Clinical Trials Networks supported by Tools and Services from Infrastructure Projects. International clinical trials are a challenge to management. Though, the number of clinical trials worldwide is increasing by around 10% per year, approvals for new molecule entities and biomedical licenses show little long-term increase. Main challenges are the need to recruit and retain sufficient numbers of patients and the successful implementing e-Clinical Trials technologies, especially for trials incorporating ePRO (patient reported outcome) and eRecruitment services. We suggest that clinical trials networks should cooperate with infrastructure projects to enable the implementation of eTrials and patient-centric trials. Clinical trials systems can be optimised by coordination through information sharing and collaboration and by building networks. Here infrastructures can function as enablers by the provision of software tools, especially patient centric trials, ePRO (Patient Reported Outcome) and data collection and recruitment using EHRs (Electronic Health Records) and the implementation of nessessary data protection, privacy protection and identity management. As example for a clinical trials network ECRIN is addressed. ECRIN is a public, non-profit organisation that links scientific partners and networks across Europe to facilitate multinational clinical research. We suggest the integration of clinical research at ECRIN with several infrastructure services developed by BBMRI, EATRIS, EUDAT, TransForm, p-medicine, BioMedBridges, etc., resulting in an increase in interoperability of clinical data management, biobanking, genetic databases, Electronic Health Records (EHR), query systems, data warehouses, data repositories and imaging data.

1. Clinical Trials Networks
supported by Tools and
Services from
Infrastructure Projects
Wolfgang Kuchinke
University Duesseldorf, Duesseldorf, Germany
ECRIN Annual Meeting
19 May, 2014, Luxembourg

2. International clinical trials
• The number of clinical trials worldwide is increasing
around 10% per year
– But approvals for new molecule entity and biologic licenses show little
long-term increase
• Pharma industry shows increased use of outsourcing;
this is no option for academic clinical trials
• Main challenge is the need to recruit and retain
sufficient numbers of patients
– About 50% of sites miss their enrolment targets
• Successful implementing e-clinical trials technologies is
a challenges for trial sponsors, especially for trials
incorporating ePRO (patient reported outcome) and
eRecruitment services
W. Kuchinke (2014)
Clinical trials networks should cooperate with
infrastructure projects to enable faster eTrials

3. How many clinical trials are
underway worldwide?
From:
www.statista.com/

4. International clinical trial
networks
• Clinical Trials Networks are collaborative
groups of clinical investigators or clinical trial
centers
• They create structures to support the conduct
of large, international, multi-centre clinical
trials
• But the conduct of large international clinical
trials has often become too demanding and
expensive for academic research institutions
• Clinical trials are getting more complex
W. Kuchinke (2014)

5. Networks can support their
members with joint services
• Trial Management and Operations
– Data management and monitoring
– Phase I Units
– Planning and conduct of clinical trials
• Quality Management
– Quality Management is at the core of every clinical research infrastructure.
– Quality documents and implementation of a QMS
– Ensuring that GCP is correctly implemented for regulatory inspections
• Supporting Tools and Services
– Study approval systems, registries, data analysis tools, efficient patient recruitment, etc.
• Local Standards & Regulations
– Compliance with local research acts, its ordinances and regulations and international
Good Clinical Practice Standards (GCP)
• Infrastructure
– Regulatory requirements (Clinical Trial Unit, Phase I Unit, Study Sites, etc.)
– Personnel, equipment, data exchange, privacy protection, identity management

6. Optimize the Clinical Trials System
• Coordination through information sharing and collaboration
• Each country adheres to its own regulatory and human
subjects protection requirements
• Each trial has a single, central coordinating center and one
data safety monitoring database
• Standardization and promotion of common tools
• Web-based portal that provides a centralized enrollment
system for registration of patients and patient
randomization
• Increase participation in clinical trials
• Allow for a patient-centric approach, as opposed to the
current approach that includes a selection bias in recruiting
patients for a trial

7. Infrastructure as enabler
• Clinical trial centers are the core element to
coordinate clinical research
– Planning and realization of clinical trials in compliance with local
rules and regulations and with the international Good Clinical
Practice Standards (GCP)
– Enforcement of uniform global standards
– Sharing of expertise by connected experts
– Sharing of training courses
• But to conduct eTrials a supporting infrastructure with the provision of
software tools is necessary
– This is especially the case for patient centric trials, ePRO (Patient Reported
Outcome) and data collection and recruitment using EHR (Electronic Health
Records)
– Patient-centric approach, personalized medicine clinical trials
– Implementation of data protection, privacy protection and identity management

