How to improve Clinical Trials in Rare Diseases?

How to improve

Clinical Trials in Rare Diseases?

Cécile COLOMBAN OrphanDev, CIC CPCET Timone, Marseille

Franco-British symposium on clinical research, 17th October 2012

National context

Specificities of Rare Diseases Clinical Trials

OrphanDev’s structuration Our experience in Rare Diseases Clinical Trials

National context



Strong lobbying of patients organizations

AFM (French organization for Muscular Dystrophies) and Téléthon (TV program which collects funds dedicated to research on Rare Diseases) Rare diseases Alliance (more than 200 organizations) European database on Rare Diseases : ORPHANET (INSERM)

website which provides information on Rare Diseases (RD) dedicated to clinicians, researchers, patients and general

population

FRANCE: A LEADING COUNTRY IN EU FOR RARE DISEASES’ HEALTH POLICIES AND INITIATIVES

National Plans for Rare Diseases To improve quality of care to patients suffering from RD 2005-2008: creation of Reference Centers (131) and

Competence Centers (501) for RD 2011-2014: develop research thanks to a National Foundation


An area of excellence in France (LEEM survey 2010 and 2012 about the place of France in international clinical research)


4,6

5,1

5,3

5,4

6,1

6,2

6,2

6,3

6,3

7,7

7,9

10,2

10,3

10,7 Scandinavie

Asie

Afr. Moyen Or.

Europe Est

Australasie

Allemagne

Espagne

Royaume Uni

Etats-Unis

Autres Eur . Ouest

Am. Latine

France

Canada

Italie

Oncology/Onco-hematology Cardiovascular/Metabolism Diabetes Neurology/Psychiatry/Alzheimer

Anti Infectious/Virology/Vaccines Rares Diseases Inflammation/Rheumatology Respiratory diseases

4,1

4,1

4,2

4,3

4,4

4,6

4,7

4,8

5,1

5,1

5,1

5,2

5,3

6,2 Europe Est

Afr. Moyen Or.

Allemagne

Canada

Autres Eur . Ouest

Espagne

Asie

Etats-Unis

Australasie

Am. Latine

France

Scandinavie

Italie

Royaume Uni

4,1

4,7

5,9

6,3

6,6

6,8

7,7

7,9

8,2

8,5

10,4

15,0

17,8

45,5 Asie

Am. Latine

Scandinavie

Allemagne

Europe Est

Espagne

France

Australasie

Royaume Uni

Canada

Etats-Unis

Afr. Moyen Or.

Autres Eur . Ouest

Italie 2,2

2,2

2,3

2,6

2,7

3,1

3,4

4,0

4,0

4,2

4,2

4,2

4,4

6,2 Asie

Autres Eur . Ouest

Royaume Uni

France

Am. Latine

Canada

Europe Est

Afr. Moyen Or.

Allemagne

Italie

Australasie

Scandinavie

Etats-Unis

Espagne

2,8

3,2

3,2

3,2

3,3

3,4

3,4

3,4

3,5

3,8

3,8

4,1

4,7

4,9 Asie

Europe Est

Am. Latine

Australasie

France

Scandinavie

Canada

Autres Eur . Ouest

Allemagne

Royaume Uni

Afr. Moyen Or.

Espagne

Italie

Etats-Unis 4,6

6,1

7,0

7,0

7,4

7,5

8,7

8,8

9,0

9,5

9,7

10,3

10,7

11,4 Scandinavie

Europe Est

Am. Latine

Asie

Australasie

Autres Eur . Ouest

Afr. Moyen Or.

Royaume Uni

Espagne

Allemagne

Etats-Unis

Canada

Italie

France 4,0

4,2

4,9

5,3

5,5

5,6

5,8

6,9

6,9

7,6

7,7

7,8

7,9

12,0 Am. Latine

Australasie

Asie

Europe Est

Allemagne

Canada

Espagne

Scandinavie

Autres Eur . Ouest

Etats-Unis

Royaume Uni

Afr. Moyen Or.

Italie

France

2,9

3,0

3,2

3,3

3,3

3,6

4,2

4,3

4,5

4,8

5,2

5,4

6,5

7,5 Am. Latine

Europe Est

Asie

Canada

Etats- Unis

Australasie

Allemagne

Espagne

France

Scandinavie

Italie

Autres Eur . Ouest

Royaume Uni

Afr. Moyen Or.

