Roma 11 febbraio 2006
INTEGRITA’ DELLA RICERCA:
programmazione, esecuzione e
utilizzo dei dati
G.W. Canonica & F. Braido
Clinica Pneumologica e Allergologia
DIMI-Dip. Medicina Interna
UNIVERSITA’ di GENOVA
Segretario
FISM
science
is
“simply common sense at its best; that is, rigidly
accurate in observation and merciless to a fallacy in
logic.”
Thomas Henry Huxley
The Crayfish: An Introduction to the Study of Zoology 1880
Biomedical research guidelines
Biomedical research: research involving human
subjects including research on identifiable human
material or identifiable data.
Medical research is only justified if there is a
reasonable likelihood that the populations in
which the research is carried out stand to benefit
from the results of the research.
PROGRAMMAZIONE
della
RICERCA
Trends of Asthma Prevalence in Europe
20
Australia
Canada
Hong-Kong
15
Israel
Japan
New Zealand
%
New Zealand
10
Papua New Guinea
Singapore
Tahiti
5
Taiwan
United States
United States
0
1955
Vietnam
1965
1975
1985
1995
Changes in atopy over 25 years
Allergic Epidemic has
spread to Old Age
Linneberg A.
British Medical Journal,
August 2005
Lenfant C.
N.E.J.M.
August 2004
Increasing burden of noncommunicable diseases and injuries
change in rank order of DALYs for the 15 leading causes
(baseline scenario)
1999
2020
1. Acute lower respiratory infections
2. HIV/AIDS
3. Perinatal conditions
4. Diarrhoeal diseases
5. Unipolar major depression
6. Ischaemic heart disease
7. Cerebrovascular disease
8. Malaria
9. Road traffic injuries
10. COPD
11. Congenital abnormalities
12. Tuberculosis
13. Falls
14. Measles
15. Anaemias
1. Ischaemic heart disease
2. Unipolar major depression
3. Road traffic injuries
4. Cerebrovascular disease
5. COPD
6. Lower respiratory infections
7. Tuberculosis
8. War
9. Diarrhoeal diseases
10. HIV
11. Perinatal conditions
12. Violence
13. Congenital abnormalities
14. Self-inflicted injuries
15. Trachea, bronchus and lung cancers
DALY = Disability-adjusted life year
Source: WHO
Evidence, Information and Policy, 2000
1990
1990
2020
2020
1
1
cerebrovascular disease
2
2
lower respiratory infection
3
4
diarrheal diseases
4
11
conditions arising during the
perinatal period
5
16
Changes in ranking for
most important
chronic obstructive pulmonary
diseases
6
3
tubercolosis
7
7
causes of death
measles
8
27
road traffic accidents
9
6
trachea, bronchus and lung cancer
10
5
malaria
11
29
self induced injuries
12
10
cirrosis of the liver
13
12
stomach cancer
14
8
diabetes mellitus
15
19
violence
16
14
war
20
15
liver cancer
21
13
HIV
30
9
gw28799
ischemic heart disease
from 1990 to 2020
C.J.L. Murray, A.D. Lopez
The LANCET 1997
WHO
the opposite trend
of communicable
and non-communicable
diseases in transition economies
Source: WHO, Evidence, Information and Policy, 2000
Respiratorydiseases
diseases in
Countries
Respiratory
in MIC
MIC&&Transition
Transition
Countries
communicable
tbc, pneumoina, etc.
%
%
changes in:
demographics, HCSs
schooling, income,
tobacco
XXth
non-communicable
asthma, COPD, lung cancer
XXIth
ASTHMA
ISAAC
most High-income
countries
most Low-Middle
income countries
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
Hygiene
hypothesis
Romagnani: Curr. Opin. Immunol., 6, 838, 1994
Th1-mediated nephropathies are increasing in poor countries
(poor hygiene),
whereas Th2-mediated nephropaties are increasing in rich
countries
(high hygiene)
Johnson et al.
Am J Kidney Dis
42, 575, 2003
L’analisi delle evidenze
scientifiche
deve costituire la base dei
successivi
indirizzi di ricerca
PROGRAMMAZIONE
&
ESECUZIONE
Biomedical research guidelines
 Subjects physical/mental condition must be necessary
to 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 should be published
Evidence-Based Health Care
J.A. Muir Gray 2001
VALUTAZIONE
dei
DATI
Why EBM is a practical and correct tool?
A filter of
medical
knowledge
and scientific
data based on
predifined
rules.
