VSPM en VSPM
Systematic Review
A Beginner’s Guide
Dr Saee Deshpande
MDS, Fellow-FAIMER, Fellow- Oral Implantology
Associate Professor
Dept of Prosthodontics, VSPM Dental College & Research Centre, Nagpur
Learning objectives
• Understand what is systematic review
• Understand the importance of systematic
review
• Learn the process of doing a systematic
review
In a nutshell….
Systematic Review: Beginner's Guide
Types of Research
Study Designs
How to identify study design?
Q1. What was the aim of the study?
• To simply describe a population (PO questions) descriptive
• To quantify the relationship between factors (PICO questions) analytic.
Q2. If analytic, was the intervention randomly allocated?
• Yes? RCT
• No? Observational study
• For observational study the main types will then depend on the timing of
the measurement of outcome, so our third question is:
Q3. When were the outcomes determined?
• Some time after the exposure or intervention?
cohort study (‘prospective study’)
• At the same time as the exposure or intervention?
cross sectional study or survey
• Before the exposure was determined?
case-control study (‘retrospective study’ based on recall of the exposure)
Situation Intervention Outcome
Traditionally……
All endodontically treated
teeth need post and core
and crowns
Never use cantilevers
Replace all teeth
Complete caries removal
Use of pit and fissure sealants
border molding, face bows
and split casts are must..!!
Antibiotic prophylaxis in PJR
Systematic Review: Beginner's Guide
Evidence Based Dentistry
• "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" -- PRISMA
statement
Systematic Review: Beginner's Guide
Why needed?
• To practice evidence based dentistry for
better quality of patient care
• To reduce Research Wastage
• Stakeholders:
– Clinicians & caregivers
– Patients & their families
– Policy makers
The systematic review in context:
Source: HLWIKI International, copied under Creative Commons (CC BY-NC-SA 2.5 CA)
Narrative vs Systematic Review
Scoping vs Systematic Review
Types of a systematic review
1. Interventions
2. Methodology
3. Diagnostic test accuracy
4. Umbrella review/ overview of reviews
Examples
• Summary Review | Evidence-Based Dentistry volume19, pages116–117 (2018)
• Occlusal schemes for complete dentures. Pei Jia Loh & Colin Levey
• Data sources : Medline, Scopus and Cochrane Library databases
• Study selection: Randomised controlled trials (RCTs) or prospective studies comparing
bilateral balanced occlusion (BBO) with other schemes, eg lingual occlusion (LO) canine
guidance (CG) and neutral-centric or zero-degree (ZD).
• Data extraction and synthesis: One reviewer extracted the data and two reviewers
assessed risk of bias using the Newcastle-Ottawa scale for non-randomised studies and
the Cochrane risk of bias tool for RCTs. A narrative summary of the findings was
presented.
• Results : Seventeen studies, 11 RCTs and six prospective studies involving a total of 492
were included. Average follow-up period was 2.96 months (range 1-6 months). Six RCTs
were considered to be at low risk of bias, two at unclear risk and three at high risk.
Studies compared BBO with LO, CG and ZD. Twelve out of 16 studies reported on
quality of life and patients satisfaction.
• Conclusions: The present systematic review indicated that BBO does not confer better
quality of life/satisfaction or masticatory performance and muscle activity. Thus,
lingualised occlusion can be considered a predictable occlusal scheme for
complete dentures in terms of quality of life/satisfaction and Masticatory performance,
while canine guidance can be used to reduce muscular activity.
Systematic Review: Beginner's Guide
Mechanical properties of provisional dental materials: A systematic
review and meta-analysis PLoS One. 2018 Feb 28;13(2):e0193162.
Background: At present, there is no systematic review, which supports the clinicians’ criteria, in
the selection of a specific provisional material over another for a particular clinical situation. The
purpose of this systematic review and meta-analysis was to assess and compare the mechanical
properties of dimethacrylates and monomethacrylates used in fabricating direct provisional
restorations, in terms of flexural strength, fracture toughness and hardness. This review followed
the PRISMA guidelines.
Method: The searches were conducted in PubMed, Embase, Web of Science, Scopus, the New
York Academy of Medicine Grey Literature Report and were complemented by hand-searching,
with no limitation of time or language up to January 10, 2017. Studies that assess and compare
the mechanical properties of dimethacrylate- and monomethacrylate-based provisional restoration
materials were selected. A quality assessment of full-text articles were performed according to
modified ARRIVE and CONSORT criteria and modified Cochrane Collaboration’s tool for in
vitro studies.
Results: Initially, 256 articles were identified. After removing the duplicates and applying the
selection criteria, 24 articles were included in the qualitative synthesis and 7 were included in the
quantitative synthesis (meta-analysis).
Conclusion: It may be concluded that dimethacrylatebased provisional restorations presented
better mechanical behavior than monomethacrylate-based ones in terms of flexural strength and
hardness. Fracture toughness showed no significant differences. Within the monomethacrylate
group, polymethylmethacrylate showed greater flexural strength than polyethylmethacrylate.
