Transcript Document

Evidence-based genetics?
Developments in
literature searching
Terence Harrison
Clinical Librarian,
Royal Melbourne Hospital
Is Genisys?
1.
2.
3.
The mis-spelled name of a once-famous rock
group from the 1970’s?
The equally mis-spelled name of a book from the
Old Testament and now used as a term to mean
how we have evolved?
Or the name of a Scottish-based organisation that
provided an early push for an evidence-based
approach to genetic medicine?
Answer: later…
EBM/Genetics searching
The problem (1)
“…the evidence base for many genetic
technologies, patient management interventions
and services is very weak…cancer services across
the world are being developed on the basis of
‘expert consensus’, not formal syntheses of
rigorous evidence’*.
‘The Challenge of developing evidence-based genetics health care in practice’, by
Brenda J Wilson. Familial Cancer, 2006; 5(55-59).
EBM/Genetics searching
The problem (2)


According to Bracken* there is a serious need for electronic
evidence-based systematic reviews for genomic
epidemiology:
– To identify publication bias
– Provide study replication
– Allow for sub-group analyses
– Enable meta-analyses of data
According to Ionnidis+, possibly 70% of published gene
association studies have unreliable results.
*’Genomic Epidemiology of Complex Disease: the need for an electronic Evidence-based
approach to research synthesis’, by Michael B Bracken. American Journal of
Epidemiology, 2005; 162(4):297-301.
+ ‘Genetic Associations: false or true?’ by J P A Ionnidis. Trends Molecular Medicine,
2003;9:135-8.
EBM/Genetics searching
The problem (3)

“There are several reasons why medical genetics has been
slow to embrace EBM.
– First, our field has so far focused on rare diseases, and the
number of patients, quite simply, is often not sufficient to allow
adequately powered studies (or to make funding of such studies
feasible).
– [Second] …medical genetics has traditionally focused on
diagnosis and not on interventions, where EBM usually holds
sway.
– [Third]…medical geneticists are highly mechanistically oriented
and, as such, are perhaps not as readily influenced by the
practical questions upon which EBM studies typically focus.” *
* Evidence based medicine meets genomic medicine, Evans, J, Khoury, MJ.
Genet. Med; 2007 Dec;9(12):799-800.
EBM/Genetics searching
The problem (4)
1.
2.
3.
4.
Clinicians expect that their practice is evidence-based; they
also recognise that they need to reference more and more
genetic content in their searches
There are scores of search facilities – large and small – that
specialise in genetic content. But many clinicians do not
know about these facilities, let alone how to reference the
results
At the recent Human Variome Project Meeting (Spain, May
2008), it was agreed that geneticists need to develop more
accessible resources for clinicians who need to identify
genetic literature that is (preferably) evidence-based
As a start, here is what is out there already…
Solutions
EBM/Genetics searching tools
Several dedicated search engines have emerged that
attempt to provide an interface between evidence-based
clinical literature and human genetics:
1. HuGE Navigator
2. PubMed Clinical Queries (Medical Genetics)
3. National Library for Health (“Genepool”)
4. TRIP (Genetics)
5. EBM Online (BMJ) – Genetics
Also:
6. PubMed Clinical Studies (if used with appropriate filters)
7. Cochrane (if used with appropriate filters)
EBM/Genetics searching
1. HuGE Navigator*

Collects/curates citations from PubMed that report
analyses of gene-disease associations
Contains in excess of 30,000 citations, with more
than 6,000 new articles added each year.
Searches by keywords and/or MeSH and/or UMLS
Search can be by disease, exposure, gene,
author, study type, country, journal, year
Results filtered by study design – e.g. metaanalysis, controlled trial
Displays results in PubMed

