SYMPOSIUM: DRUG RESEARCH UNIT FACILITATION THROUGHOUT THE TRANSLATIONAL PATH @GHENT PROF. DR. IR. S. BEKAERT
Dzau et al. (2013) NEJM 369, Transforming Academic Health Centers (AHCs) for an uncertain future AHCs need to increase the yields of research, accelerating
the translation of results into practice …in doing so requires establishing an effective ‘discovery-to-care continuum’ , by the creation of centers of clinical research…
… those centers can catalyze interdisciplinary collaborations and assemble resources into shared core services and facilities that offer natural economies of scale.
Intrinsic assets of Academic Health Centers (AHCs), such as access to biological samples and clinical data, should be better leveraged.
In the big data era, AHCs should strive to become ‘learning health systems’ by making clinical data research grade
Translational Biomedical research: challenges: AHC’s
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Angus et al., JAMA, 2015 . Fusing randomized trials (RCTs) with Big data: the key to self-learning health care systems. True success may only come when health care delivery
systems are adequately motivated to answer research questions
Thus, RCTs and big data have complementary strenghts: RCTs offer causal inference and big data offers the potential for low cost, high-volume, nuanced answers with immediate feedback (=adaptation)
In the era of precision medicine, there is a desire for estimates of treatment effects for individual patients
Adaptive clinical trials which incorporates rules to adjust aspects of the trial during enrollment, are well suited for answering those questions
Translational Biomedical research: challenges: AHC’s
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Translational Biomedical research: challenges: AH’s and … multiple helix?
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Courtesy of Kurt Zatloukal, BBMRI.eu Reproducibility? (data) Sharing versus privacy?: F(indable) A(ccessable)
I(nteroperable) R(eusable) = FAIR principle Secondary use of data/samples? Consent and/or research as route to lawfull processing Liability? Standards and accreditation? Changing regulatory environment? Structural funding? sustainability?
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Fig 2. Estimated US preclinical research spend and categories of errors that contribute to irreproducibility. (Freedman et al. Plos Biology, June 2015)
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Translational Biomedical research: challenges: AH’s and … multiple helix?
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Translational Biomedical research: challenges: AH’s and … multiple helix?
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Ioannidis JPA (2016) Why Most Clinical Research Is Not Useful. PLoS Med 13(6): e1002049.
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Translational Biomedical research: challenges: AH’s and … multiple helix?
KCE Trials program
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Translational Biomedical research: challenges: AH’s and … multiple helix?
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Bimetra: Translational research @ Gent: mission
Bimetra facilitates and integrates different aspects of translational biomedical research acting as a central point of contact (CPOC) to catalyze translational research from bench to bedside and from bedside to community and hence leveraging economical and societal valorization.
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Basic research
Preclinical research
Clinical research Care
Bimetra is the Clinical Research Centre from Ghent University Hospital in collaboration with Ghent University.
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Basic research
Preclinical research
Clinical research Care
Facilitation from BEDSIDE to
BENCH
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Bimetra: Translational research @ Gent: vision
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Bimetra Clinics: CPOC clinical trials
Central Point Of Contact (CPOC):
Investigator-initiated • Advice and submissions EC / CA • insurance • monitoring (TIV, visits, EoTV) • safety Reporting • NCE contract preview and -filalisation
Commercial (industry-initiated) research:
= COE: • Advice third parties • COE contract preview and -finalisation
Strategic policy and liaising activities: Internal
• UZ Gent (central): JuriDi, FiDi, HR, EC • >40 depts.
External • UGent (central): TechTransfer, Financ dept, • FAGG, KCE, RUZB/CHAB • >140 companies & clinical sites
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Bimetra Clinics: CPOC clinical trials
2015:
68% submissions vs. 2012
2015: 1720 NCE + 622 COE = 2342
+18% vs. 2014
2014: 1440 NCE + 548 COE = 1988
+18% vs. 2013
2013: 1173 NCE + 506 COE = 1679
+21% vs. 2012
2012: 880 NCE + 513 COE = 1393
Status 30/06/2016 vs. 30/06/2015:
859 (+16%) NCE + 423 (+35%) COE submissions
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Bimetra Biobank: CPOC Biobanking
High quality biobank facility to stimulate translational biomedical research.
• Keywords: • Transparency • Collaboration • Autonomy (no centralised model)
• use of certain minimal datasets (MDS) linked to biospecimen
• Use of service level agreements (SLA) and Material transfer agreements (MTA)
• Access flows and service-cost models
Focus: academic research with translational finality • Prospective collections • Possible intake of important historical collections • High quality all-round service provider for biobanking:
• Sample preparation, storage and post processing • Translational data management • Biobank service support center
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Biobank initiatives: at best…
High quality repositories Annotated samples Collaborative model Harmonized QA/QC Economy of scale Harmonized guidelines/rules
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= Biological back end of data driven collaborative biomedical research
Biobanks: What?
