INTEGRITA’ DELLA RICERCA:INTEGRITA’ DELLA RICERCA:programmazione, esecuzione e programmazione, esecuzione e

utilizzo dei datiutilizzo dei datiG.W. Canonica G.W. Canonica && F. Braido F. Braido

Roma 11 febbraio 2006Roma 11 febbraio 2006

Clinica Pneumologica e AllergologiaClinica Pneumologica e AllergologiaDIMI-Dip. Medicina InternaDIMI-Dip. Medicina InternaUNIVERSITA’ di GENOVAUNIVERSITA’ di GENOVA

SegretarioSegretarioFISMFISM

““simply common sense at itssimply common sense at its best; that is, best; that is, rigidly accurate in observation and rigidly accurate in observation and

merciless to a fallacy in logic.”merciless to a fallacy in logic.”

Thomas Henry HuxleyThe Crayfish: An Introduction to the Study of Zoology 1880

science science is

Biomedical research guidelinesBiomedical research guidelines

Biomedical research: research involving human subjects including research on identifiable human material or identifiable data.

Medical research is only justified ifMedical research is only justified if there is a reasonable likelihood thatthere is a reasonable likelihood that the populations in which thethe populations in which the research research is carried out stand tois carried out stand to benefit from benefit from the results of thethe results of the research.research.

PROGRAMMAZIONEPROGRAMMAZIONEdelladella

RICERCARICERCA

0

5

10

15

20

1955 1965 1975 1985 1995

AustraliaCanadaHong-KongIsraelJapanNew ZealandNew ZealandPapua New GuineaSingaporeTahitiTaiwanUnited StatesUnited StatesVietnam

%

Trends of Asthma Prevalence in EuropeTrends of Asthma Prevalence in Europe

Linneberg A. British Medical Journal,British Medical Journal,

August 2005August 2005

Changes in atopy over 25 years

Allergic Epidemic has spread to Old Age

Lenfant C.Lenfant C.N.E.J.M. N.E.J.M. August 2004August 2004

19991999 20202020

DALY = Disability-adjusted life year

1. Acute lower respiratory infections2. HIV/AIDS3. Perinatal conditions4. Diarrhoeal diseases5. Unipolar major depression6. Ischaemic heart disease7. Cerebrovascular disease8. Malaria9. Road traffic injuries10. COPD11. Congenital abnormalities12. Tuberculosis13. Falls 14. Measles15. Anaemias

1. Ischaemic heart disease2. Unipolar major depression3. Road traffic injuries4. Cerebrovascular disease5. COPD5. COPD6. Lower respiratory infections7. Tuberculosis7. Tuberculosis8. War9. Diarrhoeal diseases10. HIV11. Perinatal conditions12. Violence 13. Congenital abnormalities14. Self-inflicted injuries15. Trachea, bronchus and lung cancers15. Trachea, bronchus and lung cancers

Source: WHOEvidence, Information and Policy, 2000

Increasing burden of noncommunicable diseases and injuriesIncreasing burden of noncommunicable diseases and injurieschange in rank order of DALYs for the 15 leading causeschange in rank order of DALYs for the 15 leading causes

(baseline scenario)(baseline scenario)

ischemic heart disease 1cerebrovascular disease 2 lower respiratory infection 3diarrheal diseases 4conditions arising during the 5perinatal periodchronic obstructive pulmonary 6diseasestubercolosis 7measles 8road traffic accidents 9trachea, bronchus and lung cancer 10malaria 11self induced injuries 12cirrosis of the liver 13stomach cancer 14diabetes mellitus 15violence 16war 20liver cancer 21HIV 30

1241116

3

727652910128191415139

1990 2020

Changes in ranking for Changes in ranking for most important most important

causes of deathcauses of death from 1990 to 2020from 1990 to 2020

C.J.L. Murray, A.D. Lopez The LANCET 1997

gw28

799

1990 20201990 2020

the opposite trend the opposite trend of communicableof communicable

and non-communicableand non-communicablediseases in transition economiesdiseases in transition economies

Source: WHO, Evidence, Information and Policy, 2000Source: WHO, Evidence, Information and Policy, 2000

WHOWHO

% %

communicable

non-communicablenon-communicableXXth XXIth

Respiratory diseases in MIC & Transition Countries

tbc, pneumoina, etc.

