Tharrison

Evidence Based Medicine searching:is genetics coverage sufficient?

Terence M HarrisonClinical Librarian, Health Sciences Library, Royal Melbourne Hospital

EBM/Human Genome Variation: towards personalised health care

“…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/Human Genome Variation: identifying the interface

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.

The EBM/Human Genome Variation: at the crossroads

A wealth of Genetics and Human Genome Varaiation resources exist

Similarly, there is a wealth of clinical evidence sources

But what of the crossover? And are there other ways of searching this

interface?

EBM/Human Genome Variation: tools

A handful of dedicated search engines that provide an interface between human genetic content and EBM:– PubMed Clinical Queries (Medical Genetics)– National Library for Health (Genetic Conditions)– TRIP (Genetics)– EBM Online (BMJ) – Genetics– EBM Sources (Genetics subsection) – University of

Laval (France)

EBM/Human Genome Variation: other sources

Resources below provide for searching on Variation (Genetics) and condition:

Cochrane PubMed Clinical Queries (EBM filtered search):

PubMed Clinical Queries: Medical genetics search engine

An EBM search facility that provides for searching by: Diagnosis Differential Diagnosis Clinical Description Management Genetic Counselling Molecular Genetics Genetic TestingAlso by: Therapy, Diagnosis, Aetiology, Prognosis.URL: http://www.ncbi.nlm.nih.gov/entrez/query/static/clinical.shtml#reviews

PubMed Clinical Queries: Medical genetics search engine

Example of a PubMed CQ (Medical genetics) search string (hidden) on colorectal cancer:

("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))

National Library for Health: Genetic Conditions

Also known as Genepool, the NLH (National Library for Health) Genetic Conditions specialist library is run by the National Genetics Education and Development Centre

URL: http://www.library.nhs.uk/genepool/ Brings together information on genetics and genetic conditions,

from a variety of sources, including:– Clinical Guidelines– Systematic Reviews– Best practice articles– Patient information leaflets

National Library for Health: Genetic Conditions

Results:– Guidelines/Pathways– Evidence– Reference– Education/CPD– Patient info

National Library for Health: Genetic Conditions

Evidence synopses: 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)

National Library for Health: Genetic Conditions

Systematic Reviews: 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)

National Library for Health: Genetic Conditions

Primary Literature:o The Cochrane Central Register of Controlled Trails o Medline (normally using Clinical Queries search filter) o Health Technology Assessment database o Health Care Needs Assessment o Genisys (Edinburgh Genetics Unit)

National Library for Health: Genetic Conditions

Other sources:Gateways to evidence based resources

o OMNI o Netting the Evidence

Web search engineso National Library for Health o SUMsearch

Journalso Natureo Scienceo The Lanceto New England Journal of Medicineo New Scientisto The Scientist

Trip (Turning Research Into Practice): Genetics section

URL: http://www.tripdatabase.com/genetics/23647.html 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

EBM Online (BMJ) - Genetics

URL: http://ebm.bmj.com/cgi/collection/genetics?notjournal=ebmed&page=214

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

EBM Sources (Genetics subsection) – University of Laval (Canadian)

URL: http://132.203.128.28/medecine/repertoire/repertoire.asp

Over 114 evidence sites indexed All evidence based Includes a Genetics subsection

EBM/Human Genome Variation: searching via MeSH

MeSH term = “Variation (Genetics)” Add term to genetic condition (e.g. homocystinuria) in

search string EBM search sources include:

– PubMed Clinical Queries (filtered to systematics reviews, RCTs, etc)*

– Cochrane (as above)

*Note: you can also search by IHOP (Information Hyperlinked Over Proteins) then compare results with results from a PubMed CQ search

Genomic-based guidelines

Examples at National Metabolic Biochemistry Network (UK, NHS): http://www.metbio.net/

MetBio has an assay directory to source laboratory testing services in the UK for specialist metabolites and enzymes for inherited metabolic disorders.

Currently around a dozen guidelines available (not evidence based) at MetBio.

Example of a Genomic guideline

“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.

Where next?

More specialist EBM/Human Genome Variation sites needed; also consumer sites (such as Decode Me)

Create a global, centralised, open-access test registry, governed by evidence-based standards

Develop technologies to ‘map’ genomic information to clinical pathways: “Evidence-Based Genomic Medicine”

Seamless provision of the above to EPRs (electronic patient records)

More genetic counsellors

Evidence Based Medicine searching:is genetics coverage sufficient?

Thank you!