Download Scientific Report 2012-2013 - Institut National Du Cancer

Measures 1, 2, 3, 4 and 5
RESEARCH
1
French National Cancer Institute
Scientific Report
2012-2013
www.e-cancer.fr
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THIS PUBLICATION IS PART OF THE IMPLEMENTATION
OF THE CANCER PLAN 2009-2013.
Measures 1, 2, 3, 4 and 5 of the Research area.
All rights reserved.
This work may not be translated or copied in whole or in part without the written permission of Institut National du
Cancer. According to the Code of intellectual property, only copies strictly reserved for private use and not for a collective
one, or brief excerpts justified by the scientific character or information of the work into which they are incorporated,
are authorized.
This document was published in October 2013. It is available at the following address:
Institut National du Cancer (INCa)
Direction de la recherche
52, avenue André Morizet – 92100 Boulogne-Billancourt
www.e-cancer.fr
© 2013. Institut National du Cancer (INCa)
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TABLE OF CONTENTS
PREAMBLE
Research Indicators
Clinical trial indicators
Molecular genetics platforms: activity indicators
International actions
SUMMARY OF THE REPORT
6
8
10
12
14
19
Part 1.
SUMMARY OF PREVIOUS RECOMMENDATIONS
DRAWN UP BY MEMBERS OF THE SCIENTIFIC
ADVISORY BOARD AND PROGRESS MADE
23
Part 2.
REPORT ON CANCER RESEARCH ACTIVITY
FOR 2012-2013 AND SYNTHESIS
1. INCREASED SUPPORT FOR TRANSLATIONAL
AND INTEGRATED RESEARCH
1.1. Research programmes aiming at boosting
transdisciplinarity and transfer of knowledge
into clinical practice
31
33
33
1.2. New actions to strengthen organisation and infrastructures
devoted to translational/integrated research
44
2. INCREASED SUPPORT FOR CLINICAL RESEARCH
AND DEVELOPMENT OF EARLY PHASE TRIALS
FOR INNOVATIVE MOLECULES
54
2.1. The clinical cancer research programmes
54
2.2. Organisation of clinical research, and strengthening
of structures and infrastructures
59
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3. INCREASED SUPPORT FOR RESEARCH IN BIOLOGY,
GENOMICS AND CANCER SCIENCES
68
3.1. Dedicated research programmes
68
3.2. The genomics programme and
the epigenomics programme
73
4. INCREASED SUPPORT FOR RESEARCH IN SOCIAL
SCIENCES, EPIDEMIOLOGY AND PUBLIC HEALTH
78
4.1. The research programmes
78
4.2. Research organisation, structures and infrastructures for
epidemiology and public health research
81
5. THE CANCEROPOLES
84
6. MAIN EVENTS IN 2012-2013
87
7. INTERNATIONAL DEVELOPMENTS
90
7.1. European programmes for cancer research
90
7.2. Thailand - 1st results of the research programme
‘PapilloV’ “HPV infections and associated cervical
lesions in HIV+ Thai women”.
91
7.3. Africa - Capacity building in cancer control
and new steps towards increased coordination
92
8. OBSERVATORY FOR RESEARCH INVESTMENT
IN CANCER, AND REVIEW OF RESEARCH INVESTMENT
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Part 3.
PERSPECTIVES
101
1. STRATEGIC ORIENTATIONS FOR CANCER RESEARCH
102
1.1. The key challenges
103
1.2. Current situation and strengths in France
104
1.3. Proposals
104
2. FIVE PRIORITY ACTIONS FOR 2013-2014
108
2.1. Fight tobacco-related cancers with an ambitious
multidisciplinary programme of research/treatment/
public health actions
108
2.2. Build a shared biological, clinical and epidemiological
database
112
2.3. Foster closer ties between teaching and research and
increase support for interdisciplinary training
117
5
CONCLUSION
128
APPENDICES
131
2.4. Support ambitious French cancer research to provide
the population and patients quick and sizeable benefits 120
2.5. New challenges in cancer control:
European and global perspectives
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PREAMBLE
This is the seventh International Scientific Advisory Board report
that INCa has published since 2007. It is an opportunity to thank
the Board’s members for advising and guiding the Institute during
its structuring process and providing inspiration for its initiatives. As
two consecutive plans are drawing to a close and the third national
plan is under development, the Institut National du Cancer and the
Institut Cancer de l’Aviesan will have spearheaded and shaped farreaching changes in the cancer research landscape in France. With
support from the two supervising ministries, the International Scientific
Advisory Board and Board of Directors, INCa will have provided
continuous financial support for research projects (and maintained
and increased this support during budget restrictions) by relying on
transparent methods, international assessments and participation
of patient advocates in all the calls for proposals and in every field
of research: biology, clinical, transfer, human and social sciences,
epidemiology and public health. All of the research objectives in the
2009-2013 plan were achieved or even surpassed. In addition to the
actions that the next plan will prioritise, over the next few years efforts
will be undertaken to bolster the programmes already in progress with a
particular focus on the SIRIC Programme. The eight designated sites
have begun coordinating their programmes and should be the drivers
behind clinical genomics and the assessment and dissemination of
innovation, provide a wider platform for human and social sciences,
mathematics and physics, and serve as local and regional authorities
on clinical research and expanding the use of their scientific evidence
to benefit patients. Through their interactions with the clinical biological
databases, the molecular and constitutional genetics platforms and
the cooperative inter-groups, they are also expected to prepare France
for building large-scale interactive clinical and biological databases
available to the national and international communities to advance
our understanding of cancer and cancer treatment. The cooperative
inter-groups have pushed beyond the individual aspirations of groups
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and learned societies to organise themselves into national pathology
groups and develop major clinical and biological research projects
designed to improve patient survival. The Programme for Hospital
Clinical Research in oncology managed by INCa should help them
make their projects a reality, expand their international exposure and
embrace new opportunities to bring in international cooperation.
Primary prevention in France is still not as rooted in the collective
conscious as it should be. Our smoking rates remain dismal, particularly
among the younger generation. Talks have begun with other agencies
working on this issue and solutions will include funding research
projects on primary prevention and launching a new recurrent multidisciplinary research programme on smoking-related cancers.
In the last few years, INCa has established a highly proactive policy
that has been recognised by our European and American colleagues to
expand access to targeted therapies for patients identified as candidates
through molecular tests. In 2012, these tests were administered to
over 60,000 patients.
Our goal is to support the foreseeable development of medicine based
on the tumour’s specific biological parameters and individual patients by
providing research and treatment facilities a greater capacity to conduct
more advanced testing, including exome sequencing, RNAs and normal
or altered protein quantification. It entails bringing a serious health
issue under control to prove these sophisticated and more costly tests
are pertinent and a valuable component of treatment and therapeutic
decisions because they improve survival and quality of life.
Over the next five years, this is one of the innovation challenges that
INCa, the authorities and healthcare institutions have to tackle in order
to give patients in France the best treatment possible.
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Prof. Fabien Calvo
Director of Research
and Innovation
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RESEARCH INDICATORS
TRENDS IN THE NUMBER OF PROJECTS SUBMITTED
TO CALLS FOR PROPOSALS MANAGED BY INCa
ANNUAL FUNDING OF CANCER RESEARCH PROGRAMMES
* The 2013 amounts are calculated on a previsional budget
* No CFP for translational research in 2008
120
400
350
300
80
Nb of projects
Funding in €M
100
60
40
250
200
150
100
20
50
0
0
2007
Total
Total INCa
Total DGOS
Total Aviesan
2008
2009
2010
2011
2012
2013
2007
2008
2009
2010
2011
2012
2013
2012
2013
Clinical
Translational*
Human and social sciences, epidemiology, public health
Cancer biology and sciences
TRENDS IN FUNDING AWARDED TO CFPs MANAGED BY INCa
* No CFP for translational research in 2008
25
Funding in €M
20
15
10
5
0
2007
2008
2009
2010
2011
Clinical
Translational*
Human and social sciences, epidemiology, public health
Cancer biology and sciences
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TRENDS IN THE NUMBER OF PROJECTS SELECTED
TO CALLS FOR PROPOSALS MANAGED BY INCa
TRAINING IN TRANSLATIONAL RESEARCH
* No CFP for translational research in 2008
55
50
45
40
35
30
25
20
15
10
5
0
80
70
50
40
30
20
10
0
2012
2013
Clinical
Translational*
Human and social sciences, epidemiology, public health
Cancer biology and sciences
600
Funding in €M
500
400
300
200
100
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
0
2008
2009
2010
2011
Clinical
Translational*
Human and social sciences, epidemiology, public health
Cancer biology and sciences
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2013
FUNDING (€M) AWARDED TO CALLS FOR PROPOSALS MANAGED
BY INSERM UNDER THE CANCER PLAN
* No CFP for translational research in 2008
2007
2012
Nb of projects selected
Nb of projects submitted
TRENDS IN AVERAGE BUDGET ALLOCATED BY RESEARCH PROJET
Average budget per project, € in thousands
2011
2012
2013
2013
2012
2011
Spontaneous
tumour models
2011
25
Physics, maths,
engineering
sciences
2010
19
27
Cancer and
environment
2009
36
35
Systems
biology and
cancer
2008
52
Training in
translational
research
Nb of projects
60
2007
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CLINICAL TRIALS INDICATORS
NUMBER OF CLINICAL TRIALS OPEN FOR PATIENT RECRUITMENT
ADVERTISED IN THE NATIONAL REGISTRY (15 May 2013)
TRENDS IN RECRUITMENTS IN CANCER CLINICAL TRIALS
37,492
40,000
800
687
30,000
24,037
26,003
553
600
500
506
400
20,000
300
200
10,000
100
233
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May 13
Dec.12
June 12
Dec.11
June 11
Dec.10
Jul.10
Dec.09
July.09
Dec.08
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Jul.08
0
0
Dec.07
Nb of patients recruited
700
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EARLY PHASE CLINICAL TRIALS IN INCa-DESIGNATED CENTRES-CLIP2
2,808
3,000
2,500
2,000
1,000
500
1,788
1,569
1,500
890
230
0
2009
153
166
2010
2011
187
2012
Number of phase I/II trials
Number of patients recruited in phase I/II trials
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MOLECULAR GENETICS PLATFORMS:
ACTIVITY INDICATORS
Molecular characterisation of tumours has become a decisive factor in the choice of
therapeutic strategies for patients with cancer, and molecular testing is mandatory in
order to satisfy marketing authorisation requirements for drugs targeting molecularlystratified tumour subgroups. In order to ensure wide access to molecular profiling
of tumours, INCa and the French Ministry of Health have established and developed
a national network of 28 regional molecular genetics centres. In 2011, molecular
testing was carried out on 61,784 cancer patients as part of their care.
Predictive molecular testing in France in 2011:
genetics centres.
activity of the 28 molecular
Lille
Rouen
Brest
Paris AP-HP
Caen
Curie
Rennes
Nantes
Angers
Tours
Reims
Nancy
IGR
Strasbourg
Besançon
Dijon
Number of patients
who benefited
from predictive
molecular testing
in 2011
Poitiers
8,000
Limoges
Bordeaux
Toulouse
Lyon
Clermont
Ferrand
4,000
2,000
1,000
500
Saint-Étienne
Montpellier
Grenoble
Marseille
Nice
Source: INCa, Molecular genetics centres activity report 2011;
Drafted by Research and Innovation Division - INCa – 2013
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SCREENING FOR KRAS MUTATIONS IN PATIENTS WITH COLORECTAL CANCER
Nb of patients
20,000
17,246
18,306
16,581
10,012
10,000
17,003
1,100
0
2007
2008
2009
2010
2011
2012
SCREENING FOR EGFR MUTATIONS IN PATIENTS WITH LUNG CANCER
Nb of patients
30,000
20,750
20,000
21,995
16,834
10,000
1,269
2,667
0
2008
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2009
2010
2011
2012
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INTERNATIONAL ACTIONS
WHO
FCTC Framework Convention on Tobacco Control
WHO - Funding/participation in work
IARC - Seat on Board of Directors
US NCI
CTEP - Early phase clinical trials
Coordination - Programmes to support southern countries
INTERNATIONAL CONSORTIA
ICGC - International Cancer Genomics Consortium
ICRP - International Cancer Research Partnership
ICISG - International Cancer Information Service Group
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EUROPEAN CONSORTIA
TRANSCAN - Translational research:
25 partners, 19 countries
EPAAC - European Partnership for Action Against Cancer:
36 partners, 27 countries
BASIS - Research: Breast cancer somatic genetic study:
13 partners, 8 countries
CSA PerMed - Personalised medicine:
30 partners, 16 countries
CANCON - European guidelines for quality improvement
in comprehensive cancer control
AIEA-PACT
Capacity building, education and training, comprehensive
cancer control programmes
ASIA: THAILAND/LAOS
Research: Public health Cervical cancer (HPV/HIV)
IARC/Global initiative for cancer registry development
in LMICs
Technical support, training and help with networking
AFRICA
Telepathology network - Support for diagnosis
(lymphoma)
Mauritania - Cooperation and training agreement
Senegal - Agreement on cooperation, research
coordination, training, capacity building
Cote d’Ivoire - Agreement on cooperation, public health/
research/training
Coordination with AORTIC
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INCa’S INTERNATIONAL PORTFOLIO
Notable international activities, consortia & programmes 2013–2014
EUROPE & high income countries
EPAAC – European Partnership for actions against cancer
(INCa is co-leader of WP “research coordination” and member
of WP “cancer care/ rare cancers”).
CANCON - European guidelines for quality improvement
in comprehensive cancer control (INCa is leader of WP
“survivorship & rehabilitation”, and active member of WP “integrated
cancer control” and of WP “screening”) – start date Feb. 2014.
ICGC – International cancer genomic consortium
(INCa is founding member & sits on ICGC executive committee/4
projects funded: breast, liver, prostate and Ewing sarcoma cancer).
GLOBAL ALLIANCE (dedicated to enabling secure sharing of
genomic and clinical data).
BASIS – European research project on Breast cancer somatic
genetic study.
TRANSCAN – European network on translational research
(3 joint European calls for research proposals launched:
“validation of biomarkers”, “primary & secondary prevention”,
and “tertiary prevention”).
Clinical research
US NCI CTEP – INCa coordinates French clinical research centre’s
participation to the US NCI mass solicitation in early phase
clinical trials.
IRCI – International Rare Cancer Initiative (INCa to join the Board
of the International Rare Cancers Initiative and contribute to the
development of the initiative and delivery of its research objectives).
EPAAC – European Partnership for actions against cancer
(INCa is co-leader of WP “research coordination”/ CLIP² like pilot
project on early phase clinical research is being developed).
WHO (World Health Organization) Framework Convention on Tobacco Control.
TRANSCAN – European network on translational research
(2 joint European calls for research proposal targeting
“primary & econdary prevention” and “tertiary prevention”).
CANCON - European guidelines for quality improvement in
comprehensive cancer control (INCa is an active member of WP
“screening”) – start date Feb. 2014.
Diagnosis/
screening
Prevention
Lo
IA
co
CSA PerMed – European concerted action on personalised medicine
(global objective is to develop a European strategic research agenda
in personalised medicine).
Translational
research
PersoCancer biology/
nalised
genomics
medicine
Cancer control
International consortia
Th
inf
M
La
vs
Cancer
registries
Research
networking
Se
Co
M
IA
ed
Te
ICRP - International Cancer Research Portfolio.
ICISG International Cancer Information Service Group.
Global
health
IA
su
m
Capacity building
and training
programmes
Cancer care/
survivorship
EPAAC – European Partnership for actions against cancer
(INCa active member of WP “cancer care/ rare cancers”).
CANCON - European guidelines for quality improvement in
comprehensive cancer control (INCa is WP leader “survivorship &
rehabilitation”, member of WP “integrated cancer control) –
start date Feb. 2014.
Cancer research funders annual meeting.
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Low and medium income countries
IAEA (International Agency for Atomic Energy) – PACT programme on cancer/(INCa is contributor to PACT’s
comprehensive cancer control programmes & training directed to French speaking low & medium income countries).
Thailand: Research study funded by INCa: “PapilloV - Human papilloma virus (HPV) infection and cervical lesions in HIVinfected women receiving antiretroviral therapy in Thailand (Principal investigators: Institute for Development Research and
Ministry of Public Health of Thailand).
Laos: Research study funded by INCa: LaoCol-VP – Efficacy & cost/effectiveness of cervical lesions screening by HPV detection
vs pap smear in HIV-infected women in Laos (principal investigator: Centre Infectiologie Charles Mérieux du Laos).
IARC/Global initiative for cancer registry development in LMIC (low and medium income countries) –
support to regional network hubs/capacity building in sub-Saharan francophone countries/development of training
materials & modules in French (to be formalised).
Senegal - cooperation agreement/ research & public health, capacity building, training, cancer control
Cote d’Ivoire - cooperation agreement research & public health, capacity building, training, cancer control
Mauritania - cooperation agreement Training.
IAEA (International Agency for Atomic Energy) – PACT programme on cancer/capacity building,
education and training, cancer control programmes.
Telepathology network: lymphoma diagnosis.
Coordination with AORTIC - African Organisation for Research & Training in Cancer (to be formalised).
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SUMMARY OF THE REPORT
The seventh report for INCa’s International Scientific Advisory Board
marks the final year of cancer research actions undertaken under the
two successive Cancer Plans, 2003-2007 and 2009-2013.
The research and health landscape for oncology has undergone a
major upheaval in recent years, giving France major opportunities to
strengthen its innovative programmes and initiate new ones. Among
the key initiatives, the organisation of 8 SIRICs - integrated cancer
research sites - and 16 CLIP2 - early phase clinical trial centres - together
with the network of 28 molecular biology platforms, has established a
solid basis for cancer research activity of the highest standard in France.
The first part of the present report summarises the recommendations
of the INCa Scientific Advisory Board since 2007, and describes how
these recommendations have been followed by initiating or reinforcing
major actions. Six areas of action have been considered: translational
research: the creation of a coordination system for the SIRIC network,
a qualitative analytical study of the main organisational and scientific
challenges for the SIRICs, and preparation for the establishment of
chairs of excellence are the main actions completed in 2013.
• Molecular
genetics and research synergy: the most recent actions
reflect improved integration between research programmes and the
clinical platforms in order to spur the development of individualised
medicine
• Strategy
for public health research: the most recent actions reflect
stronger collaboration between the different agencies, particularly in
the conduct of calls for proposals.
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• Assessment
and performance of clinical research: the most recent
actions reflect the acceleration of public-private partnerships and
the establishment of early phase trials for innovative drugs (8 such
molecules since 2009), along with monitoring of recruitment, which
has shown a 72% increase from 2008 to 2013.
• International:
the most recent actions reflect the establishment of
new pilot actions to coordinate cancer research under the European
framework programme EPAAC, particularly aimed at organising and
involving stakeholders in the early phases of clinical trials.
• Communication:
scientific events organised in 2012 and 2013 had
the benefit of high visibility, notably through the presence of the most
senior representatives of the State.
The second part of this report sets out a detailed review of the situation
of research actions carried out in 2012 and 2013, and takes stock of
actions undertaken since 2007 in the 4 broad research areas:
Translational Research; Clinical Research; Cancer Biology and Sciences;
and Research in Human and Social Sciences, Epidemiology and Public
Health.
In total, for all partners involved in research actions included in the
2009-2013 Cancer Plan, 900 proposals were submitted in response
to calls for proposals in 2013, i.e. an increase of nearly 5% compared
with 2012 (859 proposals submitted in 2012). Investment for the
12 calls for proposals reviewed at the time of writing the present report
(July 2013), and which led to the selection of 154 research projects, is
over €46 M (Proposals submitted under the PHRC and PRME-K calls
for proposals for clinical research will not be reviewed until November
2013; the estimated investment for clinical research for 2013 is €22 M,
based on expenditure in previous years). The selection rate for calls
for proposals has remained stable for the investigator-driven biology
programme (15.8% vs. 16.7% in 2012-2013), and has increased slightly
for the translational research programme (12% vs. 16% in 2012). The
selection rate for the investigator-driven programme in human and
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social sciences, epidemiology and public health is over 30% (37% in
2013 vs. 39% in 2012). A selection rate of 30% (32% vs. 39% in 2012)
also applies to the programme for research in physics, mathematics
and engineering sciences applied to cancer, managed by the Aviesan
Alliance’s Multi-Organisation Thematic Institute for Cancer (ITMO
Cancer).
To these investments in research programmes can be added support
for research structures and infrastructure, which in 2012-2013 includes
designation of cooperative intergroups (a total of 8 intergroups
designated in 2012-2013, €0.8 M), support for a new genome
sequencing programme for retinoblastomas and carcinosarcomas
(€1.2 M) under the International Cancer Genome Consortium, ICGC,
construction of clinical-biological databases (BCB in French; 4 in 2012
and others to be selected in 2013).
Efforts deployed in clinical research have translated into a steady
increase in the recruitment of patients to clinical trials, up 72% since
2008. A major growth of 200% can be seen in recruitment to early
phase trials conducted by the CLIP2.
Part 2 of the scientific report also shows a synthesis on the costs of
chemotherapy in France, estimated at €2.8 billion, and a summary of
funding awarded by the canceropoles for the creation of platforms and
the sharing of resources within the scientific community.
In this part, the HELIOS pilot project is presented, as well as a review
research investment, which includes maps showing the distribution of
funding for the 4 large calls for proposals during the 2007-2012 period:
• Translational research: €34 M;
• Clinical research: €12 M;
• Cancer biology and sciences €9 M;
• Research in human and social sciences, epidemiology and public
health: €27 M.
The estimated expenditure on research in 2013 for all partners
combined is €99 M.
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The third part of this report shows the strategic orientations for cancer
research established in consultation with Aviesan ITMO Cancer, and
some perspectives in terms of priorities for action. The 5 priorities will
be discussed with INCa’s International Scientific Advisory Board at the
annual meeting of its members on 7 October 2013.
• Priority
1: initiate a cross-sectional programme in research/care/
public health to combat tobacco-related cancers;
• Priority 2: set up a system for sharing of clinical, biological and
epidemiological database;
• Priority 3: promote cooperation between Teaching and Research, and
increase support for interdisciplinary training;
• Priority 4: support French cancer research aimed at achieving rapid
and significant benefits for the population and patients;
• Priority 5: meet new challenges in the fight against cancer: European
and international perspectives.
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Part 1.
SUMMARY OF PREVIOUS
RECOMMENDATIONS
DRAWN UP BY MEMBERS OF
THE SCIENTIFIC ADVISORY
BOARD, AND PROGRESS MADE
This section brings together the main recommendations (2007-2012)
under 6 broad themes, and summarises the main actions achieved by
INCa:
1 - Priority given to translational research;
2 - Molecular genetics, cancer biology and sciences;
3 - Evaluation and key performance indicators of clinical research;
4 - Strategies for research in public health and human and social
sciences;
5 - Collaboration at national, European and international levels;
6 - Communication.
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PRIORITY GIVEN TO TRANSLATIONAL
RESEARCH AND MULTIDISCIPLINARY
TRAINING
2007
• The Board supports the investment plan prepared by INCa for training physicians/scientists
and investigators in translational research.
• Focus on a few high priority programmes.
• Reduce the number of calls for proposals.
2009
• The Board gives priority to translational research, which must be a central mission for INCa.
• It recommends establishing a specific evaluation process and developing an attractive career path.
• Define the criteria for centres of excellence (comparable to the comprehensive cancer centres in Europe
and North America), and establish a process before opening a national call.
• Strong support for existing actions to simplify the life sciences landscape.
2011
• Strong support for the SIRIC initiative (Integrated Cancer Research Sites). The Board recommends an
increase in the number of SIRICs and their budget, and the development of a system for networking the SIRICs.
• The Board recommends that balance be maintained between support for the SIRICs,
and for studies conducted by the cooperative intergroups and on the initiative of investigators.
• INCa should play an active role in promoting training and career development for the next generation
of investigators specialising in translational research.
2012
• The Board is very pleased with the implementation of the SIRIC programme and the number of eight centres
of excellence for translational research is sufficient. We strongly recommend that the SIRIC sites develop joint
activities and platforms.
• The Board highly encourages INCa to continue its investment in training and education across all disciplines,
including bioinformatics, basic, translational and clinical research, as well as behavioural science.
Actions
achieved or
in progress
Achieved
• 2009: joint strategic research orientations published by INCa and ITMO Cancer.
• Recurrent support for translational research from 2009.
• Recurrent support for translational research training from 2008.
• Creation and designation of SIRIC integrated research sites: 2 in 2011, 6 in 2012.
• Participation in the European ERA-Net initiative to support joint translational research programmes.
• 2012: first evaluation of training programme provided to medical students to perform translational research.
• 2013: working group for coordination and planning of the methodology used to evaluate the SIRICs.
In progress
• Chair of excellence for career advancement: chair in translational cancer research, and chair in prevention.
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MOLECULAR GENETICS,
AND CANCER BIOLOGY
AND SCIENCES
2007
• The Board supports the expansion of a national tumour registry.
Resource allocation would be more effective if it were based on more accurate data.
• Genomics and epigenetics are priority areas for support.
• Support for tumour banks at institutional level should be directed toward the collection
of biological resources accompanied by high-quality clinical annotation.
• Focus on a few high priority programmes.
• Reduce the number of calls for proposals.
2010
• The Board recommends that the number of molecular diagnostic platforms be reconsidered,
and recommends improved interaction with basic/translational research, and a focus
on information systems for platforms and clinical data.
• The Board supports development of research in epigenomics and on the tumour microenvironment.
• The Board supports training for clinicians and researchers in the new skills associated with the molecular
diagnosis and prognosis of cancer.
2011
• The Board encourages the development of data processing systems for bioinformatics and medical data,
and research on complex systems in collaboration with other research organisations.
2012
• The Board recommends that large scale NGS facilities be implemented at some of the SIRIC sites and
services shared with the oncology community. Complementary bioinformatics expertise and clinical data
management must be available at these centres.
• The research programme for cancer biology is an important asset, and requires sustained funding.
Actions
achieved or
in progress
Achieved
• 2011-2013: Calls for proposals (CFP)
1) Creation of national clinical-biological databases
2) Research projects in mathematics, physics, engineering sciences and cancer
3) Research projects based on systems biology
2011: publication of institutional recommendations for the creation of tumour collections for research programmes.
2013: publication of a report on advances in cancer biology research funded by CFPs from INCa and ARC
Foundation: Rôle du Microenvironnement dans la Tumorigénèse et la Progression Tumorale
(Role of the Microenvironment in Tumorigenesis and Tumour Progression).
In progress
• Strategic report for the national organisation of bioinformatics and specific requirements for oncology.
• Integration of research programmes for genomics and clinical platforms.
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EVALUATION AND
KEY PERFORMANCE INDICATORS
IN CLINICAL RESEARCH
2008
• The Board encourages the establishment of more key performance indicators (KPIs), especially for clinical
trials (e.g. time taken to put the studies in place, number of patients, closure of databases, etc.),
and clarification of clinical trial management (e.g. data centres, EMRCs [mobile clinical research teams] etc.).
• In anticipation of a less favourable economic climate, the Scientific Advisory Board suggests continuing to
provide full funding for the best projects.
2010
• The Board supports the implementation of key performance indicators (KPIs)
and milestones to confirm the efficacy of scientific strategy.
2012
• The Board encourages the design of innovative clinical trials and methodology
in assessing the value of NGS.
Actions
achieved or
in progress
INCArapportGB2013.indd 26
Achieved
• Annual review meetings to review successes and failures in clinical research.
• Performance indicators for projects selected under the Hospital Clinical Research Programme (PHRC).
In progress
• Support for randomised trials to assess the contribution of NGS to patient treatment.
• Performance indicators for public-private partnerships in early phase clinical trials.
• Health Investments Observatory (HELIOS).
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RESEARCH STRATEGIES IN PUBLIC
HEALTH AND HUMAN AND SOCIAL
SCIENCES
2007
• The Board supports the development of research on screening, early diagnosis and prevention strategies.
2010
• The Board recommends the development of a specific strategy for preventive research (including behavioural
and social sciences, epidemiology, public health, statistics, economics, etc.).
2012
• The Board endorses the main recommendations on the excellent prevention strategy report.
The key components are capacity building, coordination with other funders and development
of measures of behaviour.
• In light of the shocking increasing prevalence of smoking in France, the Board specifically recommends to
dedicate programmes that aim to develop and evaluate interventions to reverse this trend.
Actions
achieved or
in progress
INCArapportGB2013.indd 27
Achieved
Strategic report on cancer prevention research: changing health behaviours and their individual
and collective determinants.
In progress
• Preventive research programme prepared in collaboration with IReSP
(French Public Health Research Institute) (to be launched at the end of 2013).
• Preparation of a joint programme of action in research/public health to combat tobacco-related cancers.
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NATIONAL, EUROPEAN AND
INTERNATIONAL INTERACTIONS
2007
• The Board encourages an integrated approach within the European Union.
• The Board encourages financial incentives for cooperative groups wishing to consolidate
and study specific subjects.
2008
• Whenever possible, priority should be given to projects where European collaborations
are ongoing or planned.
• This information should be contained in the application.
• Need to continue our action through the use of effective methods to involve the pharmaceutical industry.
One model that could be considered is the CRADA initiative in the US NCI.
2009
• The Board encourages INCa to work with patient associations to strengthen strategic research programmes
• The Board strongly recommends the implementation of actions to simplify the life sciences landscape.
• The Board recommends that links be strengthened with the regulatory agencies and the existing large
cooperative groups, and encourages the development of new large cooperative groups in order to improve
the efficacy of clinical trials.
2010
• The Board encourages more interaction with the 2 main cancer charities and the development
of optimum synergy.
• The Board supports the efforts made to increase collaboration between the various cooperative groups
at national and international levels.
Actions
achieved or
in progress
Achieved
• INCa is a partner in 5 European projects aimed at coordinating research, namely the BASIS project
for cancer genomics research, TRANSCAN for translational research, and EPAAC for the coordination
of cancer research on a European scale, CSA PerMed, CANCON.
• Exchange/collaboration with the pharmaceutical industry and biotechnology companies.
• INCa is showing increased leadership through its international communications on personalised medicine.
• 2012-2013: designation of cooperative intergroups.
In progress
• New pilot actions under the European EPAAC programme in order to involve the pharmaceutical industry
and organise academic resources available for early phase clinical research.
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COMMUNICATION
2008
• As an integral part of its responsibility as a leader in the fight against cancer, INCa should:
- sponsor international symposia,
- continue its leading role in providing information to the public,
- take a leading role in issues related to cancer survival.
2009
• The Board recommends organising more international symposia to increase INCa’s visibility.
2010
• The Board encourages INCa to promote international scientific events regularly,
and to foster better communication with regard to scientific strategy.
2012
• The Board is very pleased with the quality and conciseness of the Scientific Report.
Actions
achieved or
in progress
INCArapportGB2013.indd 29
Achieved
• Joint funding of the Integrated Research Action Programme: PAIR
(INCa/ARC Foundation/French National Cancer League).
• Joint funding (ARC Foundation/INCa) for the “Cancer and Employment” research programme.
• Annual symposium on inequalities.
• Symposium on environment and cancer.
• Symposium on quality of life and cancer.
• International conference on the tumour microenvironment.
• 2012: symposium on Cancer and Inequalities.
• 2012: international R&D Dating.
• 2012: international forum on prospective in cancer research and treatment.
• 2013: international symposium on nutrition and cancer.
• Strategic report on a programme for cancer prevention research: changing Health Behaviours and their Individual and Collective Determinants.
• 2013: report on the main advances on the tumour microenvironment
(programme co-funded by INCa/ARC Foundation).
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Part 2.
REPORT ON CANCER RESEARCH
ACTIVITY FOR 2012-2013,
AND SYNTHESIS
INCa’s work in cancer research is based on the management of calls
for proposals and monitoring of work done on selected projects, and
the coordination of actions and programmes aimed at increasing
interdisciplinary links.
In addition to the investigator-driven calls for proposals launched each
year in the 4 main research areas, namely cancer biology, translational
research, clinical research and research in human and social sciences,
epidemiology and public health, INCa manages a call for the Integrated
Research Action Programme (PAIR programme), which targets
specific types of tumours.
INCa also renewed its call for proposals for health intervention
research on reducing inequalities related to cancer, and in the last
three years, new research programmes defined in the Cancer Plan
have been organised in cooperation with the Aviesan Alliance’s ITMO
Cancer (managed by Inserm): Physics, Mathematics and Cancer,
Environmental Risks and Cancer, Spontaneous Tumour Models and
Systems Biology.
A major effort has been committed to the creation and support of
the SIRIC - integrated cancer research sites - and the development
of public-private partnerships to support early phase clinical trials of
innovative drugs in the INCa-designated CLIP² centres.
