Journée des Industriels du Réseau TRIGGERSEP
B. François – CHU Limoges
Mercredi 3 juin 2015 – Institut Pasteur – Paris Why a sepsis network is needed?
Sepsis places a burden on the healthcare system: . 300 per 100,000 in-habitants in North America (Angus NEJM 2013) and in Europe (Annane Lancet 2005) . Increasing incidence (ageing, immunosuppressive therapy) . Kills about 25 to 40% of patients
“Lack of well-organized academic networking” identified as one reason for: . More than 3 decades of negative trials . Failure to identify any specific treatment for sepsis
Clinical research is particular by several aspects: . Population, e.g. syndrome and not disease . Timing issues, e.g. unscheduled 24/7 inclusions . Ethical issues, e.g. waiver for consent CRICS Clinical Research in Intensive Care and Sepsis
CICs’ Sepsis oriented
TRIGGERSEP TRIal Group for Global Evaluation and Research in SEPsis CRICS From a regional to a national network
BRUXELLES
ARGENTEUIL STRASBOURG HAUTEPIERRE
ORLEANS TOURS DIJON STRASBOURG NHC LA ROCHE / YON 2007 : CRICS 1 (6 ICUs) POITIERS 2010 : CRICS 2 (10 ICUs) LIMOGES 2012 : CRICS 3 (12 ICUs)
ANGOULEME
MONTAUBAN Recruiting capacity: >10,300 admissions per year (60% of ventilated patients) CeNGEPS evaluation (2013): A+
4 CICs Sepsis oriented or Sepsis friendly CICs’ Specificities
CIC1435 (Limoges) . Linked with ICU . Organization expertise in “Emergency Trials” field . Coordination of CRICS effector network
CIC1415 (Tours) . Statistic expertise . Methodological involvement in CRICS academic research . Critical Care Medicine identified as an axis
CIC1414 (Rennes) . Data management and biostatistics in Sepsis therapeutic trials . Pharmacology and pharmaco-epidemiology of Sepsis . Specific team “Pharmacology of Sepsis and septic shock” [quadrennial 2012-2015] . CIC1429 (Garches) . Scientific expertise of the coordinating physician in therapeutic trials on Sepsis
CIC1417 (Cochin Pasteur) . Scientific expertise in vaccines with possible development . High dynamic of research of the site in Resuscitation and Sepsis field TRIGGERSEP Partners Expertise: Clinical Trials Design and Coordination - Sepsis
Expertise: Logistical Research Coordination - Sepsis Expertise: Clinical Investigation Coordination Djillali Annane Coordinator Bruno François Pierre-François Co-Coordinator and WP2 Dequin « Investigation Support » WP1 « Clinical Leader Investigation Support » Leader Expertise: Sepsis Trial Expertise: Scientific Coordination – Sepsis Jean-Paul Mira WP3 « Scientific Board » Pierre-François Leader Laterre Europe Interaction WP4
Jean-Daniel Chiche Genomic Research Fabrice Chrétien Neuro-Immunology and Histology Expertise: Human and animal model Histopathology – Experimental pathology - Expertise: Basic Research, Sepsis Sylvie Chevret Neuropathology Guillaume Monneret Responsible for development on new Immunology and Cytometry trial design for Sepsis exploration
Expertise: Biostatistics, Clinical Trials, Cohort Studies, Prognosis Expertise: Immunology of Sepsis TRIGGERSEP Expertise and capabilities
Scientific expertise
Investigation network fully adaptable
High level biostatistics
Basic science expertise . Genomic . Immuno-monitoring and cytometry . Neuro-immunology and histology TRIGGERSEP Scientific Project
Toward personalized medicine for sepsis!
