ALZHEIMER’S DISEASE AND RELATED DISORDERS
THE CONTRIBUTION OF LEEM AND LEEM RECHERCHE TO
THE ALZHEIMER’S PLAN
REVIEWS OF THE CURRENT SITUATION AND PROPOSALS
22 OCTOBER 2007
LEEM
There are 300 pharmaceutical companies operating in France. They employ almost
100,000 people there, creating 550 new jobs per annum and investing approximately 3.9
billion euros there every year in research into new medicinal products. The companies
represented by Leem are responsible for 98.7% of the trade in medicinal products in
France. At international level (United States, Europe and Japan), more than 60 billion
euros are invested each year by pharmaceutical companies for the identification and
development of innovative new treatments. Indeed, the mission of pharmaceutical
companies is to create and develop new medicinal products and vaccines for human
use, for serious diseases and "societal" or man-made diseases related to wellbeing, as
well as everyday diseases. The role of the Leem is to develop and enforce professional
ethics, to facilitate exchanges between its members, to defend their collective interests
and to strengthen ties with other health professions.
LEEM RECHERCHE
Leem Recherche is a joint association between public research bodies involved in
human healthcare and the pharmaceutical and biotechnology industry. Its objectives are
to raise awareness of the key issues of therapeutic research and to promote its
development in France through proposals and initiatives.
In particular, Leem Recherche acts to facilitate research partnerships between the public
and private sectors. For the public authorities it is a privileged partner in representation.
The Inserm, the CEA (French Atomic Energy Commission), the Inra (national institute for
agricultural research), the Institut Pasteur, the CNRS (national centre for scientific
research), the AP-HP and other hospitals, the Institut Gustave-Roussy, the Institut Curie,
the genetics centre at Evry (Génopôle d´Evry), Universities and Faculties, the FHF, the
Afssa (French agency for the sanitary safety of food), the French ministry for research,
the French ministry for industry, Medicen health cluster and the Academies of medicine
and pharmacy, as well as the AFM (the French Muscular Dystrophy Association), the
INCa and the Généthon human genome research centre contribute to the Leem
Recherche Board of Directors and the Scientific Board. The private research sector is
2
represented by more than forty pharmaceutical companies with international R&D
activity.
Among its main activities, Leem Recherche proposes a Summer School every year to
train research scientists from the public sector in pharmaceutical R&D. It publishes a
directory of private sector research centres and awards 6 postdoctoral grants. Scientific
conferences are organised in the provinces, which are open to everyone.
INTRODUCTION
The pharmaceutical industry acted as soon as the French president announced his
Alzheimer’s plan.
A task force including all members of the industry involved in research into Alzheimer’s
disease and its treatment was created within Leem, and Leem Recherche set up a
specific working party within its Scientific Board.
It made possible this research-focused contribution, the aim of which is to provide an
overview of the current situation in private-sector research in France in the field of
Alzheimer’s disease, and to point out the bottlenecks and the priorities to consider in all
the stages of research into this disease (Preclinical Research, Translational Research,
Clinical Research and Epidemiological Research).
Its objective is to suggest to the commission some pragmatic avenues for progress,
which are achievable and measurable, to help it draw up the Alzheimer’s plan.
Moreover, a few figures are provided to how the "social" role of industry in this disease,
which represents a disaster for our society.
The Leem and all the companies concerned have greatly appreciated the spirit in which
Professor Ménard is conducting his mission, his efficiency, and his demand for renewal
and creativity.
Thanks to the Leem Recherche Scientific Board, Leem was involved very early on in
discussions on how to make Alzheimer’s disease a model for stimulating French
3
research, and will participate actively in the public debate on the content of the plan,
which is expected in November 2007.
Leem wants to stress here and now the important role that the healthcare industry will
be able to play if closely involved in a national body for Alzheimer’s research, as
mentioned by the French president in his speech on 21 September 2007.