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Table 1/ Call for proposals funded by INCa, DGOS (Ministry of Health) and Aviesan-ITMO Cancer
Call for proposals
Nb of proposals
submitted
Nb of projects
selected (% selection)
Funding (€M)
2012
2013
2012
2013
2012
2013
Cancer Biology and Sciences (INCa)
191
208
32 (16.7%)
33 (15.8%)
15.9
15.1
Clinical Research PHRC (DGOS)
226
240
54 (23.9%)
In progress
20.25
In progress
PRME-K (Programme for
Medico-Economic Cancer Research,
formerly STIC) (DGOS)
12
16
3 (25%)
In progress
0.5
In progress
Integrated Research Action Programme
(INCa-ARC Foundation-French National
Cancer League)
39
25
6 (15.4%)
9 (36%)
3.4
5.1
(gynaecology)
(melanoma)
(gynaecology)
(melanoma)
(gynaecology)
(melanoma)
Translational Research (INCa-DGOS)
164
163
26 (16%)
19 (11.6%)
9
8.4
Training in Translational Research
(Aviesan-ITMO Cancer)
36
52
27 (75%)
25 (48%)
2.1
1.5
Human and Social Sciences,
Epidemiology, Public Health (INCa)
41
54
16 (39%)
20 (37%)
3.8
4.8
Health Intervention Research Aimed
at Reducing Inequalities (INCa)
19
10
5 (26.3%)
3 (30%)
2.2
0.7
Research on Inequalities in Access
to Cancer Care (IReSP)
NA
5
NA
1 (20%)
NA
0.1
9
NA
3 (33%)
NA
0.48
NA
Biostatistics and
Cancer (IReSP)
NA
23
NA
9 (39%)
NA
1.3
Physics, Mathematics,
Engineering Sciences and Cancer
(Aviesan-ITMO Cancer)
57
54
21 (37%)
19 (35%)
4.1
4
Cancer and Environmental Risks
(Aviesan-ITMO Cancer)
23
22
9 (39%)
7 (32%)
2.4
2.8
Spontaneous Tumours
(Aviesan-ITMO Cancer)
9
9
4 (44%)
2 (22%)
1.45
0.57
Systems Biology (Aviesan-ITMO Cancer)
21
22
4 (19%)
4 (18%)
2.7
1.5
Cancer and Employment
(INCa-ARC Foundation)
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33
INCREASED SUPPORT FOR TRANSLATIONAL
AND INTEGRATED RESEARCH
1.1. RESEARCH PROGRAMMES AIMING
AT BOOSTING TRANSDISCIPLINARITY
AND TRANSFER OF KNOWLEDGE INTO
CLINICAL PRACTICE
As a flagship measure of the 2009-2013 Cancer Plan, and one
of the major actions in research, Action 1.1 aims to strengthen
translational research through dedicated funding based on
calls for proposals and a policy of designated multidisciplinary
integrated research sites.
INCa, in partnership with the Ministry of Health (DGOS), has
continued to support translational research by launching a
dedicated call for proposals, enabling funding for competitive
research projects.
The goal of this action, launched for the first time in 2007, and
recurrent since 2009, is to promote interdisciplinary projects,
bringing together laboratory researchers and clinicians so that
they share and combine their specific expertise in order to
foster the translation of scientific and medical discoveries into
clinical advances for cancer patients.
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1.1.1. THE TRANSLATIONAL RESEARCH PROGRAMME
Fig. 1/ Trends in selection for the translational
Research programme
Table 2/ Call for proposals in Translational Cancer Research
Year
Funding institutions
Objectives
Funding
Results:
Proposals submitted
Projects selected
Selection rate
2012
2013
INCa/DGOS (Ministry of Health)
To promote interdisciplinary projects,
by bringing together lab researchers and
clinicians to share and combine their
specific expertise in order to foster translation
of scientific and medical discoveries into
clinical advances for cancer patients.
€8.947 M
INCa: €5.065 M
DGOS: €3.882 M
€8.399 M
INCa: €4.445 M
DGOS: €3.954 M
164 letters of intent
26
16%
163 letters of intent
19
11.6%
Since 2007, 729 proposals have been submitted in response
to this call for proposals, and 111 have been selected and
funded, giving an overall selection rate of 15.2%. The total
amount invested in these projects since 2007 is €42.5 M
(Figure 1).
INCArapportGB2013.indd 34
Total budget in €M
The response to the 2013 edition of the call for proposals
for Translational Research (162 proposals submitted) has
once again shown the commitment and effort of France’s
medical and scientific community to hasten the translation
of discoveries into clinical practice for the benefit of patients.
12
30
10
25
8
20
6
15
4
10
2
5
0
0
Number of projects
34
2007 / 2009 2010 2011 2012 2013
Total funding
Nb of projects
Note that for a similar total budget (€8.4 M vs. €8.9 M
respectively for 2013 and 2012), the number of projects
funded is smaller for 2013 (19 vs. 26), the average project cost
is higher in 2013 (€442,000 compared with €344,000), and
the projects are bringing together a large number of teams,
with 12 consortia of at least 10 teams, including 2 uniting
more than 30 teams. The project selection rate in 2013 is
consistent with the quality of the projects as assessed by the
international review committee.
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Fig. 3/ Distribution of budget allocated to the translational
Research programme in 2013, shown in comparison
to the overall profile for 2007-2013
500,000
60%
50%
30%
100,000
20%
0
10%
2009
2010
2011
2012
2013
17%
14.6%
8%
The typology of projects funded in 2013 corresponds to the
characteristic profile for translational research (Figure 3),
with most of the budget allocated to two main categories of
research projects:
• projects that involve the development of techniques
or biomarkers (genetic, biological, immunochemical,
microbiological),
• projects based on the improvement of patient care, including
projects on the development of new strategies, and on
mechanisms of treatment resistance.
1%
3.3% 2%
0%
1.6% 0%
0%
0%
Aetiology
2008
24%
Biology
2007
37%
Cancer control
200,000
43.6%
Early detection,
diagnosis and
prognosis
40%
Prevention
300,000
2007-2013
2013
49%
Treatment
400,000
Scientific models
Fig. 2/ Average budget of projects funded, in euro
35
We see that nearly half the projects selected in 2013 employ
genomic analyses (genotyping, sequencing). These studies,
based on the use of high throughput technologies that
generate large quantities of data, justify an increase in the
multidisciplinary dimension of the projects, particularly in
bioinformatics for the analysis and interpretation of results.
Haematology is the most represented speciality in funding
for 2013, with 30% of the allocated budget, but many other
malignant pathologies are also studied in the selected projects
(pancreatic cancer, hepatoblastoma, paediatric tumours,
breast cancer, colorectal cancer, etc.).
2012-2013 Highlights
45 “Translational research” projects selected
for multi-year funding (INCa and DGOS) of €17 M.
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1.1.2. THE TRANSLATIONAL RESEARCH TRAINING
PROGRAMME
As part of its policy of supporting translational research, INCa,
in conjunction with Aviesan for the last three years, also offers
a specific recurrent call for applications, initiated in 2007, to
facilitate the training of medical students who wish to complete
their medical studies by performing translational cancer
research. This support is provided through the competitive
awarding of grants to applicants for one to three years to
complete a master’s degree or post-doctoral residency, or to
prepare a doctoral thesis on an outstanding research topic.
Students preparing to qualify in pharmacy or veterinary
medicine are eligible for this call.
Fig. 4/ Distribution of total funding allocated
for translational research training in 2007-2013
4.6%
28.6%
Biology= €3.2 M
Aetiology= €0.5M
Prevention= €0.01 M
Early detection,
diagnosis, prognosis
= €1.8 M
Treatment= €2.4 M
Scientific models= €0.4 M
Table 3/ Results of the Translational Research Training
Programme in 2012-2013
Year
Funding institutions
Objectives
Funding
Results:
Proposals submitted
Projects selected
Selection rate
2012
2013
Aviesan/ITMO Cancer
To promote training of students or young
medical, pharmacy and veterinary science
graduates in translational research by funding
master’s degrees, doctoral theses
or post-doctoral research.
€2.086 M
€1.511 M
36
27
75%
52
25
48%
In all, 130 training grants have been awarded for translational
research, for a total of €8.3 M, since 2007 (50% success rate),
including 11 to postdoctoral candidates and 45 to students
preparing theses (Figure 4).
INCArapportGB2013.indd 36
38.7%
21.9%
0.1% 6%
2012-2013 Highlights
52 candidates selected for training in translational
research, for a €3.5 M funding
(Aviesan-ITMO Cancer).
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1.1.3. THE EUROPEAN TRANSLATIONAL CANCER
RESEARCH PROGRAMME
The ERA-Net TRANSCAN programme, specific for translational
research in oncology, presently involves 19 countries
represented by 29 funding institutions and organisations,
including INCa.
The TRANSCAN programme is aimed at establishing
coordination at European level for national translational
cancer research programmes, and providing joint funding
for research projects selected following the 3 joint calls for
proposals planned over the duration of TRANSCAN.
37
INCa is actively involved in drawing up and organising calls for
proposals, and funding the research projects selected. INCa is
more specifically tasked with coordinating the work package
(WP) on training and promotion of multidisciplinarity. With
the help of recommendations from TRANSCAN’s Scientific
Advisory Board, the members of the network agree annually
on the definition of a topic for the next call for proposals to
be launched.
An overall analysis of funding allocated by the partners to
translational cancer research, based on the CSO classification
defined by the international ICRP network is planned.
Table 4/ ERA-NET on Translational Cancer Research/ERA-NET TRANSCAN
Objectives
of TRANSCAN
To coordinate the national and regional funding organisations’ activities in translational cancer research
at European level, with the launch of 3 joint transnational calls for proposals (JTCs).
Website: http://www.transcanfp7.eu/transcan/index.php
1- Management and network coordination.
2- Survey and analysis of national cancer research
funding for translational research.
Sharing of INCa’s experience with the TRANSCAN partners,
using the CSO classification system.
Definition by INCa and its partners, in 2012,
of the topic for the 2nd CFP (JTC 2012).
Definition in 2013 of the topic for the 3rd CFP (JTC 2013).
Implementation of their review process.
4- Implementation of the 3 joint transnational calls (JTCs).
In 2013, INCa is providing secretariat services
for the entire process of the 2nd CFP (JTC 2012).
5- Implementation of capacity building
and training activities.
INCa is the leader of this work package
for the 3 calls for proposals.
TRANSCAN Work
packages
6- Monitoring of activities network and sustainability.
Call for proposals
(JTCs)
INCArapportGB2013.indd 37
3 calls for proposals launched within 3 years
Launch dates: end of 2011, 2012 and 2013.
2-stage procedure: pre-proposals + full proposals
Publication of results in October of year N + 1
Start of funding in April of year N + 2
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Table 5/ ERA-NET TRANSCAN – Calls for proposals
Topic of calls
for proposals
1st call for proposals: JTC 2011
“Validation of Biomarkers for
Personalised Cancer Medicine”.
2nd call for proposals: JTC 2012
“Translational Research on
Primary and Secondary Prevention
of Cancer”.
3rd call for proposals: JTC 2013
“Translational Research on
Tertiary Prevention of Cancer”
Currently being drawn up
for launch in December 2013.
For the 3 calls for proposals:
Within proposals, it is possible to add a specific component related to training (short- or long-term),
or to increasing multidisciplinarity. This additional component, which must, however, be related to
the research objectives, will be funded only if it receives a favourable review.
Funding of calls
for proposals
Results of calls
for proposals
1st call for proposals: JTC 2011
15 funding partners: Germany, Austria, Belgium,
Spain, France, Greece, Israel, Italy, Latvia,
Luxembourg, Poland, Romania, Slovakia,
Slovenia, Turkey.
2nd call for proposals: JTC 2012
15 funding partners: Germany, Austria, Belgium,
France, Israel, Italy, Latvia, Luxembourg, Norway,
Netherlands, Poland, Portugal, Romania, Slovakia,
Turkey.
Total budget: €10.6 M
(of which €1.3 M from INCa).
Provisional total budget: €14.31 M
(of which €1.5 M from INCa
and €0.3/0.5 M from ARC Foundation).
1st call for proposals: JTC 2011
Number of “pre-proposals” submitted:
117, including 579 teams
Number of full proposals: 34
Number of projects selected: 10
2nd call for proposals: JTC 2012
Number of “pre-proposals” submitted:
55, including 257 teams
Number of full proposals: 22
Number of projects selected: pending
(October 2013)
Participation of French teams
60 “pre-proposals,” including 80 teams/18 coordinators. Participation of French teams
22 full projects, including 29 teams/7 coordinators.
28 “pre-proposals,” including 36 teams/7 coordinators.
6 projects selected, including 7 teams/1 coordinator. 13 full projects, including 18 teams/3 coordinators.
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Focus on projects funded
through JTC 2011
The number of responses to the 1st call for proposals indicates
the interest of European teams in working on more advanced
phases of biomarker development for clinical application.
This also stresses the enthusiasm of researchers for increasing
their scientific collaboration at a European level in order to
share complementary expertise, to benefit from access to
specific technologies and highly qualified platforms, and to
create larger patients cohorts or larger sample collections.
Of the 10 projects selected for funding by the
TRANSCAN partners, over half of funded projects deal with
biomarkers aimed at predicting the efficacy or
toxicity of treatments administered to patients:
• use of nuclear medicine to predict the efficacy of
hormone therapy for breast cancer,
• invoking DNA repair pathways to predict
the efficacy of chemotherapy for colorectal cancer,
lung cancer, and breast cancer,
• interest of monitoring immunological
biomarkers
following haematopoietic stem cell transplantation,
and during treatment for breast and ovary cancers.
This is evidence of the continued efforts devoted to
developing personalised medicine in order to tailor
therapeutic care to the characteristics of individual patient
and his/her tumour.
Two projects are specifically devoted to improving
diagnosis: one through the use of nuclear medicine
in thyroid cancer, and one through the study of genetic
changes in leukaemias.
Finally, biomarkers for prognosis are the subject
of two projects, one of which uses genomic techniques
in Ewing’s sarcoma, and the other of which uses detection
of circulating tumour cells in prostate cancer.
Focus on the JTC 2012 topic
“Translational Research
on Primary and Secondary
Prevention of Cancer”
The number of projects submitted under the 2nd
TRANSCAN call for proposals (55 vs. 117 for JTC 2011) is
evidence of the originality of the topic chosen. Indeed, the
TRANSCAN partners, supported by the recommendations
of the Scientific Advisory Board, wished to further the
contribution of translational research to questions
raised by primary and secondary cancer prevention. The
methodological complexity of the studies and the need
for access to patient cohorts make the establishment of
these projects difficult, but their impact is expected to be
significant in terms of public health and European research
organisation in this field.
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1.1.4. DEVELOPMENT OF SPONTANEOUS TUMOUR
MODELS AND ALTERNATIVES TO CLINICAL TRIALS
The strategic initiative to support the development of
spontaneous tumour models and alternatives to clinical trials,
a corollary of the first measure of the Cancer Plan, was launched
for the first time in 2011, and renewed in 2012 and 2013 with
dedicated calls for proposals. Its objectives are to encourage the
various disciplines to work together and incorporate research
carried out on spontaneous cancers occurring in animals,
particularly dogs, into studies done on a worldwide scale in the
areas of biology, diagnosis, prognosis and treatment of cancers
that affect humans. Prior to this dedicated call, and from
2009 on, INCa redoubled its efforts to mobilise the different
research communities (biologists, clinicians and veterinarians)
through specific seminars and meetings. Collaborations were
established with European partners, and cooperation put in
place with the US Comparative Oncology Trials Consortium.
Table 6/ Main features of the Research Programme
for Spontaneous Tumours Models
Year
Funding institutions
Objectives
Funding
Selection rate
2012
2013
Fig. 5/ Spontaneous tumour models 2011-2013: €2.5 M
10
9
8
7
6
5
4
3
2
1
0
2011
2012
Fig. 6/ Spontaneous tumours: funding awarded
in 2011-2013 by type of cancer
Aviesan /ITMO Cancer
To increase collaboration between
veterinarians, researchers and clinicians so
as to promote the translation of results from
cancer research, through support of research
projects and development of tools to monitor
treatment of spontaneous cancers in animals
that are diagnosed and treated in a way to be
a potential outlook for humans.
€1.45 M
€0.57 M
44%
22%
2013
Nb of projects submitted
Nb of projects selected
4 projects
1,200,000
1,000,000
Funding in €M
40
800,000
2 projects
600,000
1 project
400,000
200,000
1 project
INCArapportGB2013.indd 40
Haematology
Melanoma
Lung/UADT
Breast
0
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The establishment of a European consortium
The European dynamic in comparative oncology initiated by
INCa and ITMO Cancer has helped to mobilise veterinarians
and clinicians, who have applied to a COST action (European
Union). This application is undergoing the final phases of
processing, and brings together some ten partner countries
around a core group made up of French, British, Danish and
Italian teams.
This project, entitled ACT (Interdisciplinary Consortium for
Accelerated Cancer Translational Research) aims to promote
the development of new necessary preclinical models.
Spontaneous tumours in dogs show clinical, pathological,
immunological, molecular, diagnostic and therapeutic
characteristics similar to those that occur in humans. It is
to develop innovative therapeutic concepts for cancer from
spontaneous animal models.
Within this framework, a multidisciplinary network of
European experts in human and veterinary medicine will
be developed in order to foster discussion, training and
dissemination of information, and to expedite translation into
clinical practice in comparative oncology. Collaboration with
the CLIP² network has been initiated, and a workshop will be
held in January 2014.
2012-2013 Highlights
New call for proposals, “Spontaneous Tumour
Models”, handled jointly by INCa and ITMO Cancer;
first edition in 2011.
•
8 projects since 2011, €2.5 M
41
1.1.5. RENEWAL OF THE INTEGRATED
RESEARCH ACTION PROGRAMME
FOR A SPECIFIC TYPE OF TUMOUR
In 2007, INCa launched an annual thematic programme
devoted to a specific pathology. The programme, entitled,
“Integrated Research Action Programme” (PAIR), is aimed
at bringing together scientific and medical communities
specialising in this pathology. Projects cover all areas of
research, such as biology, clinical research, epidemiology,
innovative technologies, prevention, screening, diagnosis,
treatment and social sciences.
This specific programme is organised in two stages. The
preparatory work is performed by a scientific organising
committee in order to identify the context and define the
research areas to be targeted in the call for proposals. A
national seminar is organised before launching the call, in
order to bring together the scientific and medical communities,
and encourage the creation of large consortia.
A partnership between the three major funders of cancer
research — ARC Foundation, the French National Cancer
League and INCa — has been initiated and each of the
three partners contributes to funding the projects selected.
Following gynaecological cancers in 2012, and before early
forms of breast cancer in 2014, the 2013 PAIR is focused
on melanomas. The significant increase in the incidence of
melanoma in recent years (from 2,210 in 1980 to 9,780 in
2011, according to InVS [French Institute for Public Health
Surveillance] estimates), which affects young individuals,
together with some recent advances in research on treatment,
justifies a strong call for action.
(Aviesan-Inserm for ITMO Cancer).
•
Establishment of a European network
for comparative oncology.
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Year
Funding institutions
Objectives
Funding
Results:
Proposals submitted
Projects selected
Selection rate
2013 (melanomas)
INCa
ARC Foundation
National Cancer League
To increase collaboration between
French research teams, and to obtain original
insights on questions at the interface between
epidemiology, human and social sciences,
economics, public health, biology and clinical
medicine. It is therefore strongly recommended
that collaborative projects involving different
disciplines be drawn up in response to
this call for proposals.
€5.12 M
25
9 (including 2 projects funded
by INCa exclusively)
36%
Since 2007, 7 Integrated Research Action Programmes have
been managed by INCa. Overall, 63 projects have been
selected, for a total funding of €33.9 M (Figure 7).
Fig. 7/ Trends in the PAIR programme for 2007-2013:
number of projects selected and funding awarded
7
16
6
14
12
5
10
4
8
3
6
2
Number of projects
Table 7/ Main features of the Integrated Research Action
Programme
Funding €M
42
4
1
2
0
0
Melanoma
Gynecological
cancers
UADT
Prostate
Hepatocellular
carcinoma
Lymphoma
Colorectal
2007 2008 2009 2010 2011 2012 2013
Total funding
Nb of projects
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Since its implementation in 2007, the Integrated Research
Action Programme has covered all areas of research, in line
with the programme’s goals (Figure 8). Nearly a third of
projects selected since 2007 have studied the development
and fine-tuning of strategies for diagnosis and prognosis, and
markers of the response to treatment.
Fig. 8/ Types of projects funded and investment in PAIR
programmes over the 2007-2013 period: €34 M
43
However, it is important to note that the variety of types of
research varies with the tumour. The melanoma programme
in 2013 covers biology, screening, diagnosis and treatment;
the programmes for colorectal cancer and hepatocellular
carcinoma cover all categories of research.
Fig. 9/ Distribution of PAIR programmes 2007-2013
by CSO category
2013 Melanoma
€
3.2M
€
2012 Gynaecological
cancers (non breast)
0.9M
€
6.2M
6.6M
Biology
Aetiology
Prevention
Early detection, diagnosis,
prognosis
Treatment
Human and social sciences
Scientific models
€
2010 Prostate
2009 Hepatocellular
Carcinoma
2008 Lymphomas
2007 Colorectal
4.2M
€
1.1M
€
11.8M
2011 UADT
Biology
Aetiology
Prevention
Screening, diagnosis,
prognosis
Treatment
Human and
social sciences
Scientific models
€
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44
1.2. NEW ACTIONS TO STRENGTHEN
ORGANISATION AND INFRASTRUCTURES
devoted to translational/integrated research
This objective has been met by the designation of 8 SIRICs
(Integrated Cancer Research Sites) for a 5-year period, following
two calls for applications launched in 2010 (2 SIRICs designated
in 2011) and in 2011 (6 SIRICs designated in 2012).
1.2.1. Coordination of Integrated Cancer Research Sites (SIRIC)
The 2009-2013 Cancer Plan included among its “flagship”
objectives, to be achieved in 2013, the designation of multidisciplinary research sites linking the different dimensions
of research (basic, clinical, public health, epidemiology, and
human and social sciences), by concentrating a critical mass of
experts (physicians, researchers, engineers, healthcare workers
and patients) working within the constraints — especially
competitiveness and quality assurance — of translational
research.
The SIRICs should become national centres of reference for
cancer research, with the two main roles of preparing and
conducting integrated research programmes, and establishing
programmes for the dissemination of knowledge and new
practices.
In establishing a competitive policy for the designation of
sites, INCa hopes to offer new opportunities for conducting
translational cancer research, thus helping to optimise and
hasten the production of new knowledge and promote its
dissemination and application to cancer care.
Each SIRIC is involved in specific programmes, representing the
expertise and strategies of the site. The essential assessment
criteria used to determine the continued existence of the SIRICs
are the achievement of individual objectives, and cooperation
between SIRICs on converging objectives.
INCArapportGB2013.indd 44
The budget allocated to this programme is €64 M, jointly
funded by INCa, Aviesan-ITMO Cancer and the Ministry of
Health (DGOS).
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EIGHT INTEGRATED RESEARCH SITE ON CANCER (SIRIC) CERTIFIED BY INCa
Fig. 10/ Locations of the 8 SIRICs in France
SIRIC Institut Curie
CAncer Research and
PErsonalized Medicine
(CARPEM)
Onco Lille - C2RC
Stratified Oncology Cell
DNA Repair And Tumor
immune Elimination
(SOCRATE)
© INCA - aebk - june 2012
LYon site de recherche intégrée
sur le cancer (LYRIC)
Bordeaux Recherche Intégrée
Oncologie (BRIO)
Montpellier Cancer (MC)
Pôle régional de référence
en cancérologie de PACA-Ouest
Guadeloupe
Martinique
Guyane
La Réunion
Source: INCa, 2012
Drafted by INCa’s Research Division, 2012
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Establishment of coordination for the SIRICs
INCa is particularly committed to the establishment of
coordination, to help support and monitor the programme.
The priority objectives of SIRIC coordination can be found at
three main levels:
1) Framing the interface between SIRICs
• To allow sharing of experience and coordinated development
of managerial, organisational and institutional aspects
(annual meeting of SIRIC managers, the first of which
was held in June 2013).
• To encourage and facilitate scientific discussion among the
SIRICs to stimulate collaboration and optimise the scope
of projects. A first interface seminar brought together
the 8 SIRICs in February 2013, with the aim of sharing
information on their respective research programmes, and
identifying areas of complementarity.
• To make proposals regarding the development of
translational research, i.e., organisation of roles,
professional advancement, expertise in proposing
recommendations and priority lines of research. Each SIRIC
has appointed 2 representatives to form a committee of
“translational research” experts that will meet for the
first time in autumn 2013.
• To develop interface with clinical-biological databases,
provide leadership in the development of genomic-led
medicine in the development of immunotherapy, integrate
the “peripheral” science (mathematics, physics and social
and human sciences) and strengthen relationships with
their geographic environment to promote clinical research.
2) The choice of the creating and funding SIRICs
make them key leading partners for the expansion
of national actions, such as:
• Integration of mathematics and physics
• Expansion of tumour genetics
• Promotion of secondary advice through clinical research
• Integration of social science and public health.
Qualitative analysis of the implementation of the SIRICs will
be carried out in collaboration with a team from the Centre for
the Sociology of Organisations (CSO, UMR CNRS-Sciences
Po) whose scientific interests relate to changing the conditions
for public action, particularly in the areas of health research,
and the analysis of knowledge production.
From the CSO’s perspective, the SIRICs are a particularly
interesting example of public policy, since they are aimed at
stimulating and improving cooperation and coordination
between players. For the present purpose, it involves better
coordination of clinical and research activities—including
those that come under Human and Social Sciences, an
innovation for the biomedical sector. Communication is
expected to become faster and better, as is the translation
of research knowledge into clinical practice. In short, the
SIRICs constitute an original public initiative to promote
what is known by health players as “translational research.”
For this reason, analysing them will help to contribute to
CSO’s cross-sectional area of interest, which is focused in
changing the conditions for public action.
A second area of cross-sectional reflection for CSO concerns
the analysis and production of knowledge, particularly
scientific knowledge. Members of the laboratory particularly
intend to study the organisation of research, an activity
strongly marked by serendipity, as well as the impact of the
organisational processes on the type, nature and form of
knowledge produced. In this perspective, the relevance of
the SIRICs as a subject of research seems obvious.
2012-2013 Highlights
Coordination of the activities of the 8 integrated
cancer research sites.
3) Developing a qualitative analysis for actions
conducted by the SIRICs
Analysis of the SIRICs is eagerly anticipated, since they are
simultaneously involved in the organisation of research and
the production of new knowledge and its translation into
clinical practice.
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1.2.2. ORGANISATION OF ENHANCED SCIENTIFIC USE
OF THE BIOBANKS, AND FUNDING OF MULTI-CENTRE
CLINICAL-BIOLOGICAL DATABASES
INCa’s goal of rationalising the storage of biological resources
in tumour banks and exploiting them for cancer research, to
which it has been committed for several years, has been pursued
and strengthened in 2012 and 2013.
INCa’s actions and recommendations are still aimed at
optimising the organisation of the tumour banks with a view
to creating collections linked to databases, both at local level
and as part of multi-centre networks.
Coordination of tumour banks
The tumour banks’ index of scientific contribution, calculated
from an analysis of activity reports for 2009, led to a readjustment
of the MERRI (French Government’s education, research,
information and innovation programme of the Ministry of
Health) budget allocated to the tumour banks in 2012. The
new procedure for calculation and distribution of MERRI
support credits considers the volume of activity declared in
activity reports, i.e. inward flow (number of new patient files),
outward flow (number of samples used for research projects),
and weighting for quality certification. This reassessment has
rekindled the interest of the managers of tumour banks in
considering the scientific purposes of preparation, storage and
availability of biological samples.
INCArapportGB2013.indd 47
47
In 2012, the online activity reports for tumour banks - 20102011- was improved in consultation with INCa’s “Biological
Resources” working group (representatives from the
canceropoles). The online activity report allows comprehensive
monitoring of health- and science-related activities by
pathology (French CIM 10 for International Statistical
Classification of Diseases and Related Health Problems). The
assessment of the scientific contributions of the tumour banks
is more accurate and specific.
Not only do the data collected allow a refinement of the
assessment criteria and the index of scientific contribution, they
also help improve the visibility to local and national collections,
to the quality of organisation of the tumour banks, and to
their activities in terms of scientific contribution (specialised
networks, research programmes, listing in publications).
Selection of data will help in establishing a summary data sheet
for every tumour bank, and will allow the main characteristics
and collections of the tumour banks to be posted on the
INCa website. The wealth of data collected enables INCa to
develop a database as a resource for enhanced use and strategic
orientation for biological resources.
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48
Fig. 11/ 2010-2011 Scientific contributions from the tumour banks funded by INCa and DGOS
Indicators for the scientific contributions of tumour banks,
based on 2010-2011 activity reports,
and according to the following criteria:
- sample flows (incoming and outgoing)
- quality certification (NF S 96-900, ISO 9001)
Groupement de Coopération Sanitaire
- participation in research programs
Centre de Refence Regional
en Cancerologie
- participation in publications
Centre hospitalier
de Lens
CHU de Rouen
CHU d'Amiens
Paris area
Institut Curie
AP-HP Hôpital St Louis
AP-HP HÔTEL DIEU
Hôpital Avicenne
AP-HP, Hôpital Bichat
APHP, Hôpital Beaujon
APHP, Hôpital Foch
Hôpital NeckerEnfants Malades
AP-HP
Ambroise Paré
HEGP
Hôpital René Huguenin Institut Curie AP-HP GHU
Paris Sud
Institut
Gustave Roussy
AP-HP Groupe Hospitalier
"CancerEst"
APHP, Hôpital Saint Antoine
APHP, Groupe hospitalier
Pitié Salpêtrière
APHP Cochin St Vincent de Paul
Institut Mutualiste
Montsouris
Groupe Hospitalier
Henri Mondor
CHU de Reims CLCC Institut Jean Godinot
CHU de Caen Centre François Baclesse
Centre Hospitalier
Régional d'Orléans
CHU d'Angers
Institut Régional
du Cancer
Nantes-Atlantique
CHU de Strasbourg Hôpital de hautepierre
CHU de Dijon
CHU de Besançon
CHRU de Tours
2010-2011
Scientific contribution
indicator
Centre Paul Strauss
CHU de Nancy Hôpitaux de Brabois,
Hôpital Central
CHU de Rennes
CHU de Poitiers
CHU de Limoges
540,000
Centre Léon Bérard
Centre Jean Perrin
Hospices Civils de Lyon
Centre Hospitalier
de Chambéry
CHU de Clermont-Ferrand
200,000
CHU de Saint Etienne
Institut Bergonié
CHU de Grenoble
100,000
50,000
25,000
10,000
5,000
2,000
1,000
© INCa - aebk - juin 2013
CHU de Brest Hôpital Morvan
CHU de Bordeaux Hôpital Haut-Lévêque
CHU de Toulouse
Institut Claudius Regaud
CRLCC Val d'Aurelle
Paul Lamarque
CHU Montpellier Hôpital Gui de Chauliac
pas de données
CHU de Nice
CH du Pays d'Aix
Institut Paoli Calmettes
Assistance Publique
Höpitaux de Marseille
CH de Perpignan
Guadeloupe
Martinique
Guyane
La Réunion
CHU de Fort de France Hôpital Pierre Zobda-Quitman
Source: INCa and DGOS, 2012
Drafted by Research and Innovation Division - INCa - 2013
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Nationwide clinical-biological databases (French BCBs)
The objective of the call for proposals for BCBs initiated in
2011 is to encourage the different players to join forces to
create clinical-biological databases linked with biological
samples, for a single pathology. These BCBs should enable the
collection of information, its inclusion and cross-disciplinary
exploitation in different areas of research (epidemiological,
basic, translational, and clinical) to be optimised.
Table 8/ The clinical-biological database:
a strategic research tool
Objectives
• To perform research in analytical
epidemiology and public health.
• To perform research in biology and support
the development of clinical trials.
• To help scientists understand and explain
phenomena, from molecular interaction
to the entire metabolism of organisms
in normal and pathological situations.
• To enable identification of potential
strategies for the diagnosis and analysis
of cancer subtypes.
Structure
A multi-centre organisation to standardise
data collection and sharing with scientific
and medical communities.
Stored data
• Disease history (medical and treatment
history).
• Administrative (geographical and
occupational) and socio-economic data.
• Clinical and biological data (results of
biomedical and paramedical tests).
• Individual and collective behavioural
and environmental data.
Funding
€2.3 M (3 years).
INCArapportGB2013.indd 49
49
1) To optimise the compilation of information linked with
collections:
• by creating (or reorganising) a multi-centre medical and
scientific network, enabling work on a national scale,
• by developing interoperability among information systems
available in the different preexisting databases,
• by favouring a national quality approach for the collection,
management and exchange of clinical, epidemiological and
biological data,
• by creating (or optimising) around biological collections an
organisation of multi-centre and multidisciplinary networks
for the collection of standard data, particularly between
cohorts, biobanks, and the different healthcare players.
