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

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


Enabling Translational Research


Drivers of translation

• Culture• Creativity• People• Infrastructure & Processes


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


• 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


• 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


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


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


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


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


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 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


CRC Scientific support services

• Advice and expertise in study planning• Sample processing and management • Sample Storage • Sample Analysis


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


Sample Management Activities in the Clinical Study/trial context

Sample plan

Sample collection

Sample shipping

Sample analysis

Sample storage

CRC SCIENTIFC SERVICES


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


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,


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.


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


Sample collection and processing

• Appropriate facilities• Expertise and training• Clear, well planned protocols


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.


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


-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


-80°C ERC

Visit 8 GoldGreyGreen

SerumPlasma (Dpp4)PMBC

8 aliquots3 aliquots5 aliquots

-80°C ERC-80°C ERCLN2 CRC


DIP Study – CRC Supports

• Patient Kits• Laboratory and study protocol• Labelling and logging • Lab technician support for sample processing


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


Sample shipping

• Paperwork• Processes• Training, health and safety


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


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


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.


• 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


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


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


Key considerations

• Sample shipping, handling and storage• Sample integrity – quality control, chain of

custody• Instrument accuracy and precision –

familiarisation testing and daily QC


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


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


Sample Storage - Biorepositories

• Infrastructure• Procedures• Systems


-20 -80ln2

Secure power supply (15A breaker)

Air con

ventilation

Secure Access, monitoring etc

Physical Biobank Infrastructure


- The CRC has significant biobank facilities across both sites- LN2 crystorage facilities- over 20 freezers hosted

-collections from a wide variety of disease groups


Monitoring system – tscan

• Covers both biobank and IMP storage • 2 hospital sites, 3 networks, 58 individual sensors, 60+ users


Emergency response planning

Redundant space is a key element of response to freezer breakdown.


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


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)


• 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.


Sample plan

Sample collection

Sample shipping

Sample analysis

Sample storage

CRC SCIENTIFC SERVICES

[email protected]

mailto:[email protected]

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