4
THE INVOLVEMENT OF THE PHARMACEUTICAL INDUSTRY IN THE
FIGHT AGAINST ALZHEIMER’S DISEASE AND RELATED DISORDERS,
IN FIGURES
RESEARCH CONDUCTED BY THE PRIVATE SECTOR
1. World-wide (bibliographical data)1
 118 pharmaceutical companies, including 80 Biotech companies are
developing
148 molecules, including
57 at the preclinical stage
42 at the phase I stage
41 at the phase II stage
2. In France (Leem survey)
 6 pharmaceutical companies and 2 Biotech companies are developing
29 molecules, including
9 at the preclinical stage
5 at the phase I stage
6 at the phase II stage
12 at the phase III and IV stages
 In 2006, 17 pharmaceutical laboratories conducted:
 21 clinical studies in France, including 12 phase III and IV studies, with a
total of 4,742 patients enrolled, more than half being for the indication MCI2
 worldwide, 40 clinical studies, with 12,145 patients enrolled
SUPPORT FROM FRENCH INDUSTRY FOR RESEARCH INTO ALZHEIMER’S
DISEASE AND RELATED DISORDERS AND TREATMENT FOR PATIENTS
This support over 3 years (2004-2005-2006) has amounted to nearly
72 million €
 Support for research (PHRC hospital clinical research programmes and
epidemiological research)
> 51 million €
1
It is difficult to interpret the number of phase III and IV studies (academic and private) from these bibliographic data,
so details will not be given in this overview.
2 MCI: Mild Cognitive Impairment
5
 Support for training
> 17 million €
 Support for associations/institutions
> 3.5 million €
6
RESEARCH
The great challenge posed by Alzheimer’s disease and related syndromes for industry is
to discover and develop new drugs (whether they treat the symptoms or the cause) that
are specific for the disease, e.g. targeting amyloid protein, or not, e.g. neuroprotectors.
A REVIEW OF THE CURRENT SITUATION
A review of the current situation shows that France is well placed in terms of clinical
research into Alzheimer’s disease and related disorders (for example MCI).
Indeed, in Leem’s survey of 17 pharmaceutical companies3 representing 61% of the
French market, conducted in September 2007:
-
21 clinical studies had been conducted in France in 2006 on Alzheimer’s disease
and MCI4, in which 4,742 patients were enrolled
-
Internationally, during the same the period the same pharmaceutical companies
conducted 40 clinical studies for the same therapeutic indications, in which
12,145 patients were enrolled.
France therefore appears to be well placed in the international competition: It
participated in nearly half of the studies and represents 39% of the patients enrolled.
These results must nevertheless be tempered by taking into account the selection bias
(most responses being from pharmaceutical companies developing products for
Alzheimer’s disease in France) and the predominance of phase III studies (12 phase III
studies compared to 6 in phase II and 5 in phase I). If one vast French study in MCI is
excluded, France only represents 15% of the patients enrolled.
3
Altana-Nycomed, AstraZeneca, Boehringer-Ingelheim, Eisai, GSK, Ipsen, Janssen-Cilag, Lilly, Lundbeck, MSD,
Novartis, Pfizer, Pierre Fabre Médicament, Roche, sanofi-aventis, Servier, Wyeth.
4 MCI: Mild Cognitive Impairment
7
In contrast, France obviously falls down in terms of early research and development as
shown in a bibliographic survey5 conducted by Leem, coupled with an ad hoc survey of
22 pharmaceutical companies6 involved in research into Alzheimer’s disease.
It found that worldwide, 118 pharmaceutical companies including 80 biotechnology
companies are developing 148 molecules, whereas, in France, 6 laboratories and only 2
biotechnology companies are developing just 29 molecules.
This underperformance in the pharmaceutical industry means that only a small number
of laboratories (3 French ones) are engaged in the preclinical development in France of
just 9 molecules, compared to the 13 pharmaceutical companies mentioned in the
bibliographic survey as having at least one of the 16 molecules under preclinical
development worldwide.
This picture is identical in early clinical research (phases I and II) and translational
research, with only 5 products at the phase I stage in France, compared to 25
internationally and 6 products in phase II studies in France, versus 23 internationally.
Another indicator of this worrying situation concerns the number of biotech companies
devoted to the research and development of molecules for Alzheimer’s disease and
related disorders: only 2 biotech companies were identified in France7 with one product
under development for Alzheimer’s disease (5 if all the neurodegenerative diseases are
included).
Leem’s bibliographic analysis2 shows however that it is an extremely dynamic field with
more than 80 companies worldwide, essentially of American origin, developing 80
molecules.