2) To optimise the exploitation of data:
• by promoting the integration, pooling and sharing at national
scale of all data useful to a community of scientific experts,
• by fostering access for research teams to specialised data,
• by facilitating the cataloguing of biological resources and
the choices for building strategic collections (biological
resources linked to defined clinical and analytical data),
• by promoting cross-sectoral epidemiological studies to
examine the role of environmental factors in the occurrence of
cancer, and the influence of social factors in the occurrence,
prevention, detection and care of cancer,
• by permitting the production of an annual scorecard
to optimise decisions to support research projects. The
scorecard summary can if necessary be made available to
the public and presented by INCa in communications on its
website.
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50
This call for proposals strengthens the organisation of
specialised networks, the governance of which INCa will help
to organise, in order to develop a “model” for fostering the
sharing of data and biological resources for projects conducted
on a nationwide scale.
1.2.3. SUPPORT FOR “LIFE SCIENCES TECHNOLOGICAL
PLATFORMS”: THE IBiSA PROGRAMME
INCa, in collaboration with Aviesan-ITMO Cancer, is involved
in the organisation and support of technological research
platforms coordinated by GIS IBiSA (Scientific Interest Group
for Biology, Healthcare and Agronomics Infrastructures).
The 2012 BCB call for proposals resulted in the submission
of 14 applications, 4 of which were selected for a 3-year
funding. Nine BCBs are thus currently supported by INCa,
and the 3rd call was launched in March 2013.
Figure 12 shows all platforms designated by GIS IBiSA, and
Figure 13 shows the different platforms that have received
support for cancer research since 2008, i.e. over €9 M in total.
This support represents over half of the investment made in
these platforms at national level.
Initial impacts
• After 10 years of a national policy led by the Ministries of
Health and Research, entrusted to INCa in 2005, France
now has a genuine organisation allowing the scientific
goals of the tumour banks to be consolidated.
• A refine activity report and national monitoring of
the tumour banks’ activities, according to parameters
indicating their contribution to research.
• Provision of support funding according to measured
contributions, which strengthens those tumour banks
that become involved in local and national networks.
• An organisational approach to upgrading biological
resource collections into networks, by providing support
through a call for the creation of clinical-biological
databases.
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Fig. 12/ The IBiSA-designated life sciences platforms and infrastructures
Paris
Villeneuve-d'Ascq
Lille
Fontenay-aux-Roses
Mont-St-Aignan
Reims
Caen
Brest
Gif-sur-Yvette
Type of research carried
out at the platform
Orléans
Angers
Nouzilly
Surgères
Clermont
Ferrand
Lyon
Bordeaux
Structural biology, biophysics
Bioinformatics
Sreening and chemical banks
New therapies, vectorisation,
stem cells
Herbal treatment research
Animal house, functional
exploration
Others
Guadeloupe
Illkirch
Orsay
Proteomics
Genomics, Transcriptomics
Metabolomics
In vivo imaging
Cellular imaging
Martinique
Strasbourg
Evry
Rennes
Nantes
Vandoeuvre
les-Nancy
Versailles
Villeurbanne
Bron
La Tronche
Grenoble
Cestas
Montpellier
Toulouse
Castanet-Tolosan
Guyane
St-Paul
les-Durance
Rousset
Nice
Antibes
(Sophia Antipolis)
Marseille
La Réunion
St-Pierre
Source: INCa and GIS-IBiSA, 2012
Drafted by: Research and Innovation Division - INCa – 2013
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Fig. 13/ IBiSA-designated life sciences platforms and infrastructures for cancer research: €9 M in support provided since 2008
Guadeloupe
Guyane
Martinique
La Réunion
Paris
Villeneuve d'Ascq
Reims
Caen
Orsay
Strasbourg
Gif-sur-Yvette
Rennes
Illkirch
Evry
Angers
Share of funding
for cancer research
(INCa/Inserm)
Lyon
La Tronche
Funding for cancer research
(in euros)
600,000
Grenoble
Toulouse
400,000
200,000
Montpellier
© INCa - aebk - juin 2013
Orléans
Nantes
Nice
100,000
60,000
Type of research carried out at the platform
Proteomics
Genomics, transcriptomics
In vivo imaging
Cellular imaging
Structural biology, biophysics
Screening and chemical banks
New therapies, vectorisation, stem cells
Animal house, functional exploration
Others
INCArapportGB2013.indd 52
Marseille
Source: INCa and GIS-IBiSA, 2012
Drafted by Research and Innovation Division – INCa – 2013
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As a priority, INCa and Avisean-ITMO Cancer provide support
for platforms conducting activities partly or fully focused
on cancer research. Support is provided for a wide range of
technological specialities.
However, for the 2008-2012 period, particular efforts have
been made in the following areas:
• in vivo imaging (5 platforms, €1.4 M) and cellular imaging
(8 platforms, €2 M),
• proteomics (6 platforms: €1.4 M in total),
• genomics and transcriptomics (4 platforms, €1 M),
• screening and chemical libraries (4 platforms, €0.7 M),
• screening and combinatorial libraries (4 platforms, €0.7 M).
From 2011, INCa began to redefine national priorities in terms
of the support provided for technological platforms for the
specific requirements of each area of cancer research, taking
into account the “investments for the future” provided by the
State to laboratories of excellence and “large” equipment (See
INCa Scientific Report 2010-2011, Part 3, Chapter 1.5).
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54
2
INCREASED SUPPORT FOR CLINICAL
RESEARCH AND DEVELOPMENT
of early phase trials for innovative molecules
2.1. THE CLINICAL CANCER RESEARCH
PROGRAMMES
In France, academic clinical research on cancer is organised
through 2 annual calls for proposals managed by INCa, and
funded by DGOS (Ministry of Health).
Table 9/ Main features of the Hospital Clinical Research
Programme (PHRC) for cancer
Year
Funding institutions
Objectives
2.1.1. THE NATIONAL HOSPITAL CLINICAL RESEARCH
PROGRAMME (PHRC) FOR CANCER
The PHRC Cancer allows a competitive selection of the best
clinical research projects. The strategic plan defined by INCa
and the Ministry of Health is designed to elicit:
• large therapeutic studies in the form of cooperative multicentre trials, to establish international clinical practice
standards,
• trials for clinical validation of innovative techniques in the
areas of treatment and diagnosis.
Practical clinical objectives and the simplification of trials for
patient recruitment are important assessment criteria during
project selection.
In 2013, of 240 letters of intent submitted to the PHRC Cancer,
109 projects were short-listed for final review in November
2013.
INCArapportGB2013.indd 54
2012
2013
Ministry of Health
• To validate new medical or scientific
knowledge in the clinical field.
• To improve quality of care by evaluating
new diagnostic and therapeutic.
Funding
Proposals submitted
Projects selected
Selection rate
€20.25 M
21 (projected)
226
54
23.9%
240
-
Table 10/ Types of projects selected at the letter of intent
stage of the Hospital Clinical Research Programme (PHRC)
for cancer in 2013
Nb of projects
Systemic treatments
46
Local treatments
23
Combined local and systemic treatments
11
Early detection, diagnosis and prognosis
18
Chemoprevention, vaccines
3
Other
8
Total
109
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Nearly 75% of letters of intent short-listed were for projects
involving therapeutic studies:
• over half (57.5%) of these therapeutic study projects involved
systemic treatments,
• surgery, radiotherapy and combined treatments including
at least one of the latter treatment modes accounted for the
remaining (42.5%) projects involving therapeutic studies.
Fig. 15/ Distribution of total funding allocated to
the PHRC cancer in 2007-2012
7%
Early detection,
diagnosis, prognosis
= €26.2 M
Treatment
= €73 M
Research outcomes, QoL
= €7.5 M
Early detection, diagnosis or prognosis was the objective of
16.5% of letters of intent selected.
Fig. 14/ Trends in selection and funding of
the Hospital Clinical Research Programme cancer (PHRC)
80
25
60
50
15
40
10
30
Nb of projects
Funding €M
25%
68%
70
20
55
20
5
10
0
0
2007 2008 2009 2010 2011 2012
Note: the “early detection, diagnosis, prognosis” category includes early phase trials
(see the CSO classification in appendix)
2013 Highlights
Collaboration between INCa and the Ministry of Health
regarding the Hospital Clinical Research Programme
on cancer.
240 letters of intent submitted, 109 projects
pre-selected for final review; projected budget
€21 M.
Total funding
Nb of projects
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2.1.2. THE NATIONAL PROGRAMME FOR MEDICOECONOMIC RESEARCH ON CANCER (PRME-K)
In 2013, the Ministry of Health wished to replace the
Programme for Supporting Innovative and Costly Techniques
(STIC in French) with the PRME on cancer. In addition to
the strand for the assessment of innovative technologies, this
programme also includes a strand for the assessment of cancer
care plans that include health technologies. All innovative
health technologies, including drugs, are eligible.
The PRME-K is aimed at health technologies, for diagnostic,
therapeutic or screening purposes, which have already been
validated in a clinical trial. This programme might potentially
improve the present care system. Studies should therefore
include medical and economic assessment of the innovative
technology or the care plan that incorporates it.
Table 11/ Main features of the STIC (2012) and PRME-K
(2013) programmes
Year
Funding institutions
Objectives
Funding
Results:
Proposals submitted
Projects selected
Selection rate
2012 (STIC)
2013 (PRME-K)
2013 Highlights
Collaboration between INCa and the Ministry of Health:
the Programme for Supporting Innovative and Costly
Techniques (STIC) on Cancer has been replaced by the
Programme for Medico-Economic Research on Cancer
(PRME-K), with a strand that assesses innovative health
technologies for diagnosis, treatment or screening, and
a strand that assesses care plans incorporating these
technologies.
2.1.3. SUCCESS OF THE NEW CALL FOR PROPOSALS
FOR EARLY PHASE CLINICAL TRIALS: 9 innovative
molecules from public-private partnerships
The previous collaboration set up with NCI CTEP since 2009
(See Table 12), and the creation of the early phase clinical trial
centres network in 2010, are the two key elements that paved
the way for this new national initiative.
Ministry of Health (DGOS)
To effect significant change in the health
system via the use of technologies for
diagnosis or treatment that have been
validated in a preliminary clinical research
phase. Projects are based on medical and
financial assessment of the innovation.
€0.5 M
2 (projected)
12
3
25%
16
-
In 2013, of 16 letters of intent submitted to the PRME-K,
9 projects were short-listed for final review in November 2013,
for a projected budget of €2 M.
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Table 12/ Milestones in the cooperation between the US NCI and INCa
2010
Cooperation
US NCI/INCa
• Signature of an agreement to facilitate
access to new drugs for patients
in France.
• INCa is the only European Institution
involved in the cooperation with NCI
for these early-phase academic trials.
2011-2012
2013
• February: proof of concept established
• CHONDROG trial: draft publication.
for the CHONDROG trial (inhibitor of
• AKTIL study: 22 patients recruited to
the hedgehog signalling pathway tested
date (51 patients planned).
in advanced stage chondrosarcomas):
recruitment complete (45 patients) and
initial results presented at the ASCO
meeting in 2012.
• November: AKTIL trial (diffuse large
B-cell lymphomas) open for recruitment.
At present, international pharmaceutical companies have
agreed to provide molecules undergoing development for
calls for proposals from INCa for projects intended for the
designated early clinical phase trial centres (CLIP²). The CLIP²
present proposals for academic clinical trials designed to
test drugs for indications or pathologies different to those
intended in the companies’ development plans. After signing
collaboration agreements with different pharmaceutical
companies, INCa has launched calls for proposals on
9 innovative molecules since 2011 (see trends in Figure 16).
Fig. 16/ Innovative drugs and public-private partnerships:
performance indicators
18
16
14
12
10
8
6
4
2
0
17
13
9
6
2
2011
2012
2013
2014
2015
Table 13/ Establishment of a collaboration between INCa and the pharmaceutical companies
2010
Collaboration
with pharmaceutical
companies
• Several meetings organised to discuss a
direct collaboration between INCa and
the pharmaceutical companies.
2011-2012
2013
• Implementation of the process.
• 3 new calls for proposals launched.
• June: positive opinion from the Ethics
• 5 clinical trials due to be initiated.
Committee.
• November 2011: 1st call for proposals
launched by INCa.
• End of 2012: 6 calls for proposals
launched: 1st trial opened for recruitment:
PIK ORL for cancer of the head and neck.
To launch these calls for proposals for early phase clinical trials, 5 steps are necessary from the identification of the molecule to
the beginning of the trial.
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12 weeks
6 weeks
Fig. 17/ Scheme for organisation of public-private
partnerships
Competitive call for proposals
14 weeks
6 weeks
Projects evaluation
Study start
1
2
3
4
5
Molecules identification
• Meetings INCa and pharma companies
• Input from CLIP2 experts about the molecule
• Agreement INCa/pharma
• Independent experts
• Transfer to pharma
Definitive selection
• Answer from pharma
• 2 projects at maximum chosen by INCa
Study launch
Table 14/ Molecules offered to the early phase clinical trials
programme
Objective
Date of
launch of CFP
• To facilitate access to new molecules for patients.
A maximum of 2 projects funded for each molecule.
Funding is provided by INCa and ARC Foundation.
Innovative
Molecules
Proposals
presented
Projects selected
Nov 2011
PI3K/mTor inhibitor
PI3K inhibitor
18
4
1 (Kaposi’s sarcoma)
1 (cancer of the head
and neck)
April 2012
PI3K/mTor inhibitor
Anti CDK 4/6
13
7
1 (myeloid leukaemia
and myelodysplasia)
2 (GIST/metastatic
melanoma)
July 2012
p70/AKT inhibitor
20
2 (solid tumours/
breast cancer)
August 2013
Anti-EGFR
monoclonal antibody
14
Suspended
2013
Oncolytic virus
CFP in
progress
2013
p38 MAPK
inhibitor
CFP in
progress
2013
Anti HER3
CFP
expected
2013
Several contacts in progress with other companies
Table 14 shows the different collaborations established to
date.
2013 Highlights
Partnerships have been created between INCa and the
pharmaceutical companies in relation to 9 innovative
molecules that are currently being tested or due for
testing in the context of early phase clinical trials
following independent assessment. These studies are
being conducted via the CLIP2 organisation.
• Agreements pharma/CLIP2 and INCa/CLIP2
• Supply of the drug
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2.2. ORGANISATION OF CLINICAL RESEARCH,
AND STRENGTHENING OF STRUCTURES AND
INFRASTRUCTURES
The main objectives are as follows:
• to provide support for the development of early phase
clinical research projects through measures that facilitate
coordination and organisation, one such measure being the
designation of the CLIP2 clinical trial centres,
• to increase cooperation between the cooperative groups,
• to increase research capacity by coordinating clinical research
staff members and providing support to the data processing
centres,
• to publicise ongoing clinical research projects, and increase
recruitment to trials.
2.2.1. INITIATIVE: CLIP² NETWORK OF EARLY PHASE
CLINICAL TRIAL CENTRES
Enabling access to innovative drugs is an objective of the 20092013 Cancer Plan. This access is mostly through collaborations
arranged by INCa with the pharmaceutical companies, which
agree to make their molecules available to a structured network
of centres designated by INCa.
59
Table 15/ The INCa-designated early-phase clinical trial
centres – 16 CLIP² centres designated in 2010
Funding
€9 M over more than four years
Partnership
• ARC Foundation
• French National Centre for Management
of Trials on Health Industry Products,
or CeNGEPS (a Public Interest Group)
• Lilly Foundation
Objectives
It is hoped, by means of the CLIP²:
• to obtain better therapeutic outcomes
for cancer patients,
• to improve access to innovation for cancer
patients,
• to test drugs for indications that fall outside
the development plans of the pharmaceutical companies,
• to increase the quality and number of early
phase clinical trials,
• to cover all cancer pathologies (including haematological, paediatric, rare cancers, etc.),
• to increase the visibility and attractiveness
of French academic clinical research to
industry,
• to propose a framework for coordination
between the public and private sectors to
stimulate drug development through
academic research.
Initial impacts
INCa has become recognised as a pioneering institution in
Europe, capable of establishing a coordinated procedure.
An increase in the number of patients recruited in early
phase clinical trials (nearly 300% within three years).
Leadership among clinical research investigators: oral
presentations at major international conferences, more
and more proposals for industry-sponsored phase I trials
in the CLIP² centres.
A growing number of requests from pharmaceutical
companies to participate in this programme.
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CENTRES LABELLISÉS INCa D’ESSAIS CLINIQUES
DE PHASE PRÉCOCE (CLIP2)
Fig. 18/ Map of CLIP2 centres
ParisCHU AP-HP
CHU AP-HP HEGP Saint Louis
Institut Curie
Villejuif
Institut Gustave-Roussy
Centre François-Baclesse
Caen
CHU de Nantes
Nantes
Institut de cancérologie
de l'Ouest
Dijon
Centre Georges-François Leclerc
Clermont Ferrand
CLCC
CHU
CHU de Bordeaux
Institut Bergonié
Lyon
CHU Lyon Sud
Centre Jean-Perrin Centre Léon-Bérard
Bordeaux
Institut Claudius Regaud
Montpellier
Toulouse
Centre Val d'Aurelle
Paul-Lamarque
Guadeloupe
Martinique
Guyane
Marseille
Institut Paoli-Calmettes
La Réunion
Source: INCa, 2011
Drafted by Research Division – INCa – 2011
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Tables 16 to 18 show the number of clinical trials by phase
(I, I/II and II) conducted by CLIP², by sponsor type and number
of patients recruited since 2009. The number of clinical trials
in each phase has increased since 2010.
Table 18/ Percentage of early-phase clinical trials conducted
by CLIP² by type of sponsor
2010
Table 16/ Number of early-phase clinical trials opened
in the CLIP²
61
Total
Academic sponsor
Industrial sponsor
43.5%
56.5%
2011
46%
54%
39.6%
60.4%
2009
2010
2011
2012
2012
Phase I
41
35
43
56
2010
18%
82%
Phase I/II
30
16
20
25
2011
20%
80%
Phase II
159
102
103
106
2012
17.8%
82.2%
Total
230
153
166
187
2010
28%
72%
2011
31%
69%
2012
44%
56%
2010
53.5%
46.5%
2011
57%
43%
2012
50%
50%
Nb of clinical trials
The number of patients recruited to early phase clinical trials
has also increased each year.
Table 17/ Number of patients recruited to early-phase clinical
trials conducted by the CLIP²
Nb of patients
2009
2010
2011
2012
Phase I
186
394
551
802
Phase I/II
117
131
115
222
Phase II
687
1,044
1,122
1,784
Total
990
1,569
1,788
2,808
In early-phase clinical trials, a large part of sponsorship is
provided by pharmaceutical companies, especially for phase I.
The increasing number of trials initiated in 2012 in the 16 CLIP²
also shows increased investment in early phase clinical research
by companies in France. This willingness of the companies to
develop their molecules on the territory may be attributed to
the fact that the CLIP² offer a pledge of quality and know-how
on early-phase clinical trials.
INCArapportGB2013.indd 61
Phase I
Phase I/II
Phase II
These initiatives facilitate access to innovative molecules for
patients in France. The agreement between the US NCI and
INCa and the process implemented between INCa and the
pharmaceutical companies, are new in Europe. This type of
public-private partnership serves as a pilot scheme within
the EPAAC programme. It offers a model for coordination
between European countries. Indeed, cooperation in Europe
will help to save time on recruitment to early phase trials, most
especially where rare cancers are concerned, by combining
scientific progress with quality, and will have a positive impact
on health.
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2.2.2. NEW INITIATIVE: DESIGNATION OF
NEW COOPERATIVE INTERGROUPS
Following its designation of 16 CLIP2 (early-phase cancer
clinical trial centres) in 2010, and of 8 SIRICs (integrated
cancer research sites) in 2011 and 2012, INCa organised
a competitive evaluation aimed at designating cooperative
intergroups. The goals of this action are twofold: to invigorate
clinical research and to improve resources for multidisciplinary
research. This action is conducted in accordance with the
objectives in Measures 1 and 4 of the 2009-2013 Cancer Plan.
Table 19/ Designation of cooperative inter-groups
Funding
Objectives
€0.3 M in 2013
• To increase cooperation between cooperative
groups.
• To involve cancer cooperative groups
in the implementation of clinical research
actions from the 2009-2013 Cancer Plan.
• To increase the number of patients recruited to
cancer clinical trials.
The following cooperative intergroups were designated in
2012:
• the French Intergroup for Thoracic Oncology (IFCT),
• the LYSA-LYSARC lymphoma research intergroup (LYSA, the
Lymphoma Study Association, created by merging GELA
[Adult Lymphoma Study Group], and GOELAMS [East-west
Group for Acute Leukaemias and Other Blood Diseases]),
• the French Myeloma Intergroup (IFM),
• the ORL (ENT) Intergroup, comprising GORTEC (Oncology
and Radiotherapy Group for Head and Neck Cancer),
GETTEC (French Study Group for Tumours of the Head and
Neck) and GERCOR (Multidisciplinary Cooperative Cancer
Research Group),
• the Digestive Tumours Intergroup, which brings together
FFCD (French Federation of Digestive Cancer) and GERCOR,
• the ARCAGY-GINECO Intergroup (Gynaecological Cancer
Research Association and National Investigators Group for
the Study of Ovarian and Breast Cancers).
Two new cooperative intergroups should be designated in 2013.
In 2012 and 2013, cooperative intergroups were designated
via two calls for applications. The first call for applications
was launched in March 2012, and applications assessed by an
international review committee in July 2012. The second call
for applications was launched in March 2013, and applications
assessed by an international review committee in June 2013.
These calls for applications followed a two-year process,
initiated by recommendations from INCa’s International
Scientific Advisory Board and continued at the wishes of
INCa’s advisory committees (Committee of Patients, Friends
and Family and Users and committees of Health professionals)
to mobilise the cooperative groups.
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2.2.3. CREATION OF A NETWORK OF CLINICAL
RESEARCH TEAMS TO CONTRIBUTE TO CANCER
PATIENT RECRUITMENT FOR CLINICAL TRIALS
Since 2006, INCa and the French Ministry of Health have
established 26 Mobile Clinical Research Teams (French
acronym EMRC). The objective is to create conditions that
encourage researchers in hospitals (public and private) to
participate in clinical trials. Approximately 70 FTEs (clinical
research assistants and clinical trial technicians) have been
funded, based in over 160 different hospitals throughout
France.
Table 20/ Network of clinical teams designed to
foster patient recruitment
Funding
Initial impacts
The number of patients recruited to clinical trials doubled
between 2007 and 2012.
In 2012, 160 hospitals reported actual patient recruitment
through the network of clinical teams (at the time of
implementation, over 220 hospitals declared their interest
in receiving assistance from one of these teams).
Thanks to the positive assessment of this programme, the
Ministry of Health increased its funding to €3.4 M (13%)
in 2012.
€3 M per annum, recurrent since September
2007, granted by the Ministry of Health.
Objectives
• To promote participation in clinical trials by
hospital researchers.
• To ensure equal access to clinical trials for
patients in all types of hospitals in France.
• To ensure the good quality of data collected
during clinical trials.
Results
• Reliable quantitative indicators: number
of patients recruited to clinical trials by FTE.
• Qualitative assessment, performed by an ad-hoc
committee, based on comprehensive reports on
the organisation and management of teams.
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2.2.4. NETWORK OF DATA PROCESSING CENTRES
In order to guarantee the quality of data from clinical trials, INCa has been supporting 11 Data Processing Centres (DPCs) for
the last 6 years.
CENTRES DE TRAITEMENT DES DONNÉES
DES ÉTUDES CLINIQUES EN CANCÉROLOGIE
Fig. 19/ Map of data processing centres
Paris
Lille
St Cloud
CTD centre
René Huguenin
Caen
CTD SLS (APHP)
CTD GERCOR
CTD Institut Curie
Villejuif
CTD IGR
CTD du Cancéropôle
Nord-Ouest (CTD CNO)
CTD FFCD
Dijon
CLCC
Lyon
CHU
CTD PARCC-ARA
CTD GELARC
CTD Essais cliniques
cancer Bordeaux
Bordeaux
Montpellier
Marseille
CTD Montpellier
CTD IPC
Guadeloupe
Martinique
Guyane
Cancéropôle PACA
La Réunion
Source: INCa et DGOS, 2011
Drafted by Research Division – INCa – 2011
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Table 21/ Network of Data Processing Centres
Funding
Objectives
Results
• Pilot phase in 2008 (€1 M provided by INCa),
recurrent funding provided by the Minsitry of
health (DGOS) since 2009. In addition, DPCs
receive funding from other sources for research
projects management.
• To provide logistical assistance with data
processing in order to guarantee the quality
of data collected (up to date and quality
controlled): support in designing the
investigation report form, data entry and data
entry control, data traceability and security
specifications, freezing of databases and longterm monitoring of patient data.
• To contribute to project management expertise
by providing randomisation, coordination
of data collection, and data verification and
correction.
• To provide methodological expertise for the
design of protocols, investigation report forms
and data formats, and statistical expertise
for the analysis of results and drafting of
publications.
• Annual activity reports.
• Agreements signed between DPCs and INCa
for a formal assessment process.
65
Table 22/ DPCs’ activities
Extreme values
Headcount (number of full-time
equivalents)
2011
2010
2.0 – 48.5
3.0 – 57.7
Nb of biomedical research projects
• Including phase I to
III clinical trials (%)
• Including international projects (%)
10 – 138
10 – 139
28.6 – 100
0 – 58.3
31.6 – 100
0 - 70
Nb of patients recruited to projects
239 – 2,923
310 – 1,291
Nb of patients recruited to projects
since the creation of the DPCs*
605 – 11,611
716 – 10,512
Projects with academic sponsors
72.9 – 100
72.7 – 100
Projects analysed over the course
of the year (intermediate or final
analysis)
0 – 53
3 – 14
Nb of publications per year
0 – 77
0 – 50
3
5
8
7
8
8
Nb of DPCs providing
methodological support
Nb of DPCs which carried out their
own methodological projects
Nb of DPCs which funded research
projects
*Some facilities already existed before being designated as DPCs in 2007.
Initial impacts
Collaborations in clinical epidemiology and application
to investigator-driven calls for proposals in research
in human and social sciences, epidemiology,
and public health.
Some, in particular, manage no more than 10 studies a year,
whereas others can manage up to 139 studies a year. In addition,
they differ in their ability to provide biostatistical support to
research projects and to conduct their own methodological
studies.
The above table 22 summarizes the spectrum of DTC’s
heterogeneous activities.
DPCs’ HUB initiative in biostatistical methodology for
phase I clinical trials, especially with regard to training
the CLIP2.
DATECAN project: Common assessment criteria for
clinical trials (breast, digestive, urogenital, sarcoma).
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2.2.5. RECRUITMENT OF PATIENTS TO CLINICAL
TRIALS: A 72% INCREASE FROM 2008 TO 2012
The annual survey carried out by INCa with healthcare
organisations in receipt of funding under the Cancer Plans
allowed an evaluation of clinical cancer research activities
carried out in 2012. All of the organisations took part in the
survey. In France, a definite increase was observed in the number
of patients enrolled in clinical trials: a 72% increase from 2008
(base year) to 2012, + 90% for patients participating in academic
trials and + 24% for patients participating in industrial trials
during the same period.
Fig. 21/ Recruitment to cancer clinical trials according to
the type of care provider in 2012 (INCa survey)
11%
Community Centres
(private)
University Hospitals
Cancer Care Centres
Community Centres
(public)
Figure 20 describes the progression of patient recruitment
recorded in INCa’s annual survey, and Figure 21 shows the
distribution of this recruitment among the different types of
care facilities.
37,492
35,000
Nb of patients
30,000
25,000 24,043
26,003
40%
43%
Fig. 20/ Patient recruitment to cancer clinical trials
in France in 2012 (INCa survey)
40,000
6%
From 2008, patient recruitment to trials carried out in
Cancer Care Centres (CLCCs) increased by 78%, and by 27%
in University hospitals (CHUs). The ratio of recruitment to
academic vs. industrial trials is 82/18.
28,167
20,000
15,000
10,000
5,000
0
2004 2005 2006 2007 2008 2009 2010 2011 2012
Nb of patients enrolled - academic trials
Nb of patients enrolled - industry-sponsored trials
All
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2.2.6. INCa’s CANCER RESEARCH CLINICAL TRIALS
REGISTRY
Since 2007, INCa’s cancer clinical trials registry has allowed
easy access to cancer clinical trials conducted in France. It is
freely accessible on INCa’s website, and enables provision of
quality and regularly updated information to patients, health
professionals and the general public.
Table 23/ The cancer clinical trials registry
Objectives
Created in 2007 to provide high quality
information on clinical trials conducted in France.
Results
• 1,546 clinical trials advertised on INCa’s website
in May 2013:
• 506 recruiting trials, sponsored by more than
212 industrial and academic bodies,
• 60% of trials registered are sponsored by
academic bodies.
67
Fig 22/ Number of clinical trials advertised on 15 May 2013
Apr.07
Jul.07
Academic trials
Industry trials
All open trials
Dec.07
Jul.08
Dec.08
Jul.09
Dec.09
Jul.10
Dec.10
June 11
Initial impacts
Regular increase in the number of visitors to the clinical
trials registry.
Development of direct and interactive access for
physicians during multidisciplinary meetings.
Dec.11
June 12
Dec.12
May 13
0 100 200 300 400 500 600 700 800 900 1,000
Since its creation, the INCa cancer clinical trials registry has
been evolving, in an effort to provide information accessible
to the general public, and by facilitating the search and the
selection of clinical trials.
Since the beginning of 2012, visitors to the clinical trials
registry can, with the help of a multi-criteria search engine,
more accurately target their search using different selection
criteria, such as the sponsor or target organ, and can also
apply the geographic criterion using the geolocation module
included in the registry.
Since the new web portal was implemented in 2012 between
40,000 and 70,000 visits/month (new operating system) have
been recorded.
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3
INCREASED SUPPORT FOR RESEARCH
IN BIOLOGY, GENOMICS AND
CANCER SCIENCES
3.1. DEDICATED RESEARCH PROGRAMMES
Table 24/ Features of the research programme
for cancer biology and sciences
Research focused on cancer biology helps to increase the
basic knowledge of oncogenesis, and of the development
and progression of cancer. The understanding of biological
mechanisms opens up new prospects for advances in treatment,
inhibition of resistance mechanisms and the development of
tools through the establishment of projects involving physics,
mathematics or information technology.
Year
In order to promote and support this progress in the long term,
INCa launches a recurrent call for proposals, focused on cancer
biology and sciences, and linked to other organisations funding
research, in order to strengthen the new areas of research.
Moreover, INCa participates actively in the International
Cancer Genomics Consortium (ICGC).
3.1.1. CANCER BIOLOGY AND SCIENCES: THE MOST
IMPORTANT INVESTIGATOR-DRIVEN PROGRAMME
AND BUDGET MANAGED BY INCa
Since 2005, INCa has offered the French scientific community
an investigator-driven call for proposals for the funding of
original and promising projects in different areas and disciplines
of cognitive research in oncology. Leaving the initiative to the
creativity of the researchers, this annual call for proposals
represents 25-30% of the Institute’s total expenditure on
investigator-driven calls for proposals every year.
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2012
Funding institutions
Objectives
Funding
Proposals submitted
Projects selected
Selection rate
2013
INCa
• This call aims at acquiring new knowledge
and developing new tools to open new
therapeutic perspectives.
• Open to all areas of cognitive research
and to scientific disciplines involved in
tumour biology research, this call has been
launched to:
- enable the achievement of original projects,
- strengthen multidisciplinary collaborations,
- develop research in emerging areas.
€15.9 M
€15.1 M
191
32
16.7%
208
33
15.8%
In 2013, 33 projects were selected from the 208 proposals
submitted. At approximately 16%, the selection rate is consistent
with the recommendations of the INCa’s International
Scientific Advisory Board and international standards, in order
to maintain a competitive assessment. Overall funding for the
33 selected projects is €15.1 M.
To comply with the objectives of the call, nearly 87% of the
projects funded aim to study the biological mechanisms of cell
transformation and disease progression, according to the CSO
classification (Figure 23).
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Fig. 23/ Distribution of funding awarded to projects selected
in 2013 for the cancer biology and sciences programme
Fig. 24/ Detailed analysis of the distribution of projects
selected in 2013 by type of study (CSO categories)
8%
1.1 Normal Functioning
1.2 Cancer Initiation:
Alterations in Chromosomes
Biology
5%
Biology €13.2 M
Aetiology €0.7 M
Treatment €1.2 M
The second area of interest in the CSO classification deals
with treatment. Thus 8% of projects study either mechanisms
of response and resistance to treatments, or identification of
new therapeutic targets.
