1. Literature search in neurology: an evidence-based approach
Luca Vignatelli and Chiara Bassi
International Course of Neuroepidemiology
Chișinău, Moldova
September 24-28, 2012
the presentation addresses the challenges in making diagnostic recommendations that take in full account the impact tests have on patients’ important outcomes

2. We will cover …
Basic principles to organize the search for Evidence-Based literature
Main websites of Evidence-Based literature
Focus on
- neurology
- free websites

3. 1 Medical literature: resource or problem?
We need evidence (about the accuracy of diagnostic tests, the power of prognostic markers, the comparative efficacy and safety of interventions, etc.) about 5 times for every in-patient (and twice for every 3 out-patients).
We get less than a third of it
Reading is cool
Keeping updating is cool
But…
unfortunately!.....
Maybe is too….hard!

4. 2010
… AND NOW?

5. Hierarchy of evidence: the pyramid model (DiCenso et al. 2009)

6. Production of medical literature: bottom-up process6

7. 2 How to organize your search strategy
TIPS

8. 1st TIP
Clarify yourself what kind of information you need

9. Are you looking for … Information on clinical background … ?
New ideas, innovations, emerging technologies or drugs (horizon scanning) … ?
A prompt answer on specific clinical questions (focused search) … ?
An exhaustive analysis of literature on a specific argument (systematic search) … ?
per supportare una scelta clinica, per la risposta a un dubbio o problema pratico. Cerchiamo pochi studi, recenti e di alta qualità 9

10. I will focus on …
evidence for clinical background: clinical practice guidelines
evidence for a specific clinical question (focused search)
systematic reviews
health technology assessment documents
… but also primary studies
per supportare una scelta clinica, per la risposta a un dubbio o problema pratico. Cerchiamo pochi studi, recenti e di alta qualità
The thoroughness of the literature search is one factor that distinguishes systematic reviews from traditional reviews.
The process of conducting systematic reviews should be replicable and transparent. 10

11. 2nd TIP
Formulate an answerable clinical question: PICO model

12. Population Intervention Comparator Outcome
Clinical question: PICO model
Population
one patient, or a group of patients with a particular condition or a health problem
Intervention
the intervention of interest, which can be therapeutic (e.g. a drug), preventive (e.g. vaccination), diagnostic (e.g. blood pressure measure), prognostic (e.g. a risk factor), etc…
Comparator
a standard intervention, a placebo or no intervention
Outcome
Expected clinical result (death risk, quality of life, adverse events)

13. Population Intervention Comparator Outcome
Example: Diagnostic accuracy
Subject with mild memory impairment.
You wonder if PET is useful for diagnosis of Alzheimer’s disease.
Population
People with mild memory impairment
Intervention
Positron Emission Tomography
Comparator
Standard practice
Outcome
Sensitivity and specificity compared to reference standard of Alzheimer’s disease

14. Population Intervention Comparator Outcome
Example: Therapeutic effectiveness
Subject with drug-resistant mesial temporal lobe epilepsy.
You wonder if surgery (anteromesial temporal resection) is effective in obtaining freedom from disabling seizure.
Population
People with drug-resistant mesial temporal lobe epilepsy
Intervention
Anteromesial temporal resection
Comparator
Standard practice
Outcome
freedom from disabling seizures during year 2 of follow-up

15. Intervention = risk or predictive factor Comparator Outcome
Example: Prognosis
Asymptomatic subject with incidental MRI abnormalities suggestive of demyelinating disease.
You wonder what is the 2-year risk of clinical progression.
Population
Asymptomatic subject
Intervention = risk or predictive factor
Incidental MRI abnormalities suggestive of demyelinating disease
Comparator
Standard practice
Outcome
clinical progression at 2 years of follow-up

16. 2nd TIP
… then, choose 1 or more keywords from the PICO to search databases

17. … from high-quality summary/synthesis documents to single studies
3rd TIP
Which database?
… apply a hierarchical approach
… from high-quality summary/synthesis documents to single studies

18. Search for evidence: top-down approach18

19. 4th TIP
Searching a “large“ database is different from searching a “small” database