5
Literature review, table of molecules under development (appendix 1)
Abbott, Amgen, Astellas, AstraZeneca, BMS, Eisai, Guerbet GSK, Ipsen, Janssen Cilag (Johnson & Johnson), Lilly,
Lundbeck, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi-Aventis, Servier, Takeda, Teva, Wyeth
7 France Biotech database
2 Literature review, table of molecules under development (appendix 1)
6
8
CONCLUSION OF THE REVIEW OF THE CURRENT SITUATION
Clinical research is holding at a satisfactory level but preclinical and translational
research fall short of France’s ambitions.
9
PROPOSALS FOR THE ALZHEIMER’S PLAN
Leem Recherche’s proposals for improvement concern the four stages of research:
Preclinical Research, Translational Research, Clinical Research and Epidemiological
Research.
PRECLINICAL RESEARCH – TRANSLATIONAL RESEARCH
PATIENTS
EPIDEMIOLOGICAL RESEARCH – CLINICAL RESEARCH
They have been discussed in terms of the obstacles and bottlenecks identified by
industry and academia, and are the result of a consensus view obtained in a mixed
public/private group8 created within Leem Recherche with the participation of the
Afssaps
PRECLINICAL RESEARCH
8
AUGENDRE FERRANTE Béatrice-Lilly, BASEILHAC Eric-Janssen, OSTINELLI Juliette-AstraZeneca, CHOSSAT
Florence-CIS bio international, COROT Claire-Guerbet, DUVEAU Françoise-Eisaï, GOLDFARB Gérard-Abbott,
JUNIEN Jean-Louis-Genfit, KEIME-GUIBERT Florence-Servier, LALAUDE Olivier-MSD, LESTAGE Pierre-Servier,
MATHIEX-FORTUNET Hélène-Ipsen, PERE Jean-Jacques-Novartis, Olivier Frachon-BMS, SACCAVINI JeanClaude-CIS bio international, SAUTY Evelyne-GSK, SCATTON Bernard-Sanofi-Aventis, SOKOLOFF Pierre-Institut de
Recherche Pierre Fabre, TROY Sylvie-Pfizer, TRUFFINET Philippe-Sanofi-Aventis, AMOUYEL Philippe-Lille,
ANDRIEU Sandrine-Toulouse, BLIN Olivier-Marseille, BUEE Luc-Lille, DUBOIS Bruno-Paris, HANTRAYE PhilippeOrsay, OUSSET Jean-Pierre-Toulouse, PASQUIER Florence-Lille, RASCOL Olivier-Toulouse, ZALC Bernard-Paris,
FORNAIRON Sophie-Afssaps.
10
The obstacles or bottlenecks identified by research scientists in both the public and
private sectors firstly concern the exploitation of breakthroughs (intellectual property
etc.), which is currently far too complicated, in particular when teams affiliated with
several EPSTs (public scientific and technological institutions) coexist in the same
research centre. The lack of visibility of the academic research centres for the private
sector, and the difficulty for those in the public sector of identifying the right person to
approach in private research centres are unfortunate, and mean that public and private
researchers do not meet and communicate enough. The paucity of private research
centres, particularly international ones, is undoubtedly a handicap for France.
Scientists in the private sector also stress their desire to work with their partners in the
public sector on a project management basis.
PRECLINICAL RESEARCH: THE PROPOSALS OF THE LEEM RECHERCHE
ALZHEIMER'S RESEARCH GROUP
1. Use Alzheimer’s research as a pilot project to develop a genuine policy for
exploiting breakthroughs (intellectual property management, etc.), with a "one-stop
shop" for industry.
2. Ensure greater visibility
-
On the private sector side: refine the Leem Recherche directory, to specify
who to contact in the field of Alzheimer’s disease in France and if possible abroad
-
On the academic side: expand the national Alzheimer’s research monitoring
centre (ONRA) by identifying those academic centres that have numerous partnerships
with the private sector.
11
3. Develop
the
three
competitive clusters:
Lille/Longévité;
Nice-Montpellier-
Marseilles/Orpheme; Ile de France/Médicen, and the Toulouse gerontology centre or
Gérontopôle, encouraging the clustering of academic research centres. Increase their
visibility (through participation in international conferences and large biotech events) and
thereby attract a maximum number of international projects (pharmaceutical and
biotech).
4. Train academic research scientists in project management techniques.
12
TRANSLATIONAL RESEARCH
The purpose of translational research, also called experimental medicine, is to ensure a
continuum between research and healthcare. It is involved in all levels of the drug
discovery process, from the identification and validation of relevant targets to patient
selection through the expression of biomarkers. In this sense, high-quality Translational
Research is vital for the pharmaceutical industry, the mission of which is to discover and
develop medicinal products that are more active and more selective 9.