It is interesting to note that in 2013, nearly 5% of the projects
aim to identify and study exogenous factors associated with the
origins and causes of cancer — environmental factors, bacterial
and viral infectious agents, or lifestyle — and the interactions
between these factors and proteins involved in cell regulation.
3%
21%
9%
54%
1.4 Cancer Progression
and Metastasis
Aetiology
A more detailed analysis (Figure 24) shows that over 50% of
the biology projects are focused on processes linked to the
development of cancer and its interaction with the tumour
microenvironment (metabolic adaptations, immunological
microenvironment, invasion, metastasis or angiogenesis).
Approximately 21% of the projects specifically concern
mechanisms of DNA repair and epigenetic regulation of gene
expression, whereas 10% of them study oncogenes and tumour
suppressor genes. Finally, 3% of the selected projects are on
the subject of normal cell function.
1.3 Cancer Initiation:
Oncogenes and Tumor
Suppressor Genes
2.1 Exogenous Factors in
the Origin and Cause of Cancer
Treatment
87%
69
5.3 Systemic Therapies Discovery and Development
5%
8%
Since 2007, 235 projects have been selected from
1,436 proposals submitted to the cancer biology research
programme, for a total budget of nearly €108 M.
The number of letters of intent (LI) submitted in 2013 remains
very high. This programme is the Institute’s most attractive in
number of applications.
These observations lead to two conclusions:
• this programme is fulfilling its goals, namely by supporting
research in a number of diverse areas,
• INCa is consolidating its position as a first-rate funding
agency for cancer-related research programmes, alongside
the French National Research Agency (ANR), which funds
untargeted upstream research (cancer excluded).
This observation demonstrates that the impact of the
environment on specific cancers is becoming increasingly
important in basic research.
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Table 25/ Trends in selection and funding of the research
programme in Cancer Biology and Sciences
Year
Proposals
submitted
Projects
selected
Funding €M
Selection
rate
2007
106
40
14.4
37.70%
2008
145
30
13.5
20.70%
2009
342
27
13.5
7.90%
2010
241
43
20.8
17.80%
2011
203
30
14.9
17.78%
2012
191
32
15.9
16.75%
2013
208
33
15.1
15.80%
Total
1,436
235
108.1
16.36%
There has been a change in the distribution of projects
among the various sub-categories in biology. We note an
increase in the proportion of projects focusing on genetic and
epigenetic regulation of gene expression, especially DNA repair
mechanisms. This trend can be linked to the proliferation of
tools available for carrying out this type of research. Studies
related to the development and progression of cancer based
on interactions with the tumour microenvironment (mainly
on the regulation of processes in metastasis and angiogenesis)
also remain strongly represented.
Projects related to cancer aetiology have increased slightly
since 2012.
The number of projects focusing on early cancer detection
has decreased steadily since the Institute launched a call for
proposals for translational research. No project of this type
was funded in 2013.
3.1.2. SUCCESS OF THE PROGRAMME FOR RESEARCH
IN PHYSICS, MATHEMATICS AND ENGINEERING
SCIENCES RELATED TO CANCER
Following the success of the first call in 2011, the “Physics and
Cancer” call for proposals was renewed in 2012 and 2013,
with a significant increase in the budget for the 2nd and 3rd
editions (+70%). Among the 54 proposals examined this year,
19 were selected. The selection rate is comparable to that of
2012 (37%), as is the overall multi-year budget (€4 M). This
call for proposals is handled by Aviesan for ITMO Cancer as
part of the actions of the Cancer Plan. It is managed in close
collaboration with INCa.
Since the launch of this initiative, a total of 57 research projects
(€10 M) has been undertaken at the interface of biology,
mathematics and physics in the area of cancer.
Table 26/ Features of the programme
Year
2011
Funding institutions
Objectives
Funding
Results:
Proposals submitted
Projects selected
Selection rate
2012
2013
Aviesan - ITMO Cancer
To attract physicists, mathematicians and
engineers toward cancer research in order
to improve the understanding, diagnosis or
therapeutic management of cancer.
€2.6 M
64
17
26%
€4.1 M
€4 M
63, 57 eligible 55, 54 eligible
21
19
37%
35%
Of the 54 proposals examined in 2013, 13 had been submitted
in previous years. Innovative and daring projects proposed by
young consortia were selected.
The number of projects focusing on treatment has remained
stable, and these projects are specifically directed at
understanding mechanisms of action and resistance, the
characterisation of molecular signatures indicating response to
treatment, and the identification of new targets for treatment.
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Fig. 25/ Physics, mathematics, engineering sciences
and cancer
71
Fig. 26/ Physics, mathematics and engineering sciences
in cancer 2011-2013 (€10.8 M)
2013
2012
2011
Dosimetry
Non-nuclear
imaging
4.1M
€
Projects with non specific
type of cancer
Projects with specific
type of cancer
Nuclear imaging
6.7M
€
Instrumentation
Radiotherapy
Among the types of cancer targeted by the development of
new approaches for diagnosis and prognosis, bronchial cancer
and cancers of the central nervous system are the two most
featured types of cancer in projects funded.
Mathematical
models
0
Dosimetry
Non-nuclear imaging
Nuclear imaging
Instrumentation
Radiotherapy
Mathematical models
1
2
3
4
5
6
7
8
Nb of projects selected
2011
2012
2013
2
3
5
8
1
5
1
2
3
5
2
5
2
5
2
3
In the 2011-2013 period, over 60% of the total budget has
been allocated to projects which do not concern any specific
type of cancer, but the development of technologies or models.
INCArapportGB2013.indd 71
For the 2011-2013 period, we have 10 studies for the
development of mathematical models. These projects involve
a total of 25 teams from different research organisations and
distributed throughout the territory.
These models incorporate the multifactorial processes involved
in tumorigenesis (genetic alterations, microenvironment,
etc.) resulting from complex interactions (immunological,
inflammatory, etc.), and recapitulate invasive properties
(progression of tumour growth), as well as properties conferring
resistance to treatment (chemotherapy and radiotherapy).
The models include drug pharmacokinetics, the dynamics of
tumour growth, individual variability, response to treatment,
prediction of treatment efficacy in terms of survival, and
Darwinian evolution of malignancy.
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These models offer computer simulations aimed at:
• mimicking the biomechanical effect exerted by the stroma or
ionic composition and cell volume on the tumour,
• replacing measures of radiotherapy treatment planning
systems (TPS) by a model mimicking respiratory movements,
in order to achieve automated quality control and increase
radioprotection,
• identifying the best in silico protocols for administering two
drugs (antiangiogenic and chemotherapy) for the treatment
of colorectal cancer,
• describing the relations between the appearance/
disappearance kinetics of nuclear DNA repair foci; chromatin
condensation/decondensation, and making immunofluorescence a reliable predictive tool,
• proposing “simulated clinical trials” of survival as a function
of time taken for tumour growth,
• optimising parameters for predicting the radiation doses to
apply in hadron therapy.
2013 Highlights
New call for proposals, “Physics and Cancer” handled
jointly by Aviesan-ITMO Cancer and INCa; first edition
in 2011.
19 projects selected and funded, €4 M
(Aviesan-ITMO Cancer).
Last, projects aimed at perfecting new local treatments have
accounted for nearly 50% of investment committed since 2011.
3.1.3. RENEWAL OF THE INITIATIVE TO SUPPORT
RESEARCH IN SYSTEMS BIOLOGY FOR CANCER
Support for systems biology is a priority set out in the
2009-2013 Cancer Plan, and a first call for proposals was
implemented in 2012, managed by Aviesan for ITMO Cancer
in close collaboration with INCa. The main objectives are to
support upstream multidisciplinary research (mathematics,
physics, chemistry, information technology, biology etc.), in
order to progress to the modelling of complex processes or
integral biology in the area of cancer.
Fig. 27/ Distribution of funding awarded to the physics,
mathematics and engineering sciences in cancer programme
2011-2013 by CSO category
This new call for proposals in France led to over 20 proposals
per call. 8 systems biology projects have been selected since
2012, for a total amount of €3.6 M.
€
1.8M
€
1.1M
0.2M
€
2.5M
€
Biology
Aetiology
Screening, diagnosis, prognosis
Treatment
Scientific models
5.2M
€
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Fig. 28/ Overview of proposals submitted and projects selected
through Aviesan-ITMO Cancer managed calls for proposal,
under the cancer plan 2011-2013
73
3.2. THE GENOMICS PROGRAMME AND THE
EPIGENOMICS PROGRAMME
Genomics combines a set of analyses to enable study of
an individual’s genome, from mapping, identification and
sequencing of genes to the study of gene function and control
of gene expression.
Spontaneous
tumour models
Some cancers may be associated with hereditary transmission
of mutations, known as constitutional mutations; however, in
the majority of cases, the process of tumour development is
associated with the acquisition of somatic mutations.
Physics, maths,
engineering
sciences
Submitted 2011
Selected 2011
Submitted 2012
Selected 2012
Submitted 2013
Selected 2013
Cancer and
environment
Systems biology
and cancer
0
10
20
30
Spontaneous
Physics,
tumour models mathematics,
engineering
sciences
Submitted
2011
Selected
2011
Submitted
2012
Selected
2012
Submitted
2013
Selected
2013
40
50
Cancer and
environment
60
70
80
Nb of projetcs
Systems
biology and
cancer
9
64
2
17
9
57
23
21
4
21
9
4
6
54
22
22
2
19
7
4
Thanks to the arrival of new genotyping and high-throughput
sequencing techniques, it is now possible to identify somatic
alterations characteristic of a tumour.
3.2.1. THE INTERNATIONAL CANCER GENOMICS
CONSORTIUM
The International Cancer Genomics Consortium (ICGC) was
created in 2008, with the following objectives:
• to identify genetic alterations responsible for cancers,
• to identify new therapeutic targets,
• to select active drugs based on tumour genomics.
In order to attain these objectives, the ICGC consortium has
set itself the goal of obtaining a comprehensive description
of the genomic, transcriptomic and epigenomic variations
present in 50 different types and/or subtypes of tumours
which are of clinical and societal importance across the globe.
The minimum sample number defined for these analyses is
500 per tumour type/subtype.
The International Cancer Genome Consortium is one of the
most ambitious biomedical research projects since the Human
Genome Project. This consortium assists the coordination of
large-scale projects, and sharing of generated information. This
will boost the development of effective tools for prevention,
diagnosis and treatment of several types of cancers.
As of September 30, ICGC has received commitments
from funding organisations for 64 project teams in about
15 countries (Asia, Australia, Europe and North America) to
study the genomes of over 24,000 tumours. Other countries
and organisations have planned to join ICGC.
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Table 27/ Main objectives of ICGC and initial results
To collect approximately 500 tumour/normal pairs from each of
the 50 main cancer types.
To perform comprehensive genome analysis of each concerned tissue
(constitutional and somatic): genome, transcriptome and methylome.
To make the data available to the scientific community and public.
Initial results
7th ICGC Scientific Workshop in Heidelberg, Germany
(9-11 December 2012)
64 projects are underway, covering all the main tumour types.
22,670 adults and 2,000 paediatric cases are being analysed.
A new system for data submission has been developed.
A new data portal is expected.
The format for clinical data will be revised.
Highlights of the 7th ICGC Workshop:
• Quality of sequences obtained from paraffin-embedded tumours
appears satisfactory.
• Preliminary data suggest that RNA sequencing could also be performed on tumours that embedded with good conditions.
• Analysis of sequencing data has also been done in 20 laboratories
worldwide, showing that from the same database, laboratories identify between 500 to 2,500 mutations, depending on what filters are
applied in the laboratories.
• This is leading to a harmonisation of data handling processes.
ICGC programme:
initial results
A status report on projects in progress was presented at
the 6th ICGC Scientific Workshop, organised by INCa in
Cannes in March 2012, and at the 7th Scientific Workshop
in December 2012 in Heidelberg: over 22,000 tumour
samples have already been sequenced from around the
world, and the initial results published on the ICGC site.
Initial results on liver cancer demonstrate 4 new genes
frequently mutated in hepatic tumours, which are
implicated in the initiation of hepatocellular carcinomas
(Guichard et al., Nature Genetics, 2012, 694-698).
Study of the physiological role of proteins expressed
by these genes and signalling pathways is underway.
Teams participating in the breast cancer genomics
programme, including teams from France, have been
able to monitor tumour development in 21 breast
cancers through an extremely detailed and unequalled
analysis of sequencing results for the complete repertoire
of these tumours. These new algorithms, developed
specifically, shed light on the complexity of events leading
to oncogenesis, and help to analyse their potential
association with intratumoural heterogeneity (Nik-Zainal
et al., Cell, 2012, 979-993 and 994-1007).
Results from programmes for liver and breast cancers have
very strong implications for improving the understanding
of tumour development, and open up new prospects for
targeted treatment.
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Table 28/ Genetic data produced by the ICGC consortium
Total samples in progress
Total samples submitted to
Data Coordination Centre
Tumours
Controls
Tumours
Controls
Consenting donors
19,339
9,470
334
332
Samples for which the project confirmed
diagnosis
16,737
8,830
334
332
Pathology/annotation (primary tumour)
16,685
2,315
216
210
Clinical annotation (donor)
8,173
2,190
321
319
Exome
3,336
3,707
254
254
Whole genome
1,098
1,062
95
93
Copy Number Variation
7,001
5,820
50
52
Structural rearrangements
315
285
8
8
Transcriptome (RNA-Seq)
2,610
207
17
0
Transcriptome (Arrays)
3,042
182
1,915
4
miRNA
5,750
343
945
1
Methylation (Array)
4,204
851
1,470
0
Methylation (NGS)
49
14
70
0
A Global Alliance has been created on the fringes of this
international programme, to promote the sharing of genomic
and clinical data. Its main objective is to hasten medical
advances, by encouraging widespread access to genomic and
clinical data through the definition of a common framework
of technical, operational and ethical standards, in order to
ensure the secure and responsible interoperability of genomic
research platforms. INCa is a founding member.
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3.2.2. ICGC DATA PORTAL
In 2012, ICGC published genetic data from a series of studies
on different types of cancer. The data can now be used by
researchers worldwide, to help drive forward their own research
projects. The latest version of data from the consortium
includes the initial results from the study on myelodysplastic
syndrome in the UK, together with work on liver cancer in
France, and a project on paediatric brain tumours in Germany.
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3.2.3. OUTCOME OF FRENCH PARTICIPATION
IN THE INTERNATIONAL ICGC CONSORTIUM
The ICGC programme is an opportunity in the area of
genomics research which has been seized by INCa and AviesanITMO cancer. From the coordination of biological resources
to investment in high-throughput sequencing platforms, all
stages of genomic analysis are brought into play, with major
qualitative and quantitative challenges.
Liver cancer genome programme
(Jessica Zucman, UMRS U674)
Work conducted by Jessica Zucman-Rossi’s team (Inserm
Unit 674, “Functional Genomics of Solid Tumours”) has
identified 4 genes and signalling pathways, which had not
been previously described in liver tumours (ARID1A, RPS6KA3,
IRF2 et NFE2L2, Guichard et al., 2012, Nature Genetics, Vol
44,6,694-700).
The dissemination of data should help researchers around
the world to acquire new knowledge on mechanisms of
cancer development, and open new avenues for research on
therapeutic targets.
Furthermore, since there are important genetic and lifestyle
differences between patients, project data will be compared.
In 2013, 4 projects for functional validation were launched for
a period of one year:
• endoplasmic reticulum/oxidative stress signalling in
hepatocellular carcinoma: contribution of misfolded secreted
protein load,
• activation of the Wnt/-catenin pathway in hepatocellular
carcinomas not mutated in the CTNNB1 gene,
• role of chromatin remodelling in hepatic carcinogenesis,
• role of RSK2 protein function loss in hepatocellular
carcinomas.
This is the case, for example, with the French project, which
will compare cases of prostate cancers in patients in France
and the French West Indies, or projects on breast cancer in the
UK, France and the US.
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Breast cancer genome programme
(Gilles Thomas, Synergie Lyon Foundation)
The objective, by May 2014, is to get a whole genome analysis
(whole genome, epigenome, RNA) of 75 HER2+ cancers (15%
of breast cancers).
Comparative analysis of multiple tumours of the same tumour
type shall lead to the identification of recurrent mutations,
which may have been the source of clonal selection (driver
mutations), and identified altered metabolic pathways.
In parallel, a study of the constitutional genome on nearly
8,000 samples of breast cancer, including 3,000 HER2+
cancers is to begin in 2013 and aims to identify risk factors
specific to this tumour with poor prognosis.
Prostate cancer genome programme
(Olivier Cussenot, Hôpital Tenon)
January 2011 saw the launch of the prostate cancer genome
project “Molecular dissection of Aggressive Prostate Cancer
according to microenvironment and genetic background.” This
study should show whether aggressiveness-specific molecular
events (progression and metastasis, resistance to castration,
etc.) are early implemented in disease evolution.
77
Ewing’s sarcoma genome programme
(Olivier Delattre, Institut Curie)
The goal of this project is to identify genomic events involved
in the development of Ewing’s sarcoma. There are plans to
perform whole genome sequencing as well as RNA sequencing
on a series of 100 Ewing’s sarcomas, comparing metastatic
cases with cases that were localised at diagnosis and little
evolutive.
The first 15 samples were sequenced at the Centre for Genomic
Analysis (CNAG) in Barcelona, and 85 others are in progress.
Rare tumour genome programme
The last programme will concern the sequencing of several
types of rare tumours.
The first project, which has just been defined, involves
retinoblastoma.
Two other projects are being considered, on uterine
carcinosarcomas and leiomyosarcomas.
The project plans to include 100 tumour specimens
from aggressive prostate cancer (high grade) collected at
prostatectomy; to sequence whole genome and validate the
identified events. The programme is being done in collaboration
with the National Centre for Genomic Analysis (CNAG) in
Barcelona.
The first step involves the sequencing of DNA from 15 matched
tumour/normal pairs from Caucasian patients and from
15 matched tumour/normal pairs from patients of Caribbean
origin, whose forms of prostate cancer are more aggressive.
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4
INCREASED SUPPORT FOR RESEARCH
IN SOCIAL SCIENCES, EPIDEMIOLOGY
AND PUBLIC HEALTH
One of INCa’s goals is to bring social sciences and public
health research applied to oncology in France up to the best
international standards. In line with the Cancer Plan, particular
efforts are being devoted to increasing basic and health
intervention research in order to reduce social inequalities
related to cancer, and increase the impact of cancer prevention
measures, participation in screening and access to care.
Fig. 29/ RISP call for proposals: themes of projects
submitted since 2010
11%
To achieve this goal, INCa has established links with other
national organisations in order to combine experience and
know-how in deciding how to modify our approach to
environmental and behavioural risk factors.
INCa’s action complements exceptional support provided
nationally to large cohorts under the National “Investment for
the Future” programme.
4.1. THE RESEARCH PROGRAMMES
4.1.1. HEALTH INTERVENTION RESEARCH IN
POPULATION: 2013, A YEAR OF CONSOLIDATION
In 2013, INCa continued to support health intervention
research in population (RISP), via a dedicated call for proposals
existing since 2010.
Figure 29 indicates the distribution of the themes for proposals
submitted (N=76); 11 projects were selected of all calls for
proposals.
INCArapportGB2013.indd 78
3%
Primary prevention
Secondary prevention
Care
Post-cancer
Others
20%
21%
45%
The three 2013 projects concern:
• preventing smoking among young people (“peer” education),
• reducing in exposure of farmers to pesticides,
• reducing in inequalities regarding the burden carried by
caregivers of elderly people with cancer.
This call for proposals in health intervention research will
be replaced in 2014 by the enlisting of all players involved in
prevention and organise a joint call with IReSP (French Public
Health Research Institute) for research proposals in primary
prevention. The other funding partners are ANRS (French
National Agency for Research on AIDS and Viral Hepatitis),
CNAMTS (French National Health Insurance Fund for Salaried
Workers), CNSA (National Solidarity Fund for Autonomy),
DGS (French Directorate General for Health), ARC Foundation,
INPES (French National Institute for Prevention and Health
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Education), MILDT (Inter-ministerial Mission for the Fight
against Drugs and Drug Addiction), and RSI (Independent
Workers’ Health Insurance).
Finally, INCa’s contribution to different working groups in
relation to health intervention research in population has
revealed the important need for decision-makers and public
health researchers to work more closely (to produce conclusive
data; to select effective interventions, etc.).
4.1.2. THE RECURRENT PROGRAMME FOR SOCIAL
AND HUMAN SCIENCES, EPIDEMIOLOGY
AND PUBLIC HEALTH RESEARCH
A major objective of the 2009-2013 Cancer Plan is to bring
together the community of researchers in social sciences,
epidemiology and public health so that they undertake a
larger number of research projects in these disciplines. Beyond
coordination carried out with the canceropoles in order to
increase the size and quality of projects, and efforts made to
communicate with the community through INCa colloquia,
this support is provided through a recurrent call for proposals.
These “investigator-driven” calls are nonetheless led by the
Cancer Plan to draw the attention of researchers to important
or poorly explored questions.
Of 54 investigator-driven research projects submitted, 20 were
selected (35%), for a total amount of €4.81 M (average:
€240,000 per project), i.e a significant increase from 2012.
Research themes:
• psycho-oncology (perceived health, caregivers, quality of life,
neurology),
• sociology (social inequalities, care plans, post-cancer, re-
entering the workforce, informing relatives at risk, elderly
patients),
• economics (prevention, general practitioner, caregivers for
elderly patients),
• physical activity, genetics and ethics, care plans and
trajectories,
• risk factors (nutrition, reproduction, occupational and
environmental exposures), tertiary prevention (adjuvant
treatment),
• care trajectories, innovations.
A little over half of the projects are clearly multidisciplinary.
Fig. 30/ Human and social sciences, epidemiology and public
health research programme distributed by CSO category
6%
Table 29/ Main features of the recurrent Social and
Human Sciences, Epidemiology and Public Health Research
programme
Year
2012
Funding institutions
Objectives
Funding
Proposals accepted
for review
Projects selected
Selection rate
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INCa
To enlist the research community to work on
projects in social and human sciences,
epidemiology and public health.
€4.81 M
41
16
39%
54
20
37%
17.1%
Epidemiology
Primary prevention
Secondary prevention
Tertiary prevention
Human and social sciences,
economics
Biostatistics and
methodology
2013
€3.88 M
79
57.7%
8,6%
7%
3.7%
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4.1.3. NEW INITIATIVES DEVELOPED IN
COLLABORATION WITH OTHER ORGANISATIONS TO
SUPPORT RESEARCH ON ENVIRONMENTAL RISKS
Since 2012, a dedicated call has been launched by ITMO Cancer
to strengthen support for research in the area of environmental
risk factors: 45 proposals have been submitted.
Table 31/ Main characteristics of the Research Programme
in Employment-Health- Environment
Year
Funding institutions
Table 30/ Effects of Exposure to Environmental Risk Factors
for Cancer
Year
Funding institutions
Objectives
Funding
Projects submitted
Projects selected
Selection rate
2012
2013
Aviesan - ITMO Cancer
To improve the knowledge of delayed effects
of exposure of individuals to risk factors
associated with the environment,
in terms of analysing the risks of cancer
occurrence and progression.
€2.4 M
€2.8 M
23
9
39%
22
7
32%
The 2013 call for proposals for the National Research
Programme in Employment-Health- Environment saw a 2-fold
increase in the number of proposals submitted in the area
of assessment and analysis of environmental risks for cancer,
indicating a strong motivation of the scientific community to
work on these subjects.
In 2013, a total of 9 projects from this call were cancerrelated; 6 of these were funded under the Cancer Plan, and
the remaining 3 were supported by the Ministry of Labour
and ADEME (French Environment and Energy Management
Agency).
Objectives
2011
2012
2013
ANSES (French Agency for Food, Environmental and Occupational Health Safety) –
Aviesan - ITMO Cancer.
To evaluate and analyse environmental risks
for human health in the general population
or at work. From emerging risks to known
risks, which can generate complex scientific
polemics, and for which a single approach
can include concepts, methods and tools
from different disciplines.
Funding
€1.26 M
€1.2 M
€0.85 M
Results:
Proposals submitted
Proposals short-listed
Projects selected
Selection rate
31 letters
of intent
9
9
29%
20 letters
of intent
9
7
35%
44 letters
of intent
20
6
14%
Studies selected this year included the role of UV exposure
in the occurrence of malignant haemopathies, the role of in
utero exposure to pesticides in the occurrence of childhood
acute leukaemias (AL), the impact of multiple exposures to
carcinogenic substances and the search for biomarkers for
exposure to mixtures of pollutants or to families of (known
or suspected) carcinogenic pollutants, the impact of
environmental, occupational and behavioural risk factors in
relation to genetic predispositions, models for quantitative
assessment of the excess risk for cancer of the respiratory tract
from occupational and environmental exposure to certain
carcinogenic agents, especially at low doses.
2012-2013 Highlights
36 projects funded in human and social sciences, public
health, epidemiology and health intervention research.
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2 TGIR COHORTS
E3N
Funding for E3N enables the collection of saliva specimens
from cohort subjects in order to obtain their DNA.
Constances
The meeting for the official launch of the cohort took place
on 7 March 2013.
INCArapportGB2013.indd 81
Objectives
Funding institutions
Year
Funding
In recognition of their major role in research in epidemiology
and public health, the 2009-2013 Cancer Plan has made
support for cohorts a specific action of the measure regarding
environmental and behavioural risks (Action 3.5 of the Cancer
Plan). INCa has entered into a partnership with IReSP (French
Public Health Research Institute) and ITMO Public Health
(Multi-organisation Thematic Institute dedicated to Public
Health). ITMO Public Health and IReSP have been entrusted
by the Ministry of Research with the scientific monitoring of
all cohorts supported under the TGIR (Very Large Research
Infrastructures) and Investment for the Future schemes
(16 cohorts in all).
Table 32/ Support provided to Cancer Cohorts
Selected
projects:
4.2. RESEARCH ORGANIZATION,
STRUCTURES AND INFRASTRUCTURES
FOR EPIDEMIOLOGY AND PUBLIC HEALTH
RESEARCH
81
2009
TGIR
2011
2012
Complement to
Grand Emprunt
(Great National Loan)
To fund structural investment
in infrastructure tools for
epidemiology and public health:
large national cohorts.
€2 M
E3N,
Constances
€1 M
€1 M
5
Canto, COBLAnCE,
Cryostem,
E4N, Hope-Epi
2012-2013
INCa/IReSP: Ancillary studies (2012)
INCa/IReSP:
Research in mathematics and statistics
applied to cancer.
To fund additionnal
studies on tools for
large infrastructures.
€0.86 M
(ancillary studies)
€1.3 M
(mathematics
research).
8 projects selected
9 projects selected.
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Table 33/ Main characterictics of the “Investment for the Future” cohorts
Funding
Objectives
Expected
results
Progress
report for
2011-2012
E4N
Canto
Hope-Epi
COBLAnCE
Cryosystem
€7.95 M
€18.8 M
€5.6 M
€2 M
€3.4 M
• To analyse family
and genetic factors in
women recruited to
the E3N cohort.
• To assess the effects
of exposure to certain
environmental factors
in early life on people’s
health as adults.
(prospective cohort
of young adults).
To study the chronic
toxicity of cancer
treatments in 20,000
patients suffering from
localised breast cancer,
and identify indicators
predicting chronic
toxicity.
• To identify
environmental and
genetic risks associated
with childhood cancer.
• To identify the
disparities between
treatments, and
the short- and
long-term side effects.
To identify biomarkers to
predict bladder cancer
progression by monitoring epidemiological,
economic, urological,
pathological and
molecular biology
data from 2,000 cancer
patients, from 17 clinical
centres throughout
France, for over 9 years.
To characterise graftversus-host disease
(transplant rejection)
by taking samples of
immunological stem cells
from transplant patients,
in order to understand
the pathophysiology of
this disease, the predictive factors linked to its
occurrence, the response
to immunosuppressive
agents, and the longterm prognosis.
• Discovery of biological
and genetic risk factors
for certain diseases for
the general population.
• Implementation of procedures for prevention.
Development of new
treatments, improvement of quality of life
and reduction of health
costs.
• Optimisation of
treatments, and
improvement in patient
quality of life following
treatment.
• Several HOPE-Epidemiology partners are
directly involved in
international research
ACCIS, ENCR, IARC,
Eurocare, FCSS (PanCare) and CLIC1.
Work on more accurate
and earlier diagnoses,
and possibly on bettertargeted therapies.
A reduction in complications associated with
bone marrow transplants
used to combat blood
cancers, and increased
success rates as a result.
Design, print and mail
the questionnaire used
to recruit E4N subjects.
Initial pilot phase carried
out with this questionnaire, 5 technicians
hired.
Data collection from
209 female patients
recruited to the cohort.
The total cohort is
currently 1,300 female
patients.
The HOPE-EPI project
55 patients have been
comprises 3 strands led recruited in the first
recruitment centre.
by 3 teams.
• 25,000 patients
recruited-follow-up of
11,572 patients
(5- year survivors).
• 1,545 patients
recruited with full eCRF
from 2004 to 2011,
including
• 379 patients recruited
in 2011.
Patient recruitment has
recently begun: 4 partner
transplant units are operational for this project,
and 17 others will open
progressively during
the 1st half of 2013.
1 - ACCIS [Automated Childhood Cancer Information System], ENCR [European Network of Cancer Registries], IARC [International Agency for Research on Cancer], Eurocare), FCSS
(PanCare) and CLIC (Cancer and Leukaemia in Childhood).
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2011 CALL FOR PROPOSALS, “SUPPORT FOR
SECONDARY ANALYSIS OF DATA COLLECTED
IN THE CONTEXT OF LARGE STUDIES
IN CANCER-RELATED EPIDEMIOLOGY”
Eight proposals were selected for funding: four 24-month
projects, three 12-month projects, and one 7-month project.
Seven projects are currently in progress. Of these 7 projects,
4 underwent a mid-term review in December 2012. One project
is finished. The concluding seminar for this call (presentation
of results) is planned for mid-2014.
The cost of
chemotherapy
Chimiotherapie-2012-CVT (4)_44 pages 22/07/13 11:06 Page1
SOINS
Mesure 21
Situation
de la chimiothérapie
des cancers
The total amount spent
on hospitalisation
for chemotherapy is
increasing in France.
COLLECTION
États des lieux & des connaissances
RAPPORT 2012
ANALYSE DES TENDANCES RÉCENTES
DE LA PRATIQUE ET DES DÉPENSES
DE LA CHIMIOTHÉRAPIE DES CANCERS
EN FRANCE
As a long –term illness in
France cancer expenses is
fully covered by the State;
during a hospital stay,
funding of administrated
drugs is included in a flat
fee that covers all service of
the patient care. However
expensive drugs used for innovative therapies (e.g.
intravenously administered targeted treatments) are not
included in this fee, but entered in a supplementary list
(and paid for as long as the prescription is in accordance
with the regulatory framework for proper use).
CYTOTOXIQUES, AUTRES ANTICANCÉREUX,
THÉRAPIES CIBLÉES (INHIBITEURS
DE TYROSINES KINASES ET APPARENTÉS,
ANTICORPS MONOCLONAUX)
ET HORMONOTHÉRAPIES
www.e-cancer.fr
INCArapportGB2013.indd 83
83
2012 CALL FOR PROPOSALS, “SUPPORT FOR
RESEARCH IN MATHEMATICS AND STATISTICS
APPLIED TO CANCER”
Nine projects were selected for funding.
OTHER FUNDING
Under the 2012 call for proposals, “Therapeutic Education
of the Patient,” one cancer-related project was selected for
funding, and will be funded from the Cancer Plan budget.
“Development and Evaluation of a Therapeutic Educational
Intervention in Relation to the Compliance of Patients Receiving
Hormone Therapies as Part of Breast Cancer Treatment.”
Total cost of cancer drug in 2011:
about €2.8 billion, distributed as follows:
• in hospital: chemotherapy regimens from the
supplementary list €1.44 billion, and those included
in fees, about €70 M,
• in the community: €1.3 billion, for orally
administered cancer drugs.
Expenditure on targeted therapies is increasing
(concentrated on relatively few molecules),
• in hospital, 5 molecules represent 75% of
expenditure on the supplementary list (trastuzumab,
rituximab, bevacizumab, pemetrexed and cetuximab),
• in the community, approximately 50% of
expenditure relates to targeted therapies (such as
imatinib, erlotinib, sunitinib, sorafenib and dasatinib).
In conclusion, the estimated cost of €2.8 billion in 2011
agrees with data from the ANSM (French Medicine Agency)
report “Analyse des ventes de médicaments en France”
[Analysies of drugs sales in France], Oct. 2012, which shows
sales turnover for the health industries by treatment area.
