P.F. DEQUIN Paris, 18 mars 2014 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 Network TRIGGERSEP TRI al Group for Global Evaluation and Research in SEP sis CRICS – from a regional to a national network (12 sites) BRUXELLES ARGENTEUIL STRASBOURG HAUTEPIERRE ORLEANS TOURS DIJON STRASBOURG NHC LA ROCHE / YON POITIERS LIMOGES 2007 : CRICS 1 (6 ICUs) ANGOULEME 2010 : CRICS 2 ( 10 ICUs) MONTAUBAN 2012 : CRICS 3 (12 ICUs) Recruiting capacity: >10,300 admissions per year (60% of ventilated patients) CeNGEPS evaluation (2013): A+ CRICS – Context ”CRICS aims at developing and professionalizing clinical research in patients in critical state especially in the field of Sepsis.” Inclusions 24/7 Short inclusion “windows” Emergency consent Collective participation of all department's physician is needed (continuity of care principle which is specific of this field) Often critical state with major ability to evolve that is hardly compatible with clinical research’s rigor Objectives ◦ Reach a minimum of 10% of research participants among ICU patients ◦ Harmonization across centers ◦ Recognition (worldwide by academia and industry) Coordinating centre ◦ Limoges 2007-2012 (B. François), Tours since 2012 (E. Mercier) Scientific committee (from 2011) Charter for both general functioning and scientific committee Communication & dissemination : ◦ Unique entry door for partners when possible ◦ Annual seminar, quarterly meetings ◦ Biannual newsletter ◦ Network extranet website Standardization ◦ Centralized feasibility as often as possible ◦ Costs and budget ◦ Training (joint staff and investigators) ACCESS – EISAI CRICS 1 : 4 centers Worldwide open centers: 338 / Worldwide inclusions: 1985 CRICS = 10.1% (1.2%) JAMA 2013; 309 (11): 1154-62 IMI 6th call (CAP and AB3SI) ◦ RENARCI + « extended CRICS » IMI 8th call, WP6b ( Staphylococcus VAP) ◦ « extended CRICS » CRICS Clinical Research in Intensive Care and Sepsis CICs’ Sepsis Network TRIGGERSEP TRI al Group for Global Evaluation and Research in SEP sis ARGENTEUIL CIC-BT 1417 BRUXELLES COCHIN PASTEUR CIC-IT 1429 GARCHES CIC-P 1414 RENNES STRASBOURG HAUTEPIERRE ORLEANS TOURS DIJON STRASBOURG NHC LA ROCHE / YON CIC-P 1415 TOURS POITIERS LIMOGES CIC-P 1435 LIMOGES ANGOULEME CRICS CICs’ Sepsis network MONTAUBAN 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 CRICS Clinical Research in Intensive Care and Sepsis CICs’ Sepsis Network TRIGGERSEP TRI al Group for Global Evaluation and Research in SEP sis TRIGGERSEP – Partners PF Laterre (HCL) TRIGGERSEP BRUXELLES CRICS CICs’ Sepsis Network CIC-P 1414 RENNES STRASBOURG HAUTEPIERRE PF Dequin (CRICS) ORLEANS TOURS DIJON STRASBOURG NHC LA ROCHE / YON CIC-P 1415 TOURS POITIERS ARGENTEUIL LIMOGES F Chrétien (Pasteur) CIC-P 1435 LIMOGES S Chevret(APHP) JP Mira (APHP) ANGOULEME CIC-IT 1429 GARCHES B François (LIMOGES) G Monneret (HCL) CIC-BT 1417 COCHIN PASTEUR D Annane (APHP) JD Chiche (APHP) MONTAUBAN 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 • Inserm-certified Clinical Investigation Centers CICs’ Sepsis Network (CIC) with their own QMS CRICS Network and • In accordance to local regulations in clinical partners research and abide by policy of their institutions Inserm-certified • Own QMS research units Industrial Partners • Own QMS To realize this global QMS: ◦ Network governance and responsabilities will be made ◦ Quality manager and supervisor will be designated at each structure ◦ Inventory of all existing process and documents will be made ◦ Network process mapping ◦ Network specific documents to be done and applied ◦ Continuous improvement by evaluations, audits and process review Individual vs. population-based approach ◦ Biomarkers ◦ Immuno-Monitoring ◦ Genomic data Innovative tools for sepsis investigations ◦ Databases – datamining / « big » data ◦ Adaptive designs ◦ Research on the influence of qualitative aspects of investigation centres European projects 2014 ◦ TIMES (opTimal Management of the very Elderly with Sepsis) (D. Annane). ◦ 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) ◦ RéaNet : Internet information for relatives of septic patients (JP. Mira) ◦ Brain in Sepsis : Brain functionnal imaging and sepsis (T. Sharshar) ANR ◦ Brain functionnal imaging and sepsis (T. Sharshar) ◦ Sepsis-induced immune suppression and secondary infections (F. Pene, G. Monneret, B. François) Cohort (RaDiCo) ◦ Extreme phenotypes of sepsis Investigators ◦ Inter-university Diploma “Investigateur en Recherche Biomédicale” (Universities of Limoges, Poitiers, Rouen & Tours) Clinical Research staff ◦ GCP TRIGGERSEP – SWOT Networking for years Size Recruitment performance Lack of legal organization WEAKNESSES Experience Visibility Synergy Emerging structure Merging CRICS & à la carte networks Particularities of Sepsis Trials Certification process Absence of long term cohort Continuum from basic science to clinical WEAKNESSES research Translational research Difficult global interaction Size Professional platform Financial fragility Industry partnership Ongoing network dynamic Emerging structure Field interface Lack of legal organization Development capacity History of international Ongoing network dynamic leadership Inserm label – University hospitals Unique partner for industry Risk for decrease industry interest in sepsis Tight interaction with European networks Economic crisis THREATS Link with ISARIC and InFact Low awareness of sepsis in lay public and policy makers Difficult global interaction Slowing Translational science Ongoing networkDifficult dynamic global interaction Industry partnership High development capacity Project Manager: to be recruited Until further notice: Isabelle Herafa [email protected].