Translational Research must necessarily be conducted near to where the patients are, in
order to permit a bidirectional flow of information, where knowledge acquired in cognitive
research is applied to patient care and where observations made on patients feed back
into cognitive research.
Continuum soins-recherche : du patient au patient
Faire bénéficier le plus vite possible les patients
des découvertes les plus récentes
Recherche
Translationnelle
Recherche
Cognitive
Recherche
Clinique
Nouveaux moyens diagnostiques
Nouveaux traitements
Patients
Healthcare-research continuum: from the patient and back to the patient
Enabling patients to benefit from the latest discoveries as soon as possible
9
Working party: INCa / Leem Recherche (appendix 2)
13
Cognitive Research – Translational Research – Clinical Research - Patients
New diagnostic methods
New treatments
An innovative Translational Research organisation needs to be set up in a
multidisciplinary scientific and technical environment, providing access to research
technologies as well as to patients. This involves: high-quality technology platforms,
biological resource materials or biobanks, clinical or biochemical laboratories and/or
investigation centres devoted to research and the pooling of technology and expertise.
The obstacles or bottlenecks encountered by research scientists in the public or private
sectors are the same and concern collaboration between research centres (public or
private) and investigators (public) or developers (private); insufficiently developed
biomarkers and early collaboration with the Afssaps for the use of these biomarkers in
clinical studies, and then their validation.
In Alzheimer’s disease, biomarkers in CSF and plasma are going to play an essential
role in the development of new medicinal products, and also in clinical practice.
Nevertheless, two notable examples of technology platforms which need to be
developed concern imaging and biobanks.
Imaging occupies an important place in Alzheimer’s research (both preclinical and
clinical). France’s infrastructures and skills are recognised internationally, but its
platforms devoted to preclinical research (e.g. the "neurospin" MRI brain imaging centre)
are still insufficient and it is difficult to obtain access to the equipment for use on patients
enrolled in studies. Efforts must be made to find out more about the needs of the private
sector (e.g. ligands) and to work on standardising and validating the imaging tools
available (e.g. PIB, Pittsburgh Compound B, a PET scan imaging marker for amyloid
protein deposits in the brain).
Biobanks are also becoming a strategic issue in medical research and an important
factor in competitiveness. They have to meet high quality criteria (traceability, safety,
etc.) and very strict international standards. They require a great deal of financial
support, and current funding levels are insufficient.
14
Finally, these collections must be more easily accessible to private sector partners. By
way of an example, a charter of ethics10 was drawn up by the INCa, with the
participation of Leem, in order to clarify the current legal context surrounding the use of
samples for research purposes. It proposes rules that will assure both scientists and
patients of compliance with legal and ethical considerations, while also facilitating public
and private research.
An additional major obstacle for academics lies in the difficulty of convincing others of
the reality and the importance of translational research and to fund it (in hospitals as well
as in EPSTs).
TRANSLATIONAL
RESEARCH:
THE
PROPOSALS
OF
TH E
LEEM
RECHERCHE ALZHEIMER'S RESEARCH GROUP
1. Make use of the three competitive clusters and the gerontology centre mentioned
above to strengthen ties between research scientists and clinicians, to encourage
contact between the public and private sectors, and to increase the visibility of French
Translational Research in Alzheimer’s disease (for example, by inviting directors of
international research centres in the presence of the minister for research and higher
education and presenting the strengths of French research to them).
2. Train academic scientists and clinicians in the breadth and constraints of private
sector Research and Development, by organising courses (like the Leem Recherche
Summer School11), appointing associate professors from industry and promoting CIFRE
grants [translator’s note: PhD projects conducted jointly between a public and a private
sector laboratory].
3. Involve the Afssaps12 and the EMEA13 very early on when considering biomarkers
(advice about development), asking them to flag Alzheimer’s disease as a priority.
10
French national cancer institute (Institut National du Cancer): www.e-cancer.fr
The Leem Recherche Summer School: http://www.leem-recherche.org (appendix 3)
12 Afssaps: French health products safety agency (Agence française de sécurité sanitaire des produits de santé)
13 EMEA: : European Agency for the Evaluation of Medicinal Products
11
15
4. Encourage research into biomarkers, which are absolutely essential to the
development
of
new
molecules:
consolidate
existing
platforms,
encourage
standardisation efforts, set up centres for imaging dedicated to research, facilitate
access to biobanks for the private sector.