According to the range of anticancer drugs employed, this
turnover should be between €2.4 and 3.6 billion.
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5
THE CANCEROPOLES
Following the assessment process led by the French Evaluation
Agency for Research and Higher Education (AERES in French)
in 2011, INCa designated the 7 canceropoles for the 2011-2014
period. The end of the designation agreement in June 2014,
and the announcement of the third Cancer Plan have provided
an opportunity to take stock of the actions carried out by the
canceropoles.
The creation of the canceropoles was one of the first
organisational measures undertaken by the first Cancer Plan
in 2003, and represented a major action for strengthening the
national research dynamic, based on the enlistment of players
at regional and interregional level.
After 10 years of existence, the canceropoles have thus acquired
a geographical and institutional base which is recognised.
This allowed the generation of strong investment from local
governments, industries and the ERDF (European Regional
Development Fund), which find in the canceropoles a point
of contact for oncology research support (regional funding:
€10.3 M in 2012, INCa funding: €9.1 M).
INCArapportGB2013.indd 84
ASSESSMENT OF THEIR ACTIONS IDENTIFIES THE
FOLLOWING ELEMENTS:
• the canceropoles have developed an ability to support the
organisation and pooling of technology. Among other things,
they have established an operational coordination of biological
resources around the creation of the Regional Virtual Tumour
Banks, aimed at rationalising the creation of collections and
harmonising practices employed in the use of biological
resources for research,
• the canceropoles have also contributed to the optimisation
and growing prominence of technological platforms through
joint funding of equipment and staff, technological support,
training, etc. A number of actions created to meet local
objectives have been deployed in an interregional or even
national configuration, such as, for example, coordination
of the tumour banks, sharing of expertise in experimental
histopathology and virtual microscopy, and meeting needs in
relation to bioinformatics,
• the scientific leadership actions conducted by the canceropoles
have enabled support for academic/industrial partnerships,
particularly under schemes for funding and maturation of
projects, both nationally (MATWIN) or regionally (CLARA
PdC*),
• through their knowledge of the area, the canceropoles have
acquired a strong ability for mobilising teams and a strong
ability to respond to emerging and innovative subjects. They
have thus developed experience in making research projects
emerge and supporting them. As an illustration, from 2008 to
2012, 296 emerging projects were funded by the canceropoles
(excluding Ile-de-France), 60% of which subsequently obtained
funding from national calls for proposals.
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Table 34/ Funding awarded by the Canceropoles to platforms and organisational programmes, 2008-2013
Funding awarded by the canceropoles
for the development of platforms,
2008-2013 (in €)
Nb of platforms
funded by the
canceropole
Funding awarded by the canceropoles for
the establishment of shared resources for use by
the scientific community, 2008-2013 (in €)
Amounts awarded Platforms funded
to platforms by with a designation
the canceropole
(IBiSA, INCa)
Total Resources/
Organisational
programmes
Tumour banks
Histo-pathology
CLARA
7
56,000,000*
5
CLARA
1,535,000
PACA
20
2,630,335
12
PACA
2,481,000
114,000
998,000
NO
4
560,000
2
NO
179,045
148,545
30,500
555,000
GSO
9
1,423,000
GSO
2,058,000
1,300,000
GO
6
345,138
5
GO
1,098,525
77,892
GE
3
455,000
2
GE
400,000
200,000
49
61,413,473
26
IDF
Total
IDF
2,597,342
170,000
Total
10,348,912
2,010,437
180,000
1,763,500
*The CLARA canceropole has enabled funding for heavy equipment (MRI for example) to develop new research activities in an imaging platform.
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The assessment of the canceropoles’ actions, together with
organisational developments in cancer research, has led INCa
to propose a redefinition of the scope of the canceropoles’
mission under the 2014-2018 Cancer Plan, centred on
their ability to organise scientific leadership and to help in
the development of innovative projects and organisational
actions.
3 special scientific
leadership roles
have been entrusted to the canceropoles
to meet these priorities
• Support for the development of new projects through
Scientific leadership is critical to research, since it allows
the mobilisation and bringing together of skills and
expertise, in a spirit of institutional, disciplinary and sectoral
decompartmentalisation. From their knowledge of the area
developed over 10 years, the canceropoles remain well placed
to provide this scientific leadership country-wide, by uniting
the research players through the various scientific areas and/
or specialised relevant working groups.
This scientific leadership will have to be guided by the priorities
framing the specific actions of the canceropoles, to suit the
regional or interregional context.
7 priorities for the canceropoles
• To support the development of new projects
and organisational actions.
• To increase the scientific multidisciplinarity
and complementarity of expert opinions.
• To increase the competitiveness of research proposals
submitted in response to CFPs.
• To increase the detection of innovation
and subsequent technology transfer.
• To increase support for young researchers.
• To seek regional joint funding.
• To contribute to development of European projects
through forging links with European regional bodies.
INCArapportGB2013.indd 86
the establishment of dedicated calls for proposals for
each canceropole
These calls for proposals will have to especially focus on
projects in disruptive technology and multidisciplinary
projects, and will preferably be oriented toward young
researchers. They will also have to help foster research
in key areas in which France is lagging behind (human
and social sciences, epidemiology and public health, for
example).
• Testing organisational actions
In order to participate in development of research and
pooling of resources, the canceropoles must stimulate
the development of new technologies in their area
(support to platforms for a limited period of time).
Moreover, INCa may support and guide the
canceropoles, to create a force for proposing that
organisational actions initiated at regional level be
deployed nationally. Conversely, the canceropoles may be
requested to contribute to the local establishment
of new organisational actions led by INCa.
• Support for projects
Apart from the consolidation phase for preliminary
results (emergence), the canceropoles have the ability
to support the development of research projects by
making specific offers to researchers (support for project
management, referral to contacts for adding economic
value, preparation of European projects, and specific
support for young teams).
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6
MAIN EVENTS IN 2012-2013
PRIORITY ACTION OF THE
2009-2013 CANCER PLAN:
THE 4th INTERNATIONAL
R&D DATING
The 4th International R&D
dating, in 2012, focusing
on “Cancer: Research &
Innovations” placed under
the patronage of the French
Prime Minister, was organised
in partnership with Aviesan
and ARIIS (French Alliance for
Research and Innovation in
© Agence Fizzy
Health Industries). The meeting
brought together 28 drug and biotechnology companies and 54
academic researchers, the latter representing the excellence of
French research into understanding malignant processes.
This meeting provided an opportunity to increase the number
of collaborations between researchers and companies attending
the event. Collaborations continued after the event; 35 new
contacts were made for 13 selected researchers, involving
14 companies. This meeting also helped to formalise existing
contacts.
The Prime Minister, Mr Jean-Marc Ayrault, made a specific
address to this meeting.
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87
SEMINAR TO PRESENT RESULTS OF PROJECTS ON
TRAINING IN TRANSLATIONAL CANCER RESEARCH
Over 80 participants attended the seminar on translational
research training, organised by INCa on 27 November 2012,
to present the results of projects funded under the Cancer Plan,
and discuss the challenges and opportunities in France and in
Europe.
Mr Roger Genet, General-Director of Research and Innovation,
introduced this seminar, recalling the support provided by his
Ministry to actions deployed by INCa to promote translational
cancer research in France.
Of the 103 recipients of training grants, 8 presented their
research results, and spoke about the impact of their training
on their career plans.
Begun in 2007 and funded by INCa until 2010, and subsequently
by Aviesan’s ITMO Cancer, the recurrent call for applications
for support for translational cancer research training has
allowed investment of nearly €6.7 M in 103 training projects.
This call for applications is intended for physicians, dentists,
veterinarians and pharmacists undertaking a post-graduate
training and with an interest in research (Master 2, doctorate,
post-doctorate in France or abroad).
A survey carried out by INCa of 50 grant recipients who had
completed their project, and a survey by AERIO (French
Association of Residents in Oncology) indicated overall
satisfaction among the students in having completed this
double training as medical researchers, but also indicated
practical difficulties experienced in making a sustained
investment in research work, especially during the first years
of medical practice.
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Roger Genet (DGRI) opened the seminar
on translational research training on 27 November
2nd International Forum
on prospective in cancer research and treatment
In contrast to the many cancer-related meetings held each
year to present major advances in both basic and clinical
research, the objective of this international forum is to
bring together researchers, clinicians and representatives
from the pharmaceutical companies to discuss some
major areas from many perspectives, and to identify ways
of spurring the transformation of discoveries into future
treatments. In 2012, a special session was also organised in
order to strengthen the coordination of interdisciplinary
approaches.
The outlook for cancer genomics enabled debate on the
“perfect storm” as described by Thomas Hudson (Ontario
Institute for Cancer Research), brought about by changes
in sequencing technologies, and the need to anticipate
a flood of genomic data. To take a small step back from
this surge, the debate was joined by, in addition to Dr.
Hudson, a philosopher, Barbara Prainsack, from King’s
College, London, a physician, Jean-Yves Blay, director of the
INCa-designated integrated cancer research site (SIRIC) in
Lyon, one of the sites designated by INCa at national level
in France, and late David Cox, Vice-President of a large
pharmaceutical company (Pfizer).
INCArapportGB2013.indd 88
Two main future directions were identified from this
discussion, namely the need for a “return to biology,”
in order to better understand the processes behind
the many genomic alterations observed, and the need
for collaboration at all levels, given the explosion in
the classification of cancers generated by the molecular
characterisation of tumours.
The involvement of patients in such projects obviously
raises many ethical and social problems (Toward Precision
Medicine: Building a Knowledge Network for Biomedical
Research and a New Taxonomy of Disease, 2011). According
to Dr Prainsack, their resolution will first require empirical
research on the real needs and expectations of individuals.
And the solutions will not be “politically robust” without
additional collaborative work with researchers in social
science to guarantee equal access to these new forms of
personalised medicine. The final report on a European
project dealing with this subject, jointly led by Dr.
Prainsack, will soon be published (Personalised Medicine
for the European citizen - towards more precise medicine
for the diagnosis, treatment and prevention of disease).
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SCIENTIFIC LEADERSHIP BY INCA AND
THE CANCEROPOLES IN 2012-2013
When the designation agreement was signed in 2011, INCa
and the canceropoles established specialised working groups
with pre-defined strategic and operational challenges.
Two working groups in Human and Social Sciences, Epidemiology
and Public Health, with a focus on Nutrition and social
inequalities, are mainly aimed at facilitating the emergence of
collaborative research projects in order to boost the production
of French research in these areas.
2 colloquia were organised in 2012:
• a workshop, by the working
group on Nutrition in
collaboration with NACRe
(French National Cancer
Diet Research Network) was
organised on the fringes of
INCa’s International Colloquium
on Nutrition on 20 June
2013, it brought together
110 participants in order to
foster the development of
research projects in nutrition
and cancer,
• a workshop organised in June
2012 by the working group
on Social Inequalities. Three sessions were organised on
this occasion (resumption of work, determinants and care),
in order to facilitate discussion on these themes, identify
obstacles, and define actions needed to improve research in
these different areas.
As part of INCa-canceropole collaboration to organise
colloquia, a seminar was organised in June 2013 in Lille on an
emerging theme, namely the impact of cancers and treatments
on cognitive function (see poster). This brought together 105
individuals around measures taken by the main French players.
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7
INTERNATIONAL DEVELOPMENTS
7.1. EUROPEAN PROGRAMMES
FOR CANCER RESEARCH
EPAAC – EUROPEAN PARTNERSHIP FOR ACTIONS
AGAINST CANCER
The European partnership for actions against cancer
(EPAAC) was constituted and started working in 2010, after
the communication from the European Commission to the
European Parliament, the Council and the European Economic
and Social Committee (COM(2009) 291). This communication
provided the strategic direction to future European cancer
activities. EPAAC’s work package 8 (WP8) was given the
goal of developing a concerted approach for coordination of
one third of cancer research from all funding sources across
Europe by 2013. This goal, however, was deemed extremely
ambitious from the outset given the limited duration of the
project and the level of resources allocated. The consortium
leaded by INCa and ECCO, the European Cancer Organisation,
consequently decided to focus their efforts on selected areas/
topics were there was a clear need for coordination. Input from
the cancer community was sought as well as from funders to
gain crucial knowledge about the mechanisms for decisionmaking, funding and execution of cancer research. Areas of
cancer research expected to bear most benefits from European
coordination were identified and prioritized for further actions.
Important guiding principles for coordination emerged from the
intelligence-gathering exercises and stakeholder meetings. Two
areas were deemed highly relevant for potential pilot initiatives
which could lead as examples of new coordination ways: a)
clinical trials aiming at personalised cancer medicine and b)
outcomes research.
A specific focus on the pilot project which allows patients an
accelerated access to new drugs under development, leaded by
the INCa in the area of early phase clinical research is made below.
This proposed pilot project aims at testing a novel approach
to European cancer research coordination by opening to other
INCArapportGB2013.indd 90
countries and/or interfacing national coordination programmes
that have proven of highest utility. Several reasons contributed
to select the area of early clinical studies (e.g studies are now
decisive from early phases of clinical development for the more
complex trials and targeted populations; large countries have
started to structure clinical cancer research activities through
coordinated networks and programmes, and subsequent publicprivate partnerships have become critical to both industry
strategies and public authorities in meeting this challenge). The
patient-centred national programmes are particularly promising
in spurring coordination of cancer research at European level,
since they usually deliver high quality services and provide access
to clinical and scientific expertise through a single portal of
entry. Of particular interest in this context, are the French CLIP²
and the UK Alliance programmes for early phase therapeutic
cancer research.
A meeting was hosted by INCa in Paris in October 2012 led to
the agreement amongst participants that the suggested pilot
coordination should be pursued in a stepwise way, with an
initial assessment of the feasibility of linking the UK and French
programmes, taking full advantage of their commonalities:
• an organizational framework (i.e. a network of designated
clinical research centres linked with molecular biology
infrastructures), which allow delivering state-of-the-art
biomarker-driven early phase trials in a competitive timeframe,
• a partnership with the pharmaceutical industry,
• scope of phases I/II trials considered for investigational new
drugs on indications outside the company main programme.
Subsequently, the lead organizations of both the UK and France
programmes and a pharmaceutical company met in April 2013
and reviewed their programmes’ steps. It was decided to focus
collaboration on conducting trials that each setting cannot
perform on its own in rare cancer for example to achieve critical
mass of patients or on new therapies/combination for unmet
medical needs. The main conclusion of this meeting was that
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it appears feasible, despite some discrepancies in the respective
procedures, to coordinate both programmes and launch joint
calls for proposal across the UK and French networks that would
lead to transnational multi-centre studies. The next steps were
agreed upon and full methodologies for coordination are under
development.
Exploratory discussions are under way with Netherlands and
Italy to expand the pilot project. One essential milestone
concerns the definition of common ways for assessing
excellence. For pharmaceutical companies, centre designation
is indeed key to the company’s decision to give access to its
drugs, and has increased visibility and quality of the centres,
and Europe attractiveness. Defining a common set of criteria
for quality assurance, however, should not result in erasing each
centre’s specificities. The value of the network relies also on
the complementarities of the centres. As seen in the national
examples, the overall quality/scientific level in early phase trials
and molecular biology tests is expected to increase globally.
TRANSCAN – COORDINATION IN TRANSLATIONAL
RESEARCH
The TRANSCAN programme which started in 2011 is another
example of a coordinated initiative supported by the European
commission. The European Commission funds the networking
activities, while the joint research activities resulting from the
ERA-NET calls are funded through member organizations
involved.
TRANSCAN links translational cancer research funding
programmes in 19 European States.
Main achievements under TRANSCAN comprise the rapid setup
of the network governance structure, including an international
scientific advisory board, allowing the timely preparation
and implementation of joint transnational calls. The first call
launched in 2011 related to “Validation of biomarkers for
personalised cancer medicine” with an earmarked budget of
about €14 M. The second call has been launched in 2012 on
“Translational research on primary and secondary prevention
of cancer”. Review is ongoing. Please refer to paragraph 1.1.3,
page 37 for details on the scientific outcomes of the joint calls.
INCa is currently entrusted with the task of call secretariat. The
TRANSCAN network has enlarged to 29 funding organizations
across Europe, after the recent accession of 3 charities. The
TRANSCAN consortium has opted for the use of the Common
Scientific Outline (CSO) classification system to code projects
and programmes of research within the respective member’s
portfolio. Midterm evaluation of TRANSCAN will be conducted
based on a set of performance indicators and will help plan for
the network sustainability and/or its renewal under the next
framework, Horizon 2020.
7.2. THAILAND
1st results of the research programme ‘PapilloV’ “HPV
infections and associated cervical lesions in HIV+ Thai women”.
In Thailand, cervical cancer ranks second as the most frequent
cancer among women with an annual incidence of 24.5
cases per 100,000 women-years and 5,216 deaths per year
and remains a major threat to HIV-infected women even
under treatment. At the end of 2009, an estimated 210,000
women was living with HIV. Thailand provides free access to
antiretroviral treatment since 2003.
The main objective of the ‘PapilloV’ study2 is to palliate the lack
of information concerning HPV ecology and the risk factors of
cervical cancer in HIV-infected women in Thailand, by assessing
the prevalence, incidence, and clearance rate of HPV cervical
infections and associated cervical lesions. The study will also
provide the distribution of the HPV genotypes involved and
will assess the other risk factors of cervical lesions. A goal is to
help design screening algorithms for early detection of cervical
cancer based on the identification of HPV-HR and to allow the
assessment of a HPV vaccine policy in this specific population.
RCN
LAS
CR-UK
ZonMw BMBF NCBiR
DLR
FWO
MMCI
SAS
FWF NIO
INCa
IOB
MHEST
MoH
ISS
ACC
FCT
ISCIII
MIUR
GSRT
LR
KEELPNO
91
TUBITAK
CSO-MOH
2 - Institut de recherche pour le Développement (IRD), Thailand Ministry of Public Health, Faculty of Associated Medical Sciences of Chiang Mai University, Centre National de Référence
des Papillomavirus Humains, Pasteur Institute, Institut National d’Etudes Démographiques (INED)
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This 3-year study is conducted within the PHPT cohort (HIVinfected women receiving antiretroviral treatment in Thailand)
(and will enrol 884 women The follow-up of these women
includes Pap-smear and HPV testing every year, with treatment
and more intensive follow-up for women with cervical lesions
or HR-HPV infection. Enrolment started in February 2012. As
of 1st January 2013, a total of 640 women have been enrolled in
25 hospitals throughout Thailand. The median age of women
is 40.2 years. Median duration of antiretroviral treatment is
7.3 years. Most women are responding well to their antiretroviral
treatment with 96% of them having an undetectable viral load
and immune restoration (CD4 > 250 cells/mm3) in 95% of
them. A baseline gynaecological visit, including a Pap-smear
and HPV testing, was performed in all participants.
Preliminary results:
• among 614 women indicate an overall prevalence rate of HRHPV at 25% at baseline,
• HPV 16 and 18 are respectively present in 2.7% and 1.1% of the
women,
• the most frequent genotypes are HPV 39 and 52 with 9.2% of
the HPV tests positive for one or both of these genotypes,
• among the women infected with HR-HPV, 21% have multiple
infections,
• pap-smear results are currently available for 557 women.
Among them, 6.8% have an abnormal result with 24% high
grade lesions.
The study is funded by INCa, Fondation de France and the
Global Fund to Fight AIDS, Tuberculosis and Malaria.
7.3. AFRICA
Capacity building in cancer control and new steps towards
increased coordination
Joint efforts with our sub-Saharan African partners were mostly
directed towards enhancing the medical and technical capacity
to cancer control and facilitating fellowship exchanges. As
confidence increases, research priorities are now being discussed
to address relevant cancer control issues in a context of low
resource settings. Current topics include the role of human
papillomavirus in cervical cancer as well as evaluations of the
effectiveness of screening and treatment methods.
A step of great importance to expand the cancer control
perspective in low and medium income countries is the
development of a national cancer control plan. INCa has joined
the effort with the PACT programme of the International Atomic
Energy Agency in this area and funded the organization of a sub
regional meeting in Nouakchott on November 2012, dedicated
to the design and implementation of national cancer control
plans with the participation of 5 Francophone Western African
countries. The selected countries had an imPACT mission.
During the three-day meeting, emphasis was placed on the
relevance of the National Cancer Control Plan for enhancing
the effectiveness of cancer treatment through radiotherapy.
In September 2012, a two-day conference entitled “Cancer
in Africa: Building transnational research collaborations to
alleviate the cancer burden” was jointly organized by Africa
Oxford Cancer Foundation (AfrOx), African Organisation for
Research and Training in Cancer (AORTIC), National Cancer
Institute USA, National Cancer Institute (InCa Brazil) and
National Cancer Institute (INCa France) at the British Medical
Association in London. The need for locally relevant research
was highlighted to support the implementation of effective and
affordable cancer control programmes. Several issues related
to the importance of cancer research for development in Africa
were discussed (e.g. appropriate model to support clinical and
translational research to the benefit of African patients). This
was considered as a first coordinated milestone to increased
global response to cancer in Africa.
3 - PHPT is an International Research Unit of the Institut de Recherche pour le Développement (IRD) in France and the Faculty of Associated Medical Sciences at Chiang Mai University in
Thailand
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93
OBSERVATORY FOR RESEARCH INVESTMENT
IN CANCER, AND REVIEW OF RESEARCH
INVESTMENT
A mission of evaluation was created within the Research and
Innovation Division, as well as a cross-sectional network
of focal points for evaluation to help get an overall view to
conduct a coherent evaluation of research, care and public
health’s actions.
The prototype developed for data visualisation shows that:
Data related to grants may be redesigned to identify who is
supported—the principal investigators as well as individuals
from the research teams. These data may be used to describe
existing collaborations at the outset of projects.
The evaluation mission devoted its activity to the creation of
an observatory for research investment.
Text data from grants are sufficient to describe what research
is being carried out, by summarising terms used in grant
applications and publications. Text information may be used to
generate specialised research areas and provide another idea on
the type of research being carried out. Furthermore, it is possible
to draw a comparison for the same thematic areas in other
federal agencies such as the US National Institutes of Health.
HELIOS is an observatory for documenting investments and
outcomes of investments in cancer research. The underlying
framework of the study is based on the idea that funding for
research influences scientific production through its effects
on the creation and dissemination of scientific ideas through
the scientific networks. In the long term, the project is aimed
at monitoring activities of networks to measure the scientific,
social, economic and professional “products” generated as a
result of interactions.
INSTITUTIONS
employ
PEOPLE
train
Fig. 31/ View of the Helios web prototype
GRANTS
awarded to
pay for
produce
support
PRODUCTS
use
co-author
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Links between researchers in receipt of cancer-related funding
and researchers in France and other areas, especially in the
private sector, can be identified to describe with whom the
research is being done, i.e. collaborative scientific networks.
These links between researchers or between research centres or
research laboratories can be visualised.
The data may also be used to describe where the research
funded by INCa is being conducted, whether by research
institution or by collaborating institutions.
Data on investment cover nearly 1,300 research projects and
infrastructures. Outcomes in terms of scientific productions are
illustrated by a corpus of 100,000 publications, 2/3 of which
include as an author a researcher in receipt of research funding
for the 2007-2012 period, and 2,000 patents associated with
researchers are referenced in HELIOS.
This Observatory acts as a proof of concept for the
development of similar tools for measuring and visualising
investments made in France under different health plans,
and thus for providing tangible evidence of the impact of
funding committed. The Observatory provides new indicators
of relations with the private sector, collaboration, links with
international research and INCa’s geographic reach, as well as
funding of the Aviesan/ITMO Cancer, and funding of cancerrelated clinical research by DGOS.
The most represented topics among projects for the 2007-2012 period
Rank
Nb of
projets
1
152
Pathway mechanism target molecular model team therapeutic identify cellular cancer approach…
2
130
Trial arm patient phase randomized year treatment iii standard survival month rate experimental qual…
3
116
Molecular clinical analysis gene biomarker marker sample genomic profile identify signature prognost…
4
97
Patient month criteria year inclusion treatment secondary evaluation rate primary follow number week…
5
64
Chemotherapy response patient survival advanced treatment metastatic cancer rate gemcitabine cisplat…
6
55
Treatment therapy anti clinical therapeutic therapies agent efficacy targeted drug combination trial…
7
52
Cancer breast women invasive impact colon diagnosis increase determine diagnosed frequent analyze…
8
52
Aml leukemia acute myeloid leukemic cell blast prognosis flt leukaemia patient pim therapeutic lymph…
9
48
Cell immune tlr response responses mechanism effector dendritic system lymphocyte function innate…
10
47
Survival patient prognostic year recurrence free factor prognosis disease stage analysis outcome poo…
11
46
Radiation radiotherapy dose irradiation therapy doses local volume treatment toxicity irradiated ext…
12
43
Pathway kinase activation signaling phosphorylation activated protein akt inhibitor erk tyrosine inh…
13
41
Model human cell vivo vitro mice animal mouse line effect murine xenograft experimental tested nude…
14
41
Endothelial vegf angiogenesis hypoxia angiogenic factor vascular growth anti hif vessel cell effect…
INCArapportGB2013.indd 94
Topic
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The most represented topics in publications during the 2000-2011 period
Rank
Nb of
publication
1
4,999
Patient month year median follow range cases age method percent underwent occurred died time twenty…
2
4,965
Binding domain structure protein site terminal interaction peptide residues structural acid complex…
3
4,884
Case diagnosis cases report rare year pancreatic lesion examination duct revealed cyst man biliary w…
4
4,308
Reaction compound derivative acid ring synthesis yield dot synthesized methyl step amino prepared bo…
5
4,116
Expression gene mrna protein expressed level transcription regulation human regulated transcriptiona…
6
3,921
Surgery surgical resection postoperative complication procedure morbidity patient laparoscopic opera…
7
3,891
Pathway kinase activation signaling phosphorylation activated protein akt inhibitor erk tyrosine inh…
8
3,758
Alpha tnf cytokine factor ifn production beta macrophage kappa inflammatory necrosis induced interle…
9
3,719
Sequence gene region genome site element promoter human protein family conserved repeat transcriptio…
10
3,589
Cd cell lymphocyte blood peripheral tcr subset ccr antigen expression expressed surface specific mol…
11
3,380
Cell apoptosis death induced apoptotic caspase fas activation mediated induce effect dependent induc…
12
3,371
HIV infection virus infected viral human viruses immunodeficiency load antiretroviral aid count HHV…
13
3,348
Ratio interval risk age confidence association regression analysis odd factor multivariate hazard ad…
Topic
This work, conducted over the 2007-2012 period, has permitted
the distribution of research investment to be visualised by city
of the project coordinator for the 4 investigator-driven research
programmes in biology, translational research, clinical research
and human and social sciences research.
INCArapportGB2013.indd 95
Figure 32 shows that 30-40% of the budget went to projects in
research centres and hospitals in Paris and in the Paris region.
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Fig. 32/ Distribution of funding by research areas and cities
Cancer biology and
cancer sciences
Paris/IDF
2.17%
Lille
34.46%
Translational research
2007-2012
Paris/IDF
Lille
43.6%
5.2%
Rouen
5.2%
Caen
Roscoff
Nancy
Paris/IDF
Rennes
Brest
Strasbourg
Paris/IDF
Strasbourg
Rennes
9.66%
2.94%
Orléans
2.72%
€ 92 M
Angers
Nantes
Dijon
Nantes
Dijon
€ 34.5 M
Lyon
6.3%
Clermont
Ferrand
Grenoble
Bordeaux
€M Funding
Lyon
Limoges
9.24%
3.37%
Besançon
5.9%
Grenoble
3.7%
Bordeaux
3.38%
Toulouse
Montpellier
7.83%
Nice
Marseille
Toulouse
4.01%
7.47%
3.6%
Nice
Montpellier
5.6%
Marseille
8.78%
Guadeloupe
Martinique
Guyane
Guadeloupe
La Réunion
Martinique
Guyane
La Réunion
Source: INCa
Drafted by: Research and Innovation Division,
Assessment Office, INCa 2013
Clinical research
2007-2012
Paris/IDF
Lille
40.3%
4.3%
Lens
Rouen
2.3%
Senlis
Sources: INCa, DGOS
Drafted by: Research and Innovation Division,
Assessment Office, INCa 2013
Social sciences,
epidemiology
and public health
2007-2012
Reims
Caen
Paris/IDF
Rennes
Lille
Strasbourg
Tours
€ 122 M
Nantes
Besançon
3.7%
5.8%
Limoges
Clermont
Ferrand
4.38%
€ 27.4 M
Poitiers
Lyon
Lyon
10.4%
Saint-Étienne
Grenoble
2.03%
3.4%
Toulouse
3.8%
Martinique
Guyane
Grenoble
8,28%
Montpellier
2.7%
Nice
Toulouse
Marseille
2.58%
7.1%
Guadeloupe
La Réunion
Sources: INCa, DGOS
Drafted by: Research and Innovation Division,
Assessment Office, INCa 2013
INCArapportGB2013.indd 96
8.79%
Bordeaux
Bordeaux
Martinique
Pointe-à Pitre
Guyane
more than 30%
Dijon
Tours
2.80%
Saint-Étienne
Guadeloupe
Strasbourg
3.97%
Dijon
15
10
5
2
1
Share of funding
Nancy
4.91%
Paris/IDF
Rennes
Angers
2%
50
40,21%
Caen
Nancy
2.7%
2.94%
Nantes
Paris/IDF
2.53%
5.07%
2.5%
Brest
5.61%
6.0%
Nimes
Montpellier
4.94%
Marseille
5.31%
10 to 20%
5 to 10%
2 to 5%
city below 2%
La Réunion
Source: INCa
Drafted by: Research and Innovation Division,
Assessment Office, INCa 2013
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2013 TOTAL FUNDING AND CANCER PLAN
2009-2013-RELATED OVERALL FUNDING
For 2013, the new budget allocations for calls for proposals
amount to €47.5 M; we can estimate, with the expected
funding for clinical research projects (PHRC and PRME-K),
a total funding amounting to €70 M. This explains why this
year’s project profile shows a 40% funding for projects on
cancer biology, and only 21% on treatment.
For 2013, and at the time of writing this report (July 2013),
we estimate expenditure on cancer-related research at nearly
€100 M; this is distributed between the following five
categories:
• investigator-driven projects (these concern the 4 large research
areas, namely biology, clinical, translational, and human and
social sciences/public health),
• projects targeted on one tumour type (INCa and the nonprofit organisations ARC Foundation and National Cancer
League support an integrated research action programme on
one tumour type, see page 42),
• thematic projects (targeted research programmes, particularly
focused on cancer-related inequalities, environmental risks,
innovative molecules at the early clinical trial phase, cancer
and employment, etc.),
• platforms, resources and infrastructures (the SIRICs, CLIP2,
cooperative intergroups, cohorts, clinical-biological
databases, etc.),
• training and young teams of excellence (especially ATIP Avenir
teams, and translational research training).
INCArapportGB2013.indd 97
97
Of about €100 M spent, nearly €45 M relates to investigatordriven research programmes; this is in accordance with action
5.3 of the 2009-2013 Cancer Plan, (“Maintain the level of
research funding for free researcher driven projects, for 4 to
5-year programmes, at the level of 50% of the INCa’s call for
research proposals”)
Fig. 33/ Funding for cancer research 2013 €47.4 M
(Not including clinical research)
9% 3%
21%
Biology= €19 M
Aetiology= €4.9 M
Prevention= €0,4 M
Early detection, diagnosis,
prognosis= €7 M
Treatment= €10 M
Human and social sciences,
= €4.4 M
Scientific models= €1.5 M
15%
40%
1% 11%
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Fig. 34/ Distribution of 2013 cancer funding
(INCa, DGOS, Aviesan-ITMO Cancer): €99 M spending
3.54%
18.34%
29.36%
Since 2009, we note a strong increase in the budget allocated
(trebled between 2009 and 2013) to the research platforms
and infrastructures, as well as a steady increase in investment
on priority research areas in the Cancer Plan (budget trebled
between 2009 and 2013), see Figure 35.
Fig. 35/ 2009-2013 Trends in funding per programme
50
40
€M
4.62%
30
20
10
0
44.15%
Social sciences, epidemiology, public health
Translational
2009
4.45%
7.59%
Biology and cancer sciences
15.46%
Clinical
16.68%
Investigator-driven calls
Strategic research programs dedicated to specific
types of tumours
Strategic research initiatives (thematic calls)
Platforms/resources/infrastructures
Research training young teams of excellence
INCArapportGB2013.indd 98
2010
2011
2012
2013
Investigator-driven projects
Projects dedicated to specific type of cancer
Projects dedicated to a specific research issue
Platforms/resources/infrastructures
Research training/young teams of excellence
Among the priorities in the Cancer Plan, research on cancer
risk factors has been addressed through the development
of dedicated programmes, and collaborations with
funding agencies such as ANSES (French Agency for Food,
Environmental and Occupational Health Safety) and
IReSP (French Public Health Research Institute) have been
strengthened since 2011; thus the number of projects selected
in the area of environmental, behavioural and genetic risk
factors has advanced very significantly.