Non restorative treatment of carious lesions on
primary teeth
American Dental Association: Centre for EBD
HOW IS IT DONE?
Systematic review……
• Step 1 - A clear and focused question.
• This may require preliminary searching to see what evidence is already available.
• Step 2 - Develop a protocol.
• This is your plan (or recipe) for your review.
– Search strategy and databases
– Eligibility criteria
– Screening process
– Critical appraisal process
– Data analysis / synthesis process
• Register your protocol with Prospero or publish it in a relevant journal.
• Step 3 - Conduct systematic searches.
• Step 4 - Screen search results for relevant studies that meet your eligibility criteria.
• Step 5 - Critically appraise the quality of the included studies.
• Step 6 - Extract relevant data from the included studies.
• Step 7 - Data synthesis.
• Step 8 - Summarise and interpret the evidence to answer your question.
PRISMA
Preferred Reporting Items for Systematic Review and Meta-Analysis
• PRISMA is an evidence-based minimum set of items for reporting
in systematic reviews and meta-analyses.
• PRISMA focuses on the reporting of reviews evaluating
randomized trials, but can also be used as a basis for reporting
systematic reviews of other types of research, particularly
evaluations of interventions.
• Several PRISMA extensions have been published in 2015 so far.
• PRISMA-P for developing review protocols was published in
January 2015 in Systematic Reviews and the BMJ.
• PRISMA-IPD (individual patient data) was published in JAMA in
April
• PRISMA-NMA (Network Meta-Analyses) was published in Annals
of Internal Medicine in June.
Systematic Review: Beginner's Guide
Systematic Review: Beginner's Guide
Other guidelines
• CONSORT Consolidated Standards Of Reporting Trials,
is a transparent and consistent procedure for reporting
trials.
• MOOSE Guidelines for Meta-Analyses and Systematic
Reviews of Observational Studies Meta-analysis of
observational studies in epidemiology.
• STROBE statement STrengthening the Reporting of
OBservational studies in Epidemiology.
• Modified ARRIVE (Animal research: reporting in in vivo
experiments)
• Modified CONSORT (for in vitro studies)
Formulating a research question
It is important you have a clear, well-formed,
focused question.
Benefits of doing this include:
• it makes searching for evidence easier
• you can easily apply the key concepts in your
question to your search.
Systematic Review: Beginner's Guide
The Protocol
• It is the plan or methodology of your
systematic review. You need to develop your
protocol at the beginning, before you start
your searches.
• You may refine your protocol as you progress
through your review.
What to include in your protocol
• Questions / aims of the review.
• Use your PICO breakdown (or the relevant
framework you are using).
• Your eligibility criteria (inclusion and exclusion).
• Where you will search (databases).
• How you will:
– screen your records.
– extract and manage the data.
– assess bias.
– analyse data.
Eligibility Criteria
Search
• How to search
• Where to search
• MeSH
• Report search results
Common tips
• It is best practice to search using both subject headings
and keyword searches.
• Always search one database at a time.
• Start your search in MEDLINE so you can use the
MeSH when mapping out your search.
• Always search one concept at a time.
• If you use a subject heading make sure you also run it
as a keyword search ('back up' subject headings with
keyword searches).
• You should not need to search for your outcome as
this is often implied in your results
What is MeSH?
• Medical Subject Headings (MeSH) is a controlled
vocabulary thesaurus of terms created by the
National Library of Medicine and used for
MEDLINE (PubMed) article records.
• They:
• give uniformity and consistency to the indexing
and cataloging of biomedical literature.
• are updated yearly and selected based on their
importance to clinical care and research.
Mapping your search
1. Different terminology - physiotherapy or physical therapy
2. Different spellings - labour or labor
3. Singular and plural word forms - child or children; foot or feet;
sport or sports
4. Other word forms - diabetic or diabetes; obese or obesity
5. Generic vs specific - acetylsalicylic acid, aspirin, aspro clear
6. Common acronyms - cognitive behavior therapy or CBT
7. Words spelt with and without a dash - nonsurgical or non-surgical
Truncation
• Truncation - Most databases allow you to find word
variations by using a feature called truncation. Use a symbol
(often the *) to substitute for characters after a word stem.
• It is highly recommended you use truncation to include all
variations of a word in your search.
• diabet* finds diabetic, diabetes exercis* finds exercise,
exercises, exercising
• Limited truncation - allows you to specify how many letters
you want to find after a root word. This is only available in
some databases, for example MEDLINE, EMBASE and
PsycINFO.
• hospital$1 finds hospital or hospitals but NOT hospitalisation
Find different word spellings
• Wildcards - allow you to find different word
spellings.
• The wildcard symbol can vary in different
databases so always check the help screens.
• tumo?r finds tumor or tumour
• behavio?r finds behavior or behaviour
• urbani?ation finds urbanisation or urbanization
Phrase Searching
• It forces words together in one direction.