5. Set aside ANR14 and OSEO15 funding for Alzheimer’s disease, providing funding
in particular for projects undertaken by private-public partnerships, but also for platforms
or infrastructures (e.g. biobanks, imaging).
6. Participate actively in the European IMI project16 (innovative medicines initiative)
by proposing French
projects involving partnerships between academia, the
pharmaceutical industry and biotech companies.
14
ANR: French national research agency (Agence Nationale de Recherche)
OSEO: a joint enterprise between the French innovation agency and the SME development bank
16 European Commission: http://ec.europa.eu/index_fr.htm
15
16
CLINICAL RESEARCH
As a result of the 2002 and 2004 surveys 17-18 conducted with AEC Partners, the Leem’s
findings made to possible to sound the alarm about French clinical research, which led
to lengthy consideration at the French Healthcare industries strategic council meeting in
2005. Measures were taken, the most symbolic of which was the creation of the
CeNGEPS (national healthcare products trial management centre), a public interest
group, entirely financed by industry (approximately 10 million euros per annum) in the
form of a tax on turnover. Its goal is to help hospital investigators to recruit more, faster
and better, particular by placing additional staff at their disposal. The CeNGEPS is still in
the process of being set up, and it is therefore too soon to be able to assess its
effectiveness, however a real dynamic has been generated around clinical research, and
in 2006 a small increase was seen in the number of studies submitted to the Afssaps,
although the percentage in each therapeutic field remained stable, notably in the
central nervous system field.
Afssaps data
2004
2005
2006
1,223
1,045
1,148
Central nervous system
15
18
17
Onco-haematology
23
23
25
Infectious diseases
9.5
10
9
9
8
9
Number of clinical trials
Therapeutic field (%)
Cardiovascular
D’Enfert J, Lassale C, Prod’Homme P, et al. Attractivité de la France pour les essais cliniques : évaluation par les
laboratoires promoteurs. Thérapie 2003 ; 58 : 283-9.
18
Courcier-Duplantier S, Bouhours P, Pinton P, Sibenaler C, Lassale C et le groupe de travail « attractivité de la
France » du Leem. Attractivité de la France pour la recherche clinique internationale : une étude dresse un constat
peu favorable et suggère des voies d’amélioration. Thérapie 2004 ; 59 : 629-38.
17
17
Nevertheless, France has held its position well in the international competition. As was
shown in the Leem’s 2006 survey19, it maintained its place as the second largest
European recruiter of patients (0.19 patients / 1000 population) after Scandinavia, with
8% of patients recruited worldwide.
As far as Alzheimer’s disease was concerned, the following obstacles to the
development of clinical research in France were identified.
 For the private sector: insufficient visibility regarding recruitment capacity,
methodological difficulties, placebo-controlled studies impossible, scales not
translated into French, problems with obtaining consent, with long-term follow-up
of patients, and difficulties getting authorisation from the Afssaps to conduct for
clinical trials on certain highly innovative molecules.
 For the academic sector: insufficient resources (doctors, clinical research
technicians, secretaries, etc.), too many people to liaise with in the
pharmaceutical companies (the CRO, the subsidiary, the parent company),
consent difficult to obtain on account of dissuasive patient information leaflets
which put off many patients, ethical difficulties posed by stopping treatment at the
end of the study, which are sometimes not dealt with in the protocol, or where a
competitive recruitment system means that patients who passed the prescreening process are not actually enrolled.
19
La France est un pays attractif pour la recherche clinique internationale : enquête du Leem 2006. S. Courcier, C.
Sibenaler, M. Couderc, F. Trinquet, Y. Plétan, C. Lassale et le goupe de travail « Attractivité de la France » du Leem
18
CLINICAL RESEARCH: THE PROPOSALS OF THE LEEM RECHERCHE
ALZHEIMER'S RESEARCH GROUP
1.
Make use of the CeNGEPS to divert additional resources (doctors, nurses, clinical
research technicians, etc. who will have to be trained specifically in the disease and, as
far as possible, follow the patients until the end of the trial) to studies on Alzheimer’s
disease that have sponsorship from the pharmaceutical or biotech industry.
