Improving patients` recruitment

Improving patients’recruitment
October, 16th 2012
Marie LANG
Director of CeNGEPS
CeNGEPS
The picture of French commercial clinical research
Lille
Robert Debré
Bichat
Île-de-France
St Louis
Amiens
Cochin
R.Poincaré
Necker
CNO 15/20
St Antoine
Caen
Rouen
Reims
Albert Chenevier
HEGP
Brest
Nancy
Ile-de-France
Strasbour
g
PitiéSalpêtrière
IGR & Curie
Henri
Mondor
Rennes
Angers
Tours
264 000 French medical doctors
= potential investigators
Nantes
Dijon
Besançon
Poitiers
Limoges
CHU &
CLCC
Lyon
Clermont Ferrand
A very fragmented
landscape with
multiple different
research institutions
Saint Etienne
CHU &
CLCC
Grenoble
Bordeaux
Map legends
Nîmes
Interregional Clinical Research Office (DIRC)
Toulouse
Montpellier
CHU &
CLCC
Nice
Hospital Clinical Research and innovation
department (DRCI)
Marseille
Clinical investigation center (CIC-P)
Clinical Epidemiology center (CIC-EC)
Clinical investigation center integrated in
biotherapy (CIC - BT)
Clinical investifation center specializedi n
technologic innovations (CIC-IT)
Fort de FrancePointe à Pitre
GH Sud
Réunion
Centers / Networks on care and research
CTRS / RTRS
National center for trials management on health products
Registered clinical trials :
French national regulatory Authority (ANSM)
- 40%
in 10 years
National center for trials management on health products
In all Western Europe, rate of participation in CTs is close
and globally in decline
Average speed of recruitment between 2004 and 2012/per study/ per month
Scandinavie
Europe
13,0
13,1
Allemagne
11,0
9,7
Espagne
9,0
7,2
France
7,0
7,4
8,3
6,8
8,1
6,6
6,5
8,1
6,7
6,6
6,3
6,1
6,1
7,8
5,2
Royaume Uni
5,0
6,3
5,6
7,6
4,8
Italie
4,8
4,7
5,1
3,8
3,0
2004
2006
2008
2010
2012
Seules les études impliquant la France ont été retenues
5
National center for trials management on health products
Average speed of recruitment 2012 : heterogeneity between
Nombre moyen de patientstherapeutic
recrutés parareas
centre actif :
hétérogénéité entre les aires thérapeutiques
Average speed of recruitment in 2012 : 4,7 patients recruited by active center per month
Nombre moyen de patients recrutés par centre actif
O nc olog ie /O nc o-hématolog ie
Asie
Europe Est
C ardiovas c ulaire/Métabolis me
4,9 Moy.
Scandinavie
Monde 3,8Europe Est
Am. Latine
Australasie
3,8
France
Scandinavie
3,8
3,5
4,1
Moy.
Europe
Autres Eur . Ouest
3,8
Afr. Moyen Or.
Royaume Uni
Espagne
Royaume Uni
Afr. Moyen Or.
3,3
3,2
Allemagne
Etats-Unis
3,4
Espagne
Italie
Etats-Unis
3,2
2,8
France
Anti Infec tieux / Virolog ie/Vac c ins
45,5
17,8
15,0
10,4
Allemagne
Europe Est
Australasie
Royaume Uni
Canada
Etats-Unis
Afr. Moyen Or.
Autres Eur . Ouest
Italie
7,9
6,6
6,3
7,0
4,6
Maladies R ares
6,2
Moy.
Europe 7,6
Allemagne
Italie
Australasie
3,1
2,7
2,6
5,6
Etats-Unis
5,5
5,3
4,9
Italie
4,2
France
4,0
Moy.
Europe
3,9
6,5
5,4
5,2
Canada
4,8
Am. Latine
4,4
France
Scandinavie
Italie
4,3
4,1
Royaume Uni
4,1
4,2
10,7
Scandinavie
10,3
Asie
Afr. Moyen Or.
10,2
Europe Est
7,9
6,2
6,1
4,3
Espagne
4,2
3,6
7,7
6,3
6,3
6,2
Scandinavie
Etats-Unis
2,3
Italie
3,3
Am. Latine
5,4
4,7
2,2
Autres Eur . Ouest
3,2
France
5,3
4,1
Espagne
2,2
5,9
S eules les études impliquant la F rance ont été retenues
Moy.
Monde 5,0
4,7
Autres Eur . Ouest
Allemagne
Moy.