www.hugenavigator.net/HuGENavigator/startPagePubLit.do





EBM/Genetics searching
2. PubMed CQ: Medical Genetics
search engine*


*
Users search by keyword and/or MeSH
Filters searches by:
– Diagnosis
– Differential Diagnosis
– Clinical Description
– Management
– Genetic Counselling
– Molecular Genetics
– Genetic Testing
www.ncbi.nlm.nih.gov/entrez/query/static/clinical.shtml
EBM/Genetics searching
PubMed CQ: Medical Genetics
search engine
Example of a PubMed CQ (Medical genetics)
hidden search string:
("colorectal cancer") AND ((Diagnosis AND genetics) OR (Differential
Diagnosis[MeSH] OR Differential Diagnosis[Text Word] AND
genetics) OR (Natural History OR Mortality OR Phenotype OR
Prevalence OR Penetrance AND genetics) OR (therapy[Subheading]
OR treatment[Text Word] OR treatment outcome OR investigational
therapies AND genetics) OR (Genetic Counseling OR Inheritance
pattern AND genetics) OR (Medical Genetics OR genotype OR
genetics[Subheading] AND genetics) OR (DNA Mutational Analysis
OR Laboratory techniques and procedures OR Genetic Markers OR
diagnosis OR testing OR test OR screening OR mutagenicity tests
OR genetic techniques OR molecular diagnostic techniques AND
genetics))
EBM/Genetics searching
3. Genepool (National Library for
Health: Genetic Conditions)



Run by National Genetics Education & Development Centre
Brings together information on genetics and genetic conditions, from
sources including:
– Clinical Guidelines
– Systematic Reviews
– Best practice articles
– Patient information leaflets
Provides results by:
– Guidelines/Pathways
– Evidence
– Reference
– Education/CPD
– Patient info
* www.library.nhs.uk/genepool/
EBM/Genetics searching
National Library for Health:
Genetic Conditions


Searches by keyword and/or MeSH
Primary sources:
o
o
o
o
o
The Cochrane Central Register of Controlled Trails
Medline (normally using Clinical Queries search filter)
Health Technology Assessment database
Health Care Needs Assessment
Genisys (Edinburgh Genetics Unit)
EBM/Genetics searching
National Library for Health:
Genetic Conditions
Evidence synopses sourced from:
 Guidelines produced by genetics professional body/
government /health authority
 Clinical evidence
 Guidelines Finder
 NICE
 SIGN
 Prodigy
 Effective Health Care : Bulletin on the effectiveness of health
service interventions
 National Guideline Clearing House (USA)
 GHR (Genetics Home Reference)
EBM/Genetics searching
National Library for Health:
Genetic Conditions
Systematic Reviews sourced from:
 Cochrane Library
 CATS ( Critical Appraised Topics)
 POEMs ( Patient-Oriented Evidence that Matters)
 Best BETS ( Best Evidence Topics)
 DARE
 Bandolier
 Medline /PubMed (Using filter to retrieve systematic reviews
only)
 CINAHL (Using filter to retrieve systematic reviews only)
EBM/Genetics searching
National Library for Health:
Genetic Conditions
Other sources:
Gateways to evidence based resources
o OMNI
o Netting the Evidence
Web search engines
o National Library for Health
o SUMsearch
Journals
o Nature
o Science
o The Lancet
o New England Journal of Medicine
o New Scientist
o The Scientist
EBM/Genetics searching
4. Trip (Turning Research Into
Practice): Genetics section*



Searches by keyword and/or MeSH
Journals indexed:
– Nature Genetics
– Nature Reviews. Genetics
– Journal of Medical Genetics
– Trends in Genetics
– Annual Review of Genetics
– American Journal of Human Genetics
– American Journal of Medical Genetics
– Clinical Genetics
– BMC Medical Genetics
– European Journal of Human Genetics
– Cytogenetics
www.tripdatabase.com/genetics/23647.html
EBM/Genetics searching
5. EBM Online (BMJ) – Genetics*