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At the time of writing this report, we can estimate the proportion
of the budget allocated for these areas at 13% of allocations
for all calls for proposals in 2013; indeed, for a multi-year
allocation of €46 M (while awaiting the results for clinical
research programmes), €6.2 M is for projects focused on the
study of risk factors. The objective of 15% set by the Cancer
Plan has therefore been practically achieved.
To finish, an analysis was carried out on 1,292 projects selected
over the 2007-2013 period (i.e. over 100 calls for proposals
and calls for applications for designation of infrastructures).
Investment for this period was €469 M, and the distribution
over different research categories is shown in Figure 37.
Fig. 37/ Cancer research funding 2007-2013 - Projects
and infrastructures: €469 M
Fig. 36/ Cancer plan priority: research on risk factors
12%
7
6
€M
5
4
3
2
1
31%
0
2009
Behaviour
Environment
Genetics
INCArapportGB2013.indd 99
2010
2011
2012
99
4%
23%
Biology= €110 M
Aetiology= €39 M
Prevention= €16 M
Screening, diagnosis,
prognosis= €90 M
Treatment= €143 M
Human and social sciences,
= €55 M
Scientific models= €16 M
8%
3%
2013
19%
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Part 3.
PERSPECTIVES
The strategic orientations for cancer research were drafted by INCa and
Aviesan – ITMO cancer with the contributions of the SAB members.
From this reflection, 5 priority actions are issued for 2013-2014.
1 - To fight tobacco-related cancers with an ambitious
multidisciplinary programme of research/treatment/public
health actions.
2 - To build a shared biological, clinical and epidemiological
database.
3 - To foster closer ties between teaching and research and increase
support for interdisciplinary training.
4 - To support ambitious French cancer research to provide the
population and patients quick and sizeable benefits.
5 - To face new challenges in cancer control: European and global
perspectives.
This section presents within each priority action a set of potential
actions that could be implemented.
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1
STRATEGIC ORIENTATIONS
FOR CANCER RESEARCH4
The incidence of cancer in France, which has increased steadily
until recently, is currently stabilising. Sustained efforts in
primary prevention, along with the development of screening
programmes for precancerous or early forms of tumours in
the last ten years, have enabled a reduction in incidence rates.
Despite a steady decrease in overall mortality, cancer still
remains the leading cause of death (nearly 148,000 in 2012).
On closer inspection, the figures show that some tumour types
are clearly declining or are being much better treated, whereas
others, with a poor prognosis, are marked by a significant
increase. The impact of cancer on society remains considerable.
It is the leading cause of health-related worry among the
French. Since 2003, the State has made a special effort to fight
cancer in our country with the help of three successive plans,
the most recent of which is in preparation, to cover the period
2014-2018. The previous plan, 2009-2013, had set research
as a primary objective, with solid support for the continuum
of research, from basic principles to transfer to the patient. It
encouraged inter-disciplinary collaborations and the arrival of
new themes in the cancer field, and emphasised and identified
translational and clinical research as priorities for the benefit
of patients and citizens. It also enabled advances in organising
cancer research through the creation of 8 integrated cancer
research sites (SIRIC), and the harmonisation of responsibilities
and consistency of work between the French National Cancer
Institute (INCa) and the French National Alliance for Life
and Health Sciences (Aviesan), who proposed joint strategic
orientations for research in 2010.
Given the size of the medical, economic and social problem
posed by cancer, planning of research to fight tumour diseases
continues to aim at reducing the mortality associated with
these pathologies, reversing the overall frequency and that
of the most serious tumours, and improving survival and
quality of life for patients using more effective and less toxic
treatments. In view of increasing survival, it requires a wider
reflection in order to improve the chances of returning to a
normal social life following the treatment phase.
ANALYSIS OF CANCER DETERMINANTS AND ACTIONS TO
REDUCE THEIR IMPACT REQUIRE:
• increasing basic research in the health area (primary,
secondary and tertiary prevention) and fostering its transfer,
up to intervention, implementation in the population and
therapeutic care,
• further breaking down of barriers between disciplines,
• exploiting the advances made by developments in genomics,
while increasing efforts and investments in technology.
This document also anticipates the 3rd Cancer Plan announced
by the President of France. It is the contribution of those
involved in research and the bodies responsible for planning
research and innovation.
4 - The following people were involved in the reflection and in the drafting of this document:
ITMO Cancer
Fabien Calvo (Director of ITMO Cancer), Alain Eychene (Deputy Director of ITMO Cancer),
Jean-Paul Borg, Salem Chouaib, Jean Clairambault, Jacqueline Clavel, Catherine Dargemont,
Olivier Delattre, Robin Fahraeus, Jean-Jacques Feige, Jacqueline Godet, Sophie Gomez,
AnnickHarel-Bellan, Urszula Hibner, Claire Julian Reynier, Claudine Junien, Claude Leclerc,
Patrick Mehlen, Patrick Peretti-Watel, Eric Solary, Bertrand Tavitian, Valérie Thibaudeau
(scientific affairs coordinator at INCa), Gilles Thomas, Nathalie Varoqueaux.
INCArapportGB2013.indd 102
Scientific Advisory Board of the French National Cancer Institute
Geneviève Almouzni, Jean-Pierre Bizzari, Jean-Yves Blay, Nancy Davidson, Anne Eichman,
Judy Garber, YannGauduel, Denis Hémon, Daniel Louvard, Bernard Malissen, Theresa
Marteau, Michel Marty, Jacques Pouyssegur, Jean-Charles Soria, Michael Stratton, Karin
Tarte, Bruno Varet, Robert Weinberg, Otmar Wiestler.
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1.1. THE KEY CHALLENGES
Scientific challenges
As with other pathologies, cancer research covers a vast area of
human knowledge, including the study of a cell’s physiological
regulatory mechanisms and interactions with its environment,
in order to gain an understanding of their pathological
dysregulation. The scope of this area of endeavour requires
the study of model systems, from the most rudimentary to
the most complex, to allow the analysis of tumour growth,
development, migration and colonisation, and mechanisms
of resistance to treatment. Analysis of cancer determinants
and actions aimed at reducing their impact require effort
and investment in the area of technology (biotechnologies
for health, sequencing and genomics technologies, imaging,
robotics, instrumentation, information technology, drugs,
etc.) and in the area of public health (epidemiology, screening
and prevention) indispensable to the development of clinical,
therapeutic and translational research. The big challenge
remains the transition from the current precision medicine to
a medicine genuinely tailored to each individual.
This redefinition of tumour pathologies requires continued
development and use of large-scale technologies, the creation
of links between these (genomics/proteomics/metabolomics),
and integration of all data into our understanding of cancers
and their development.
Medical and public health challenges
The Aviesan Cancer Alliance and INCa hope to prioritise, in
addition to indispensable fundamental research, the impact
of which cannot be predicted, three strategic areas of research
based on population health objectives. These areas will
generate exchange and cross-fertilisation of ideas between
basic and applied research.
INCArapportGB2013.indd 103
103
Areas
1. Research and innovation for a new definition
of “cancerous diseases,” tailored to the objectives of early
diagnosis and the development of new tools for treatment.
This area embodies an objective for the development of
personalised medicine over the next five years. It justifies
investment in equipment and staff dedicated to the
analysis of data, interactivity between data, and sharing
of data between scientists on a European and worldwide
scale. It extends to research on medication, research on
less invasive surgery, and novel approaches to innovative
technologies and developments, including the use of
ionising radiation.
2. Research on primary prevention, particularly
on high-risk behaviour, and analysis and correction of
its failures, i.e. identification of patterns of exposure to
risk factors, and approaches targeting individuals and
populations, particularly the more vulnerable. This research
draws on genetics, understanding of addictions, hostenvironment interaction, and proteomic and metabolic
studies, and its outcomes have implications for the political,
economic, human and social sciences.
3. Research that helps to identify populations
exposed to cancer risks and facilitate monitoring by early
detection strategies (secondary prevention). This research
involves molecular and genetic epidemiology, imaging and
technological development around biological markers. It
extends into interventions in populations already cured of
a cancer with a view to prevention of its recurrence or the
occurrence of a new cancer.
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1.2. CURRENT SITUATION AND STRENGTHS
IN FRANCE
The impetus from the cancer plans has been supported by
the coordination of activities undertaken by INCa, which
provides funding for research programmes, and by AVIESAN,
which brings together those carrying out cancer research. The
Director of Research at INCa is the Director of AVIESAN’s
ITMO (Thematic Multi-Organisation Institute) Cancer.
Together, AVIESAN and INCa have defined all of the strategic
orientations in this document, the result of reflection by the
international scientific board of INCa and experts from ITMO
Cancer. The most recent cancer plan has enabled important
modifications to the structures dedicated to cancer research,
with the creation and designation of 8 integrated cancer
research sites (SIRIC) and 16 designated early-phase clinical
trial centres (CLIP2). It has enabled better visibility for French
research, and a clear improvement in its quality, now ranked
third in Europe. This research planning has also allowed
increased involvement in this area of health by research teams
working in human and social sciences, and in epidemiology,
physical sciences and mathematics. A census has been taken
of the teams working on cancer in different organisations.
Similarly, regionally or nationally based equipment (Biology,
Healthcare and Agronomics Infrastructures, “investment
for the future”) has been tracked. Some weaknesses are still
apparent in the genomics areas with respect to equipment and
especially data analysis, and in engineering sciences, as well
as in the translation of basic research into patient-oriented
applications.
French oncology teams have demonstrated their strong
attractiveness for international healthcare industries, especially
with regard to clinical research, a strongly performing and
highly visible area that benefits patients. Developments in
upstream research cooperation have also been enabled, with
the support of ARIIS (Alliance for Research and Innovation
in Health Industries), as manifested at the 4th edition of the
international R&D Dating, inaugurated by the French Prime
Minister in November 2012. An analysis of over 2,000 patents
relating to cancer was made on this occasion.
It is advisable to maintain this effort to share this scientific
visibility with our fellow citizens, with better communication
and information accessible to all.
INCArapportGB2013.indd 104
1.3. PROPOSALS
1.3.1. ORGANISATIONAL
The efforts at organisation made in recent years, particularly
in the context of investment for the future, and the creation
of the SIRICs, indicate that these efforts are worth extending
by linking the structures to enhance their impact. The
continuum between basic research, observation of cancers,
translational research, clinical research, and technology
transfer must be guaranteed, together with the enrichment
provided by the human and social sciences across all areas.
Links between disciplines and improved interaction between
research organisations (EPST: Public Scientific and Technical
Research Establishment) and universities for networking and
translational research, Inserm (French National Institute of
Health and Medical Research), CNRS (French National Centre
for Scientific Research) and INRA (French National Agronomic
Research Institute) for metabolism, etc.) are also necessary,
and are among the goals of Aviesan Cancer and INCa. Finally,
at the level of Alliances, links between the ITMOs for Public
Health, Metabolism, Genetics, Haematology, Infection and
Immunity with ITMO Cancer are a permanent reality and
should support inter-alliance cooperation, especially with
ATHENA (French National Alliance for the Humanities and
Social Sciences) and AllEnvi (French National Alliance for
Environmental Research). For strategic reasons, links must be
deepened with schools of engineering, information technology,
mathematics and veterinary medicine.
1.3.2. SCIENTIFIC, TECHNOLOGICAL AND MEDICAL:
Genomics and personalised medicine
The transition toward personalised medicine includes
several components, including technological and biological
developments. Since 2010, France has undertaken the
sequencing of 2,500 tumours within the framework of the
International Cancer Genome Consortium (ICGC). This effort
must be maintained until completion, and complemented by in
vitro and in vivo validation of identified signalling pathways, and
the development of relevant animal models useful in diagnosis
and treatment. An interface must be created between geneticists
and experts in proteomics to further the area of biomarkers.
The development of minimally invasive techniques (plasma,
puncture, fluids, etc.) must be encouraged, along with detailed
analysis of tumour heterogeneity. Finally, it remains crucial to
ensure, under proper conditions, the transition from cognitive
research on patient cohorts to the clinical level on an individual
scale. This transition requires strong involvement from
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researchers and specialists in bioinformatics to support the
clinical biology teams. It is anticipated that analyses of gene
panels will be accomplished in two years, and that complete
genome sequencing will then be extended in another five years
to those patients that justify its use.
At the same time, it is essential to prove that these extensive
genome analyses have a genuine impact on patients. It is
desirable, at least for frequently occurring pathologies, that
there be proof that genomics, through its consequences for
treatment choices, offers a genuine benefit for patient survival.
For this to happen, randomised clinical trials must be carried
out quickly.
The investment made in recent years in proteomics and new
technologies at the sites involved indicate that France has
the necessary structures for the analysis of cancer-associated
proteins. It seems justifiable to develop quantitative and
targeted analysis, using patient serum, plasma, or tissues,
in the light of tumour genomics or hypotheses generated by
knowledge of pathophysiology.
Advances in genomics have allowed the demonstration of a
large number of molecular alterations, the consequences of
which are very little understood at the level of structure, function
and quantity of proteins. The combination of proteomic and
genomic data would enable us to rethink our way of diagnosing
cancers, to develop a new generation of biomarkers, and to
better treat patients. These programmes are accompanied by
a growing demand for information technology for the storage,
tracking, sharing and rapid flow of information between
clinical services, biobanks and researchers and, of course, for
data analysis. Despite recent efforts, it remains difficult to
maintain the visibility of French resource centres alongside the
large North American and British infrastructures. Apart from
our own capacity, it therefore seems advisable to incorporate
our data into those generated throughout Europe, probably
through the EMBL (European Molecular Biology Laboratory).
Medication, molecular pharmacology and biomarkers
The emergence in recent years of treatments that target specific
abnormalities of the tumour cell or its environment has led to the
appearance of a new range of treatments acting on molecular
targets other than DNA repair or duplication or mitosis. Clinical
results have helped to demonstrate that patients not selected
on the basis of a target molecular abnormality are primary
resistant, and that for patients with a sensitive tumour, the
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development of secondary resistance is frequent. Identifying
and overcoming this resistance are recurring problems, which
require contributions from fundamental biology, medicinal
chemistry and clinical research.
Sites capable of making progress on the analysis of proteinprotein interactions now exist in France, and might on the one
hand accelerate knowledge of biology of cellular regulation as
well as diagnosis, and on the other hand lead innovation in the
development of new targeted treatments. It seems necessary to
continue the collaborative effort with industries in these fields
that are still essentially academic, for better technology transfer
from research, and to combine it with strengths in structural
biology, medicinal chemistry, mathematical modelling and
information technology.
The development of a drug sector, from the identification
of targets to proof of concept, is desired by researchers
and public authorities alike. The obstacles seem essentially
associated with a rigidity in research structures that does not
facilitate the movement of staff, especially researchers, and
with cultural problems. Many obstacles could be removed by
freeing engineering, technical and academic staff for work in
a valued applied sector. A marked introduction of engineering
sciences into research teaching modules is needed for the
adaptation of future graduates, together with the creation of
links with specialist schools.
Metabolism, infection, inflammation, immunology and cancer
These problems at the interface of other disciplines concern
the genesis, control and escape of tumours, and primary
and tertiary prevention, and are a source of great hope for
treatment among patients. Taking ownership of them by
researchers requires collaboration between the specialised
institutes of the Alliance in the various fields of discipline,
through the facilitation of cross-disciplinary activities in these
areas. They justify a reinvestment in training in disciplines that
have been neglected in recent decades, such as biochemistry,
physiology and health technologies, together with recruitment
of researchers. Many active new drugs have been developed
from basic research carried out in France, particularly in the
regulation of immune effectors, without any benefit to society
or the economy. Other related areas of research, such as
proteomics and lipid research, know almost nothing about
one another. Finally, as will be seen below, the incorporation
of varied approaches into a complex system with the help of
mathematicians and physicists will undoubtedly form a basis
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for progress in our understanding of cancers. The development
of animal models for the validation of these approaches makes
the need for veterinary pathologists even more urgent.
Human and social sciences and public health
France is one of the countries in Europe where cancerrelated health inequalities associated with social status
are the most marked. They are essentially associated with
a failure in prevention, poor uptake of screening, and late
diagnosis. Studies on prevention, vulnerability in relation to
serious illness, social integration through job retention and
return to work, life during and after cancer, etc. are a first
response to major societal needs. Research efforts in these
areas must be continued and expanded, and include detailed
technological approaches (geolocation, social epidemiology,
territorial cartography, etc.) and multidisciplinarity, including
infrequently consulted fields such as ethics and political
science. Moreover, in a context of increasing restrictions on
public expenses, the efficacy and efficiency of preventive actions
must be demonstrated by studies in the areas of prevention
economics and innovation. An initial strategic reflection on
prevention was conducted by INCa, IReSP (French Public
Health Research Institute), ITMO Public Health and ITMO
Cancer in 2012, culminating in recommendations for research
already being implemented in 2013. These will be the subject of
targeted calls for proposals led by a variety of research groups,
the creation of university chairs in prevention, and support for
basic research and field studies aimed at intervention, and with
a policy for implementing interventions found to be positive.
At organisational level, better efficiency must be sought by
grouping teams of diverse disciplinary origin, especially in the
environment of the integrated cancer research sites (SIRICs),
allowing the development of common biological and social
approaches to risk exposure (exposome, biological and social
markers, populations, environment, etc.). Finally, a reduction
in inequalities still remains a very considerable challenge in the
cancer area, which must be addressed in a general manner by
stimulating research into its technological, social and political
components, and promoting action for intervention, to be
followed by implementation in target populations.
Epidemiology, epigenetics and environment
Recent efforts made in investment for the future with broadbased cohorts and pathology-specific cohorts must be
continued and expanded, with maintenance of funding being
a serious preoccupation. It is also hoped that research may be
guided by large surveys on attitudes, beliefs and behaviours
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related to cancer. Finally, there is general agreement that
registry and cohort data should be more easily matched with
medico-administrative databases of healthcare consumption
and hospitalisation.
In addition to analysis of the role of the epigenome in tumour
development and targeted therapy, improved coordination
between specialists in these disciplines is desirable, together
with the linking together of epigenomic data and data on
exposure to environmental risk, in cohorts, for example. It
would be beneficial to analyse these exposures beyond one
generation, and include foetal life. Work on coordination
within the framework of the new health and environment plans
and with the AllEnvi alliance is already underway.
Systems biology
It enables dynamic modelling of the organisation of tumour
cells and tissues, complex by definition, describing their
development and the prediction of drug efficacy, enabling
progress toward a better understanding and better care of
cancers. Systems biology requires interactions between
disciplines; it involves physics, bioinformatics, biostatistics,
bioimaging, biophysics, biochemistry and biomechanics;
mathematics and theoretical information technology share
a central position. It is developing in close association with
fundamental biology, which helps to validate experimentally
the hypotheses that emerge from the building of models. It
lays the groundwork for personalised medicine by supplying
the methodological foundations (individual characterisations
based on systemic response to treatment) for the creation
of patient clusters. Systems biology helps to create relevant
pathophysiological profiles based on phenotype, and opens
up the field of personalised medicine.
In the long term, it would be desirable to bring together various
specialities, from cancer development to treatment, within a
systems biology institute (which may be an institute without
walls, i.e. a network).
It is necessary to improve the visibility of systems biology as
an interdisciplinary crossroads giving rise to new perspectives
and, in the longer term, innovative cancer treatments, with the
establishment of collaborations and the creation of predictive
models with therapeutic applications. Universities must invest
in this discipline, and ad hoc assessment committees capable
of judging this type of project must be created.
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Physics/mathematics and cancer interfaces: fundamental
aspects and transfer toward clinical application
The contribution of “hard” disciplines and researchers in these
areas, physics, mathematics and engineering, must be increased
to enable a new outlook on cancer. Traditional themes must
be reinforced, especially radiobiology, and should benefit from
the input of recent technologies to generate an understanding
of the toxicity and benefits of radiation, the effects of low
doses (particularly in diagnosis), and very high dose rates, etc.
The development of new non-traditional radiation sources
(particle acceleration by ultrashort laser pulse, synchrotron
and micro- and nanobeam sources, heavy ion beam) should
allow the development of innovative research on radiation
biology and its applications, and on dosimetry at the subcellular scale. These efforts must be translated into benefits for
patients by improving and personalising treatment protocols,
in combined cancer treatment (vector delivery of treatment,
radiosensitisation, dose control in real time, etc.).
The synergies between instrumentation and treatment centres
must be facilitated by training (acquisition of various new
skills, training in physics/biology, mathematics/medicine, etc.)
and by large communal equipment for physics/care, carried by
the universities and the Alliances.
It appears, moreover, that the interoperability and sharing
of data from genomic databases, clinical and biological
databases, socioeconomic data and larger databases such
as health insurance might be an instrument of progress and
a major source of analysis and research. On a larger scale,
a worldwide reflection on access to anonymised genomics
data, for example, would enable a better understanding of
rare variants and exceptional and highly informative clinical
situations with regard to cancers and their development.
Clinical research
The previous cancer plan enabled a considerable development
and deployment of clinical research through the designation of
early-phase clinical trial centres (CLIP2), the strengthening of
the Programme for Hospital Clinical Research, and designation
of cooperative intergroups for clinical research. This has been
reflected in a trebling of the number of patients enrolled in
early phase trials since 2009 and an overall increase in patient
participation in clinical research of over 70% in 4 years.
New steps could be taken in relation to support for projects
directed by cooperative intergroups that were ambitious in
terms of demonstration of improved survival. These groups
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can conduct large-scale trials, with creation of clinical and
biological databases. These groups, by their size and visibility,
are likely to propose large international trials enabling essential
questions to be addressed more quickly. Conversely, it seems
desirable to propose an attempt to de-escalate treatment of
some pathologies in order to limit treatment sequelae. The
structures in place and existing means currently allow these
advances.
Training and technology transfer
Many areas of research justify the creation of new training
sectors as mentioned in this document. Training in translational
research remains a separate objective that should be prioritised.
It is likely to benefit patients by improving every stage of their
illness, and likely to benefit society by providing answers to
questions concerning health and economic value. To continue
the development of personalised medicine, it would be
advisable to foster innovation, especially in the area of new
treatments. Some targets and strategies are not currently
monitored by industrial research, and must be energetically
supported through substantial funding. This would enable the
repositioning of France in the sector in the long term.
Society/patient information
Special efforts should be made to increase information for
patients and users on research in the area of cancer. Much has
been done in the last ten years, but our fellow citizens still remain
mistrustful about the role of researchers, their independence,
and their ability to approach problems that may arise for
patients before, during and after their illness. In particular,
and often with reason, the problem of post-treatment sequelae
seems to them to be completely overlooked. The constant
presence of patient representatives, their “advocates” in all
matters of discussion, selection of research projects and
strategic choices, should probably be expanded. Similarly,
the opinion of these representatives must be expressed and
recognised in all contents of clinical research projects. The
recognition thus obtained may be extended, with patient
advocates becoming the most relevant intermediaries in large
programmes for prevention, screening or treatment of cancers.
All technological advances, especially in genomics, involve
acceptance by patients and users, together with ethical
consideration of the limits of interpretation and dissemination
of results, which will in turn require the participation of public
authorities and representatives of the national community.
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2
FIVE PRIORITY ACTIONS FOR 2013-2014
2.1. TO FIGHT TOBACCO-RELATED CANCERS
WITH AN AMBITIOUS MULTIDISCIPLINARY
PROGRAMME OF RESEARCH/TREATMENT/
PUBLIC HEALTH ACTIONS
In 2012, tobacco is still the leading preventable cause of cancer
in France. The latest estimate of the number of deaths caused
by tobacco-related cancer in France is approximately 44,000,
not counting cancer induced by second-hand smoke, which
can also lead to lung cancer (Hill, 2012) (IARC 2004).
In recent years, France has seen a resurgence in the prevalence
of smoking, which contrasts with an underlying long-term
decline in tobacco use evidenced by a sharp drop in tobacco
sales when the 2003-2007 Cancer Plan was launched.
In the 15-75 age group, the smoking rate rose from 31.8% in
2005 to 33.6% (2010 data) (Beck, 2011).
This increase is most prevalent in three different populations:
women (up 6 points from 2005 to 2010), the unemployed (up
from 40% in 2000 to 51% in 2010) and young people.
The leading indicator of the effects of smoking is death from
lung cancer, but tobacco is a significant factor in 16 other types
of cancer: mouth, pharyngeal, throat, pancreatic, bladder,
kidney, nasal cavity, sinus, oesophagus, stomach, liver, cervical,
myelogenous leukaemia, colon, rectum and ovarian. Smoking
can also be a cause of breast cancer (IARC 2012).
Although the 2009-2013 Cancer Plan is currently the
government’s only anti-smoking measure, the objectives on
reducing the smoking rate and righting the inequalities in the
public health law of August 2004 will not be achieved. The gap
is over 7 points for men and 6 points for women.
Several reports bear witness to the historical failure of the antismoking policy in France, despite the series of initiatives that
have been undertaken5.
• The WHO Framework Convention on Tobacco Control
(FCTC), ratified by the French Parliament in 2004.
• The report from the French Ministry of Labour, Employment
and Health by Yves Bur entitled “Propositions pour une nouvelle
politique de lutte contre le tabac” [Recommendations on a
new anti-smoking policy], February 2012.
• The analysis report on anti-smoking policies from the French
Controller and Auditor General, December 2012.
• The White Paper issued by the Alliance contre le tabac (AntiTobacco Alliance), February 2013.
• The information report on the assessment of policies to fight
tobacco use presented to the French National Assembly by
deputies Denis Jacquat and Jean-Louis Touraine, February
2013.
This failure is mainly caused by insufficient prevention in our
healthcare system, poor support to help people quit smoking,
and regulations lacking inspection for enforcement. Research
efforts should be boosted in epidemiology of tobacco use and
its health effects as well as social science-related factors and
industry’s economy.
A recent paper showed that out of all the types of cancer listed,
35% can be attributed to tobacco use. According to a study
by EPIC (European Prospective Investigation into Cancer and
Nutrition), tobacco can be blamed for nearly one in five cases
of cancer. These latest estimates confirm findings published
by IARC in 2007.
5 - Countries where the FCTC recommendations have been implemented achieved a dramatic drop in tobacco consumption: England, 21% of adult smokers, United States 15%, Australia
15%, Canada 13%. In France, the tobacco use had begun falling in the 1970s but started rising again in 2005, primarily among women and populations lower on the socio-economic
scale, to reach nearly 34% of adults.
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To this end, INCa would like to develop a multidisciplinary programme of initiatives to determine
a strategy on reducing tobacco-related cancer.
This long-term programme will operate with visionary
management aims to:
1. foster research to cover all the strategies that were
devised after consulting a wide range of actors. It will
culminate in a set of recommendations on establishing
new government prevention policies,
2. set priorities for actions to boost prevention.
2.1.1. INITIATE AN AMBITIOUS PROGRAMME
FOR RESEARCH AND DISSEMINATION OF GOOD
PRACTICES TO FIGHT SMOKING-RELATED CANCERS
In an effort to establish the priority actions to revive the antitobacco policy, INCa could develop a partnership programme
of multidisciplinary actions to fight against tobacco-related
cancers. Key partners include the ministries of Health and
Research, Inpes (National Health Prevention and Education
Institute), IRESP (Research Institute for Public Health), InVS
(French Institute for Public Health Surveillance), MILDT (Interministerial programme to fight drugs and drug addiction), DGS
(General Directorate of Health), SFSP (French Public Health
Society), national education, anti-smoking associations, etc.
There are several objectives:
• to determine the priority research themes (working group and
international hearings),
• to improve evaluation measures for initiatives,
• to increase distribution of good practices,
• to share the knowledge generated and guarantee the
independence of expertise.
Furthermore, one of the programme’s main objectives is to
accelerate the pace of putting these research findings into
practice among decision-makers and practicians.
Much like the Centre for Tobacco Control Studies UK, longterm funding6 for the programme and critical mass for projects
should make it possible to build scientific teams.
In addition, INCa and its partners could set aside a portion of
the budgets in their own calls for proposals on research, not to
stir up competition among funding agencies, but rather to unite
all of our initiatives under one strategic umbrella.
109
POTENTIAL AREAS OF RESEARCH/PUBLIC HEALTH
ACTIONS TO DEVELOP FOR THE PROGRAMME
Research in epidemiology, human/social sciences
and prevention
Tobacco as a risk factor of many cancers: research on other types of
cancer than lung cancer should be expanded and include multiple
exposures and addictions (alcohol and/or environmental/
occupational exposure).
Health intervention research7: mainly for preventive interventions
in schools with primary and secondary pupils.
Promotion of smoking cessation in patients with cancer: definition
of awareness strategies for health professionals and patients,
definition of intervention strategies, measure of the impact on
quality of life, cancer mortality and all-cause mortality.
Bio-monitoring: primarily saliva cotinine (or other biological
markers) that can provide additional information to
environmental monitoring and valuable insight on the various
sources of exposure (particularly in children).
The benefits of quitting, risks associated with second-hand smoke8.
Tobacco substitutes associated risks.
Research in political science, economics, the behavioural
and cognitive sciences and the neurosciences
Taxation and health policy analysis: possible studies could include:
• costs of smoking-related morbidity and mortality for the health
insurance system and the community as a whole and studies
on resistance and protest among stakeholders who rely on the
income generated by tobacco,
• economic evaluation of the use of a screening programme for
tobacco related cancers in target populations,
• feasibility of the implementation of a national lung cancer
screening programme (low dose CT scanners, training, surgery,
methodology…).
New public policy strategy9: current talks about the “Tobacco
Endgame” strategy ; nudging (influencing choices through
incentives10,11): the theory behind nudging is to set up an
environment where people make the best decisions for their
health without necessarily forcing them to do so. It is based
on the premise that despite informing the public, some public
health prevention policies do not produce the intended results.
Applying these techniques offers a new way of designing health
prevention policies.
6 - Funding should be set aside that matches the importance of the public health threat.
7 - Necessary attentiveness to the adverse effects of the interventions introduced.
8 - Hill C, “Les effets sur la santé du tabagisme passif” [The health effects of second-hand smoke]. BEH 2011,20-21 :233-235.
9 - Special edition, Tobacco Control 2013,22.
10 - Marteau T « Judging nudging :can nudging improve population health ? » BMJ 2011,342:d228.
11 - Behaviour change. Report House of Lords. HL Paper 179.
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Research in Information and Communications Technologies
(e-tools, technological innovation12)
The Internet and smartphones are alternatives with strong
potential for collecting data that offer numerous options
yet to be explored and validated. The convergence of these
technological and epidemiological advances is opening new
avenues to enhance prevention strategies, improve public health
recommendations and ultimately the state of health among
populations.
Clinical research
Effectiveness of nicotine substitutes;
Innovation in developing new molecules and/or new treatments;
Join the international discussion on reducing the nicotine
content in cigarettes13.
Biological research
• Improve the analysis of biological markers for tobacco and
second-hand smoke14.
• Expand the knowledge on genetic influences in treating or
preventing dependence, for example, the role of monoamine
oxidase inhibitors (MAOI)15, nicotine receptors.
• Electronic cigarettes should be included in considerations on
the programme. This research should be multidisciplinary
(noxiousness, cessation support, ethical aspects, etc.) and
financially supported to expose the reasons behind this new
trend, which is seeing an exponential rise.
The programme will also have to provide resources
for the following projects:
• consumption trajectories,
• the social image of smoking, the portrayal of tobacco use,
• resistance to prevention efforts,
• health inequalities,
• quality of life,
• the role of health professionals in smoking prevention,
• developing metrology to document personal and collective
exposure,
• social marketing, marketing practices in the tobacco industry16 and
their impacts17, marketing to people’s smoking-related attitudes and
habits, unmarked packaging, under-the-counter sales.
IMPROVE SCIENTIFIC MONITORING
AND COMMUNICATION
As part of gaining recognition for the programme, evaluations
will be completed and collective works will be distributed to
help answer a list of questions previously issued by the working
group, clarify the political and administrative directors,
researchers and people in the field working on smoking-related
cancer prevention and screening.
2.1.2. BOOST PREVENTION OF SMOKING-RELATED
CANCER OVER THE NEXT FIVE YEARS
Measures to fight the onset of smoking
and denormalise tobacco
Using taxation as a public health objective to reduce tobacco use:
international organisations (such as the World Bank, World
Health Organization, International Agency for Research on
Cancer (IARC)) consider raising the price of tobacco as the most
effective and least costly anti-smoking measure. The impact of
higher prices is mostly seen among young people who are the
most sensitive to price changes18. These efforts must persist.
The Haut Conseil de la Santé Publique (High Council for Public
Health) recommends steadily and incrementally raising the price
by a wide margin, at least by 10% of the total retail price for
tobacco products19.