• Most databases require you put phrases in
double quotes, for example:
• "carpal tunnel syndrome" Most databases
require you to put your phrases in double
quotes. The one exception is Ovid databases
(for example: MEDLINE, EMBASE, PsycINFO)
Mining for keywords
• Some of the following tools may be useful to explore: PubMed
PubReMiner
• When you submit your query (which can be any query that can be
processed by PubMed), PubReMiner will process the result of that query
and display its results (in the form of selectable "keywords") in frequency
tables, which can be added/excluded from the query to optimize the
results.
Connectors
Understanding how to combine your terms using AND and OR is critical.
AND - connects different concepts to narrow your search
OR - connects similar concepts (synonyms) to broaden your search
NOT - removes terms. Avoid using NOT as it will likely remove relevant results
converting search terms into
search strategy
Systematic Review: Beginner's Guide
Systematic Review: Beginner's Guide
National Library of Medicine - Bethesda, MD, United States.
US Dept of Health & Human services:
The United States National Library of
Medicine (NLM) at the National Institutes of
Health maintains the database as part of the
Entrez system of information retrieval.
Some Concepts
• Both PubMed and PubMed
Central index millions of
biomedical articles. They
are provided by the
National Library of
Medicine and the National
Institute of Health.
• PubMed Central (PMC)
contains ALL full-text
articles and documents. It is
a subset of PubMed.
• MedlinePlus: for patients,
families and other
consumers
National Center for Biotechnology Information
• The NCBI houses a series of databases
relevant to biotechnology and biomedicine
and is an important resource for
bioinformatics tools and services.
• Major databases include GenBank for DNA
sequences and PubMed, a bibliographic
database for the biomedical literature. Other
databases include the NCBI Epigenomics
database.
Systematic Review: Beginner's Guide
Searching gray literature
• "...literature that is not formally published in
sources such as books or journal articles." This
can include information such as government
reports, conference proceedings, graduate
dissertations, unpublished clinical trials, and
much more.
Why search the gray literature if it
hasn't been peer-reviewed?
• There is a strong bias in scientific publishing
toward publishing studies that show some
sort of significant effect. Meanwhile, many
studies and trials that show no effect end up
going unpublished. But knowing that an
intervention had no effect is just as important
as knowing that it did have an effect when it
comes to making decisions for practice and
policy-making. Thus, the gray literature can
be critical.
• Identify and record the sources you will search, including some
indication of search terms used if appropriate.
• Try searching databases that specialize in gray
literature like OpenGrey.
• Conference proceedings: Identify professional organizations that have
conferences at which researchers might be presenting work related to
your topic. Search those conference proceedings on the organization's
website or by contacting organizational boards for access to past
proceedings that may not be online.
• Theses and dissertations: There are a number of databases dedicated
to theses and dissertations, which you can search using your search
terms.
• Identify government agencies, international and non-governmental
organizations, that might publish technical papers and reports on your
topic. Search their websites or any online libraries that they may
provide.
• Contact known researchers in the field to determine if there are any
ongoing or unpublished studies that s/he may be aware of.
A systematic search is an iterative
process.
• You will need to constantly evaluate, validate,
and verify your search results, as well as revise
and re-run your searches as required.
Your search strategy should be:
• comprehensive
• transparent
• replicable
• validated
• unbiased
Elements for peer review of electronic search strategies
Reporting your search
Record the following
• Title of database searched.
• Name of the database platform e.g. MEDLINE
(OvidSP).
• Database date range.
• Date search conducted.
• Years covered by the search.
• Complete search strategy (include all search
terms and limits).
Systematic Review: Beginner's Guide
Screen
• What is Screening?
• Screening is a two-part process in
which you determine whether
each individual article meets your
inclusion criteria, and therefore
should be included in your
review.
• To reduce bias, you should have a
minimum of two reviewers to
screen results (yourself and
someone else from your team).
• The Two Stages of Screening
• First Pass (Title/Abstract): This is
where you examine titles and
abstracts to remove obviously
irrelevant material. At this stage you
may not need to provide a
justification for your exclusions.
• Second Pass (Full Text): This is where
you examine the full text for
compliance with your eligibility
criteria. At this stage you must
provide reasons why you exclude
documents.
How do I screen?
• After you've finished creating
(building/developing) your search, save it as
the final version in each database that you
identified in your protocol. Once you have
them all ready to go, run each one and export
all of your results to Endnote, using a separate
group to store the results from each database.
From Endnote, export your references. Then
import to Covidence to commence screening.
Systematic Review: Beginner's Guide
Critical Appraisal
“Critical Appraisal Skills enable you to assess the
trustworthiness, relevance and results of published
papers so that you can decide if they are believable
and useful.” -- Critical appraisal skills, CASP (2013)
Methodological quality:
internal and external validity
Risk of bias
AMSTAR check-list
a measurement tool to assess the methodological quality of systematic
reviews.
MECIR
The Methodological Expectations of Cochrane Intervention
Reviews (MECIR) standards specify methodological expectations for
Cochrane Protocols, Reviews, and updates of reviews on the effects of
interventions.