First introduction definition Biobank: Law 19th December 2008 and adjustments ‘Wet houdende diverse bepalingen inzake gezondheid’, dd. 29.03.2013; dd. 22.06.2016
concerning access and use of human body material for clincial application on human subjects or for scientific research purposes (‘inzake het verkrijgen en het gebruik van menselijk lichaamsmateriaal met het oog op geneeskundige toepassing op de mens of het wetenschappelijk onderzoek):
27° « biobank » : structure that stores and provides human body material exclusively for scientific research purposes, and which use is not intended for any (therapeutic) application on human subjects. (de structuur die menselijk lichaamsmateriaal bewaart en ter beschikking stelt, uitsluitend voor wetenschappelijk onderzoek en dat niet bestemd is voor enige toepassing op de mens)
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Biobank initiatives: at best…
Courtesy of Kurt Zatloukal, ESBB Annual meeting – Verona, October 2013 [email protected] - © 2016
Bimetra BIOBANK: CPOC phenotype management & access
1 harmonised guideline (Flemish Biobank Initiative) Based upon:
ISO9001 OECD Best Practice Guidelines for Biological Resource Centers OECD Guidelines on Human Biobanks and Genetic Research Databases Toekomst: ISO-norm voor biobanken (betrokken in ISO working group) (ISO15189 & ISO17025: test labs
NOT biobanks) 45 ULT (-80°C) freezers
“tailormade” airconditioning Double monitoring control: device independent alarms
Focus: academic research with translational finality Establishing a central point of contact for phenotype management & access
Prospective collections Possible intake of important historical collections High quality all-round service provider for biobanking:
Sample preparation and storage Translational data management Biobank service support center
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Bimetra BIOBANK: CPOC phenotype management & access
Minimal data sets < standardisation Flemish Biobank Initiative < based on general accepted minimal data parameters for
samples (SPREC codes) combined with essential parameters from BRISQ Recommended by
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Bimetra BIOBANK: CPOC phenotype management & access
Biobank initiatives: international participation
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Currently ~500 Biobanks connected
Flemish Biobank Network: hub-and-spoke model 23
5 Locally installed components : • Each biobank can make
pseudonymized data available from one or more local Biobank Information Management Systems through its local Opal
• and can make aggregated results of a subset of the variables available to the central catalogue
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Flemish Biobank Network: ICT infrastructure 24
1 central catalogue of biobank samples:
• mapping different datasets and subsets from autonomous database systems
• enabling aggregated query results and
threshold induced notifications for participating researchers
• publish with Mica web portal
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Flemish Biobank Network: facts and figures
Results to date: 4 decentral biobank facilities linked via
central ICT-backbone
Harmonized quality management system cfr international standards
Harmonized ethical-legal framework
>30.000 cases uploaded: 227.990 by 2016
5% cases used in research
collaborations: ~16% by 2016
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= Biological back end of data driven collaborative biomedical research
Cardiovascular diseases
Metabolic disorder s
Viral infectious diseases
Immune mediated inflammation
Oncology
Neurodegenerative diseases
COPD/Asthma
Reproductive medicine
Rare diseases
Ageing
5 selected focus
biobanks
xx biobanks proposed for later
integration
Other
Hepatotropic disorders
Sudden Cardiac Death
Rheumatoïde arthritis Inflammatory bowel Disease
Diabetes
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Demonstrated scientific excellence Research collaboration Available patient populations Valorisation potential High quality samples + data
Flemish Biobank Network: focus biobanks
Flemish Biobank Network: ICT infrastructure 27
Future development: Opal-Opal data sharing Specific datasets shared through a system of “remote views
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Bimetra TDM: CPOC Translational Data Management
Consulting Best practices BIMS, privacy, traceability, sharing Clinical/Biobank/meta data collection, processing,
management Integration throughout the sample/data process
flow (‘cradle to grave’)
Use of selected LIMS tool Project-specific customization Software validation Data linkage /data sharing
Evaluation software translational data management Clinical data management systems Protocol design software
Networks CRC / Biobanks Data sharing policy Management central ICT backbone / catalogue
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Project tracking
Lab software
Sample storage
Patients
Clinical trial
ELN
Slims
EHR4CR
OpenClinica, REDCap
Bimetra TDM: service
Esperity
Sample locator BE node BBMRI directory
CMI backbone, Mica, Opal
Basic research
Preclinical
research
Clinical research Care
Digitale pathologie
Jira (admin + service desk)
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Bimetra Valorisation: CPOC translational innovation
Funding/ R&D
Project Results
Protection Project results
Validation Valorisation
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Bimetra networking: sharing and linking beyond UZGent
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STR
ATEG
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ATIO
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Biobanking networks Translational initiatives and networks EU-H2020:
ESFRI: BBMRI.EU ?EATRIS, ECRIN, ELIXIR
EIT Health big data’:
Champion program EHR4CR (biomedical) innovation initiatives Industry Government PATIENT PARTICIPATION
Patient information Patient recruitment Patient engagement
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Bimetra networking: coördinatiecellen
Research
Validation
Valorisation
Medical Devices
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Contact: www.bimetra.be 33
Prof. Sofie Bekaert Head of dept. Bimetra [email protected] Philippe Van Rompaey, PhD Bimetra Clinics [email protected]
Veronique T’Joen, PhD Biobank Manager [email protected] Lieven Vaneeckhaute Bimetra TDM [email protected]