Evidence-Based Health Care
J. A. Muir Gray 2001
A critical appraisal of
“evidence-based medicine”
in allergy and asthma
Bousquet J. et al.,
Allergy 2004
Bousquet J. et al.,Allergy 2004
META-ANALYSES
Bousquet J. et al.,Allergy 2004
USA criteria of evidence
Bousquet J. et al.,Allergy 2004
Bousquet J. et al.,Allergy 2004
Bousquet J. et al.,Allergy 2004
EBM,
Do we have better criteria??
Presently, NO!!!!!
STANDARDS FOR PRACTICAL
ALLERGEN-SPECIFIC
IMMUNOTHERAPY
E Alvarez-Cuesta (chairman),
J Bousquet, G W Canonica,
S Durham, H-J Malling, E Valovirta
EAACI
Immunotherapy Task Force
2005
SIT Efficacy by E.B.M.
SCIT : Ia for Asthma
Ib for Rhinitis
SLIT: Ia for Rhinitis
Ib for Asthma
EAACI Immunotherapy Task Force 2005
NIH-NIAID Meeting
Bethesda, November 14,2005
Charles Hackett,
Deputy Director, Div.Allergy, Immunol &Transplantation
NIAID,NIH
-Immune Tolerance Network
(Sublingual administration of 4 allergens to 18-30 months old kids)
-Consortium for Food Allergy Research
(Mucosal Immunotherapy for peanut allergy)
-Inner City Asthma Consortium
(SLIT for Asthma)
Evidence-based Medicine (EBM)
Integrates pathophysiologic rationale, care-giver
experience, patient preferences with valid and
current clinical research evidence.
Must be able to critically review the research and
know if it applies to your patient-care problem.
“…the conscientious, explicit, and
judicious use of current best evidence
in making decisions about care of the
individual patients”.
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 the 21st
century will focus on these major areas
Crystal RG JAMA. 2001
INTEGRITA’
della
RICERCA
“fudge factor”
Fattore di falsificazione
Sapendo, sulla base di speculazioni puramente
teoriche, quali devono essere i risultati cambiare il
valore dei parametri valutati finché non si ottengono i
risultati desiderati.
Metodo 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 1988
Anti-IgE Ab obtained injecting human IgE in animals
Diluted anti IgE by a factor of 10 until no trace of
antibodies was detected
Added white cells derived from human blood
Obtained basophil degranulation!
High-dilution experiments a delusion
Maddox J Randi J Stewart WW
Nature 1988
“Repeating Dr Benveniste experiments we were surprised
that do not always work”
What to do for a scientific research:
Review international literature
Collect/ produce data
Analyse data
Control repeatability and reproducibility of methods
Draw conclusions
Impact Factors
The journal impact factor is a measure of the frequency
with which the "average article" in a journal has been cited
in a particular year.
The impact factor will help you evaluate a journal’s
relative importance, especially when you compare it to
others in the same field.
WARNING:
a higher I.F. means
a higher commercial value of the journal
RESEARCH FOUNDING
PUBLIC
RESOURCES
PRIVATE
RESOURCES
Foundations
Associations
etc.
Companies
Industries
etc.
INTEGRITA’
della
RICERCA
…e utilizzo dei dati….
1
Biomedical research guidelines
 Subjects physical/mental condition must be necessary
to 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
should be published
authors’ disclosure of interests
authors’ disclosure of interests
Dr.G.W.Canonica reports having received
honoraria for educational presentations,
and/or funding for research, and/or travel
expenses, and/or for service in advisory
boards from:
A.Menarini, Alk Abello, Almirall, Altana, Astra
Zeneca, Boeringher Ingelheim, Chiesi
Farmaceutici, Gentili, GSK, Lofarma, MSD,
Novartis, Pfizer, Schering Plough,
Stallergenes, UCB Pharma, Uriach.
1998
USD
302 millions
2003
971 millions
N.E.J.M. 2005
ROME, April 25 - 26 , 2004
Milan
Rome
Rome
Rome
- March
- October
- April
- April
2003
2003
2004
2005
USA-EUROPE: SHARING THE EDUCATIONAL
EFFORT
INTERNATIONAL RECIPROCITY OF CME CREDITS
Participants
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,
London, UK
Royal
College
of
Physicians,
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
B.M.J. May 2004
Responsibilities
Responsibilities of the learner to be fulfilled
in order to claim credit,
Learners have responsibility for,
1. Participating in CME/CPD that is based on their
individual educational needs.
2. Ensuring that the needs are relevant to their
professional practice.
3. Evaluating the extent to which their needs
have been met, in the context of a change in
knowledge, competence or performance.
4. Verifying that mechanisms are in place to keep
educational activities free of commercial bias.
INTEGRITA’
della
RICERCA
…e utilizzo dei dati….
2
CONCLUSIONI
senza integrità
della ricerca
X
Systematic Reviews to support EBM
Khalid S Khan et Al
Royal Society of Medicine Press 2003