Risk of bias assessment
Cochrane risk of bias assessment tool
Summary assessments of risk of bias for each important outcome
Example presentation of risk of bias assessments for studies in a Cochrane
review of therapeutic monitoring of antiretroviral drugs in people with HIV
Risk of bias assessment
Data Extraction
The information that you extract from the studies included in
your systematic review will depend on the purpose of your
review and your question.
• Only extract the data that is relevant to your particular
systematic review question.
• Develop a data extraction worksheet or workbook as part of
your protocol. This should include the key constructs you are
interested in as part of your review.
• Your worksheet or workbook should be comprehensive
enough that you should not have to go back to those studies.
Checklist of items - data extraction
• Source
• Study ID (created by review author).
• Report ID (created by review author).
• Review author ID (created by review
author).
• Citation and contact details.
• Eligibility
• Confirm eligibility for review.
• Reason for exclusion.
• Methods
• Study design.
• Total study duration.
• Sequence generation*.
• Allocation sequence concealment*.
• Blinding*.
• Other concerns about bias*.
• Participants
• Total number.
• Setting.
• Diagnostic criteria.
• Age.and Sex.
• Country.
• [Co-morbidity], [Socio-demographics], [Ethnicity].
• [Date of study].
• Interventions
• Total number of intervention groups.
• For each intervention and comparison group of
interest:
• Specific intervention.
• Intervention details (sufficient for replication, if
feasible).
• [Integrity of intervention].
Items without parentheses should normally be collected in all reviews; items in square brackets
may be relevant to some reviews and not others.
Data extraction Contd..
• Outcomes
• Outcomes and time points (i) collected; (ii)
reported*.
• For each outcome of interest:
• Outcome definition (with diagnostic criteria if
relevant).
• Unit of measurement (if relevant).
• For scales: upper and lower limits, and whether
high or low score is good.
• Results
• Number of participants allocated to each
intervention group.
• For each outcome of interest:
• Sample size.
• Missing participants*.
• Summary data for each intervention group (e.g.
2×2 table for dichotomous data; means and SDs
for continuous data).
• [Estimate of effect with confidence interval; P
value].
• [Subgroup analyses].
• Miscellaneous
• Funding source.
• Key conclusions of the study authors.
• Miscellaneous comments from the study
authors.
• References to other relevant studies.
• Correspondence required.
• Miscellaneous comments by the review
authors.
•
GRADE assessment of quality of evidence
Registering Protocol
• Registering your protocol helps avoid duplication of work. You do not
want anyone else to do the exact same review you are doing.
• Once you register your review will be available open access through their
database. It will have a unique registration number. This number can be
cited in publications and reports to provide the link between your planned
and completed review. This is recommended by PRISMA (2009) and many
publishers.
• These are international databases of prospectively registered systematic
reviews in health and social care. Key features from a review protocol are
recorded and maintained as a permanent record.
• The database is free to search and provides a comprehensive listing of
systematic reviews registered at inception to enable comparison of
reported review findings with what was planned in the protocol.
• Reviews should have health related outcome
Cochrane
• Archibald Leman Cochrane CBE (12 January 1909 – 18 June
1988) was a Scottish doctor noted for his book Effectiveness
and Efficiency: Random Reflections on Health Services.
• This book advocated the use of randomized control trials to
make medicine more effective and efficient.
• His advocacy of randomized controlled trials eventually led
to the development of the Cochrane Library database
of systematic reviews, the establishment of the UK
Cochrane Centre in Oxford and the international Cochrane
Collaboration.
• He is considered to be the originator of the idea of
evidence-based medicine in the current era.
• Cochrane, previously known as the Cochrane
Collaboration, was founded in 1993, is a British
charity formed to organize medical research findings
so as to facilitate evidence-based choices about health
interventions faced by health professionals, patients,
and policy makers.
• Cochrane includes 53 review groups that are based at
research institutions worldwide. Cochrane has
approximately 30,000 volunteer experts from around
the world.
• The group conducts systematic reviews of health-care
interventions and diagnostic tests and publishes them
in the Cochrane Library.
Cochrane
PROSPERO
• The International Prospective Register of
Systematic Reviews, better known
as PROSPERO, is an open access online database
of systematic review protocols on health-related
topics. Researchers can choose to have their
reviews prospectively registered with PROSPERO.
• The database is produced by the Centre for
Reviews and Dissemination at the University of
York in England, and it is funded by the National
Institute for Health Research.
Data set for a registry of systematic
reviews
• Research question, including:
– patients and population
– intervention or exposure
– comparison (if relevant)
– outcomes
• Search strategy and date of execution of search
• Criteria for inclusion and exclusion, including types of:
– Participants
– interventions or exposures
– Outcomes
– studies
Data set for a registry of systematic
reviews
• Methods used to assess risk of bias
• Method of analysis (including statistical
analysis if relevant)
• Anticipated start date
• Investigators
• Source of funding
• Competing interests of authors
• Date of registration
Review manager- RevMan
• Cochrane collaboration’s Software for
systematic reviews
• For all steps including protocol writing,
statistical analysis and editorial process.