asthma, COPD, lung cancer

changes in:demographics, HCSsschooling, income, tobacco

Respiratory diseases in MIC & Transition CountriesRespiratory diseases in MIC & Transition Countries

ISAAC

most Low-Middlemost Low-Middleincome countriesincome countries

most High-income most High-income countriescountries

ASTHMA

Several changes in the lifestyle have resulted in the reduction of microbial burden during childhood, thus

provoking a missing immune deviation from Th2 to Th1

Romagnani: Curr. Opin. Immunol., 6, 838, 1994

Hygiene hypothes

is

Th1Th1-mediated nephropathies are increasing in poor countries (-mediated nephropathies are increasing in poor countries (poor poor hygienehygiene),),

whereas whereas Th2Th2-mediated nephropaties are increasing in rich -mediated nephropaties are increasing in rich countries countries

((high hygienehigh hygiene))

Johnson et al. Am J Kidney Dis 42, 575, 2003

L’analisi delle evidenze L’analisi delle evidenze scientifichescientifiche

deve costituire la base dei deve costituire la base dei successivisuccessivi

indirizzi di ricercaindirizzi di ricerca

PROGRAMMAZIONEPROGRAMMAZIONE&&

ESECUZIONEESECUZIONE

Subjects physical/mental condition must be necessaryto research. Protocols have to be approved by IEC. Informed consents have to be obtained from subject or legal representative.Sources of funding, institutional affiliations, conflicts of interest specified

Negative and positive results shouldNegative and positive results should be publishedbe published

Biomedical research guidelinesBiomedical research guidelines

Evidence-Based Health CareEvidence-Based Health CareJ.A. Muir Gray 2001J.A. Muir Gray 2001

VALUTAZIONE VALUTAZIONE dei dei

DATIDATI

A filter of A filter of medical medical knowledge knowledge and scientific and scientific data based on data based on predifined predifined rules.rules.

Why EBM is a practical and correct tool? Why EBM is a practical and correct tool?

Evidence-Based Health CareEvidence-Based Health CareJ. A. Muir Gray 2001J. A. Muir Gray 2001

Bousquet J. et alBousquet J. et al.,.,Allergy 2004 Allergy 2004

A critical appraisal of A critical appraisal of ““evidence-based medicine”evidence-based medicine”in allergy and asthmain allergy and asthma

Bousquet J. et al.,Allergy 2004 Bousquet J. et al.,Allergy 2004

Bousquet J. et al.,Allergy 2004 Bousquet J. et al.,Allergy 2004

META-ANALYSESMETA-ANALYSES

Bousquet J. et al.,Allergy 2004 Bousquet J. et al.,Allergy 2004

USA criteria of evidenceUSA criteria of evidence

Bousquet J. et al.,Allergy 2004 Bousquet J. et al.,Allergy 2004

Bousquet J. et al.,Allergy 2004 Bousquet J. et al.,Allergy 2004

EBM,EBM,Do we have better criteria??Do we have better criteria??

Presently, NO!!!!!Presently, NO!!!!!

STANDARDS FOR PRACTICALSTANDARDS FOR PRACTICAL

ALLERGEN-SPECIFIC ALLERGEN-SPECIFIC IMMUNOTHERAPYIMMUNOTHERAPY

E Alvarez-Cuesta (chairman),E Alvarez-Cuesta (chairman), J Bousquet, G W Canonica, J Bousquet, G W Canonica,S Durham, H-J Malling, E ValovirtaS Durham, H-J Malling, E Valovirta

EAACIEAACI

Immunotherapy Task Force Immunotherapy Task Force 20052005

SIT Efficacy by E.B.M.SIT Efficacy by E.B.M.

SCIT SCIT : Ia for Asthma: Ia for Asthma Ib for RhinitisIb for Rhinitis

SLITSLIT: Ia for Rhinitis: Ia for Rhinitis Ib for Asthma Ib for Asthma

EAACI Immunotherapy Task Force 2005EAACI Immunotherapy Task Force 2005

NIH-NIAID Meeting NIH-NIAID Meeting Bethesda, November 14,2005Bethesda, November 14,2005

-Immune Tolerance Network-Immune Tolerance Network((Sublingual administration of 4 allergens to 18-30 months old kidsSublingual administration of 4 allergens to 18-30 months old kids))

-Consortium for Food Allergy Research-Consortium for Food Allergy Research(Mucosal Immunotherapy for peanut allergy)(Mucosal Immunotherapy for peanut allergy)

