Searching for Trials for a Systematic Review

US Cochrane Eyes and Vision GroupCompleting a Cochrane Systematic Review Workshop

July 18, 2013

Describe the major available electronic resources

Describe how to build a search strategy Describe some alternate sources for finding

trials Describe what to do once you get your

search results

Objectives

OK, I Have a Title- What next?

If you are doing a Cochrane review, work with the Trials Search Coordinator for the relevant Cochrane review group.

Work with an information specialist trained in searching for systematic reviews

Use Chapter 6 in the Cochrane Handbook as a guide Include the search protocol in your protocol (strategy

and sources) Document everything you do and when you do it!!!!

Identification of evidence

Develop your protocol for conducting the search: What sources

• Databases• Hand searching

How – search strategies How to make decisions (duplicate screening?) How to document – dates, numbers included,

excluded

Cochrane Central Register of Controlled Trials (CENTRAL) (www.thecochranelibrary.com)

Includes about 650,000 citations Includes MEDLINE and EMBASE searches Includes Cochrane group specialized registers

MEDLINE/PubMED (www.ncbi.nlm.nih.gov/sites/entrez)

Includes 22 million citations; > 5,600 journals in 39 languages Citations fully indexed from 1966 forward PubMed has most recent – but non-indexed articles

EMBASE (www.embase.com) Includes 25 million citations > 7,600 journals Includes MEDLINE Includes > 6 million conference abstracts

Major electronic databases used to search for clinical trials

Other important databases National and regional databases (often local language)

LILACS (bases.bireme.br)

Subject-specific databases CINAHL (www.cinahl.com) PsycINFO (www.apa.org/psycinfo/) OTSeeker (www.otseeker.com)

Citation databases Web of Science (www.thomsonreuters.com) Scopus (www.scopus.com)

Dissertations, thesis databases ProQuest (www.Proquest.com)

Grey literature databases Opengrey (www.opengrey.eu) – formerly SIGLE

Will review be limited to RCTs or will it include other study designs?

Will adverse events be included?

Is there any geographic consideration?

Is there a limited time period when the intervention was used?

Other issues to consider

Add to search strategy

Plurals - (acuity, acuities) Abbreviations - (e.g., CNV for choroidal neovascularization) Synonyms -

Lucentis, ranibiuzumab Avastin, bevacizumab

Spelling variations - (randomized/randomised) Truncation – (antibod* for antibody or antibodies)

Medical Subject Headings (MeSH) - Descriptors (with thesaurus) - Most specific term used

Textword searching - titles for all records, abstracts since 1975 - truncation useful

Publication type Sensitivity (recall) vs Specificity (precision)

- no gold standard available

Searching trials on PubMed

1. Start with simple search strategy

2. Run search and retrieve reports

3. Analyze MeSH and text words of studies fitting your criteria

4. Re-run search with revised strategy

5. Repeat steps 2 – 4 if necessary

6. Run optimal search strategy

7. Retrieve reports identified with optimal search strategy

Development of MEDLINE search strategy

To develop simple search strategy, start with your question

Population Intervention(s) Comparison(s) Outcome

P

I

C

O

For patients with choroidal neovascularization associated with age-related macular degeneration, do intravitreal injections of Lucentis, when compared with Avastin, prevent vision loss?

Individuals with choroidal neovascularization associated with age-related macular degeneration

Lucentis, ranibizumab

Avastin, bevacizumab

Change in visual acuity or visual field

Searching PubMED Start with the general format:

(Population OR synonym# 1 OR synonym #2) AND (Intervention OR synonym # 1 OR synonym#2) AND

(Comparator OR synonym#1 OR synonym#2) AND

(Outcome OR synonym# 1 OR synonym # 2) AND

Add study type filter terms

How do we find the terms to use in the search strategy?

macular degeneration AND lucentis AND avastin

Text wordsText words

Use the MH – MeSH termsin known articles to build your search strategy

Angiogenesis Inhibitors/

Administra-tion & dosage/

Antibodies Monoclonal/ Administra-tion & dosage

Choroidal neovascularization /drug therapy

Macular degeneration/ complications/ drug therapy/ physiotherapy

Visual acuity/ physiology

Visual fields/ drug effects

CATT X X

Paper 2 X X X

Paper 3 X

Paper 4 X x X X

Paper 5 X X

MeSH Analysis

Completed search strategy(this is added to the Cochrane “highly sensitive search strategy”)