20. 4th TIP
Small database:
use few words
Large database:
use more words

21. 3 Searching in practice

22. Your perspective: general clinical background
Why should we need clinical practice guidelines?
to define the clinical pathway of a disease
to assist decisions about appropriate health care for a specific disease
to choose relevant clinical questions 22

23. Clinical Practice Guidelines
What are they?
"systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances“
Essential features:
identification and assessment of the evidence: systematic review
judgment of the strength of the evidence: grading
review and critique of all these elements by methodologists, clinicians, and other relevant parties: multidisciplinary
Field and Lohr, Institute of Medicine, 1992

24. Who produces clinical practice guidelines?
INTERNATIONAL HEALTH AGENCIES
guidelines published on their websites
SCIENTIFIC SOCIETIES
guidelines published in medical journals or on their websites

25. The search method Main websites a guidelines database: NGC
some guidelines websites:
national health agencies: NICE, SIGN
scientific societies: AAN, EFNS*, ILAE

26. National Guideline Clearinghouse™
an initiative of the Agency for Healthcare Research and Quality (AHRQ), U.S. Department of Health and Human Services
database: 2421 guidelines (access 6th June 2012)
“search” engine and index by argument
you can find
summary of single guidelines and link to full text
comparitve documents (guidelines syntheses)
free access:
NGC mission is to provide physicians and other health professionals, health care providers, health plans, integrated delivery systems, purchasers, and others an accessible mechanism for obtaining objective, detailed information on clinical practice guidelines and to further their dissemination, implementation, and use

27. NICE - National Institute for Health and Clinical Excellence

28. SIGN – Scottish Intercollegiate Guidelines Network

29. X Scientific societies Clinical Practice Guidelines in Neurology
American Academy of Neurology (AAN)
Practice Parameters and Assessments
Free full text
European Federation of Neurological Societies (EFNS)
More than 70 guidelines since 2000
Very recently: access restricted only to EFNS members
International League Against Epilepsy (ILAE)
Few documents X

30. EXAMPLE
How thrombolysis should be provided in subjects with major ischemic stroke? P
Ischemic stroke I
Thrombolysis C O

31. EXAMPLE

32. EXAMPLE

33. EXAMPLE

34. EXAMPLE
How healthy lifestyles recommendations should be provided in subjects with vascular risk factors? P I
Healthy Lifestyles C O

35. Your perspective: utility of a single technology
Why should we need HTA documents?
to assist decisions on acquiring, buying or applying a technology
Technology = any intervention used to promote health, to prevent, diagnose or treat acute or chronic disease, or for rehabilitation 35

36. Health Technology Assessment
What is it?
The systematic evaluation of properties, effects, and impacts of health care technology
Its main purpose is to inform technology-related policymaking in health care
HTA is conducted by interdisciplinary groups using explicit analytical frameworks drawing from a variety of methods
from HTA glossary -

37. Who produces HTA reports?
INTERNATIONAL HEALTH AGENCIES
HTA reports published on their websites
AHRQ (US)
NICE (UK)
HTA – NETSCC (UK)
CADTH (CAN)

38. The search method
Main websites
one database: HTA database included in the Centre for Reviews and Dissemination website, University of York, UK
national health agencies websites:
AHRQ, NICE, HTA – NETSCC, CATDH

39. Centre for Reviews and Dissemination
3 databases: DARE, HTA database, ECON
Centre for Reviews and Dissemination, University of York, funded by National Institute of Health Research, (National Health System, UK)
focused on systematic reviews and HTA reports that evaluate the effects of health care interventions and the delivery and organization of health services
Free access: abstracts and critical appraisal of 9,000 systematic reviews, and 10,000 HTA documents 39

40. EXAMPLE
Is DaTSCAN (123I-Ioflupane; GE Healthcare) useful to diagnose central neurodegerative disorders? P I
DaTscan C O

41. EXAMPLE

42. Your perspective: focused clinical question42

43. Systematic Reviews What are they?
a review that has been prepared using a systematic approach to minimising biases and random errors which is documented in a materials and methods section
A systematic review may, or may not, include a meta-analysis: a statistical analysis of the results from independent studies, which generally aims to produce a single estimate of a treatment effect
Chalmers and Altman 1995