Searches using keywords and/or MeSH

Includes following journals:
The BMJ, Molecular Pathology, Journal of Clinical Pathology, British
Journal of Ophthalmology, Tobacco Control, Postgraduate Medical
Journal, Injury Prevention, Practical Neurology, Heart, BMJ Career
Focus, Archives of Disease in Childhood - Education and Practice,
Annals of the Rheumatic Diseases, Archives of Disease in Childhood Fetal and Neonatal Edition, Journal of Epidemiology and Community
Health, Journal of Neurology, Neurosurgery, and Psychiatry, Journal of
Medical Genetics, Journal of Medical Ethics, Quality and Safety in
Health Care, Emergency Medicine Journal, Evidence-Based Mental
Health, Archives of Disease in Childhood, Gut, Medical Humanities,
Thorax, Occupational and Environmental Medicine, Evidence-Based
Nursing, British Journal of Sports Medicine, and Sexually Transmitted
Infections
*
http://ebm.bmj.com/search.dtl
EBM/Genetics searching
6. PubMed Clinical queries*





Tips on searching…
Search condition by MeSH or keyword.
Add in either “Genetics, Medical” or (Variation
(Genetics), as appropriate
Results are fewer than if searching via PubMed CQ
Medical Genetics Searches because the results are
entirely evidence-based
www.ncbi.nlm.nih.gov/entrez/query/static/clinical.shtml#studies
EBM/Genetics searching
7. Cochrane*





Tips on searching…
Search by keyword and/or MeSH
MeSH term for human variome = “Variation
(Genetics)”; for genetics = “Genetics, Medical”
Add either of above term(s) to another MeSH term
for a condition – e.g. “colorectal neoplasms”
Use Search History to combine results
* www.mrw.interscience.wiley.com/cochrane/cochrane_search_fs.html
Solutions
Example of a “systematic
review” (re. genetic testing)



“Review of evidence for genetic testing for CYP450
polymorphisms in management of patients with nonpsychotic
depression with selective serotonin reuptake inhibitors”.
Thakur M, et. Al. Genet Med. 9(12):826-35, 2007 Dec.
Method: “systematic review” of literature
Evidence-based?
Solutions:
Guidelines (1)


Edinburgh Clinical Genetics (Genisys) and the UK Public
Health Genetics Network attempted to develop clinical
guidelines for a range of inherited conditions – e.g. Marfan
syndrome, Huntington’s.
Methods:
– Uses standard EBM methods – SRs, CA, applying levels of
evidence, etc – based on SIGN (Scottish Intercollegiate
Guidelines Network) procedures.
– Translate guideline into clinical pathway
– Map against individual patient medical records
Solutions
Guidelines (2)



Other examples of evidence-based guidelines at National
Metabolic Biochemistry Network (UK, NHS):
http://www.metbio.net/
Currently around a dozen guidelines are available (not all are
evidence based)
“The use of folic acid for the prevention of neural tube defects
and other congenital anomalies”* A systematic review of
literature, including specialist literature. Recommendations
include evidence levels (Oxford CEBM).
* Wilson, R Douglas, et al. Journal Obsts & Gyn. Canada, 2003; November:138.
More solutions
Where to next?
1. Short term needs: Develop a meta-search engine (and
‘portal’) to search the various existing search engines that
specialise in either
a) genetics literature that is “evidence-based”, or
b) evidence-based studies that have a genetics content
c) Testing/researching search facility needs/availability for
inherited colorectal cancer
We have begun working on this.
2. Medium term needs: Develop technologies to ‘map’
genetic information to clinical pathways: “Evidence-Based
Genetic Medicine” (!!!)
This can happen once evidence-based clinical pathway
technologies (such as the ‘Map of Medicine’) are acquired.
More solutions
Meanwhile…

As an interim solution, links to each of the search
facilities mentioned are now available on the
Evidence Direct site:
– go to ‘EBM/Genetics’ on the Evidence Direct menu.

This section of the Evidence Direct site also
includes a ‘primer’ on genetics (courtesy of
YouTube and aimed at the general public). Here is
a snippet…
Thank you!
Note: this presentation will also be available on the
Evidence Direct site (www.evidence-direct.net )
[email protected]