Standardised unmarked packs and larger graphic warnings labels:
the Framework Convention on Tobacco Control (FCTC) and
related guidelines have demonstrated the effectiveness of
placing large graphic warnings labels on tobacco products and
standardising the use of unmarked packs20. Findings from three
studies21,22,23 funded by INCa on the impact of graphic warnings
labels and standardised unmarked packs in France confirm
the results obtained around the world24: reasonably sized
warnings are known to better inform consumers and the people
around them. Combined with the introduction of standardised
unmarked packs, large graphic warnings labels can “break” the
advertising and promotional component of packaging, thereby
helping to “denormalise” tobacco consumption.
12 - For example, on its website NCI has an interactive application called NCI QuitPal http://www.cancer.gov/cancertopics/tobacco/smoking/quitting/nciquitpal-app
13 - Benowitz N et al. “Reducing the nicotine content to make cigarettes less addictive.” Tob Control 2013 ;22 :i14-i17.
14 - Avila-Tang, “Assessing second-hand smoke using biological markers,” Tobacco Control 2013 ;22 :164-171.
15 - Reference sheet “Sevrage tabagique et prévention des cancers” [Smoking cessation and cancer prevention], INCa.
16 - In 2008, NCI published a study on tobacco and the media. The same study could be conducted in France.
17 - Centre d’analyse stratégique « Nouvelles approches de la prévention en santé publique » 2010, n°25 [Strategic analysis centre new prevention approaches in public health].
18 - Effectiveness of Tax and Price Policies for Tobacco Control, International agency for Research on Cancer (IARC), Handbooks of Cancer Prevention, volume 14 (2011).
19 - Opinion on raising tobacco taxes to reduce the prevalence of smoking.
20 - Idem
21 - http://www.who.int/fctc/text_download/fr/index.html - http://www.who.int/fctc/protocol/guidelines/adopted/article_11/fr/index.html
22 - Karine Gallopel Morvan: “Impact des avertissements sanitaires visuels et des paquets de cigarettes génériques sur des français” [The impact of visual health warnings and generic cigarette packs
on the French population], report submitted to INCa in August 2010.
23 - CNCT: “Comment mettre en oeuvre les dispositifs de la CCLAT pour parvenir à une dénormalisation de la consommation de tabac” [How to implement the FCTC measures and ultimately
denormalise tobacco consumption], report submitted to INCa in June 2009.
24 - CNCT: “Tapaqfi: produits tabac packagings et coût dissuasifs” [The Tapaqfi Project: tobacco products, packaging and dissuasive prices], report submitted to INCa in December 2011.
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Tobacco advertising at the point of sale and during television
broadcasts of motor sports: a 2010 study by the Comité National
Contre le Tabagisme (French National Anti-Smoking Committee,
CNCT) showed that over 80% of tobacconists do not obey
current laws regulating tobacco advertisements in retail outlets,
i.e. displaying cigarette packs and selling to minors.
111
Measures on quitting tobacco use
These measures include:
• involvement of health professionals in smoking prevention,
• reimbursement of cessation aids by the health insurance system,
• identification of people or population groups at a higher risk
for cancer to develop plans customised for individuals or groups
(people with high exposure, former cancer patients, etc.).
Neither is the legislation being followed in terms of:
• the image of tobacco in the media. A study conducted by the
Ligue Contre le Cancer (French National Cancer League) in
201225 showed that 80% of the most popular French films at
the box office from 2005 to 2010 showed an average of 2.4
minutes of footage where smoking was evident, the equivalent
of five tobacco ads,
• messages about tobacco aimed at the general public and
prevention messages for health professionals. Findings from
the INPES/INCa Cancer Barometer revealed that although
virtually everyone polled was aware of the risk of cancer from
smoking, 65% of them thought that smoking is just as bad for
your health as breathing city air.
INCa is currently working on a campaign to rank the risks
of cancer. It is expected to be operational in 2014 and will
focus on two objectives: help the public put the risk factors
into perspective in terms of how they actually impact the
occurrence of cancer and strengthen awareness on the vital
role of prevention as a way to deal with cancer.
Potential actions
1. Make the prevention of smoking a full-fledged priority
in the French Ministry of National Education’s health
education policy, mainly by providing resources to
develop and monitor health education initiatives in
schools and involving youths, the entire education
community and parents in the process.
2. Expand prevention and support initiatives that target
women, young people and vulnerable populations.
3. Organise regular local campaigns that contain both
proactive messages and positive images that show the
virtues of being a non-smoker.
25 - https://uwaterloo.ca/applied-health-sciences/news/report-highlights-successtobacco-control - Do larger pictorial health warnings diminish the need for plain packaging
of cigarettes? Wakefield M et al. Addiction, 107, 1159–1167, 2012.
26 - Ligue Contre le Cancer: “Tabac et Cinéma: La ligue révèle les résultats édifiants d’une
enquête inédite menée depuis 2005 sur 180 films français” [Tobacco and the Cinema: La
Ligue issues some eye-opening findings from an unprecedented study of 180 films since
2005]. Ligue contre le cancer and Ipsos, 31 May 2012.
27 - Projet ITC. Second national report ITC France. University of Waterloo, Waterloo,
Ontario, Canada; Institut National de Prévention et d’Éducation pour la Santé (National
Health Prevention and Education Institute, INPES), Institut National du Cancer (French
National Cancer Institute, INCa), Paris, France. October 2011.
INCArapportGB2013.indd 111
Provide smoking cessation treatment plans for patients with
a tobacco-induced illness or for whom tobacco exacerbated or
accelerated the illness. Findings26 from a study by URC Eco d’Ile de
France used a probability model to show the strategy of offering
full coverage for smoking cessation is, in a vast majority of cases, a
better approach than the current lump-sum coverage system.
The referring doctor’s role in raising patient awareness on the
prevalence and toll of tobacco in causing diseases and the benefits of
quitting. France ranks low among countries that participated in the
International Tobacco Control study, with only 27.5% of smokers
who receive smoking cessation counselling from their doctor during
a routine check-up27. The issue related to the inclusion of smoking
cessation in the public health goal-related remuneration (ROSP in
French) could be discussed.
The role of smoking cessation in cancer-related treatment.
Scientific studies28 show the multiple benefits of stopping
smoking for patients in the short and long terms, such as reducing
the risks posed by surgery, reducing side effects and reducing
the return of tumours. For example, benefits were observed in
subjects in the EPIC cohort (European Prospective Investigation
into Cancer and Nutrition) who were long-time ex-smokers. The
risk models are the same for smokers who had quit smoking
10 years or more before joining the cohort and people who had
never smoked. Many other studies have shown that continuing
to smoke after being diagnosed with cancer increases the risk
of a relapse while quitting smoking lowers the risk. This was
supported by three studies that looked at lung cancer patients
(small-cell lung cancer), who had a higher risk of a second primary
cancer, especially second primary lung cancer (NSCL)29,30,31.
28 - Licaj I et al, “Impact du tabac sur la mortalité totale et sur la mortalité par cause dans
l’étude européenne EPIC (European Prospective Investigation into Cancer and Nutrition) [The
role of tobacco consumption on total and cause-specific mortality in the European Prospective
Investigation into Cancer and Nutrition (EPIC) study], BEH 2013,20-21:234-238.
29 - Richardson, G.E., et al., Smoking cessation after successful treatment of small-cell
lung cancer is associated with fewer smoking-related second primary cancers. Ann Intern
Med, 1993. 119(5): p. 383-90.
30 - Tucker, M.A., et al., Second primary cancers related to smoking and treatment of small-cell lung
cancer. Lung Cancer Working Cadre. J Natl Cancer Inst, 1997. 89(23): p. 1782-8.
31 - Johnson, B.E., Second lung cancers in patients after treatment for an initial lung cancer. J Natl
Cancer Inst, 1998. 90(18): p. 1335-45.
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They also reveal that patients are usually willing to quit whereas
oncologists say smoking is often the last pleasure left for the patient
going through this ordeal. In English-language literature, a cancer
diagnosis appears to motivate the vast majority of patients to quit
smoking32,33.
Potential actions
1. Include tobacco use in the Cancer Communication
Record (DCC).
2. Draft a guide for health professionals about the
effects of smoking and the benefits of quitting after a
diagnosis of cancer (education, involving the workplace
physician, dentists, teaching doctors and nurses, etc.).
3. Raise awareness among cancer patients on quitting
smoking (partnership with patient associations,
targeted initiatives for teens and young adults who had
cancer as a child to prevent the onset of smoking).
2.2. TO BUILD A SHARED BIOLOGICAL,
CLINICAL AND EPIDEMIOLOGICAL DATABASE
2.2.1. OBJECTIVES OF DATA SHARING
The database will draw data sources from the healthcare system
(medical administrative data generated by hospital institutions,
like PMSI (Programme for the Medicalisation of Information
Systems) or SNIIR-AM (National Inter-Plan Health Insurance
Information System) and clinical, biological and epidemiological
datasets generated by research.
Over the last few years, the massive amount of new data acquired
through genomic analysis (particularly high throughput
sequencing) has boosted the production of biological data. These
genomic analyses now provide unprecedented opportunities for
cancer research and treatment. Genomic data can essentially
be used to devise a new classification of tumour sub-types
resulting in approaches to the tumour development process
that have never been studied. Before these genomic data can be
used, they must be correlated with clinical, epidemiological and
biological data. Furthermore, the complexity and diversity of
cancer requires immense datasets in order to conduct relevant
clinical comparisons and research for therapeutic purposes.
One of the biggest issues to resolve at the local, national and
international levels is using these data in an integrated manner to
advance the knowledge and understanding of the mechanisms
of cancer and its medical care.
In addition, the current fragmented or aggregated format of
existing databases means they accumulate substantial volumes
of data that are not always used. However, these data serve as
research potential that methodologists can analyse after the
fact. Their skills provide an opportunity to offer treatment and
analysis methods and to guide researchers toward new topics.
Using these data in research projects requires widening the shared
channels (pooling data sources and types and professionally
managing databases) and improving how they are analysed (bioinformatics and statistical skills and analysis tools designed to
handle extremely large files and massive numbers of variabilities).
Correlation studies of the data collected or generated should
then make it possible to formulate functional hypotheses or
answer new research questions.
2.2.2. STAKES OF DATA SHARING
The data that will need to be shared, integrated and used is
extremely broad in terms of classification, type and format.
The classification is defined by whether the source of the data is
public or private, which may ultimately determine its accessibility.
Even for data that is public, the concept of “producer” will also
need to be considered, who the promoter is, for example, for
the clinical trials. In effect, the promoter could claim rights to
use the data before making it available to the entire research
community.
The type of data pertains to how they are collected or generated:
• clinical data (medical files and clinical research data), health
expenses,
• biological diagnostics data (laboratories),
• epidemiological data (surveys and/or public health cohorts
and/or research groups),
• molecular data (genomics, proteomics, transcriptomics, 3D
structures),
• imaging data (biological/medical imaging, microscopy and
cellular imaging in research).
In the cancer research field, the current challenge of managing and
integrating large volumes of data mainly involves molecular data
and more specifically the genomics data related to clinical data.
The format of the data is determined by their classification and type
(quantitative, textual, raw, metadata, images, etc.) and by nature
varies greatly, which necessitates planning for special storage and
processing functionalities when designing a shared database.
32 - Demark-Wahnefried, W., et al., Riding the crest of the teachable moment: promoting long-term health after the diagnosis of cancer. J Clin Oncol, 2005. 23(24): p. 5814-30.
33 - McBride, C.M. and J.S. Ostroff, Teachable moments for promoting smoking cessation: the context of cancer care and survivorship. Cancer Control, 2003. 10(4): p. 325-33.
INCArapportGB2013.indd 112
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In terms of a purpose, data pooling and data sharing are
designed to integrate them to allow analyses and interpretations.
However, when organising them it would be wise to differentiate
the assembly, integration and usage phases.
• Assembly phase: for the centres that generate or collect data
(hospitals, research laboratories, institutional databases) it
entails making them available in line with scientific or medical
objectives. In theory, the only goal of this availability is to make
information public that was obtained using taxpayer money.
Yet, they should be made available while keeping potentially
identifiable information confidential. Data assembly is based
on the interoperability of databases from different sources,
i.e. the ability of many different data management systems
to exchange information. Achieving this interoperability
involves technical factors (different software), syntactical
factors (exchange format) as well as semantic considerations
(determining a common definition of data).
• Data integration phase: it relies on a capacity to link different
types of data (clinical, biological, medical imaging criteria,
genomic or proteomic profiles, etc.) for the same patients.
It requires anticipating and organising data traceability
(username) and linking these data so they can be used at a
later time.
• Data usage phase: it should be managed only within a research
strategy that will lead to designing and planning correlation
studies between the data and pre-defined criteria for each
research project. Usage is the scientific reason for sharing and
integration and should be conceived to provide answers to the
questions raised within the project framework.
The professionalization of data sharing, integration and usage
Building and using databases should be professionalised and
drawn from a chain of disciplines bringing together clinicians,
biologists, pathologists, data managers, bio-informatics
specialists, epidemiologists, IT specialists and mathematicians.
Furthermore, it is beyond the capabilities of outlying institutions
and highly-specialised disciplines to organise data sharing and
they need concerted interconnected systems built as national
infrastructures.
Considerations on introducing dedicated data sharing
infrastructures will need to account for existing organisations
that provide resources for collecting, producing, storing or
accessing data as well as new requirements to accommodate
the exponential growth of genomic and imaging data.
INCArapportGB2013.indd 113
113
Potential organisational models rely on both existing structures
and uniting scientific teams around a research strategy. The
existing structures will need to be considered for their industry
expertise and service capacity, to manage and process data
(collection, quality control, storage) and, for their expertise
and capacity for analysis (bio-informatics, bio-statistics).
Forming scientific consortia with a research strategy is a
determining factor in the design and multi-centre organisation
of data collection and of designing and using databases in line
with a range of scientific questions. The research strategy involves
planning for the data collection, integration and usages, not
only at the research project level but also, and most importantly,
for the multiyear scale of a scientific theme.
Optimising the healthcare-research continuum to collect and
access the data with a view to sharing it
In light of technological, scientific and medical advances, the
potential to generate and use data will grow exponentially. We
must plan for this growth, by optimising the development of
the projected benefits for society and individuals alike and,
controlling the quality and use of the data in line with a national
code of ethics and laws.
This system involves a large number of participants from the
scientific, medical and institutional worlds, whose professional
interactions will not be evident in terms of objectives and
responsibility – as well as resources. This can only be established
through societal choices and the introduction of legal constraints
and obligations for doctors, scientists and health/research
institutions. INCa is perfectly positioned as an institution
to organise and even steer the thought process and offer
recommendations on behalf of its two regulatory ministries. In
following on the work done by ASIP (Health Information Systems
Agency) and beyond the scope of the Cancer Communication
Record (DCC), INCa is bringing together all the elements to
organise and optimise the healthcare-research continuum.
From this perspective and in our vision of the legal framework,
consideration would have to be given to the concepts of
“ownership” and “responsibility” for the data to be able to
plan the addressing and access rights tasks, not to mention an
obligation on resources to ensure the quality and integrity of
the data. If accepted, these concepts would play a major role in
organising the healthcare-research continuum.
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It will be impossible to compile the individual data without
instituting a unique username and password that create a link
between all the data generated at healthcare institutions or
laboratories.
The job of organising access to the patient data for scientific use
could be easier if the data were already compiled and the terms
of use for scientific purposes pre-defined. The use of data for
scientific purposes could be modulated based on the research
project’s ultimate objective. It would thus be easier to plan the
projects by clarifying or simplifying the no-objection/consent
procedure.
As far as resources, information and communications
technologies (ICT) enable general-purpose 24-hour access from
anywhere in the world to all the resources (data, computing
power), but also carry with them adverse effects in terms of
security and ethics. Therefore, it would be advisable to set up
a common framework to organise hospital and healthcare IT
systems by defining specifications and requiring the management
of traceability, links and access to patient data.
2.2.3. OBTAINING AND INTEGRATING GENOMICS AND
CLINICAL DATA
Context
The challenge in the cancer research field of managing and
integrating large volumes of data mainly involves molecular
data and more specifically the genomics data. The development
of genomics analysis techniques that can decipher molecular
mutations linked to cancer has profoundly changed how
cancer is classified, diagnosed and treated. Since 2006, INCa
and the French ministry in charge with Health have been
building a national network of 28 molecular genetic platforms
that conduct molecular tests, primarily tests that determine
access to targeted therapies for all patients throughout the
country. In 2012, 68,000 cancer patients in France were
administered molecular predictive tests: 20,000 patients had
lung cancer, 17,000 colorectal cancer, 8,000 breast cancer
and 4,000 melanoma.
Some 17 medications that target specific molecular tumour
abnormalities have been developed in the last 10 years and
are already available to patients. Current projections for
pharmaceutical companies are counting on the introduction
of four to five new and original drugs every year that target
new molecular pathways. The increased number of molecular
abnormalities to unravel on an individual level for an increasing
INCArapportGB2013.indd 114
number of patients will require using “all-in-one” approaches
that employ high-speed technologies like next-generation
sequencing (NGS).
This situation is leading to molecular genetics platforms that are
incorporating NGS into clinical practice. For the moment, this
pertains to “targeted” NGS where a panel of a dozens to a few
dozen genes are analysed. However, INCa is now anticipating the
development of extensive tumour genome sequencing, which is
expected to begin deployment in the next few years.
Genomic data will then have to be generated in the healthcare
context for a majority of patients as early as 2014. In addition to
molecular epidemiological data, there is a unique opportunity
to generate new knowledge by collecting these data in terms
of patient clinical characteristics and their treatment and
monitoring. For example, we could determine the therapeutic
effects of some rare mutations or identify subgroups of patients
with atypical response profiles.
The “France Biomarkers” project, funded by INCa, collected
molecular, clinical, treatment and follow-up data from
20,000 lung cancer patients, making it the first pilot study
that can help assess strengths and weaknesses of a project of
this kind.
Methods and conditions
INCa will need to work towards:
1. Modifying the functions of the molecular genetics
platforms and providing them the means to
systematically collect clinical patient data for which it
generated genomics data.
2. Supporting the molecular genetics platforms to design a
system to integrate and store clinical and genomics data.
3. Continuing and steering the programme to identify
and set up clinical biological databases with systematic
collection of genomics data.
That is why embarking now on the development of a national
database that collects these data is a strategic national
endeavour. It does, however, carry a number of challenges that
have barely been considered until now:
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Ethical aspects: the goal of developing these sorts of databases
and sharing stored information will be to accelerate oncology
research. Yet, in most if not all cases, these clinical and genomics
data will be collected in a healthcare setting. This dichotomy
raises a number of questions in terms of ethics (i.e. identifying
a molecular abnormality without a treatment targeting that
abnormality), regulations (i.e. storing data outside the country
that by national law belongs to the patients, personal data
security, etc.), complete and accurate patient information as
well as the ability to meet the requirements of French and
European regulatory agencies.
Data protection, criteria for data access and sharing,
determining patient consent methods to use treatment-related
data for research projects – there are several issues that will
have to be addressed when these databases are introduced.
Consideration will also have to be given to the current context,
where the 1995 European directive regulating private data is
undergoing revisions.
Therefore, the implementation of this project will have to:
• anticipate questions on the ethics of collecting, compiling,
storing and using private data,
• account for French and European legal requirements on
accessing private data.
Technical aspects: in order to facilitate the data sharing
component, we would need to develop a database that
could be centralised where the information can be accessed.
In this context, the different sources generating the data to
be integrated, for example molecular genetics platforms and
clinical biological databases will have to provide their data to
this database. The ‘large data’ community is a large number of
stakeholders involved in the data to integrate, and thereby IT
tools, software and methodological tools, in the selection of
data banks and databases, and the wide variety of data. This
sort of community requires extensive planning to make the
data accessible and shareable.
INCArapportGB2013.indd 115
115
Therefore, we will need to:
• make the data management systems interoperable by using
software, exchange formats and validating the data itself,
• develop and/or use an academic or private centralised
infrastructure, perhaps something like the Cloud or a
hierarchical system (i.e. the CERN model) to store the data.
Data analysis and use: research teams can analyse and the stored
data by importing useful data locally or, since the volume of
data is so large, it would be more practical to access it from
the centralised database directly, perhaps in the cloud, without
importing the data locally. In the first case, all or almost all the
teams should have not only the right hardware and software to
handle big data, but also the skills required to perform these
tasks. For example, these teams would have to have skills in
bio-informatics as well as technical computer skills to resolve
issues with IT technologies that are still unstable. Thus, there
is still some concern right now about data transfer speeds and
maintaining the integrity of the data being transferred. Some
solutions are more practical than others:
• developing and/or using the Cloud provides a secure
environment (platform) to analyse data and backup findings,
with data, administrative and analysis software, analysis
models and storage space for off-site findings that can be
viewed remotely on demand,
• develop and provide access for research teams to a centralised
technical support platform comprised of IT specialists and a
methodological support platform of bio-informatics experts,
• provide support for training in the skills required to develop
and sustain the chain that begins with data collection and
ends with sharing integrated data,
• plan for and encourage an expanding community, for example
an academic community, at the national or European level of
analysis, calculation and modelling methods (i.e. algorithms),
programming, more shared licences and other tools that
enhance the large data environment.
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Structures contributing to data production
Structures
Data processing centres
(CTDs)
Nb
11
Missions
Logistics and methodology support for
clinical research projects, particularly in
data management, quality control and
data analysis.
Refers to investigators, qualified personnel
(working in clinical research, clinical study
technicians) to ensure inclusions and data
quality.
Interfaces
Cooperative inter-groups
PHRC (clinical cancer
research hospital)
CLIP2
Cooperative inter-groups
PHRC (clinical cancer
research hospital)
Mobile clinical research
teams (EMRCs)
26
Molecular genetic
platforms (PFGM)
28
Conducts molecular testing (diagnostics,
prognostics) that help determine access
to targeted cancer therapies and conduct
disease monitoring.
SIRIC
CLIP²
Cooperative inter-groups
Rare cancer initiative
Constitutional oncogenetic
laboratories
25
Conducts molecular tests to identify
people with a high risk for cancer.
Tumour banks
58
Organises and rationalises biological
resources conservation and access for
cancer research.
SIRIC
Data collection
CLIP2
Storage and quality
Cooperative inter-groups
Rare cancer initiative
Builds clinical biological databases associated with biological samples around a
common pathology. Organise and optimise data collection to integrate and use
data in research projects.
SIRIC
Integration, storage, mining
CLIP2
Cooperative inter-groups
Rare cancer networks
Clinical biological
databases
9
Call for
proposals
in
progress
Registries
Generalists
Specialists
(qualified) Oversees ongoing exhaustive basic data
12
collection within a geographically defined
16
population for research and public health
purposes.
Rare cancer programmes
INCArapportGB2013.indd 116
Organises and structures treatment and
research frameworks.
Data
Management
Storage
Processing
Data collection
Quality
Production
Data collection: Lung database:
Projet Biomarqueurs France (France
Biomarker Project) directed by IFCT
(Francophone Thoracic Oncology
Inter-group)
Production
Data collection: database of BRCA
and MMR gene mutations
BCB
Tumour banks
Screening management
facilities
Rare cancer networks
Data collection, mining
Cooperative inter-groups Production, collection,
CLIP2
storage, mining
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2.3. TO FOSTER CLOSER TIES BETWEEN
TEACHING AND RESEARCH AND INCREASE
SUPPORT FOR INTERDISCIPLINARY
TRAINING
The landscape of cancer research has changed considerably
in recent years, particularly with the 2009-2013 Cancer Plan
that allowed research and care centres to work together and
forces and skills to concentrate on eight SIRIC sites designated
in 2011 and 2012. For the years to come efforts have to be made
beyond SIRICs and higher participation from teaching hospitals
(University hospitals, CHU, including affiliated Cancer care
centers (CLCC)) in oncology research through and in addition
to clinical research is to be obtained. This objective is not specific
to cancer, but it could be a driving force in a broader discussion.
Moreover, actions should be set up to assign accountability
and foster independence among young researchers and support
training and an interdisciplinary approach.
2.3.1. ENCOURAGE INTERFACES BETWEEN
UNIVERSITIES AND HOSPITALS
In addition to the recently designated SIRIC (Integrated Cancer
Research Sites), a hospital cancer research policy could be
established at CHUs and CLCCs not designated as SIRICs.
The goal is to promote the scientific quality of these centres,
encourage and support research partnerships outside of the
actual centres, increase and harmonise the centres’ research
activities with national initiatives led by INCa and the Aviesan
cancer alliance, and make translational cancer research one of
their core activities.
The goal is to leverage these centres’ institutional resources
that thereby incorporate fundamental, clinical and population
health research into a large cross-disciplinary translational
programme that is built and carried out with researchers and
clinicians working side by side where translational research
warrants a work organisation and exchanges that imply a change
in practices and methods.
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117
Potential actions
1. Set up a call for projects aimed at CHUs and CLCCs
that demonstrate exemplary research activities linking
clinical/population health and prevention to intensify
interactions between research and healthcare.
2. The programme could also include targeted support
for basic training aimed at oncology clinicians and
bring in both local drivers led by hospitals and
universities and national actions run by INCa that
would enable complementary coordinated financing
for M2 Master’s degrees, PhDs, international
internships, discharges from hospital activity.
3. Set up the conditions making it easier to hire teaching
hospital staffs that meet the needs of both clinics and
research.
The expectations of centres that would receive this type of
funding are to:
• be the main centres contributing to exploring the very nature
of cancer and developing more effective preventive, diagnostic
and treatment approaches,
• provide a substantial contribution to the expansion of shared
resources for research,
• collaborate and coordinate translational research projects
with other programmes assigned and directed by INCa and
the DGOS.
The projected impacts of this process are ultimately better
uniformity between programmes led by hospitals, universities
and research centres working on cancer, optimised use of
the CHU Cancer Platforms and improved training for young
oncologists.
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2.3.2. BACKING TO CREATE A CHAIR OF EXCELLENCE
IN TRANSLATIONAL RESEARCH
Oncology is an especially suitable field for deploying
translational research given the steady pace of the advances in
describing oncogenesis-related molecular and cellular events
and the development of new high-speed technologies, which
are providing a unique opportunity to translate these discoveries
into tangible advantages for patients with the personalised
treatment approach.
New Chairs of Excellence in translational research would
enhance the support mechanisms introduced in the last few
years by universities promoting a culture of translational
cancer research through educational and research programmes
designed to build a continuum with hospital care.
The Chairs of Translational Oncology Research would draw
recognition to the teaching hospital career path of physicians
and pharmacists qualified to do this research, open doors to toppriority fields of cancer research and promote multidisciplinary
education that will improve the quality and visibility of this
research.
The specific objectives are:
In education, to develop a shared culture for the translational
research process by organising and facilitating an educational
programme of seminars and workshops:
• seminars led by international scientists who are experts in their
field and invited to come and stay to share organisational and
scientific experiences as part of the Chair programme,
• workshops in methodology (biostatistics, bio-informatics
analysis, data management, etc.) and technology (high-speed
genomics analysis, imaging, etc.).
In research, within a hospital or special institution (SIRIC),
to lead a research programme on a specific theme supported
by interfaces between fundamental and clinical research, give
visibility to an area/field/process of original and/or top-priority
research, form European/international working partnerships
and enlist the Chair programme in an international network.
Priority themes in translational research:
• personalised medicine: developing new diagnostic tests and
companion tests alongside the marketing of new therapeutic
molecules, developing alternatives to clinical trials,
• new therapeutic technologies: advancing developments in surgery,
radiobiology, interventional imaging, etc.,
INCArapportGB2013.indd 118
• post-genomic research: functional validation and interpretation of
genomic abnormalities identified with high-speed techniques,
• integrative biology: integrating data from genomics analyses
with clinical and epidemiological data to devise decisional
algorithms, developing research programmes on biology
resulting from the integration of clinical and epidemiological
data (reverse phase).
In transfer, to develop interfaces with industry, pharma and
biotech, and strengthen and develop ties with national and local
promotional entities.
Potential actions
The first joint INCa-CPU (Conference of University
Presidents) call for candidatures could be launched in late
2013 to create three INCa-University chairs in the first
year and two in the second year. They would be backed
for four years.
2.3.3. ASSIGN ACCOUNTABILITY AND FOSTER
INDEPENDENCE AMONG YOUNG RESEARCHERS
This is a general topical subject in research and could be
furthered in terms of its structures involving medical interfaces.
We could envision a few tangible proposals:
Processes for gaining independence in France by forming
teams, like the ATIP/Avenir model (a five-year version)
Holding a competitive selection process to obtain resources to
develop an innovative independent research programme is an
excellent premise for fuelling the French scientific community.
The initiatives conducted during the ATIP/Avenir programme will
need to be continued and expanded. Nevertheless, it is obvious
that three years with a five-year extension (ATIP +) is not long
enough for the international initiatives to, for example, prepare
a smooth transition to the next phase. Other programmes in
neighbouring countries generally allow for five years with a twoyear extension with guidance, assessment/consulting after three
years and then after five years to help prepare for transitions
from one facility to another and ensure that skills are actively
flowing between the different structures.
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Potential actions
2.3.4. SUPPORT TRAINING AND
AN INTERDISCIPLINARY APPROACH
1. Propose adding two more years to ATIP/Avenir
Advanced hybrid training programmes
The significance of multidisciplinary training, like biology/
mathematics, biology/physics, etc. has long been acknowledged.
Since 2010, INCa and then since 2011, Aviesan-ITMO Cancer
have most notably been supporting the PhD programme
“Frontiers in Life Sciences” (Paris 5 and Paris 7) and there are other
institutes like Institut Curie partnering with various universities
and PhD programmes supporting this type of training. Projects
in the current system range from the most fundamental with
cellular and developmental studies that include mathematical/IT
applications to processing complex biological data (genome and
post-genome) and are also developing educational programmes
that are more oriented toward “cancer” applications.
projects, selected by EPSTs* with their current criteria
in the cancer field or a cancer-related field. This would
secure a five-year programme and be comparable to the
ERC Junior format.
2. Propose two more years, making it seven years
following a selective evaluation.
3. Encourage the introduction of a mentoring
programme for young groups and tools that could be
used for this purpose.
4. Motivate young researchers to lead large national
programmes, for example the open programme
on biology and cancer sciences research, an open
translational research programme. The majority
of these programmes is run by high-profile senior
researchers, some of whom coordinate or are involved
in numerous demands. An incentive policy aimed at
programmes run by young oncology researchers would
secure the independence of the initiators (reserved
budgets or targeted programmes) and thereby continue
fuelling innovative programmes.
Prior to the junior team phase, discussions in interdisciplinary
education and increased independence
Associations like the ARC Foundation, French National Cancer
League and FRM (French Foundation for Medical Research)
support young people getting involved in cancer research
through Master’s, PhD and postdoc grants.
Translational projects receive dedicated support from INCa and
the Aviesan Alliance. These funding help build independence
among the younger population. Interdisciplinary projects
contribute to the emergence of skills in interfacing, skills that
are increasingly needed as the scope of research and cancer
medicine expands.
Translational projects receive dedicated support from INCa and
the Aviesan Alliance. These funding help build independence
among the younger population. Interdisciplinary projects
Increase the
for thesis
and/or
contribute
to support
the emergence
of skills
in Master’s
interfacing, skills that
scholarships
on competitively
subjects
are
increasinglybased
needed
as the scope selected
of research
and cancer
(selection
process could be based on work done by PhD
medicine
expands.
programmes).
Potential actions
Training future oncologists in biology
INCa could step in to support training for doctors interested in
biology. A compelling advantage would be actions to incentivize
current training programmes in oncology to join forces or work
in tandem with institutions that offer major biology programmes
by combining students from many different fields in a space that
makes room for the international aspect.
Translational projects receive dedicated support from INCa and
the Aviesan Alliance. These funding help build independence
among the younger population. Interdisciplinary projects
Consider to
special
programmes
contribute
the emergence
of that
skillsare
in original
interfacing, skills that
and
competitiveneeded
and include
projectofbetween
are
increasingly
as theascope
researchtwo
and cancer
laboratories
with different expertise, a bit like the EIPODS
medicine
expands.
programmes between two laboratories at the EMBL.
Potential actions
* EPST: Établissements Publics à caractère Scientifique et Technologique (Public Scientific and Technical Research Institutes).
INCArapportGB2013.indd 119
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2.4. TO SUPPORT AMBITIOUS FRENCH
CANCER RESEARCH TO PROVIDE
THE POPULATION AND PATIENTS QUICK
AND SIZEABLE BENEFITS
From a public perspective, the goals of fighting cancer are
to prevent both individuals and population groups from
contracting cancer, diagnose them early so treatment is short
and barely debilitating, cure them and offer them, as far as
possible, a quality of life similar to the pre-diagnosis’ one.
