Literature search in neurology: an evidence-based approach Luca Vignatelli and Chiara Bassi http://asr.regione.emilia-romagna.it 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

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

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!

2010 … AND NOW?

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

Production of medical literature: bottom-up process 6

2 How to organize your search strategy TIPS

1st TIP Clarify yourself what kind of information you need

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

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

2nd TIP Formulate an answerable clinical question: PICO model

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)

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

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

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

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

… 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

Search for evidence: top-down approach 18

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

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

3 Searching in practice

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

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

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

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

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: www.guideline.gov 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

NICE - National Institute for Health and Clinical Excellence http://www.nice.org.uk/

SIGN – Scottish Intercollegiate Guidelines Network http://www.sign.ac.uk/guidelines/published/index.html

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

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

EXAMPLE

EXAMPLE

EXAMPLE

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

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

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 - www.htaglossary.net

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

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

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 www.crd.york.ac.uk/crdweb/ 39

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

EXAMPLE

Your perspective: focused clinical question 42

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

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

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

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 (www.thecochranelibrary.com) Free access: abstracts of systematic reviews With fee: full-text of systematic reviews 46

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 http://neuronet.cochrane.org/ 47

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

EXAMPLE

EXAMPLE

Your perspective: focused clinical question 52

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 5.394 biomedical journals published in 70 countries Goes back to 1950 Access free (from 1997): http//www.pubmed.gov 53

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

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

EXAMPLE

EXAMPLE

Too much information, too little time

Sistemi di Monitoraggio Meta-engines Sistemi di Monitoraggio 59

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: http://www.tripdatabase.com/ 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 (www.cebm.net) 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

P.S. … 2 final suggestions

… when You need … … a reporting guideline, i.e. recommendations on how to write your clinical research papers … … search EQUATOR Network http://www.equator-network.org/home/

… 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 http://www.cebm.net/

vigna@interfree.it lvignatelli@regione.emilia-romagna.it