UCD School of Medicine & Medical Science Scoil 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 Science Scoil an Leighis agus Eolaíocht an Leighis UCD Enabling Translational Research

UCD School of Medicine & Medical Science Scoil an Leighis agus Eolaíocht an Leighis UCD Drivers of translation Culture Creativity People Infrastructure & Processes

UCD School of Medicine & Medical Science Scoil 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 Science Scoil 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 Science Scoil 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|

UCD School of Medicine & Medical Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil an Leighis agus Eolaíocht an Leighis UCD TimepointBlood tubeProcessAliquotsStorage Visit 2Purple Gold Grey Green DNA Serum Plasma (Dpp4) PMBC Red blood cell lysis 8 aliquots 3 aliquots 5 aliquots -20°C ERC -80°C ERC LN 2 CRC Visit 3GoldSerum8 aliquots -80°C ERC Visit 4GoldSerum8 aliquots -80°C ERC Visit 5Gold Grey Green Serum Plasma (Dpp4) PMBC 8 aliquots 3 aliquots 5 aliquots -80°C ERC LN 2 CRC Visit 6Gold Serum 8 aliquots -80°C ERC Visit 7GoldSerum8 aliquots -80°C ERC Visit 8Gold Grey Green Serum Plasma (Dpp4) PMBC 8 aliquots 3 aliquots 5 aliquots -80°C ERC LN 2 CRC

UCD School of Medicine & Medical Science Scoil 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 Science Scoil an Leighis agus Eolaíocht an Leighis UCD DIP Study – CRC supports Samples to be taken Processing required Sample storage Access policy Patient kits Order of draw info etc Clear labelling, processing protocols Technical support Precise storage and logging instructions Research clinical facilities laboratory biobank

UCD School of Medicine & Medical Science Scoil an Leighis agus Eolaíocht an Leighis UCD Sample shipping Paperwork Processes Training, health and safety

UCD School of Medicine & Medical Science Scoil 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 Science Scoil 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 Science Scoil 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 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 Science Scoil 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 Science Scoil 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 Science Scoil an Leighis agus Eolaíocht an Leighis UCD

UCD School of Medicine & Medical Science Scoil 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 Science Scoil 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 Science Scoil 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 reportDaily testing logData spread sheet Reagent accountability Core lab study file

UCD School of Medicine & Medical Science Scoil an Leighis agus Eolaíocht an Leighis UCD

UCD School of Medicine & Medical Science Scoil an Leighis agus Eolaíocht an Leighis UCD Sample Storage - Biorepositories Infrastructure Procedures Systems

UCD School of Medicine & Medical Science Scoil an Leighis agus Eolaíocht an Leighis UCD ln 2 Secure power supply (15A breaker) Air con ventilation Secure Access, monitoring etc Physical Biobank Infrastructure

UCD School of Medicine & Medical Science Scoil 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 Science Scoil an Leighis agus Eolaíocht an Leighis UCD

UCD School of Medicine & Medical Science Scoil 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 Science Scoil an Leighis agus Eolaíocht an Leighis UCD

UCD School of Medicine & Medical Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil 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 Science Scoil an Leighis agus Eolaíocht an Leighis UCD Sample plan Sample collection Sample shipping Sample analysis Sample storage CRC SCIENTIFC SERVICES