44. Who produces Systematic Reviews?
International health agencies
Cochrane Collaboration
Scientific societies
Single researchers

45. The search method two databases: Main websites
Cochrane Database of Systematic Reviews, included in the Cochrane Library
DARE, included in the Centre for Reviews and Dissemination website, University of York, UK

46. Cochrane Database of Systematic Reviews
Best reliable source for information on the effectiveness of healthcare interventions
Electronic publication updated monthly
5102 systematic reviews (access June 2012)
Since 2008: you can find also few Diagnostic Test Accuracy systematic reviews
Published by Wiley Interscience (
Free access: abstracts of systematic reviews
With fee: full-text of systematic reviews 46

47. Cochrane Neurological Field
A source of useful information for people around the world who are involved with or interested in the practice of evidence-based neurology
The primary aims and activities
Facilitate the production of systematic reviews in neurology and neurosurgery
Serve as liaison for neurological Cochrane Review Groups
Facilitate access to Cochrane reviews and disseminate reviews to a worldwide neurological audience
Promote an evidence-based approach to healthcare in the field of neurology 47

48. first demyelinating event I C O
EXAMPLE
Are interferon or glatiramer effective in delaying conversion of the first demyelinating event to multiple sclerosis? P
first demyelinating event I C O

49. EXAMPLE

51. EXAMPLE

52. Your perspective: focused clinical question52

53. PubMed
U.S. National Library of Medicine's® (NLM) premier bibliographic database
Over 19 million references to journal articles in life sciences with a concentration on biomedicine
Citations from biomedical journals published in 70 countries
Goes back to 1950
Access free (from 1997): http// 53

54. PubMed: some tips
An electronic search strategy should generally have different sets of terms:
terms to search for the health condition of interest [P]
2) terms to search for the intervention(s) evaluated [I]
terms to search for the types of study design to be included
filters from the CLINICAL QUERIES function

55. first demyelinating event I interferon / glatiramer C O
EXAMPLE
Are interferon or glatiramer effective in delaying conversion of the first demyelinating event to multiple sclerosis? P
first demyelinating event I
interferon / glatiramer C O

56. EXAMPLE

57. EXAMPLE

58. Too much
information,
too little time

59. Sistemi di Monitoraggio
Meta-engines
Sistemi di Monitoraggio 59

60. TRIPdatabase … is not a database but
… a search engine designed to allow clinicians to quickly find answers to their clinical questions using the best available evidence
It permits the simultaneous searching of multiple websites (mainly EBM)
Free access:
The TRIP Database is a clinical search engine designed to allow clinicians to quickly find answers to their clinical questions using the best available evidence.
The TRIP Database started in 1997 as a result of the work of the founders (Jon Brassey and Dr Chris Price) in answering clinical questions. They recognised that searching multiple websites separately for relevant information was time-consuming. The creation of the TRIP Database allowed the simultaneous searching of multiple sites, hence speeding up the question answering process.
The evolution of the TRIP Database has been guided by the desire to answer real clinical questions using the principles of evidence based medicine.  TRIP Database Ltd’s involvement in clinical question answering has shown the type of material that is useful in answering genuine questions health professionals have.  In 2006 the site was been externally evaluated by a team from the Centre for Evidence-Based Medicine ( led by Professor Paul Glasziou.  More recently we have created a TRIP Advisory which has given us further input into the development of the site.
For additional information on TRIP we recommend you look at our FAQs section or why not get in touch we us (via our Contact us page), we love to hear from our users
The TRIP Database is produced by TRIP Database Ltd (for more information on TRIP Database Ltd see below). 60

62. P.S. … 2 final suggestions

63. … when You need …
… a reporting guideline, i.e. recommendations on how to write your clinical research papers …
… search EQUATOR Network

65. … when You need…
… FREE tools for practice and teaching of evidence-based medicine …
… go to the Centre for Evidence-based Medicine (CEBM), University of Oxford