These resources could be allocated to teams responding to the CeNGEPS’s calls for
projects on the networks:
2.
-
from 2007 via the Alzheimer’s networks that already exist
-
from 2008 on a national network if it can be set up
Increase resources, particularly in terms of staffing, giving greater consideration
to the total production of clinical trial activity, irrespective of the sponsorship sources, in
the MERRI20 system.
Develop clinical research in the CM2R21 memory disorder centres by selecting the
most outstanding ones and getting them to focus on early-phase studies, especially if
they have the support of a CIC clinical investigation centre, but also in other memory
disorder centres with large clinics, which are necessary for conducting phase III studies.
Increase the visibility of the PHRC hospital clinical research programmes and studies
with academic sponsorship to encourage partnerships with industry.
3.
Work in partnership to improve patient information leaflets and consent forms
(industry, investigators, patient associations).
4.
Train CROs (clinical research organisations) in the particularities of Alzheimer’s
disease, adding a specific module to the training modules which are currently being
finalised between industry and the CROs, and the Afssaps22.
5.
Flag early clinical studies conducted in Alzheimer’s disease as a priority for the
Afssaps, and use Alzheimer’s as a pilot project to develop effective coordination between
national agencies in multicentre trials.
MERRI: Missions for teaching, research, reference, and innovation (Missions d’Enseignement, de Recherche, de
Référence and d’Innovation) in healthcare establishments
21
CM2R: Memory resource and research centres (Centres Mémoire de Ressources et de Recherche)
22 Afssaps : French health products safety agency (Agence française de sécurité sanitaire des produits de santé)
20
19
6.
Include a round-table every year in the Giens workshop on Alzheimer’s disease:
methodology, scales and biomarkers, and invite a representative from the EMEA23 or the
CHMP24.
23
24
EMEA: European Agency for the Evaluation of Medicinal Products
CHMP: Committee for Human Medicinal Products
20
EPIDEMIOLOGICAL RESEARCH
Epidemiology is used to observe populations and diseases and to generate hypotheses
about the factors determining health, whether they be environmental risk factors or
genetically programmed molecular mechanisms.
As such, it plays a major role in the development of our scientific knowledge and of
medical and therapeutic progress.
French epidemiological research, which is essentially academic, needs supporting,
because there are too few courses and teachers, which in turn is reflected in the
country’s small scientific output in this field. Indeed, if one compares the number of
epidemiological scientific publications produced by countries with the same level of
development and relate this to population size, France is in 18th place, far behind the
northern European countries (Denmark, Norway, Sweden and Finland), the Netherlands
and the United Kingdom, which are remarkably dynamic in this field of activity.
Another obstacle in France to the development of knowledge and expertise in the field of
epidemiology is a lack of effective, long-term tools: the existing databases are not
always widely and easily accessible, systems for long-term observation (e.g. the Paquid
and Trois Cités/E3C cohorts) do not have the diverse sources of funding which would
guarantee their continuity, and there are too few genetic epidemiology studies
conducted using clearly identified cases, which are essential for translational research.
Yet, for both drugs companies and public health professionals, epidemiology is now
clearly emerging as a major issue.
Indeed, epidemiological studies are essential, firstly in order to make progress in the
discovery of medicinal products that are increasingly targeted and specific for the
populations identified by such studies, and secondly to fulfil the legitimate requirement to
monitor the risks and proper use of drugs that goes with the marketing of health
products.
21
As regards this point, Alzheimer’s disease represents a considerable objective for all
parties concerned because it is condition in which epidemiological data is currently
particularly lacking.
In order to discover and develop specific medicinal products, it is imperative that the
pharmaceutical firms have observational data that only epidemiological studies, with
their wide variety of approaches (cohorts, case/control studies, genetic epidemiology),
will be in a position to provide. These types of study already exist of course, and industry
has in fact contributed considerable sums in recent years to the funding of some of
them. However, a lot of human and financial investment is still needed, firstly in order to
facilitate access to the data and communication between all those concerned (from
industry and academia) and secondly to develop new, effective, long-term tools. More
training for doctors in CM2R and other memory disorder centres is essential in order to
encourage research and enable the collection of standardised, computerised medical
data.
EPIDEMIOLOGICAL
RESEARCH:
TH E
PROPOSALS
OF
TH E
LEEM
RECHERCHE ALZHEIMER'S RESEARCH GROUP
1.