• Free of cost
Archie
• Central database – stores all reviews
published and in progress along-with and
contact information
• Needs login : username and password
Cochrane Handbook
Funding systematic review
The NIHR Cochrane Programme Grant Scheme
Useful Resources
Now What…
• Topic
• In vivo
• In vitro
• Registration ??
• Desirable
• Preparation
• Read
• Decide your area of interest
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Systematic Review: Beginner's Guide

  • 1. Systematic Review A Beginner’s Guide Dr Saee Deshpande MDS, Fellow-FAIMER, Fellow- Oral Implantology Associate Professor Dept of Prosthodontics, VSPM Dental College & Research Centre, Nagpur
  • 2. Learning objectives • Understand what is systematic review • Understand the importance of systematic review • Learn the process of doing a systematic review
  • 7. How to identify study design? Q1. What was the aim of the study? • To simply describe a population (PO questions) descriptive • To quantify the relationship between factors (PICO questions) analytic. Q2. If analytic, was the intervention randomly allocated? • Yes? RCT • No? Observational study • For observational study the main types will then depend on the timing of the measurement of outcome, so our third question is: Q3. When were the outcomes determined? • Some time after the exposure or intervention? cohort study (‘prospective study’) • At the same time as the exposure or intervention? cross sectional study or survey • Before the exposure was determined? case-control study (‘retrospective study’ based on recall of the exposure)
  • 9. All endodontically treated teeth need post and core and crowns Never use cantilevers Replace all teeth Complete caries removal Use of pit and fissure sealants border molding, face bows and split casts are must..!! Antibiotic prophylaxis in PJR
  • 12. • "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" -- PRISMA statement
  • 14. Why needed? • To practice evidence based dentistry for better quality of patient care • To reduce Research Wastage • Stakeholders: – Clinicians & caregivers – Patients & their families – Policy makers
  • 15. The systematic review in context: Source: HLWIKI International, copied under Creative Commons (CC BY-NC-SA 2.5 CA)
  • 18. Types of a systematic review 1. Interventions 2. Methodology 3. Diagnostic test accuracy 4. Umbrella review/ overview of reviews
  • 20. • Summary Review | Evidence-Based Dentistry volume19, pages116–117 (2018) • Occlusal schemes for complete dentures. Pei Jia Loh & Colin Levey • Data sources : Medline, Scopus and Cochrane Library databases • Study selection: Randomised controlled trials (RCTs) or prospective studies comparing bilateral balanced occlusion (BBO) with other schemes, eg lingual occlusion (LO) canine guidance (CG) and neutral-centric or zero-degree (ZD). • Data extraction and synthesis: One reviewer extracted the data and two reviewers assessed risk of bias using the Newcastle-Ottawa scale for non-randomised studies and the Cochrane risk of bias tool for RCTs. A narrative summary of the findings was presented. • Results : Seventeen studies, 11 RCTs and six prospective studies involving a total of 492 were included. Average follow-up period was 2.96 months (range 1-6 months). Six RCTs were considered to be at low risk of bias, two at unclear risk and three at high risk. Studies compared BBO with LO, CG and ZD. Twelve out of 16 studies reported on quality of life and patients satisfaction. • Conclusions: The present systematic review indicated that BBO does not confer better quality of life/satisfaction or masticatory performance and muscle activity. Thus, lingualised occlusion can be considered a predictable occlusal scheme for complete dentures in terms of quality of life/satisfaction and Masticatory performance, while canine guidance can be used to reduce muscular activity.
  • 22. Mechanical properties of provisional dental materials: A systematic review and meta-analysis PLoS One. 2018 Feb 28;13(2):e0193162. Background: At present, there is no systematic review, which supports the clinicians’ criteria, in the selection of a specific provisional material over another for a particular clinical situation. The purpose of this systematic review and meta-analysis was to assess and compare the mechanical properties of dimethacrylates and monomethacrylates used in fabricating direct provisional restorations, in terms of flexural strength, fracture toughness and hardness. This review followed the PRISMA guidelines. Method: The searches were conducted in PubMed, Embase, Web of Science, Scopus, the New York Academy of Medicine Grey Literature Report and were complemented by hand-searching, with no limitation of time or language up to January 10, 2017. Studies that assess and compare the mechanical properties of dimethacrylate- and monomethacrylate-based provisional restoration materials were selected. A quality assessment of full-text articles were performed according to modified ARRIVE and CONSORT criteria and modified Cochrane Collaboration’s tool for in vitro studies. Results: Initially, 256 articles were identified. After removing the duplicates and applying the selection criteria, 24 articles were included in the qualitative synthesis and 7 were included in the quantitative synthesis (meta-analysis). Conclusion: It may be concluded that dimethacrylatebased provisional restorations presented better mechanical behavior than monomethacrylate-based ones in terms of flexural strength and hardness. Fracture toughness showed no significant differences. Within the monomethacrylate group, polymethylmethacrylate showed greater flexural strength than polyethylmethacrylate.
