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UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Scientific Supports for Clinical Trials -UCD Clinical Research Centre
Dr Eoin J Cotter
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Enabling Translational Research
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Drivers of translation
• Culture• Creativity• People• Infrastructure & Processes
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Role of CRC
• Research Support– Grants, nurses, databases etc
• Research Oversight– Sponsorship of Clinical Trials
• Research Infrastructure – Biomarker Laboratory
• Partnerships– Industry and academic networks
• Education and Training
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
• In addition to MMUH and SVUH sites The UCD CRC has active research investigators and protocols at :
– Our Lady’s Children’s Hospital, Crumlin
– James Connolly Memorial Hospital, Blanchardstown
– Children’s University Hospital, Temple St
– Coombe Women’s and Infant’s University Hospital
– St Columcille’s Hospital, Loughlinstown
– National Maternity Hospital, Holles St
– Rotunda Maternity Hospital
Clearly demonstrates how wider network can leverage the core CRC investment and capacity
UCD CRC| Footprint
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
• 36,000+ Patient Contacts
• 91 Active Projects
• 190 Users
• 82 Principal Investigators
• 27M+ leveraged Funding
• Activity at 9 hospital sites
• First to routinely build and deploy clinical research databases
• First IMB audited CRC
• First University Sponsor of Investigator Initiated Clinical Trial
• First compliant biobank facility
• First compliant IMP storage and monitoring systems
• First Irish non-commercial core lab for clinical trial
• First Graduate taught programme in Clinical research
UCD CRC| 2006-2014
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Clinical Trials
• Key activity domain for UCD
– Early access to novel treatment for our patients
– Rare diseases
– Development of strategic partnerships
• Clinical Trial Types
– Industry initiated
– Investigator initiated
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Investigator Initiated Clinical Trials
• Importance
– Investigative culture of academic medicine
– Novel indications for established medicines
– Rare disease clinical trials
– Combinations of treatments from different manufacturers
– Translation of basic lab findings
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Sponsorship
• EU Clinical Trials Directive 2004
– Simplify & harmonize the regulation of clinical trials across
the EU, thereby facilitating the internal market in
medicinal products and protect participants & public
health
• Every clinical trial, whether commercial or non-commercial
must have a sponsor, under the clinical trials directive
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Responsibilities of the Sponsor
• Authorisation & Regulatory
– Clinical Trial Authorisation (Ethics Committee and Competent
Authority)
– Insurance
– Subcontracts & Delegation
• Good Clinical Practice
– GCP compliance
– Safety Measures
• Pharmacovigilance
– Adverse events monitoring
– SUSAR reporting
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Impact of Clinical Trial Directive on Academic Medicine
• Study must have named sponsor
• Sponsor responsibilities are significant
• However….
– Still need to support Investigator
initiated research
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
UCD as Sponsor
• UCD can act as sponsor for investigator initiated studies
• Bank of SOPs developed (and growing) as part of QMS
• Master CT insurance policy
• Core template agreements developed and used
• Currently Sponsor for 12 Trials (3 complete, 9 ongoing)
– (Nephrology, Obstetrics, paediatrics, endocrinology, dermatology )
• Critical step in funding success
• Developed specific scientific supports for Investigator Initiated
Clinical Trials
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
CRC Scientific support services
• Advice and expertise in study planning• Sample processing and management • Sample Storage • Sample Analysis
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
CRC Scientific Services Activity
• Laboratory support– Over 70 ongoing clinical trials and studies
• Analytical testing/core biomarker lab – 7 International Studies– 2 Multicentre clinical studies– 3 Local research programmes
• Biorepository– 11 Major ongoing collections and registries – 40+ Historical/archive collections– Indirectly support studies at other sites
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Sample Management Activities in the Clinical Study/trial context
Sample plan
Sample collection
Sample shipping
Sample analysis
Sample storage
CRC SCIENTIFC SERVICES
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Study Design - Sample plan
• Synergise Study activities across disciplines and physical locations
• Concept of ‘sample utility’ – maximising sample value
– Sample integrity– Data protection/ethical concerns– Appropriate collection, processing and storage– Logging and documentation
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Samples to be taken
Processing required
Sample storage
Access policy
Ethics application, Study SOP, Patient kit design etc
Location,Materials, Transport,Tracking
Facilities, Expertise Facilities,
systems +supports,
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Cardiac Biobanking Studies - Initial Meetings
• Collection of LV/RV tissue samples from explanted hearts with associated plasma samples for future molecular and histological analysis.
• Samples for Molecular post mortem in cases of suspected SADS (national scope)
• Potentially expand to collect cardiac biopsies and blood
• Studies involve coordination of efforts between histopathology, biochemistry, cardiology, surgery and CRC.
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
CRC Supports
• Contribution to drafting of protocol and ethics applications
• Design of sampling plan/collection logistics • Design and provision of patient kits, sample
tracking, labelling and logging• Provision of space in monitored biobank
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Sample collection and processing
• Appropriate facilities• Expertise and training• Clear, well planned protocols
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
DIP Study
• Currently ongoing at SVUH (PI Brian Kirby)• Examining effect of (Dipeptidyl peptidase-4)
DPP4 inhibition on psoriasis • Primary endpoint clinical improvement• Secondary endpoints include examination of
PBMC cytokine expression, inflammation biomarkers, cardiovascular risk factors etc.