-Inner City Asthma Consortium-Inner City Asthma Consortium(SLIT for Asthma)(SLIT for Asthma)

Charles Hackett,Charles Hackett,Deputy Director, Div.Allergy, Immunol &TransplantationDeputy Director, Div.Allergy, Immunol &TransplantationNIAID,NIHNIAID,NIH

IntegratesIntegrates pathophysiologic rationale, care-giver pathophysiologic rationale, care-giver experience,experience, patient preferences with valid and patient preferences with valid and current clinicalcurrent clinical research evidence.research evidence.Must be able to critically review the research andMust be able to critically review the research andknow if it applies to your patient-care problem.know if it applies to your patient-care problem.

“…“…the conscientious, explicit, and the conscientious, explicit, and

judicious use of current best evidence judicious use of current best evidence in making decisions about care of the in making decisions about care of the

individual patients”.individual patients”.

Evidence-Evidence-based Medicine (EBM)based Medicine (EBM)

Areas where EBM has helped to clarified some issues:

COPD Therapy Asthma Therapy ARDS Management Airway Management Weaning Upper Respiratory Infections Community Acquired Pneumonia Lung Cancer

Pulmonary research in the first quarter of Pulmonary research in the first quarter of the 21st centurythe 21st century will focus on will focus on thesethese major major

areasareas

Crystal RG Crystal RG JAMA.JAMA. 2001 2001

INTEGRITA’INTEGRITA’delladella

RICERCA RICERCA

““fudge factor”fudge factor”Fattore di falsificazioneFattore di falsificazione

Sapendo, sulla base di speculazioni Sapendo, sulla base di speculazioni puramente teoriche, quali devono essere i puramente teoriche, quali devono essere i risultati cambiare il valore dei parametri risultati cambiare il valore dei parametri valutati finché non si ottengono i risultati valutati finché non si ottengono i risultati desiderati.desiderati.

Metodo utilizzato da Newton per calcolare la velocità del suonoMetodo utilizzato da Newton per calcolare la velocità del suono

Federico Di Trocchio: Le bugie della scienza Mondadori 1993

Human basophil degranulation triggered by very dilute antiserum against IgE

E. Davenas, F. Beauvais, J. Amara, M. Oberbaum, B. Robinzon, A. Miadonnai, A. Tedeschi, B. Pomeranz, P. Fortner, P. Belon, J. Sainte-Laudy, B. Poitevin, J. Benveniste Nature 1988Nature 1988

Anti-IgE Ab obtained injecting human IgE in animalsDiluted anti IgE by a factor of 10 until no trace of antibodies was detected

Added white cells derived from human bloodObtained basophil degranulation!

High-dilution experiments a delusion

Maddox J Randi J Stewart WW Nature 1988Nature 1988

““Repeating Dr Repeating Dr BenvenisteBenveniste experiments we were experiments we were surprised that do not always work”surprised that do not always work”

Review international literatureReview international literature

Collect/ produce dataCollect/ produce data

Analyse dataAnalyse data

Control Control repeatabilityrepeatability and and reproducibilityreproducibility of methods of methods

DrawDraw conclusions conclusions

What to do for a scientific research:What to do for a scientific research:

Impact FactorsImpact Factors

The The journal impact factorjournal impact factor is a measure of the is a measure of the frequency with which the "frequency with which the "average articleaverage article" in " in a journal has been cited in a particular year. a journal has been cited in a particular year.

The The impact factorimpact factor will help you evaluate a will help you evaluate a journal’s relative importance, especially journal’s relative importance, especially when you compare it to others in the same when you compare it to others in the same field. field.

WARNING:WARNING: a higher I.F. means a higher I.F. means a higher commercial value of the journala higher commercial value of the journal

RESEARCH FOUNDINGRESEARCH FOUNDING

PUBLIC PUBLIC RESOURCESRESOURCES

PRIVATE PRIVATE RESOURCESRESOURCES

FoundationsFoundationsAssociationsAssociations

etc.etc.

CompaniesCompaniesIndustriesIndustries

etc.etc.

INTEGRITA’INTEGRITA’delladella

RICERCA RICERCA

……e utilizzo dei dati….e utilizzo dei dati….

11

Subjects physical/mental condition must be necessaryto research. Protocols have to be approved by IEC. Informed consents have to be obtained from subject or legal representative.

