Journée des Industriels du Réseau TRIGGERSEP

B. François – CHU

Mercredi 3 juin 2015 – Institut Pasteur – 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 HAUTEPIERRE

ORLEANS STRASBOURG NHC LA ROCHE / YON 2007 : CRICS 1 (6 ICUs) 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 () . 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

 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, & 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