Major progress has been made in the last decades in the fight
against blood diseases, breast cancer and testicular cancer.
However, a speeding-up is awaited in a number of cancerrelated pathologies, particularly the types of cancer with grave
prognoses like pancreatic or lung cancer, where no conclusive
therapeutic advances have been made, or brain tumours.
Every year during the 2003-2007 and 2009-2013 Cancer
Plans, support was provided for many research projects and
infrastructures, tools and competitive research networks were
identified or set up. The 2009-2013 Cancer Plan will have given
€469 M to support cancer research in all its forms.
It stands to reason, then, that French cancer research is
equipped to design, bring about and lead ambitious projects
with the specific objective to reduce the incidence, mortality
and morbidity of cancer. One of the largest contributions is
INCa’s recognition of inter-group cooperatives focusing on
major cancer-related pathologies that are likely to spearhead
wide-scale national projects targeting these objectives.
Translational projects receive dedicated support from INCa and
the Aviesan Alliance. These funding help build independence
among the younger population. Interdisciplinary projects
contribute to the emergence of skills in interfacing, skills that
are increasingly needed as the scope of research and cancer
medicine expands.
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Potential actions
Set aside a portion of the budget for each of INCa’s calls
for projects in clinical research, human sciences and
public health to support projects designed to significantly
reduce the risks and incidence of severe cancer and
improve patient quality of life.
INCa’s calls for proposals, some of which are led with partners,
cover all the anti-cancer disciplines and fields. These calls for
proposals are not targeted; the researchers devise the themes
themselves. While all of these projects are competitive, the
stakes involved in the issues they address are disproportionate.
As an example, over a period of 10 years these calls for
proposals funded more early-phase clinical trials than phase
III clinical trials at a rate of 2.5-3 times more in some years. The
timeline researchers set for these projects is not a determining
selection criterion, despite the feeling of urgency expressed by
the general public, patients and their loved ones. One of the
selection criteria should be a capacity for quick inclusion so the
studies are completed in a shorter time.
We need the participation of ambitious and competitive
research teams and infrastructures when solving questions on
the severity, duration and toxicity of treatments. In order to
motivate research teams, especially the top ones, to design
and submit projects that target these aspects, we will have to
set aside a considerable part – estimated to 50% - of calls for
proposals’ budgets for them. These scientific challenges would
be led by collaborative efforts among the most competitive
teams or managed by cooperative intergroups. Accordingly,
support to studies on low doses irradiation could benefit
secondary and tertiary prevention.
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2.4.1. SUPPORT RESEARCH PROJECTS WITH THE
SPECIFIC OBJECTIVE OF SUBSTANTIALLY REDUCING
THE RISKS AND INCIDENCE OF CANCER.
Research projects, primarily in prevention, epidemiology,
public health (PH) and health-intervention research will be
funded if they convey a stance on helping slow down or reverse
a growing curve or accelerate a reduction in incidence.
For example, it would entail projects to identify and analyse
risk factors for cancers that keep being little known or not
yet known, risk factors that significantly contribute to the
occurrence of cancer or risk factors that can be modified by
health-intervention projects including their estimated effect.
This objective requires stepping up INCa’s actions to attract
the best research teams in human and social sciences,
epidemiology or public health to the field of cancer and foster
translational research projects aimed at using fundamental
or biological studies to understand epidemiological or public
health observations.
Preferred actions
1. Identify and provide innovative researchers,
methods and tools in human and social sciences,
epidemiological, public health and health intervention
research.
2. Organise and support collaborative networks
of researchers.
3. Increase the calls for proposals budget for translational
research and understanding the behavioural
and environmental factors.
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2.4.2. IDENTIFY AND TIGHTLY MONITOR COGNITIVE
RESEARCH PROJECTS WHOSE EFFECTS OR
APPLICATIONS COULD BE SIGNIFICANT IN THE SHORT
OR MEDIUM TERM FOR REDUCING THE INCIDENCE
AND MORTALITY RATE AND IMPROVING PATIENT
QUALITY OF LIFE
Findings from upstream research can provide a wide array of
opportunities, ideas, avenues of validation research and clinics
applications. A crucial component is far-reaching financial
support for technological innovation to apply fundamental
advances.
Ensure that the potential/expected impacts or applications of
ambitious projects in submissions for calls are systematically
explained. Make it one of the selection criteria by committee.
Identify a significant and dedicated funding to research team
projects that support these approaches.
Improve INCa’s internal methods on scientific monitoring and
guidance for research projects.
2.4.3. SUPPORT TRANSLATIONAL RESEARCH
PROJECTS IN HUMAN AND SOCIAL SCIENCES WHOSE
OBJECTIVE IS TO SIGNIFICANTLY IMPROVE QUALITY
OF LIFE FOR CANCER PATIENTS
A key objective of the French Ministry of Health and INCa has
been the quality of life of cancer patients, most notably in
conducting actions in the 2009-2013 Cancer Plan. It is an area
of research in many of the calls for proposals managed by INCa,
especially the investigator-driven call for proposals in human
and social sciences research, epidemiology and public health
and the call for proposals for PHRC Cancer projects.
Potential actions
1. Conduct a scientific assessment of the research projects
that are funded and focus on the improvement of
quality of life.
2. Promote research on the understanding of quality
of life and how to measure it in the calls on clinical
research.
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2.4.4. IDENTIFY, SUPPORT AND MONITOR CLINICAL
TRIALS AIMED AT PROACTIVELY IMPROVING THE
OVERALL SURVIVAL RATE OF CANCER PATIENTS
Major therapeutic advances have been made for a number of
cancers in the last few years. Many types of cancer, such as
pancreatic cancer, brain tumours, ovarian cancer, lung cancer
and bladder cancer are still posing challenges for research.
Rare types of cancer are also a scientific challenge, primarily
because the clinical trials are difficult to manage. INCa should
encourage teams to conceive and submit clinical trials that
aim to substantially improve survival and, in some cases, large
pragmatic clinical trials that closely reflect treatments and work
to standardise good practices and reduce therapeutic risks and
lost opportunities. This objective should be supplemented by
trials that specifically address therapeutic de-escalation and
reducing treatment-related after-effects.
The objectives will be achieved with a collaborative teambased approach via cooperative inter-group. INCa-designated
cooperative inter-groups are collaborative and competitive
international networks capable of quickly managing phase III
clinical trials. They have a proven ability to unite research teams,
recruit over 25% of the patients enrolled in clinical oncology
trials each year in France (nearly 10,000 patients in 2011)
and contribute to approximately 80% of the French academic
papers in the authoritative international scientific publications.
They need to receive more financial and institutional support.
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Preferred actions
1. Fund a special research call for proposals for
understanding, preventing and reducing treatmentrelated after-effects in the short and medium terms.
2. Shift the funding ratio of early-stage clinical trials to
phase III clinical trials through a call for proposals
managed by INCa and set aside a large part of the
PHRC Cancer budget for large-scale clinical trials
focused on improving the overall patient survival rate
and therapeutic de-escalation.
3. Enlist the cooperative inter-groups designated by INCa
to head large phase III clinical trials aimed at improving
the survival rate by reserving competitive funding for
them (50% of the PHRC).
4. Interactively join the talks with the DGOS on
identifying, recognising and supporting clinical
investigation networks.
5. Intensify the designation programme for cooperative
inter-groups by bringing in new cooperative groups and
delineating the cooperative inter-groups.
6. Put in place public-private partnerships to manage
the phase III clinical trials and develop a European
cooperation policy on these trials.
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2.4.5. NARROW THE GAP BETWEEN RESEARCH
AND PRACTICE
Implement the use of findings from research in clinical
practice to narrow the gap between research and practice
and reduce the rate of lost opportunities
Despite recommendations from health authorities, it is still a
complex process to transfer research findings over to practice for
the benefit of populations and patients in many types of cancer.
There are economic, organisational and cultural factors involved
caused by the separation between research environments and
places where medicine is practised. This gap between research
and practice can lead to delays, digressions and even bad
practices. INCa must interact with its partners to propose and
set up actions that provide support for projects designed to
narrow the gap between research and practice.
Potential actions
1. Support research projects that aim to identify and
analyse the factors and conditions of transferring
research findings to practice, incorporating them in
the political decision-making process and having them
assimilated by the general public.
2. Propose the positioning of INCa’s health-intervention
research call for proposals to the Ministry of Health as
tools to aid the government decision-making process
on public health issues.
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In clinical research, the management of therapeutic trials,
most importantly in healthcare institutions, is still perceived
by healthcare professionals, hospital administrators, patients
and their loved ones as an extra-clinical activity in the sense that
they do not seem like an alternative to medical management
but rather as an “experiment” whereby day-to-day healthcare
practices can occur. For many cancer patients, therapeutic trials
may be the only remedial treatment solution available. Thus, for
example, it may be useful to propose.
Potential actions
Liaise with the DGOS (MoH) to experiment in a handful
of healthcare facilities on integrating clinical trials aimed
at improving overall survival, quality of life, therapeutic
de-escalation and the reduction of therapeutic aftereffects into day-to-day cancer care practices.
More generally, the transfer of innovations in practices would
naturally be a priority insofar as in this instance these innovations
contributed to achieving the goal of reducing cancer-related
incidence, mortality and morbidity.
Potential actions
Accelerate the introduction of the INCa programme to
detect, bring about, guide and disseminate innovations.
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Use research to ensure the findings observed in practice
comply with and compare to the research findings
The gap between research and practice can also lead to
obtaining results in practice that are considerably lower (effect
size) than in research. To optimise the results from research for
the benefit of populations and patients, INCa could expressly
support research projects with objectives to understand the
mechanisms, strategies and conditions for reproducing the
effect size obtained by research in public health and clinical
practices.
Optimise research findings in preventive, screening and
treatment practices
Once the factors and mechanisms limiting the reproducibility
of research findings in practice and their effect size have been
identified, it must be associated with support for research
designed to reduce them. Many calls managed by INCa could
be used to this effect.
The health intervention research call and those on the quality
of care would thereby help, for example, finance projects that
aim to deal with these factors and mechanisms to optimise
the reproduction of the effect size seen in research findings in
practice.
Similarly, some rare tumours or tumours for whom therapeutic
drifts were experienced should be treated exclusively in
specialised centres.
Potential actions
1. Support research projects whose objective is to
identify and reduce the factors limiting the effect size
in practice compared to the effect size observed in
research.
2. Interact with the DGOS to have the wording changed
in the “Treatment track” section of the call for
proposals for PRME-K (Medical Economic Cancer
Research Programme) to allow research teams to
submit projects aimed at reproducing the optimum
conditions for duplicating the research results in
practices.
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2.5. NEW CHALLENGES IN CANCER
CONTROL: EUROPEAN AND GLOBAL
PERSPECTIVES
2.5.1. EUROPEAN COLLABORATIONS
Beyond the European partnership against cancer EPAAC –
Continuation and expansion of cancer research coordination
in early phase clinical studies. Horizon 2020 perspectives
and potential synergies with IMI2 (the innovative medicine
initiative 2)
Early clinical trials should well be considered as the first
milestone to the implementation of personalised/precision
medicine and should be pursued through concerted actions
and strategic public-private partnerships. As explained
under chapter 7 above, EPAAC WP8 was instrumental in the
development of an embryonic European coordination scheme
in early-phase therapeutic cancer research. We view the renewal
of the Innovative Medicine Initiative under the frame Horizon
2020 as an opportunity to expand further this embryonic
action and reach to a pan European organizational framework
using the public-private scheme of IMI2. Two targeted areas
in the field of early phase clinical trials clearly emerged from
intelligence-gathering exercises carried out within WP8: i) Early
phase clinical trials based on molecular diagnosis, ii) Early
phase clinical trials for targeted drug combination.
Advances in the molecular profiling of tumour tissues have
opened up an era of precision cancer treatment. Molecular
profile of individual tumour now guides therapy and has
become a decisive factor. Market approval of targeted drugs
makes molecular testing mandatory and commands the
development of subsequent organizational framework to ensure
a fair access to tumour molecular profiling for all patients. Stateof-the-art biomarker-driven early phase trials are important
components of the whole framework. They are essential to
evaluate the efficacy and safety of new drugs, new therapeutic
strategies or administration routes, and make optimal choices
about dosages and durations of treatment. They entail public/
private coordination of resources to explore all the potential
indications and develop new adequate designs of clinical trials.
The Innovative Medicine Initiative is certainly an appropriate
place to reach the level of collective think tank needed between
the pharmaceutical industries and academic representatives
regarding these new types of trials.
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Targeted therapies have also shown some limitations. Chief
among these is the potential for cells to develop resistance.
Combination of targeted therapies, either with other targeted
therapies or with more traditional therapies is a promising
way, as it may overcome resistance, synergize the effects of
the drugs and increase the efficacy of the treatment. The
high number of targeted drugs offers large opportunities to
improve treatments. Collaboration between companies would
facilitate access to multiple combination and drug association
and would spur collaboration with academic groups. Again
IMI seems to offer a platform of choice to initiate discussions
and conduct this type of study.
Promote the new European concerted and support action in
the area of personalised medicine (CSA PerMed)
The implementation of personalised medicine is a major
challenge in Europe and beyond. It calls for appropriate
governance strategies at the European level as it defies the way
in which healthcare systems are set up. It requires strategic
rearrangements in academic and industrial research to support
these organizational changes. A consortium of 28 public and
private agencies, government bodies, health care professionals,
private enterprises, regulatory bodies and leading charities,
representing 14 countries, has joined forces to accelerate the
development and uptake of personalised medicine in Europe,
and submitted a proposal for a “Concerted and Support
Action” entitled: Personalised Medicine 2020 and beyond –
Preparing Europe for leading the global way (PerMed). This
proposal, coordinated by the Federal Ministry of Education
and Research of Germany, was successfully evaluated by the
European Commission and is expected to start by the end of
2013. It sets the work plan towards the development of a shared
vision and a technology roadmap to promote the development
and uptake of personalised medicine in Europe. The consortium
will first assess the available research and innovation resources,
identify leading organizations, gaps and needs, and will point
towards possible mechanism to help deploy common activities
under Horizon2020, including future alignment of research
policies. A technology roadmap will set the long-term objectives
and provide a tentative framework to help plan and coordinate
technology and system developments. Thematic areas will
be identified during 2 workshops to be attended by people
representing a wide range of stakeholders (medical companies,
charities, health care representatives, clinicians and researchers
from across a number of disciplines, and representatives of
public sector bodies). The roadmap will capture the range of
views expressed by this broad group of stakeholders.
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The INCa will contribute to workpackage 1 “Inventory of
activities, key players and identification of gaps and needs” and
workpackage 3 “Recommendations for strategic development
(Research Agenda)”. The duration of the project is 24 months
(2013-2015).
Develop a new joint action to reach out the aims of the
European cancer partnership set out in the Commission
Communication COM(2009)291 of 24 June 2009
The objective of this new joint action, called “CANCON”
is to develop a European guide on quality improvement in
comprehensive cancer control. The guide will address various
aspects of coordinated and integrated cancer control, aiming
at improved quality of cancer screening programmes, better
integration of cancer care through models for comprehensive
cancer care networks, promotion of community-based primary
level cancer care approaches and concerted efforts in all
aspects of survivorship and rehabilitation, including supportive
and palliative care. Other key activity is the organization of a
platform, providing Member States with the opportunity to
debate and share information and knowledge in topical areas,
as the guide develops. This action will contribute to reaching
the aims of the European cancer partnership set out in the
Commission Communication COM(2009)291 of 24 June 2009
on Actions against cancer: European Partnership (EPAAC),
and will build on its achievements and on the outcomes of
previous EU actions on cancer. CANCON currently combines
26 associated partners from across Europe. The expected
benefits are combined European interdisciplinary knowledge,
innovative interventions, future guidelines to improve cancer
care and quality of life of cancer patients, and overall decreased
inequalities across Member States.
The INCa will lead the workpackage 8 on “Survivorship and
rehabilitation”, which addresses the life of cancer survivors
as they transition from treatment to recovery and beyond.
WP8 features content on the role of general practitioners and
specialists in providing follow-up care to cancer survivors, the
management of late and long-term medical and psychosocial
effects of cancer and its treatments, work-related aspects of
survivorship for both patients and society and the importance
of survivorship care planning.
The INCa will also contribute to the workpackage 6 “integrated
cancer control” which aims at expanding further the concept
of comprehensive cancer centre towards comprehensive
cancer care network, that reach out to the patients. Specific
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objectives of WP6 include, within the network organizational
framework, the uptake of clinical recommendations and
advanced technologies by the network, access to clinical
trials, management of rare tumour, development of common
infrastructures and professional coordination, integration of
research and care.
The INCa will finally contribute to the workpackage 9 on
“Screening”, which overall purpose is to create further guidance
to members States, based on the best available evidence, to
implement or improve the implementation of populationbased cancer screening programmes.
The duration of the Joint Action is 36 months (2014 – 2017).
2.5.2. GLOBAL CANCER CONTROL
While non-communicable diseases are currently seen as true
epidemics that have to be fought using strategies modelled
after those used to counteract infectious diseases, it makes
sense to use the networks and infrastructures developed
to fight HIV. This type of coordination is needed to quickly
attain international standards and organise patient care. Our
cooperation strategy with low and middle income countries is
part of a global context where the human cost of cancer seems
to be endlessly mounting. This effort inevitably encompasses
the training-research-public health continuum. A coordinated
effort was set up with international agencies like the IAEA, local
partners and health authorities in these countries, of course,
as well as French agencies and institutions that had installed
infrastructures abroad. Training courses for healthcare teams
were organised and research projects launched to build capacity
in the countries and while the actions were coordinated with
local forces and were part of a national action plan, they remain
isolated and difficult to assemble because they mobilise scarce
available human resources. Therefore, the objective is to put
together some transnational actions and further intensify our
coordination efforts with French partners gathered in Aviesan
Sud, operators developing a global strategy like the US NCI
and networks like AORTIC to deepen the potential impact and
introduce programmes that would encourage investigators in
low and middle income countries to rely on research and its
discipline as they address public health issues.
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The pressing need to collect epidemiological data with
appropriate population-based registries is regularly reasserted
by cancer professionals in low and medium income countries
(LMICs). Reliable data are needed to guide cancer control
interventions, evaluate the requisite resources, convince
policymakers in Ministries of Health and other governmental
bodies and monitor the outcomes. The Global Initiative for
Cancer Registry Development in Low- and Middle-Income
Countries (GICR) convened by the International Agency
for Research on Cancer (IARC) with the backing of several
organizations worldwide addresses the complex problems
facing cancer registries in LMICs (staff availability and
qualifications, inadequate information technology support,
verification of data, etc) in a systemic way. GICR is implemented
through “hubs” –regional resource centres capable of providing
developmental support towards cancer registries.
The INCa intends to collaborate closely with IARC, in particular
with the regional network hub for sub-Saharan Africa to help
develop cancer registration as a foundation for cancer control.
Possible involvements of INCa include the support of training
activities and the development of tailored training material to
improve the technical and managerial capacity of cancer data
professionals, with a particular attention to French-speaking
countries.
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CONCLUSION
The launch of a new cancer plan was proposed by the President Francois
Hollande in December 2012, to start in 2014. He focused its objectives
on five directions and priorities:
1 - Prevention, in particular towards primary prevention to strongly
reduce cancers which are avoidable, and secondary prevention
to reinforce early diagnostic and reduce sequelae and mortality,
2 - Research with the aims to develop a better understanding
of the disease and access to better therapies through more
personalised treatments,
3 - Better training of professionals involved in cancer care and
research including general practitioners (GPs) and clinical
nurses,
4 - Increase the quality of care through coordination and interaction
of clinical centres with GPs,
5 - Improve the quality of life of patients during their disease and
after, through facilitation of the return to work, insurance
access, and for children continuity in their school life.
The president has commissioned Prof. Jean-Paul Vernant to make
proposals for the future who released a report to the ministries in charge
of Health and Research in September 2013. This report will be the
frame of a series of measures and actions for the future plan, currently
being drafted by representatives of the ministries, INCa, scientific and
medical experts, public and patients’ advocates. The future plan should
be made public in early 2014 and will line the roadmap for the next
5 coming years. Major outcomes for research have been addressed
in the present report to the International Scientific Advisory Board of
INCa. They represent the contribution of the research community and
INCa to the joint reflection to decreasing the burden of cancer in our
country.
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This year has seen profound changes in the INCa organization
and instances. A large number of the members of its International
Scientific Advisory Board have been renewed, including its Chair. A
broad range of disciplines involved in cancer research is represented
with the international recognition of these members. This will help
our strategic decisions not only in research but also in quality of care,
innovation and public health orientations. The deontology committee
has been changed to an ethical and deontology committee since we
are facing important decisions about screening strategies, active
prevention, and access to new therapies through individual genomics
and relationships with pharmaceutical industry through research. Our
relations with professionals working in the cancer field, patients and
public representatives have been clarified through a unique institutional
committee, COMUP, with the aim to bring experience and outlook of
the healthcare users and providers to constantly improve the quality,
the relevance and the value of the strategies developed by INCa and to
sustain its legitimacy and its ownership by everybody.
These priorities and changes are the INCa 2014 action plan blueprint.
Prof. Agnès Buzyn
Chairwoman of the
National Cancer Institute
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Appendices
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1. TUMOUR BANKS
Monitoring of activity
Recommendations
INCa’s Strategic initiatives
National and international
collaborations
2005-2007
2006: first activity report
on the tumour banks.
2007: audit of
policy for organisation.
• 2005: initial recommendation from
INCa (ethics charter, indications for
cryopreservation as part of care).
• 2007: national recommendations
(system for management and quality
control of a biological resource
collection).
2008-2011
Annual activity reports
• INCa recommendations for local
2010: declaration form
organisation: governance and
available online.
operating costs incurred
Production of activity report. in facilitating partnerships.
• INCa recommendations for organisation at local and network scale:
governance and scientific priorities
for national collections.
• 2008: call for proposals for “Genomic • European BBMRI project: active particiand Scientific added value of Biological pation by INCa.
• BIOBANQUES (National infrastrucResources.”
(8 projects selected, €5.3 M)
ture): INCa is a member of both
the management committee
• 2011: first call for proposals on
specific multi-centre multidisciplinary
and the scientific advisory board.
databases: tumours and biological
collections. (5 projects selected,
€2.8 M).
2012-2013
• 2012: implementation of
• 2012: written notification of health
the online activity report.
facilities of the new terms of support
Comprehensive monitoring for the scientific contributions of
of health- and science-rela- tumour banks, to be based on
ted activities by pathology.
an index calculated from activity data.
Better evaluation of the
implementation of INCa’s
recommendations from
2011.
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• 2012: 2nd call for proposals on BCBs
• 2013: launch of a 3rd call for proposals
(4 projects selected, €2.6 M).
on clinical-biological databases, in coo• 2013: development of a national dataperation with Aviesan (BIOBANQUES).
base (tumour collections and related
expertise) as a resource for enhanced
use and strategic orientation.
• 2013: development of a new index of
scientific contribution, which favours
tumour banks that implement INCa’s
recommendations from 2011.
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2. IBISA PLATFORMS
Type of Platform
Name of Centre
City
Proteomics
MaP, (Marseille Protéomique)
Pole Protéome de Montpellier-LR (Montpellier Proteome Hub)
Plate-forme protéomique Paris 5 (Paris 5 Proteomics Platform)
Pasteur Proteomics
Biogenouest Proteomics Core Facility
Plateforme de Protéomique Lille IFR 147 (Lille IFR 147 Proteomics Platform)
MARSEILLE
MONTPELLIER
PARIS
PARIS
RENNES
VILLENEUVE D’ASCQ
Novel Therapies,
Vectorisation, Stem Cells
Plate-forme anticorps monoclonaux-PADAM (PADAM Monoclonal Antibody Platform)
ANGERS
In vivo Imaging
CYCERON
Imagerie Sciences du Vivant - In vivo (Life-Sciences Imaging – In vivo)
PRIME
Imagerie Petit Animal Paris Descartes (Paris Descartes Small Animal Imaging)
Plateforme d’imagerie in vivo (In vivo Imaging Platform)
CAEN
GRENOBLE
ORSAY
PARIS
STRASBOURG
Cellular Imaging
Imagerie Sciences du Vivant-in vitro (Life-Sciences Imaging – In vitro)
Type of Platform
Montpellier RIO Imaging
Cochin Imagerie (Cochin Imaging Platform)
ImagoSeine
PICT-IBiSA Institut Curie
Cell and Tissue Imaging
Toulouse RIO Imaging
MICA: Microscopie Imagerie Côte d’Azur (French Riviera Imaging Microscopy)
LA TRONCHE
MONTPELLIER
PARIS
PARIS
PARIS
REIMS
TOULOUSE
NICE
Genomics, Transcriptomics IGBMC Microarray and Sequencing Platform
Transcriptomic Genomic Marseille-Luminy
MGX - Montpellier GenomiX
Plateforme Puce à ADN BioGenOuest (BioGenOuest DNA Microarray Platform)
ILLKIRCH
MARSEILLE
MONTPELLIER
NANTES
Screening and Chemical
Libraries
Plateforme ARN interférence (PARi) (RNA Interference Platform)
Plate-forme G5C (G5C Platform)
PCBIS
CDithem
GIF SUR YVETTE
GRENOBLE
ILLKIRCH
PARIS
Structural Biology,
Biophysics
Structural Biology and Genomics Platform – Strasbourg
PICT
ILLKIRCH
TOULOUSE
Animal Facilities,
Functional Exploration
AniRA
Fonctions du système immunitaire (Immune System Function)
CARDIEX (THERASSAY)
INTRAGENE-TAAM
LYON
MARSEILLE
NANTES
ORLEANS
Others
TILLING
Immunomonitoring en Cancérologie (Oncology Immunomonitoring)
The C. elegans functional genomics platform
Pharmacology-Screening-Interactome
High Throughput MAb Development
EVRY
MARSEILLE
MARSEILLE
MONTPELLIER
MONTPELLIER
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3. CLINICAL TRIALS REGISTRY
Milestones in managing the INCa research clinical trials registry.
National collaborations
International collaborations
Figures
2007-2008
Initiation of dialogue with ANSM
(French Medicine Agency, formerly AFSSAPS)
Collaboration with the US NCI:
direct relaying of data from French
clinical trials for entry into the NCI PDQ
registry.
• 100 trials advertised from 50 academic
sponsors.
• 2008: advertisement of clinical trials
conducted by industry.
Due to modifications made by NCI to
the trials registration process, end of
direct INCa submissions to
the NCI PDQ registry.
Over 1,000 clinical trials advertised
in the registry.
2009-2010
• 2009: Agreement concluded between INCa and ANSM for relaying
of information on clinical trials of drugs authorised by ANSM.
• 2010: operational collaboration with ANSM
• Several meetings with ASIP santé (French Shared Health Information Systems Agency) to develop access to the registry for physicians
during multidisciplinary patient consultations
2011-2012
• A total of 325 trials were relayed by ANSM (From September 2010);
174 trials were registered in the INCa registry.
• Discussion with ANSM with regard to relaying information on nondrug trials.
• Collaboration with the 3 main national public health insurers: posting the link to the INCa registry on their websites.
Most visited INCa’s web page:
over 200,000 visits in May 2011.
2013
• Initiation of reflection with the Santor and Springer companies for
the development of a mobile application, “Clinical Trials Registry,”
available to practising oncologists.
• Initiation of a collaboration with the National Cancer League
to make the patient committees aware of clinical research
and how to use the clinical trials registry.
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Over 1,500 clinical trials advertised
in the registry.
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Distribution of clinical trials registered according to several criteria on 15 May 2013.
Total
Open
1,546
506
Academic
948
393
Industrial
598
113
ANATOMIC CLASSIFICATION*
Total
Open
INTERVENTION*
Total
Open
Breast
235
68
Drug**
1,156
433
Prostate
89
36
Radiotherapy
166
57
Respiratory system
164
45
Imaging
91
36
Colon and rectum
127
43
Surgery
88
49
Upper aerodigestive tract (UADT) and ENT
77
28
Transplant
51
16
Liver and bile ducts
68
22
Pharmacology – Translational Research
138
62
Total
Urinary system
61
16
Female genital organs
87
29
Digestive system (other than colon or rectum)
88
26
PHASE
Total
Open
Skin – Melanomas
56
15
I
134
46
Blood – Haematology
332
105
I-II
106
36
Nervous system
79
25
II
553
156
Sarcomas
51
22
II-III
25
8
Male genital organs
7
-
III
432
138
Endocrine system
22
6
IV
28
4
Metastases
64
19
None
268
118
Others
142
42
**Also includes vaccines.
TYPE OF FUNDING***
Total
Open
***Only for non-industry-sponsored trials.
Public
288
171
Industrial
266
77
*The sum may be greater than the total, since some trials belong to several categories.
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Mixed
70
24
Not specified
324
121
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4. HEALTH INTERVENTION RESEARCH
IN POPULATION (FRENCH ACRONYM: RISP)
Main features of the 2013 programme.
Year
Funding institution
Objectives
Funding
Results:
Letters of intent submitted
Letters of intent selected
Full project received
Projects selected
Selection rate
INCArapportGB2013.indd 136
2013
INCa
• To mobilise the research community involved in exploring these research methods in order to develop multidisciplinary
research combining biology (genetics, immunology, carcinogenesis, etc.), environment, epidemiology, public health
and economic, social, cultural and psychological dimensions.
• To implement interventions to assess public health actions in the field.
• To analyse, through research, the impact of these policies or the obstacles encountered.
• To promote health intervention research that tests the effects of changes to the environment, individual behaviours
(e.g. diet, drugs, vaccinations and sporting activities) and collective behaviours (e.g. work organisation).
• To extend measures with proven impact to the population.
€708,000
10
4
3
3
33%
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5. CSO
• Complementary and Alternative Prevention Approaches
• Resources and Infrastructure Related to Prevention
The Common Scientific Outline, or CSO, is a classification
system organized around seven broad areas of scientific
interest in cancer research:
• Biology
• Etiology (causes of cancer)
• Prevention
• Early Detection, Diagnosis, and Prognosis
• Treatment
• Cancer Control, Survivorship, and Outcomes Research
• Scientific Model Systems
CSO 4 Early Detection, Diagnosis, and Prognosis
• Technology Development and/or Marker Discovery
• Technology and/or Marker Evaluation with Respect to
Fundamental Parameters of Method
• Technology and/or Marker Testing in a Clinical Setting
• Resources and Infrastructure Related to Detection, Diagnosis,
or Prognosis
The development of the CSO is laying a framework to improve
coordination among research organizations, making it possible
to compare and contrast the research portfolios of public,
non-profit, and governmental research agencies. The types
of research projects funded by INCa, Ministry of Health and
Inserm that are presented in this report are based on this CSO
classification.
The different categories CSO include:
CSO 5 Treatment
• Localized Therapies - Discovery and Development
• Localized Therapies - Clinical Applications
• Systemic Therapies - Discovery and Development
• Systemic Therapies - Clinical Applications
• Combinations of Localized and Systemic Therapies
• Complementary and Alternative Treatment Approaches
• Resources and Infrastructure Related to Treatment
CSO 1 Biology
• Normal Functioning
• Cancer Initiation: Alterations in Chromosomes
• Cancer Initiation: Oncogenes and Tumour Suppressor Genes
• Cancer Progression and Metastasis
• Resources and Infrastructure
CSO 6 Cancer Control, Survivorship, and Outcomes Research
• Patient Care and Survivorship Issues
• Surveillance
• Behavior
• Cost Analyses and Health Care Delivery
• Education and Communication
• End-of-Life Care
• Ethics and Confidentiality in Cancer Research
• Complementary and Alternative Approaches for Supportive
Care of Patients and Survivors
• Resources and Infrastructure Related to Cancer Control,
Survivorship, and Outcomes Researc
CSO 2 Etiology
• Exogenous Factors in the Origin and Cause of Cancer
• Endogenous Factors in the Origin and Cause of Cancer
• Interactions of Genes and/or Genetic Polymorphisms with
Exogenous and/or Endogenous Factors
• Resources and Infrastructure Related to Etiology
CSO 3 Prevention
• Interventions to Prevent Cancer: Personal Behaviors that
Affect Cancer Risk
• Nutritional Science in Cancer Prevention
• Chemoprevention
• Vaccines
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CSO 7 Scientific Model Systems
• Development and Characterization of Model Systems
• Application of Model Systems
• Resources and Infrastructure Related to Scientific Model
Systems
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Published by the French National Cancer Institute
All rights reserved – Siren 185 512 777
ISSN 1964-5961
OCTOBER 2013
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For more information
RAPCSANG13
www.e-cancer.fr
Institut National du Cancer
52, avenue André Morizet
92100 Boulogne-Billancourt
France
Tel. +33 (1) 41 10 50 00
Fax +33 (1) 41 10 50 20
[email protected]
www.e-cancer.fr
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