  • 23. Non restorative treatment of carious lesions on primary teeth American Dental Association: Centre for EBD
  • 24. HOW IS IT DONE? Systematic review……
  • 25. • Step 1 - A clear and focused question. • This may require preliminary searching to see what evidence is already available. • Step 2 - Develop a protocol. • This is your plan (or recipe) for your review. – Search strategy and databases – Eligibility criteria – Screening process – Critical appraisal process – Data analysis / synthesis process • Register your protocol with Prospero or publish it in a relevant journal. • Step 3 - Conduct systematic searches. • Step 4 - Screen search results for relevant studies that meet your eligibility criteria. • Step 5 - Critically appraise the quality of the included studies. • Step 6 - Extract relevant data from the included studies. • Step 7 - Data synthesis. • Step 8 - Summarise and interpret the evidence to answer your question.
  • 26. PRISMA Preferred Reporting Items for Systematic Review and Meta-Analysis • PRISMA is an evidence-based minimum set of items for reporting in systematic reviews and meta-analyses. • PRISMA focuses on the reporting of reviews evaluating randomized trials, but can also be used as a basis for reporting systematic reviews of other types of research, particularly evaluations of interventions. • Several PRISMA extensions have been published in 2015 so far. • PRISMA-P for developing review protocols was published in January 2015 in Systematic Reviews and the BMJ. • PRISMA-IPD (individual patient data) was published in JAMA in April • PRISMA-NMA (Network Meta-Analyses) was published in Annals of Internal Medicine in June.
  • 29. Other guidelines • CONSORT Consolidated Standards Of Reporting Trials, is a transparent and consistent procedure for reporting trials. • MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies Meta-analysis of observational studies in epidemiology. • STROBE statement STrengthening the Reporting of OBservational studies in Epidemiology. • Modified ARRIVE (Animal research: reporting in in vivo experiments) • Modified CONSORT (for in vitro studies)
  • 30. Formulating a research question It is important you have a clear, well-formed, focused question. Benefits of doing this include: • it makes searching for evidence easier • you can easily apply the key concepts in your question to your search.
  • 32. The Protocol • It is the plan or methodology of your systematic review. You need to develop your protocol at the beginning, before you start your searches. • You may refine your protocol as you progress through your review.
  • 33. What to include in your protocol • Questions / aims of the review. • Use your PICO breakdown (or the relevant framework you are using). • Your eligibility criteria (inclusion and exclusion). • Where you will search (databases). • How you will: – screen your records. – extract and manage the data. – assess bias. – analyse data.
  • 35. Search • How to search • Where to search • MeSH • Report search results
  • 36. Common tips • It is best practice to search using both subject headings and keyword searches. • Always search one database at a time. • Start your search in MEDLINE so you can use the MeSH when mapping out your search. • Always search one concept at a time. • If you use a subject heading make sure you also run it as a keyword search ('back up' subject headings with keyword searches). • You should not need to search for your outcome as this is often implied in your results
  • 37. What is MeSH? • Medical Subject Headings (MeSH) is a controlled vocabulary thesaurus of terms created by the National Library of Medicine and used for MEDLINE (PubMed) article records. • They: • give uniformity and consistency to the indexing and cataloging of biomedical literature. • are updated yearly and selected based on their importance to clinical care and research.
  • 39. 1. Different terminology - physiotherapy or physical therapy 2. Different spellings - labour or labor 3. Singular and plural word forms - child or children; foot or feet; sport or sports 4. Other word forms - diabetic or diabetes; obese or obesity 5. Generic vs specific - acetylsalicylic acid, aspirin, aspro clear 6. Common acronyms - cognitive behavior therapy or CBT 7. Words spelt with and without a dash - nonsurgical or non-surgical
  • 40. Truncation • Truncation - Most databases allow you to find word variations by using a feature called truncation. Use a symbol (often the *) to substitute for characters after a word stem. • It is highly recommended you use truncation to include all variations of a word in your search. • diabet* finds diabetic, diabetes exercis* finds exercise, exercises, exercising • Limited truncation - allows you to specify how many letters you want to find after a root word. This is only available in some databases, for example MEDLINE, EMBASE and PsycINFO. • hospital$1 finds hospital or hospitals but NOT hospitalisation
  • 41. Find different word spellings • Wildcards - allow you to find different word spellings. • The wildcard symbol can vary in different databases so always check the help screens. • tumo?r finds tumor or tumour • behavio?r finds behavior or behaviour • urbani?ation finds urbanisation or urbanization
  • 42. Phrase Searching • It forces words together in one direction. • Most databases require you put phrases in double quotes, for example: • "carpal tunnel syndrome" Most databases require you to put your phrases in double quotes. The one exception is Ovid databases (for example: MEDLINE, EMBASE, PsycINFO)
  • 43. Mining for keywords • Some of the following tools may be useful to explore: PubMed PubReMiner • When you submit your query (which can be any query that can be processed by PubMed), PubReMiner will process the result of that query and display its results (in the form of selectable "keywords") in frequency tables, which can be added/excluded from the query to optimize the results.