Europe
5,1
4,6
3,3
4,5
Australasie
France
5,1
5,1
Moy.
Australasie
Monde 4,8
Allemagne
Moy.
Espagne
Europe
Royaume Uni
4,4
Etats-Unis
4,8
EtatsUnis-
Scandinavie
5,2
5,1
R es piratoire
7,5
Am. Latine
Asie
4,2
4,0 Moy.
Monde 3,7
4,0
3,4
Moy.
Europe
6,5
5,8
Europe Est
4,2
4,2
5,3
Asie
Etats-Unis
Australasie
6,9
Inflammation/R humatolog ie
4,4
6,2
Europe Est
Afr. Moyen Or.
7,8
Allemagne
7,7 Moy.
Canada
7,6 Monde 7,0 Autres Eur . Ouest
Espagne
6,9
Autres Eur . Ouest
Afr. Moyen Or.
6,1
Europe Est
Afr. Moyen Or.
Australasie
Royaume Uni
7,0
Asie
12,0
7,9
Scandinavie
7,4
Am. Latine
Canada
8,2
6,8
8,7
Neurolog ie/P s yc hiatrie/Alz heimer
Am. Latine
Asie
Moy.
Europe Est
Monde 9,1
Moy.
Allemagne
Europe
Canada
9,1
Espagne
7,5
Autres Eur . Ouest
Moy. Monde
Royaume Uni
10,1
France
8,5
7,7
9,5
9,0
8,8
Canada
Italie
3,2
Asie
Am. Latine
Scandinavie
9,7
Asie
Australasie
3,4
3,4
10,3
Am. Latine
Canada
Autres Eur . Ouest
Allemagne
Espagne
France
11,4
10,7
4,7
Diabète
Royaume Uni
3,0
Canada
Afr. Moyen Or.
2,9
Italie
Moy.
Monde 7,0
Moy.
Europe
6,8
5,1
4,6
National center for trials management on health products
« Public interest group »: CeNGEPS
National center for trials management on health products
A public/private partnership created in 2007 …
…for a high performing commercial clinical research :
« recruit more patients, faster and better »
CeNGEPS : gathering the main clinical research stakeholders in
France
PUBLIC members
DIRC Est
6%
DIRC Ile de France
6%
51%
PRIVATE members
49%
DIRC Grand Ouest
6%
Following positive evaluation
of AERES : renewal of
Syndicat représentant les
DIRC Nord
Ouest
«6%CeNGEPS
» 2011-2015
laboratoires
pharmaceutiques en France
DIRC Rhône Alpes Auvergne
6%
DIRC Sud Méditerranée
6%
4 partenaires associés
DIRC Sud Ouest Outre Mer
6%
Inserm
9%
•
Agence nationale de sécurité du médicament et des produits de santé (ANSM)
•
Fédération hospitalière de France (FHF)
•
Fédération nationale des centres de lutte contre le cancer (FNCLCC)
•
Conférence des présidents d’université (CPU)
Action plan : 10,5M€/year for 7 priorities to improve
performance of French commercial clinical research
CeNGEPS works as a funding agency : 2 national calls
Set up «points of contact / one stop-shops » in hospitals
More human resources (CTAs, study nurses) to support investigators
Reduce the number of centres without recruitment to <15%
 Encourage the assessment of feasibility / trial site evaluations
Support of 23 national disease-oriented research networks
Find new investigators and patients
Speed up study start up and costing/contract negotiations providing
standard templates
« to take part in clinical research, a right/a duty for French citizens »
( Information on clinical research towards the general public)
National center for trials management on health products
CeNGEPS
Funding of 230 CTAs/study nurses
helping investigators to recruit
and support commercial clinical trials
carried out in French hospitals
Funding of resources to set up 7 « points of contact » in France
and funding of 300 jobs to support recruitment, mainly CTAs
 DIRC Est
Alban DUPOUX
[email protected]
03 80 29 35 84
 DIRC Ile de France
Francis WILLIG
[email protected]
01 40 27 57 46
 DIRC Nord Ouest
Mariam PETROSYAN
[email protected]
03 20 44 67 37
 DIRC Rhône Alpes Auvergne
Dr Marie-Claire MAZE
[email protected]
04 72 40 68 54
Samia ATOUI
[email protected]
04 72 40 68 70
 DIRC Grand Ouest
Stéphanie DUMONT
[email protected]
02 99 28 41 17
 DIRC Sud Méditerranée
Véronique REY
[email protected]
04 91 38 11 51
 DIRC Sud Ouest Outre Mer
Eric DONOIS
[email protected]
05 57 82 08 48
Identify high performing (or new) sites
To
Know their reliability/availability
Solve problems in the set up of trial
National center for trials management on health products
230 « CeNGEPS CTAs», what for ?