Develop high-level training in public health in epidemiology, particularly on the
themes of aging and mental health, making use of the creation of the postgraduate
school of public health (Ecole des Hautes Etudes de Santé Publique). Provide more
training for doctors from the CM2R and other memory disorder centres and develop a
standardised, computerised system for the collection of medical data.
2.
Make optimal use of the published data (meta-analyses) and consider using the
data from clinical studies conducted by pharmaceutical firms for pharmacoepidemiological purposes.
3.
Make the best use of the existing databases through wider and easier access.
4.
Develop and continue cohort studies, long-term observation systems, like the
Paquid and Trois Cités cohorts, through more and inevitably multiple partnerships, the
22
pharmaceutical industry being only one possible player alongside other public and
private bodies (other manufacturers, insurance companies, etc.).
5.
Create databases of "cases" with well determined phenotypes, particularly for
genetic epidemiology studies, involving industry in the planning stages.
23
THE SOCIAL ROLE OF THE PHARMACEUTICAL
COMPANIES
Anti-Alzheimer drugs have profoundly altered the management of the disease, by
encouraging acknowledgement of patients by society and by health professionals.
At the same time, through their action and funding, the pharmaceutical companies have
also participated considerably in academic research (PHRCs and epidemiological
research25) and in the training of healthcare workers, carers and families.
Over 3 years from 2004 to 2006, the industry contributed a total sum of nearly 72 million
euros to the fight against Alzheimer’s disease. More than 51 million euros were given to
support academic research (PHRC) and particularly epidemiological research. More
than 17 million euros were spent on training and 3.5 million euros have been used to
help patient associations and institutions.
25
Large cohorts have received support from industry: Paquid, Suvimax, E3C, and other studies have received
subsidies: PsyII studies, observatoire Imagine, the EHPAD MA survey, the Regard study, the monitoring centre for
rapid cognitive decline, rapid cohort and real.fr, etc.
24
CONCLUSION
Although the "social" role of the private sector is far from negligible, the priority of the
pharmaceutical companies is research into and development of new drugs to combat this
disease, which is devastating for patients and for those around them, and currently
incurable.
The Alzheimer’s plan must enable France to maintain and consolidate a satisfactory
position in the field of clinical research and considerably strengthen its research in this
area (preclinical research and translational research). Leem Recherche has suggested
some concrete and attainable proposals in order to achieve this, which could use
Alzheimer’s disease as a model for future work
1. Make use of the three competitive clusters (Lille/Longévité; Nice-MontpellierMarseilles/Orpheme; Ile de France/Médicen) and the Gérontopôle (gerontology centre) de
Toulouse to attract pharmaceutical and biotech companies
2. Simplify procedures for exploiting research breakthroughs, patenting etc. (onestop shop for companies).
3. Teach academics about industrial constraints (associate professors from industry,
CIFRE grants, "interface" contracts …) and project management techniques. Expand
courses in public health and epidemiology. Develop training for doctors from CM2R26 and
other memory disorder centres and enable the collection of standardised, computerised
medical data.
4. Develop funding for projects and infrastructures, making use of what already
exists (ANR-OSEO-IMI27, etc.).
5. Designate Alzheimer’s disease as a priority for the Afssaps (biomarkers, clinical
studies) and give the Afssaps a mandate to work in close collaboration with the
EMEA28/CHMP29.
26
CM2R: Memory resource and research centres (Centres Mémoire de Ressources et de Recherche)
IMI: European Commission: http://ec.europa.eu/index_fr.htm
28 EMEA:
29 CHMP
27
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6. Make use of the CeNGEPS30 and the Giens clinical pharmacology workshops to
support clinical studies (recruitment, methodology) and give greater consideration to the
total production of clinical trial activity, irrespective of the sponsorship sources, in the
MERRI31 system.
7. Improve patient information leaflets and consent forms together (industry and
academia) with plenty of involvement from patient associations.
8. Develop cohorts (long-term observation systems), case-control studies, databases
and broaden access to them.
30
CeNGEPS: French national healthcare products trial management centre (Centre National de Gestion des Essais
de Produits de Santé)
31 MERRI: Missions for teaching, research, reference, and innovation (Missions d’Enseignement, de Recherche, de
Référence and d’Innovation) in healthcare establishments
26