Individual vs. population-based approach . Biomarkers . Immuno-Monitoring . Genomic
Innovative tools for sepsis investigations . Databases – Datamining / Big data . Adaptive designs . Research on the influence of qualitative aspects of investigation centres TRIGGERSEP Organization TRIGGERSEP PMO, Mgt board, Communication
Full time project manager
Monthly TC
Participation to all F-CRIN activities
Brainstorm meeting to elaborate new projects
Dedicated website . www.triggersep.org . [email protected] 13 TRIGGERSEP Emergency department collaboration (I)
Key player for Sepsis: . Increasing role of emergency department in hospital patient flow . Most of community Sepsis admitted through ED Absence of true Emergency research network
Organisationnal and research complexity: . Numerous similarity with ICU . Patient flow much higher . Numerous physician with a 24/7 shift
Important unmet medical need: . Biomarkers . Early treatment approach TRIGGERSEP Emergency department collaboration (II)
Previous successful collaboration: . TESS study (PHRC 2009): • Pharmaco-epidemiological study • 3642 patients enrolled . Septiflux 2 (PHRC 2013) • Biomarker evaluation • 1100 patients enrolled
Ongoing networking through current ongoing biomarker study
“Twin approach” with ICUs in order to propose a “full investigation package” TRIGGERSEP Interest for pharmaceutical companies
Tailored and customized collaboration
Phase II & Phase III (Phase I possible through CICs)
Privileged access to Clinical Coordination Center
“All inclusive approach”: . Scientifc advise . Protocol design . Data and biostatistics with easy access to F-CRIN plateform . Site selection through existing networks . Feasibilities . Overcost calculations . Boards (DSMB, EAC, CEC….) TRIGGERSEP Collaboration and contracting
Direct collaboration with the network within a global Inserm contract or trough individual contract with partners and site
Unique point of contact (PMO)
Use of “unique contracting approach” with investigation sites
Collaborative trial management with pharma companies through executive steering committee (previous experience) TRIGGERSEP European interaction
Previous and numerous European collaborative experience
Contact and access to both networks and European scientific societies
Expertise in European contracting with sites (IMI example)
CLIN-net contact in France
ECRIN opportunity as ARO TRIGGERSEP Quality Assurance
• Inserm-certified Clinical Investigation Centers (CIC) with CICs their own QMS
• In accordance to local regulations in clinical research and CRICS Network and partners abide by policy of their institutions
Inserm-certified research units •OwnQMS
Industrial Partners •OwnQMS
To realize this global QMS:
CICs ◦ Network governance and responsabilities will be made
◦ Quality manager and supervisor will be Regulations ECRIN CRICS designated at each structure F-CRIN Network QMS ◦ Inventory of all existing process and TRIGGERSEP documents will be made QMS ◦ Network process mapping ◦ Network specific documents to be done and Inserm- applied certified Industrials research Partners units and ◦ Continuous improvement by evaluations, laboratories audits and process review TRIGGERSEP Training
Investigators . Inter-university Diploma “Investigateur en Recherche Biomédicale” (Universities of Limoges, Poitiers, Rouen & Tours)
Clinical Research staff . GCP
Investigators . Master’s degree in Clinical Trials Methodology; 10-hour training module on Intensive Care ; Descartes University, Paris
CRA . Project of training on “ICU specificities” for CRO and pharmaceutical companies TRIGGERSEP Network projects
European projects 2014 & 2015 . TIMES (opTimal Management of the very Elderly with Sepsis) (D. Annane) . SEPCELL (MSCs in Sepsis CAP related) (P.F. Laterre – B. François)
. Neuro-inflammation and sepsis (F. Chretien)
ANR 2014 . OCCSUD (D. Annane)
PHRC 2014 . CAP-CODE (Community-Acquired Pneumonia: COrticosteroids Drug Evaluation (PF. Dequin) . CARS (Corticosteroids in ARdS) . Brain in Sepsis : Brain functionnal imaging and sepsis (T. Sharshar)
PHRC 2015 . IMPERIUS: IMmuno-PERsonalIzed therapy dUring Sepsis (T. Daix) Experience
Synergy
Merging CRICS and “à la carte” networks
Certification process
Continuum from basic science to clinical research
Tight interaction with European networks