Mean number of patients recruted by active center (Preliminary results, Soizic Courcier, oct 2012)

National context



SPECIFICITIES OF CLINICAL TRIALS IN RARE DISEASES

Usual quality and regulatory requirements for all clinical trials (CT)

Difficulties specific to rare diseases are added:

Translational research

The need: To overcome these organizational and methodological difficulties to: optimize the design and management of RD CT speed up the access to innovative therapeutics

The answer: A network dedicated to the clinical DEVelopment of ORPHAN therapeutics : OrphanDev Aim to increase the number and the quality of RD CT

RARE DISEASES CLINICAL TRIALS: A NECESSARY ORGANISATIONAL MODEL

National context



2009: creation of OrphanDev In the Clinical Pharmacology Unit of the Timone Hospital,

Marseille (CIC-CPCET), in a team with more than 25 years experience in CT

Coordinated by Dr Joëlle MICALLEF Regional network Supported by CeNGEPS (National center of health products

trials management)


www.cengeps.fr

http://www.cengeps.fr/





OrphanDev since 2011: National network Renewal of the CeNGEPS’ support Member of the French National Foundation for RD, directed by Pr Nicolas LEVY


www.fondation-maladiesrares.org

http://www.fondation-maladiesrares.org/







Involved in ECRIN-IA European Clinical Research Infrastructure Network –

Integrating Activity Coordinated by Jacques DEMOTES To structure pan-European investigating networks, focused

on rare diseases, medical devices and nutrition.

Involved in F-CRIN French part of ECRIN Directed by Vincent DIEBOLT, coordinated by Olivier RASCOL To reinforce the French Clinical Research in Europe and

worldwide


OrphanDev’s customized solutions Adapted to each stakeholder’s need (researcher, clinician, phamaceutical company, start-up…) Adapted to the specificity of each rare disease

Few examples: Support in the translational process Scientific support in the study design Identification and choice of investigation centers Help in research of funding (call for projects…) Access to an expert platform in therapeutic evaluation Optimization and acceleration of the patients’ recruitment

And many other solutions…

ORPHANDEV: DEDICATED SKILLS FOR RARE DISEASES CLINICAL TRIALS REALISATION

National context



Clinical Trial in Charcot-Marie-Tooth 1A (CMT 1A)

Clinical Trial in Rett Syndrome

Clinical Trial in Progeria

OUR EXPERIENCE IN RARE DISEASES: TRANSLATIONAL RESEARCH

OUR EXPERIENCE IN RARE DISEASES: FOCUS ON CMT 1A, A SUCCESS STORY

2005: First CT on CMT 1A phase II randomised placebo-controlled multicenter CT Dr Joëlle MICALLEF (PI), Clinical Pharmacology Unit, Marseille Collaboration of researchers, clinicians, pharmacologist, patients organizations A public-private partnership An orphan designation


The recruitment Multicenter study: 3 French centers Specific disposal to improve recruitment :

• a Call Center in Marseille • Involvement of the patients organizations

180 CMT 1A patients included in 28 months Highest number of patients recruited in a RD CT at this time


2010: First industrial promoted CT on CMT 1A (ongoing) SAS Pharnext, EudraCT N° 2010-023097-40 phase II randomised placebo-controlled multicenter CT Pr Shahram ATTARIAN (PI), reference center for neuromuscular disorders, Marseille The recruitment Multicenter study: 6 French centers Involvement of the patients organizations before the CT A Call Center in Marseille


The recruitment

Role of the call center: Information for patients (single contact) pre-screening by a CRA and a physician travel and time saving for non eligibles patients time saving for investigators screen-failure

80 CMT 1A patients included in 6 French centers in 8 months

Respect of the inclusion period

59%

41%

Call center contribution in the recruitment of patients

Call center recruitment

Active list of patients recruitment

OUR EXPERIENCE IN RARE DISEASES: A STRATEGY TO ACHIEVE THE RECRUITMENT

The need for a strategy of recruitment set up before the trial adapted to each case Number of subjects required (choice of the good design – alternative methodologies) Reference and competence centers Others care units (trajectory of patients in the healthcare system) Registries of patients Early involvement of patients organizations Centralized Call Center - pre-screening process

OUR EXPERIENCE IN RARE DISEASES: COMMUNICATION / TRAINING

Training of investigators, students, patients organizations… Workshops in congresses

CONCLUSION

High standards required for CT Need for professional dedicated infrastructures All the more true for RD CT, due to: methodological and logistical difficulties existing public-private partnership model ORPHANDEV network dedicated to RD CT aims to meet the specific needs of support and synergy expressed by clinicians and researchers, whether academic or industrial acts in true partnership with existing structures

Thank you for your attention…

Documents

How to improve Clinical Trials in Rare Diseases?