The Role of Clinical Trials Units Helen Hill Senior Regional Advisor Clinical Trials

Specialist units to design, conduct, analyse and publish clinical trials and other well-designed studies. Expert statistical, epidemiological and other methodological advice Co-ordination of trials involving investigational medicinal products (CTIMP) within the UK Medicines for Human Use CT Regulations resulting from the EU Directive for Clinical Trials. Clinical Trial + Units

30 Fully Registered Clinical Trial Units +16 provisional or pending Registration approved by an international review committee capability to centrally coordinate multi-centre clinical trials portfolio design development recruitment data management publicity analysis Robust systems to ensure conduct and delivery of clinical trials to the highest quality standards.

North West Clinical Trials Collaborative Manchester Academic Health Science Centre MAHSC / Christies Trials Co-ordinating Unit Liverpool Trials Collaborative Liverpool Cancer Trials Unit /Liverpool Clinical Trials Research Centre North West Clinical Trial Each CTU has expertise in different disease areas or different trial designs

North West Surgical Trials Centre Developing new surgical trials and methodology Educating new surgical researchers Increasing surgical trial recruitment in NW England Developing reliable data on surgical trials Developing a NW surgical trainee collaborative Contact Jenna Paglia North West Surgical Trials Centre Launch Event Friday 20th September 2013: Newton-le-Willows 10.00am – 4.30pm

NIHR Clinical Trial Tool Kit (MRC DOH) CTU Provide support at each stage

Development of new trials Research question, methodology and design Statistical Analysis Costings (CTRC & whole trial) Direct Research costs (Grant) NHS Treatment costs (funded by the Trust even cost of IMP) NHS Support Costs includes consent ! (NIHR/CLRN) Grant applications –submit early Feasibility very important to funders is it realistic ! Patient public Involvement

Clinical Trial Set up Trial Supplies (IMP Investigational Medicinal Product) ** Case report form development (infermed MACRO) Web-based & automated telephone randomisation system development Trial Management Establishment & constitution of Independent Data IDSMC & TSC Approvals – ethical, regulatory & institutional Essential documents centrally Multi centre site coordination and initiation (international) Patient Identification Centres or follow up sites **

Clinical Trial Conduct Monitoring (Patient Safety, rights and confidentiality, data reliability) Consent ‘ innovative’ approaches prospective or emergency deferred consent Pharmacovigilance safety monitoring/ reporting ** Exclude anticipated events limit reporting proportionate to the risk Serious and Non-serious adverse event reporting Accrual

Regulatory and governance issues MHRA Good Clinical Practice Guide Risk Assessment –proportionate EMeA guidance pharmacokinetics, paediatrics and bacteria 1996/97 ICH Guidelines on Good Clinical Practice 2001 EU directive on Clinical Trials (2001/20/EC) 2001 Research Governance Framework for Health and Social Care 2004 Medicines for Human Use (clinical Trials) Regulations 2004 Human Tissue Act (UK) 2005 Mental Capacity Act (UK) 2005 EU Directive on Good Clinical Practice (2005/28/EC)

Risk Proportionate Approach Association of Medical Science reported the trial regulations were a barrier to research Risk to patient safety, data reliability and rights and confidentiality MHRA Risk Proportionate Approach reduces regulatory requirements Daily Temperature monitoring Drug accountability records Pharmacovigilance reporting Substantial amendments Inspections Low to high risk Type A Type B Type C

Wider remit Systematic Reviews Health Economics Clinical Research Networks Negotiations with pharmaceutical industry

N NIHR Clinical Trials Units Support Funding Birmingham Clinical Trials Unit -University of Birmingham Bristol Randomised Trials Collaboration - University of Bristol Liverpool Clinical Trials Research Centre - University of Liverpool Imperial Clinical Trials Unit - Imperial College London Kings Clinical Trials Unit - Kings College London Leeds Clinical Trials Research Unit -University of Leeds Leicester Clinical Trials Unit - University of Leicester London School of Hygiene & Tropical Medicine Clinical Trials Unit National Perinatal Epidemiology Unit (NPEU) Clinical Trials Unit -University of Oxford Newcastle Clinical Trials Unit - Newcastle University Norwich Clinical Research & Trials Unit - Norfolk and Norwich University Hospital Nottingham Clinical Trials Unit -University of Nottingham Oxford University Trials - University of Oxford Peninsula Clinical Trials Unit - Peninsula Medical School Pragmatic Clinical Trials Unit - Barts and The London School of Medicine and Dentistry PRIMENT Clinical Trials Unit - University College London Sheffield Clinical Trials Research Unit - University of Sheffield University of Southampton Clinical Trials Unit University of Southampton Warwick Clinical Trials Unit - University of Warwick York Trials Unit - University of York

When to involve a CTU As early as possible! CTIMP (Clinical Trial Investigating a Medicinal Product) Multi-centre RCT (CTIMP/ nonCTIMP) Multi-centre pilot/ feasibility Methodology High risk Proposed funder – e.g. NIHR HTA, EME Cost of the service applies if funded

Commissioning & funding research Streamlined and simple knowledge management systems CTU ↑

North West Research Design Service (RDS) NIHR Develop and design research proposals for funding competitions NIHR Research for Patient Benefit ProgrammeNIHR Research for Patient Benefit Programme and Programme Grants for Applied Research)Programme Grants for Applied Research Liverpool, Lancaster and Manchester Universities free of charge to anyone intending to apply for open competition peer review funding and who is an NHS researcher or working in partnership with the NHS  Research Design  Funding  Patient Public Involvement RESOURCES FOR PUBLIC INVOLVEMENT IN THE RESEARCH PROCESS

MRC Hubs for Trials Methodology Research Regional centres of excellence clinical trial methodology. MAST Methodology Advisory Service for Trials non-standard methodology North West Hub Liverpool Lancaster and Bangor to improve patient care by improving the validity and relevance of the healthcare evidence base 3 themes 1.Early phase trial design and analysis PK/PD 2. Later phase trial design and analysis 3. Patient perspectives - RECRUIT Funding extended for 5 years – today …

Hub educational opportunities Online MSc Clinical Research University of Liverpool ethical, legal and regulatory,Good Clinical Practice, the design and conduct of the clinical protocol, biostatistics, data management, product development and health economics. MSc Medical Statistics, Lancaster University Training workshops, research days

Thank you Helen Hill Senior Regional Advisor – Clinical Trials/Research Design Service

Pancreatic cancer Head and neck cancers Lung cancer Haematology Palliative care cancer work Urological cancers Pharmacogenetics and non-cancer trials Liverpool Cancer Trials Unit

Clinical Trials Research Centre (UOL based at Alder Hey Children’s NHS FT) Medicines for Children (except cancer) Pharmacogenetics Infection Neurology Reproductive and child health Vision Science and more

Manchester Academic Health Science Centre Trials Co-ordination Unit Christies Trials Co-ordinating Unit Cancer Mental Health Metabolic and Endocrine and more

NIHR Support – and resources Topic Specific Research Networks Comprehensive Research Network Diabetes Medicines for Children Dementia and Neuro- degenerative Stroke Primary Care National Cancer Mental Health

Networks Support Researchers Adopted by NIHR within Clinical Study Group Remit Funding research nurses at Trust site (non study) Recruitment Data collection Follow up of patients activity based funding Site approvals NRES R&D MHRA