#1 exp macular degeneration/#2 exp retinal degeneration/#3 exp retinal neovascularization/ #4 exp choroidal neovascularization/#5 exp macula lutea/#6 maculopath$.tw.#7 ((macul$ or retina$ or choroid$*) adj3 degener$).tw.)#8 ((macul$ or retina$ or choroid$*) adj3 neovasc$).tw.) #9 ((macula$ adj2 lutea.tw#10 or/1-9#11 exp angiogenesis inhibitors/#12 exp angiogenesis inducing agents/#13 exp vascular endothelial growth factors/#14 (lucentis$ or avastin$ or ranibizumab$ or bevacizumab$).tw#15 (anti adj2 VEGF$).tw.#16 (endothelial adj2 growth adj2 factor$).tw.#17 or/ 11-16#18 10 AND 17

P

I, C

Add study filter terms to identify study type

Common errors in search strategies

Spelling errors Missed spelling variant (randomized instead of random) Truncation error (methods* instead of method*) Logical operator error (using NOT instead of AND) Wrong line number (when combining lines) MeSH and free text terms on same line Irrelevant MeSH term Missed MeSH term Unwarranted explosion of MeSH terms Redundancy without rationale Search strategy not tailored for other databases

Sampson et al, J Clin Epi 2006

Use of all databases may be necessary to identify all reports

Lawrence et al Inj Prev 2008

Registers of ongoing or completed trials

www.clinicaltrials.govwww.clinicaltrials.gov

www.controlled-trials.comwww.controlled-trials.com

www.who.int/ictrp/en www.who.int/ictrp/en (WHO portal)

Clinical Trial registers

Google Scholar vs PubMed

Search engine No citations

Mean (SD) Median (IQR)

Google scholar 2211 (3999) 1040 (339,1958)

PubMed 44 (47) 35 (20,53)

Identified 22 Drug Information Rounds review articles Searched PubMed or Google Scholar with 2 keywords (MeSH) or text

Google presented “older” literature first compared with PubMed - Freeman et al Pharmacotherapy 2009

Similar results reported using clinical query (PubMed) and advanced scholar search (Google scholar)

- Anders et al (Resp. Care 2010)

Journals in topic area

Conference proceedings in area

Bibliographies of related systematic reviews

More efficient and more accurate to use SCOPUS to download all references in a review than to review them manually - Chapman et al, Health Information and Libraries J 2010)

Handsearching

Other sources of trial results

FDA Pharmaceutical company registers Communication with experts in the field www.clinicaltrials.gov

Systematic Snowballing

Use included articles as a source to identify missing studies:

Reference lists - check cited articles = backward searching

Web of Science, SCOPUS - check citing articles = forward searching

(“Related articles”/ “Find Similar”) in MEDLINE, EMBASE) – also could use to find new terms to expand your search strategy

Use of all sources may be necessaryto identify all reports

Sources of studies for a systematic review for studies promoting a shift from use of cars to walking or cycling

Source Total No. No. in review %Health databases 4 3 14Citation databases 8 3 14Other databases 8 2 9Transport database 33 9 41Internet search 10 3 14Handsearch abstracts 6 2 9Total 69 22 100

Ogilvie et al JECH 2005

Screening search results Full record citations downloaded from electronic databases

into an electronic file – either a text file or a reference manager file

Files distributed to two team members for screening Yes, Maybe, No Systematic reviews - obtain full copy for review of references

Disagreements resolved by consensus or by third team member

Electronic documentation Reference manager – use new field to enter yes/no/maybe/ref Word – identify using highlighted text, comment box, copy/paste to

new file Excel – possible, but difficult to manage

Screening full text articles Develop and use a data collection form (paper or electronic)

Query inclusion/exclusion criteria Duplicate screening - Yes, no, unclear Disagreements resolved by consensus or by third team member

Responses for excluded studies provide “reason for exclusion” in RevMan

Articles with unclear designation usually need author contact –go into “awaiting assessment” in RevMan

Start to identify multiple articles from same trial Authors Numbers of randomized participants Interventions

Document your findings

When you searched (month/year) Where you searched

Electronic databases Handsearches Trial registers Communications with experts, industry Bibliographies, etc. Internet

How you searched Search strategies

What you found PRISMA flow diagram

PRISMA Flow of InformationNo. records identified

through database searchingNo. additional records identified

through other sources

No. recordsscreened

No. studies includedin qualitative synthesis

No. full-length articles assessed for eligibility

No. records after duplicates removed

No. records excluded

No. full-length articles excluded, with reasons

No. studies included in quantitative synthesis

Conclusions

Develop a search strategy for electronic database searching using an iterative approach, starting with your question

Make sure to perform searches from all additional sources (adapting strategy as necessary)

Document when, where, and how you searched and what you found