8. What services are suited for
infrastructures to provide
• Coordination of monitoring,
• Logistics and pharmacy
• Training
• Genomic Informatics
• Phenotypic and genotypic data
• Facilitation of recruitment, enrollment, and analysis
• Databases, linking with external data sources, data warehousing
• Inclusion of data from patient records, EHR
• Secondary use of data to identify patients meeting particular research
criteria
• X-Rays, imaging
• Biobanking of specimens
• Personalised medicine clinical trials

9. Complementing clinical trial networks with
services and tools of research infrastructures
W. Kuchinke (2014)
“Hub-and-spoke”
arrangement of clinical
trial network between
network coordination
and local clinical trial
centers or health care
providers

10. Example: ECRIN
• ECRIN is an example for a Clinical Trials Network
• ECRIN is a public, non-profit organisation that
links scientific partners and networks across
Europe to facilitate multinational clinical research
• IT provides advice, management services and
tools to overcome hurdles to multinational trials
• Support areas include the preparation of
applications for funding, protocol evaluation, trial
management, quality assurance

11. Integration of clinical research
with Infrastructure services
• ECRIN is member in several European FP7 and
IMI projects
• ECRIN collaborates with several infrastructure
projects: BBMRI, EATRIS, EUDAT, etc.
• Limitations of existing methods of clinical trial
data management
• Objectives
– Integration and use of new tools into the
international clinical research infrastructure of
ECRIN
– Increase interoperability of clinical data
management, biobanking, genetic databases,
Electronic Health Records (EHR), query systems,
data warehouses and imaging systems

12. Collaboration of ECRIN with EU infrastructure projects projects
EU Project Type of data Role of ECRIN
TRANSFoRm • GP care data / EHR
• patient data registries,
death registries, cancer
registries
• Legal & ethical framework
• Information model
• Using TRANSFoRm tools for clinical trials with
primary care data
• GCP compliance
• Knowledge transfer and training
EHR4CR HIS data / EHR • Requirements engineering
• GCP compliance
• International clinical trials expertise
• Use of EHR4CR tools for feasibility analysis,
patient recruitment, study conduct, safety
p-medicine Images, biobank data,
simulation data, HIS
data, clinical trials data,
lab data
• GCP compliance
• International clinical trials process expertise
• Legal & ethical framework
• Cooperation with other research infrastructures
• Use of p-medicine tools for personal medicine
clinical trials
BioMedBridges Research data, lab data,
genomic data, structural
data, clinical data,
images
• Standards description and harmonization
• Technical Integration
• Secure access (privacy requirements, legal
framework and data security)

13. Three levels of integration

14. Reciprocal integration
• Suggestion: Reciprocal integration of services is
beneficial for clinical research networks and
infrastructure projects
• ECRIN can help to improve integration of tools into
the infrastructure (requirements, process
descriptions, legal requirements)
• ECRIN can help to develop suitable business models
– Business Planning / sustainability plan / continuity plan
– GCP training for developers (GCP, CSV)
– Knowledge Transfer regarding Computer
System Validation
– Knowledge Transfer regarding international
clinical trials

15. Service provision for ECRIN
• Tools may be installed at an ECRIN data
centre
• Tools may be provided as services (ASP,
SaaS, AaaS, IaaS)
• Tools must be configured for every trial
anew (e.g. CRF design)
• Sustainability of service provider
• Business model for using tools / services
• Use of tools / services in a regulated
environment

16. Service provision integration
W. Kuchinke (2014)

17. Two types of service provision
• Central service provision
– Central database, local users
– Easy to integrate
– Extension of training, validation
• Local services (EHR data and alerts,
HIS data push and pull services)
– Local databases, local service provision, local
users
– Difficult to integrate (care zone)
– Future challenge, intense involvement of local
investigators, EUCos, GPs, HIS/EHR vendors
W. Kuchinke (2014)

18. Local service provision
CRF
W. Kuchinke (2014)

19. Summary
• Infrastructure projects can provide tools
and services for clinical trials network to
enable them more easily to adapt to
eTrials, personalised medicine trials,
inclusion of data from Biobanks, Patient
Reported Outcome and Electronic Health
Records
• With reciprocal integration both partners,
clinical trials network and infrastructure
projects can gain from each other

20. Thank you!
Contact
Wolfgang Kuchinke
University Duesseldorf, Duesseldorf, Germany
e-mail: wolfgang.kuchinke@uni-duesseldorf.de
More information:
https://ecrin.org/
http://www.p-medicine.eu/
This presentation contains additional explanatory
material for Q&A session and workshop