  • 44. Connectors Understanding how to combine your terms using AND and OR is critical. AND - connects different concepts to narrow your search OR - connects similar concepts (synonyms) to broaden your search NOT - removes terms. Avoid using NOT as it will likely remove relevant results
  • 45. converting search terms into search strategy
  • 48. National Library of Medicine - Bethesda, MD, United States. US Dept of Health & Human services: The United States National Library of Medicine (NLM) at the National Institutes of Health maintains the database as part of the Entrez system of information retrieval.
  • 49. Some Concepts • Both PubMed and PubMed Central index millions of biomedical articles. They are provided by the National Library of Medicine and the National Institute of Health. • PubMed Central (PMC) contains ALL full-text articles and documents. It is a subset of PubMed. • MedlinePlus: for patients, families and other consumers
  • 50. National Center for Biotechnology Information • The NCBI houses a series of databases relevant to biotechnology and biomedicine and is an important resource for bioinformatics tools and services. • Major databases include GenBank for DNA sequences and PubMed, a bibliographic database for the biomedical literature. Other databases include the NCBI Epigenomics database.
  • 52. Searching gray literature • "...literature that is not formally published in sources such as books or journal articles." This can include information such as government reports, conference proceedings, graduate dissertations, unpublished clinical trials, and much more.
  • 53. Why search the gray literature if it hasn't been peer-reviewed? • There is a strong bias in scientific publishing toward publishing studies that show some sort of significant effect. Meanwhile, many studies and trials that show no effect end up going unpublished. But knowing that an intervention had no effect is just as important as knowing that it did have an effect when it comes to making decisions for practice and policy-making. Thus, the gray literature can be critical.
  • 54. • Identify and record the sources you will search, including some indication of search terms used if appropriate. • Try searching databases that specialize in gray literature like OpenGrey. • Conference proceedings: Identify professional organizations that have conferences at which researchers might be presenting work related to your topic. Search those conference proceedings on the organization's website or by contacting organizational boards for access to past proceedings that may not be online. • Theses and dissertations: There are a number of databases dedicated to theses and dissertations, which you can search using your search terms. • Identify government agencies, international and non-governmental organizations, that might publish technical papers and reports on your topic. Search their websites or any online libraries that they may provide. • Contact known researchers in the field to determine if there are any ongoing or unpublished studies that s/he may be aware of.
  • 55. A systematic search is an iterative process. • You will need to constantly evaluate, validate, and verify your search results, as well as revise and re-run your searches as required. Your search strategy should be: • comprehensive • transparent • replicable • validated • unbiased
  • 56. Elements for peer review of electronic search strategies
  • 58. Record the following • Title of database searched. • Name of the database platform e.g. MEDLINE (OvidSP). • Database date range. • Date search conducted. • Years covered by the search. • Complete search strategy (include all search terms and limits).
  • 60. Screen • What is Screening? • Screening is a two-part process in which you determine whether each individual article meets your inclusion criteria, and therefore should be included in your review. • To reduce bias, you should have a minimum of two reviewers to screen results (yourself and someone else from your team). • The Two Stages of Screening • First Pass (Title/Abstract): This is where you examine titles and abstracts to remove obviously irrelevant material. At this stage you may not need to provide a justification for your exclusions. • Second Pass (Full Text): This is where you examine the full text for compliance with your eligibility criteria. At this stage you must provide reasons why you exclude documents.
  • 61. How do I screen? • After you've finished creating (building/developing) your search, save it as the final version in each database that you identified in your protocol. Once you have them all ready to go, run each one and export all of your results to Endnote, using a separate group to store the results from each database. From Endnote, export your references. Then import to Covidence to commence screening.
  • 63. Critical Appraisal “Critical Appraisal Skills enable you to assess the trustworthiness, relevance and results of published papers so that you can decide if they are believable and useful.” -- Critical appraisal skills, CASP (2013) Methodological quality: internal and external validity Risk of bias
  • 64. AMSTAR check-list a measurement tool to assess the methodological quality of systematic reviews. MECIR The Methodological Expectations of Cochrane Intervention Reviews (MECIR) standards specify methodological expectations for Cochrane Protocols, Reviews, and updates of reviews on the effects of interventions.
  • 65. Risk of bias assessment Cochrane risk of bias assessment tool
  • 66. Summary assessments of risk of bias for each important outcome
  • 67. Example presentation of risk of bias assessments for studies in a Cochrane review of therapeutic monitoring of antiretroviral drugs in people with HIV
  • 68. Risk of bias assessment
  • 69. Data Extraction The information that you extract from the studies included in your systematic review will depend on the purpose of your review and your question. • Only extract the data that is relevant to your particular systematic review question. • Develop a data extraction worksheet or workbook as part of your protocol. This should include the key constructs you are interested in as part of your review. • Your worksheet or workbook should be comprehensive enough that you should not have to go back to those studies.