Mission : thorough evaluation of the recruitment capabilities of
a potential site and support to recruitment at the site level
Pre-screening and screening of medical records of all patients
eligible in a trial given inclusion/exclusion criteria, recruitment
capabilities of the site , number of trials under way in the site
Evaluation of adequate resources to conduct the trial
Participation to the trial set up meeting with sponsors
Organisation and taking care of targeted patients (contact;
invitation ; RDV ; medical records…
« CeNGEPS » CTAs differ from CTAs supporting recruitment until study delivery
National center for trials management on health products
Types of clinical trials supported by CeNGEPS CTAs
2011/2012 (DB EXTRANET)
RÉPARTITION DES CENTRES SUIVIS PAR
RÉPARTITION DES CENTRES SUIVIS PAR PHASE
THÉMATIQUE
#
THEMATIQUE
Nbre
de centres
%
Phase I
7%
Phase II
19%
1
Cancérologie
483
27%
2
Gastroentérologie / hépatologie
203
11%
3
Neurologie
179
10%
4
Cardiologie
123
7%
5
Pneumologie
98
5%
717
40%
Autres
3%
3%
2% 1%
2%
4%
Phase IIa
Phase IIb
Phase III
59%
Phase I-II
Phase II-III
National center for trials management on health products
Gold standards and incentives : National
call 2013 for the 7 interregions
 2013: 3 international « Gold-standards » to measure
performance :
- Objective 1 : 60 days for signature of contract for 80% centres
- Objective 2 : < 15 % centres showing recruitment = 0
- Objective 3 : 80 % of centres recruiting over 80% patients/target
number of patients planned according to protocol
Comparison of each region‘s performance
with gold standards gives +/-5% in funding
National center for trials management on health products
Impact of CeNGEPS CTAs’ support ?
Approximately 20% of French commercial clinical trials supported by
CeNGEPS CTAs
Performance in 2011 in completed clinical trials supported by CeNGEPS CTAs:
+ 68% improvement in rate of
recruitment
- 51% of closed centers without
recruitement
(median rate= recruited patients/target number)
WITHOUT CTA
WITH CTA
67%
WITHOUT CTA
WITH CTA
26.6%
40%
13.1%
National center for trials management on health products
20% [15 – 26%] clinical trials supported by
CeNGEPS CTAs…
What about the rest ?
 Ensure feasibility check/site evaluation and
try to reduce the number of centres showing
recruitment = 0 to a rate under 15%
National center for trials management on health products
Reduce the number of centres
« open/closed without recruitment »
Centres in 2011
À 0% d'inclusion
Entre 1% et 49 %
d'inclusion
…
À 100%
d'inclusion et
plus
22,4%
45
68
…
54
Grand Ouest
21,8%
71
76
…
108
Ile de France
30,5%
195
141
…
181
Nord Ouest
24,2%
44
45
…
46
Rhône Alpes et
Auvergne
20,1%
53
56
…
102
Sud Méditerranée
19,6%
58
0
…
84
Sud Ouest et Outre
Mer
19,3%
40
0
…
71
National
23,9%
506
511
…
646
% centres fermés
sans inclusion
Est
DIRC
National center for trials management on health products
Reduce the number of centres
« open/closed without recruitment »
8 possible explanations for lack of recruitment
Design of protocol too complex trial impossible to
be carried out (inclusion/exclusion criteria too
complicated/too numerous)
No precise knowledge by investigator of recruiting
possibilities
Over-estimation of recruitment by investigator in
order to be selected
Bad management of clinical research activity in the
centre (too many trials under way; no follow-up)
« Key opinion leaders »,often insufficient recruiters
No/bad preparation of trial (multicentres …)
Accident (investigator or member of
staff/collaborator leaving…)
Solution ?
Feasibility assessment
Use of database, EMR
allowing
good evaluation of
the patient population
calculation of recruitment
Funding 2011 = 540k€
to support new proactive tools :
data warehouses,
web browsers..