Sources of funding, institutional affiliations, conflicts of interest specified

Negative and positive Negative and positive results results

shouldshould be publishedbe published

Biomedical research guidelinesBiomedical research guidelines

authors’ disclosure of interestsauthors’ disclosure of interests

authors’ disclosure of interests authors’ disclosure of interests

Dr.G.W.CanonicaDr.G.W.Canonica reports having received reports having received honoraria for educational presentations, honoraria for educational presentations, and/or funding for research, and/or travel and/or funding for research, and/or travel expenses, and/or for service in advisory expenses, and/or for service in advisory boards from:boards from:

A.Menarini, Alk Abello, Almirall, Altana, Astra A.Menarini, Alk Abello, Almirall, Altana, Astra Zeneca, Boeringher Ingelheim, Chiesi Zeneca, Boeringher Ingelheim, Chiesi Farmaceutici, Gentili, GSK, Lofarma, MSD, Farmaceutici, Gentili, GSK, Lofarma, MSD, Novartis, Pfizer, Schering Plough, Novartis, Pfizer, Schering Plough, Stallergenes, UCB Pharma, Uriach. Stallergenes, UCB Pharma, Uriach.

302 millions302 millions 971 millions971 millions

1998 2003 USDUSD

N.E.J.M. 2005N.E.J.M. 2005

ROME, April 25 - 26 , 2004ROME, April 25 - 26 , 2004

Milan - March Milan - March 20032003 Rome - OctoberRome - October 20032003 Rome - April Rome - April 20042004 Rome - April 2005Rome - April 2005

G. Walter Canonica, Chairman, European Academy of Allergology & Clinical Immunology Accreditation Council, Secretary General, World Allergy Organization, Secretary, Italian Federation of Scientific Medical Societies, Genoa Italy

Murray Kopelow, Chief Executive, Accreditation Council for Continuing Medical Education,Chicago, IL USA

Kate Lancey, Royal College of Physicians, London, UK

Bernard Maillet, Secretary General, European Union of Medical Specialists, Brussels, Belgium

Herve Maisonneuve, French National Agency for Accreditation and Evaluation in the Health Sector, Paris, France

Alfonso Negri, Secretary General, Italian Council for Accreditation in Pneumology, Milan, Italy

Helios Pardell, Director, Spanish Accreditation Council for Continuing Medical Education Barcelona, Spain

Teodor Popov, European Academy of Allergology and Clinical Immunology, Sofia Bulgaria

Barbara Schneidman, Vice President for Education, American Medical Association, Chicago, IL USA

Pasquale Spinelli, Vice President, Italian Federation of Scientific Medical Societies Milan, Italy

Riccardo Vigneri, Chairman, Long Distance Learning Sub-Committee, Italian Continuing Medical Education Commission of the Ministry, Catania, Italy

Maria Grazia Cali, President, Serono Symposia International Foundation Rome, Italy

Participants

USA-EUROPE: SHARING THE EDUCATIONAL USA-EUROPE: SHARING THE EDUCATIONAL EFFORTEFFORT

INTERNATIONAL RECIPROCITY OF CME CREDITSINTERNATIONAL RECIPROCITY OF CME CREDITS

B.M.J. B.M.J. MayMay 2004 2004

ResponsibilitiesResponsibilities of the learner learner to be fulfilled in order to claim credit,

Learners have responsibility for, 1.1. Participating in CME/CPD that is based on Participating in CME/CPD that is based on their their individual educational needs.individual educational needs.2.2. Ensuring that the needs are relevant to their Ensuring that the needs are relevant to their professional practice.professional practice.3.3. Evaluating the extent to which their needs Evaluating the extent to which their needs have been met, in the context of a change in have been met, in the context of a change in knowledge, competence or performance. knowledge, competence or performance.

4. Verifying that mechanisms are in place to keep 4. Verifying that mechanisms are in place to keep educational activities free of commercial bias.educational activities free of commercial bias.

INTEGRITA’INTEGRITA’delladella

RICERCA RICERCA

……e utilizzo dei dati….e utilizzo dei dati….

22

Systematic Reviews to support EBMSystematic Reviews to support EBMKhalid S Khan et AlKhalid S Khan et AlRoyal Society of Medicine Press 2003Royal Society of Medicine Press 2003

CONCLUSIONICONCLUSIONIsenza integritàsenza integrità

della ricercadella ricerca

XX