  • 70. Checklist of items - data extraction • Source • Study ID (created by review author). • Report ID (created by review author). • Review author ID (created by review author). • Citation and contact details. • Eligibility • Confirm eligibility for review. • Reason for exclusion. • Methods • Study design. • Total study duration. • Sequence generation*. • Allocation sequence concealment*. • Blinding*. • Other concerns about bias*. • Participants • Total number. • Setting. • Diagnostic criteria. • Age.and Sex. • Country. • [Co-morbidity], [Socio-demographics], [Ethnicity]. • [Date of study]. • Interventions • Total number of intervention groups. • For each intervention and comparison group of interest: • Specific intervention. • Intervention details (sufficient for replication, if feasible). • [Integrity of intervention]. Items without parentheses should normally be collected in all reviews; items in square brackets may be relevant to some reviews and not others.
  • 71. Data extraction Contd.. • Outcomes • Outcomes and time points (i) collected; (ii) reported*. • For each outcome of interest: • Outcome definition (with diagnostic criteria if relevant). • Unit of measurement (if relevant). • For scales: upper and lower limits, and whether high or low score is good. • Results • Number of participants allocated to each intervention group. • For each outcome of interest: • Sample size. • Missing participants*. • Summary data for each intervention group (e.g. 2×2 table for dichotomous data; means and SDs for continuous data). • [Estimate of effect with confidence interval; P value]. • [Subgroup analyses]. • Miscellaneous • Funding source. • Key conclusions of the study authors. • Miscellaneous comments from the study authors. • References to other relevant studies. • Correspondence required. • Miscellaneous comments by the review authors. •
  • 72. GRADE assessment of quality of evidence
  • 73. Registering Protocol • Registering your protocol helps avoid duplication of work. You do not want anyone else to do the exact same review you are doing. • Once you register your review will be available open access through their database. It will have a unique registration number. This number can be cited in publications and reports to provide the link between your planned and completed review. This is recommended by PRISMA (2009) and many publishers. • These are international databases of prospectively registered systematic reviews in health and social care. Key features from a review protocol are recorded and maintained as a permanent record. • The database is free to search and provides a comprehensive listing of systematic reviews registered at inception to enable comparison of reported review findings with what was planned in the protocol. • Reviews should have health related outcome
  • 74. Cochrane • Archibald Leman Cochrane CBE (12 January 1909 – 18 June 1988) was a Scottish doctor noted for his book Effectiveness and Efficiency: Random Reflections on Health Services. • This book advocated the use of randomized control trials to make medicine more effective and efficient. • His advocacy of randomized controlled trials eventually led to the development of the Cochrane Library database of systematic reviews, the establishment of the UK Cochrane Centre in Oxford and the international Cochrane Collaboration. • He is considered to be the originator of the idea of evidence-based medicine in the current era.
  • 75. • Cochrane, previously known as the Cochrane Collaboration, was founded in 1993, is a British charity formed to organize medical research findings so as to facilitate evidence-based choices about health interventions faced by health professionals, patients, and policy makers. • Cochrane includes 53 review groups that are based at research institutions worldwide. Cochrane has approximately 30,000 volunteer experts from around the world. • The group conducts systematic reviews of health-care interventions and diagnostic tests and publishes them in the Cochrane Library. Cochrane
  • 76. PROSPERO • The International Prospective Register of Systematic Reviews, better known as PROSPERO, is an open access online database of systematic review protocols on health-related topics. Researchers can choose to have their reviews prospectively registered with PROSPERO. • The database is produced by the Centre for Reviews and Dissemination at the University of York in England, and it is funded by the National Institute for Health Research.
  • 77. Data set for a registry of systematic reviews • Research question, including: – patients and population – intervention or exposure – comparison (if relevant) – outcomes • Search strategy and date of execution of search • Criteria for inclusion and exclusion, including types of: – Participants – interventions or exposures – Outcomes – studies
  • 78. Data set for a registry of systematic reviews • Methods used to assess risk of bias • Method of analysis (including statistical analysis if relevant) • Anticipated start date • Investigators • Source of funding • Competing interests of authors • Date of registration
  • 79. Review manager- RevMan • Cochrane collaboration’s Software for systematic reviews • For all steps including protocol writing, statistical analysis and editorial process. • Free of cost
  • 80. Archie • Central database – stores all reviews published and in progress along-with and contact information • Needs login : username and password
  • 82. Funding systematic review The NIHR Cochrane Programme Grant Scheme
  • 84. Now What… • Topic • In vivo • In vitro • Registration ?? • Desirable • Preparation • Read • Decide your area of interest

Notas del editor

  1. "Review authors are strongly encouraged to include a study flow diagram as recommended by the PRISMA statement (Liberati 2009)“-- chapter 4.5, Cochrane Handbook 2011