Trial stopped (recruitment completed in other
countries)
National center for trials management on health products
Disease-oriented
investigators’networks
Support in 2012 of 23 national disease-oriented
investigators networks = 3,2M€
Priority therapeutic areas
 Infectiology/Vaccines
 Neurosciences « Brain disorders »
(Alzheimer, psychiatry…)
 Oncology / Onco-hematology
 Cardiology/thrombosis
 Rare diseases
 Pediatry
 Nutrition/diabetes
 Digestive inflammatory
(rhumatology, …)
 Respiratory diseases
 Intensive care
+ 50 employees
For coordination and management :
Medical Doctors, clinical trials assistants,
Trial managers, study nurses
Organisation :
 National level
 Access to new patients  general
hospitals and not only CHU
 Access to new investigators : GPs
/Hospitals  for Chronic diseases
National center for trials management on health products
Une Charte pour orienter et harmoniser 
Un texte incitatif
Définition: « Un réseau d’investigation
clinique (RIC) est composé de médecins
investigateurs et/ou un groupement de
structures de recherche clinique (CIC,
services cliniques, Unité de recherche
clinique…) qui s’engagent à travailler
ensemble sur des projets communs
d’investigation clinique conformément aux
BPC et à la réglementation française »

Un coordonnateur assisté d’une équipe +
Un comité de pilotage
Engagements des membres du réseau
Base de données communes
Une identité ou un support juridique

Stick to the principles of
the Charter
 Gold standards
 coordination ?
 Harmonisation
 Objectives and projects
National center for trials management on health products
OBJECTIVES
Create interactions between researchers, paediatricians and pharmaceutical
industries to conduct clinical research projects in order to :
Develop clinical research and collaborate with all medical and
surgical departments, medico-technical departments, Inserm and
University research units.
Provide scientific, ethical and practical information on clinical
research
Train physicians and nurses to clinical research and Good Clinical
and Laboratory Practices
Give support to children and their parents during participation in
medical research
THE PAEDIATRIC CIC NETWORK
Contribute to translational research from bench to bed-side, by collaborating with researchers and
paediatric investigators.
Contribute to biological and technical innovations, to their validation and standardisation, in order
to optimise investigations.
Identify the best design for the trial and provide support to investigators, from design through the
conduct of investigator initiated or industrially sponsored clinical research protocols.
Insure high ethical standards and conduct trials in accordance with Good Clinical Practice (GCP)
guidelines.
Develop all the procedures, recruiting centers and allowing the collaboration between partners.
Provide physicians, pharmacists, and nurses with specific training in paediatric clinical research.
Develop and provide competences required to conduct clinical research in paediatrics, including
paediatric experts, competences in pharmacology, methodology, epidemiology, statistics
modelisation.
Make facilities available for the conduct of research in children and support parents and their
children during participation in medical research.
Ensure the general coordination of the high standard research activities and smooth
communication between partners.
National center for trials management on health products
Speed up study start up and
costing/contract negotiations by
providing standard templates
Several national Templates :
www.cengeps.fr
Purpose : Speed up delays in negotiations
Convention hôpital - promoteur
industriels
Grille nationale de calcul des
surcoûts hospitaliers
Updated  Standard contracts : January
2012/ national costs template : August 2012
National center for trials management on health products
Signature of hospital contracts
Median time between submission to Authorities and 1st hospital
contract signature (in days) : gain of 29 days
-11%
-10%
Études 2010 :
117 jours
Études 2011 :
104 jours
* Signature du 1er contrat hospitalier
26:01:2011 26
Increase trial participation
and recruitment by informing
the general public about
clinical research :
www.notre-recherche-clinique.fr
Clinical research in the mass
media : mistrust and fear
National center for trials management on health products
http://notre-recherche-clinique.fr
October 2012 :
Over 200 000 visits
900 000 pages since April 2010
118 Clinical trials in directory
(both academic and industry sponsors)
Four items :
• Take part in a trial
• Clinical trials in France
• Research stakeholders
• Our mission
National center for trials management on health products
Take part in a trial
priority trials for sponsors; information for patients
Look for a trial
• interactive map: localisation of centers
• Web browser
• “e-volunteer” alerts
• Inclusion/exclusion criteria
• contacts
Directory
30
National center for trials management on health products
Videos :
patients share their experience of clinical research,
Patients’ associations explain their role and vision of
clinical research.
Diabète
Diabète
AFD
Rhumatismes infantiles
KOURIR
Cancer
Maladies cardio-vasculaires
Cancer
Europa Donna
Join www.notre-recherche-clinique.fr…
notre-recherche-clinique.fr
www.facebook.com/NotreRechercheClinique
www.dailymotion.com/cengeps_capl
www.vimeo.com/cengeps
Thank you for your attention