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Timepoint Blood tube Process Aliquots Storage
Visit 2 PurpleGoldGreyGreen
DNASerumPlasma (Dpp4)PMBC
Red blood cell lysis8 aliquots3 aliquots5 aliquots
-20°C ERC-80°C ERC-80°C ERCLN2 CRC
Visit 3 Gold Serum 8 aliquots
-80°C ERC
Visit 4 Gold Serum 8 aliquots
-80°C ERC
Visit 5 GoldGreyGreen
SerumPlasma (Dpp4)PMBC
8 aliquots3 aliquots5 aliquots
-80°C ERC-80°C ERCLN2 CRC
Visit 6 Gold
Serum
8 aliquots
-80°C ERC
Visit 7 Gold Serum 8 aliquots
-80°C ERC
Visit 8 GoldGreyGreen
SerumPlasma (Dpp4)PMBC
8 aliquots3 aliquots5 aliquots
-80°C ERC-80°C ERCLN2 CRC
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
DIP Study – CRC Supports
• Patient Kits• Laboratory and study protocol• Labelling and logging • Lab technician support for sample processing
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
DIP Study – CRC supports
Samples to be taken
Processing required
Sample storage
Access policy
Patient kitsOrder of draw info etc
Clear labelling, processing protocolsTechnical support
Precise storage and logging instructions
Research clinical facilities laboratory
biobank
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Sample shipping
• Paperwork• Processes• Training, health and safety
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Sample shipping
Sample receipt
• Sample receipt logs • Package temperature records• Sample transfer to long term storage• Reconciliation with shipment manifest• Safe handling of dry ice
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Sample shipping
• Health and safety considerations with dry ice handling• Appropriate packaging and labelling (IATA requirement)• Creation of shipping manifest • Liaising with recipients, couriers etc • Cold chain management
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Akinesis Study
• Co-funded by Abbott and Alere, this study recruited some 930 patients across 15 sites worldwide between spring 2011 and autumn 2013.
• CRC SVUH acted as core lab for the Abbott portion of this study, received 76 shipments over 3 years, as well as shipping samples to Alere and other and other sites.
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
• We drafted a series of forms and protocols to capture all essential elements of the shipping process– Package sign in log– Sample receipt and storage logs– Package temperature reporting – Shipping manifest forms
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Biomarker Analysis at CRC
• Biomarker core lab – analysis facility at CRC SVUH
• Abbott architect ci4100, clinical analyser – both standard clin chem panels, and novel biomarker immunoassays (ie NGAL, TnI)
• In discussions with other vendors to expand capability of core lab
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
q1 q2 q3 q4 q1 q2 q3 q4 q1 q2 q3 q4 q1 q2 q3 q42011 2012 2013 2014
0
5000
10000
15000
20000
25000
30000
CRC Core Biomarker Lab Activity
tests completed
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Key considerations
• Sample shipping, handling and storage• Sample integrity – quality control, chain of
custody• Instrument accuracy and precision –
familiarisation testing and daily QC
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
AKINESIS study
• Testing of region 4000 urine samples in 5 batches over 3 years.
• Working closely with study sponsors to report progress, instrument performance/QC etc
• Working with both sponsors to report final study data
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Core lab workflow – AKINESIS study
Sample receipt
Testing list
Reagents etc
FAM Daily testing
Data compilation +
validation
Testing report
FAM report Daily testing log Data spread sheet
Reagent accountability
Core lab study file
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Sample Storage - Biorepositories
• Infrastructure• Procedures• Systems
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
-20 -80ln2
Secure power supply (15A breaker)
Air con
ventilation
Secure Access, monitoring etc
Physical Biobank Infrastructure
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
- The CRC has significant biobank facilities across both sites- LN2 crystorage facilities- over 20 freezers hosted
-collections from a wide variety of disease groups
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Monitoring system – tscan
• Covers both biobank and IMP storage • 2 hospital sites, 3 networks, 58 individual sensors, 60+ users
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Emergency response planning
Redundant space is a key element of response to freezer breakdown.
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Recent developments
• New 2D barcode labelling system in place• Improved, standardised soft and hard copy
logs • SOPs updated in line with best practise• Biocollections handbook for investigators
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Biobanking – national developments
• ISO TC 276 – biotechnology• Development of standards around a number
of related areas, including biorepositories• Consultative committee formed under the
chair of Suzanne Bracken (MMI)
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
• Irish biobank association • Development team formed, actively seeking feedback from
stakeholders involved or interested in clinical biobanking. – To develop of a corpus of support materials and to disseminate new
material to members. – To develop of a directory of biobanking activity in Ireland.– To act as a focal point for interactions between the biobanking
community other agencies– To increase awareness and understanding of the importance of
biobanking.
UCD School of Medicine & Medical ScienceScoil an Leighis agus Eolaíocht an Leighis UCD
Sample plan
Sample collection
Sample shipping
Sample analysis
Sample storage
CRC SCIENTIFC SERVICES
Eoin.cotter@ucd.ie
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