Clinical Trials in the UK achieving our potential

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Clinical Trials in the UK - achieving our
potential

• Dr Mark Lewis
• Commercial Research and Clinical Trials Advisor
• Department of Health
• London

Mark Lewis Consulting
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The course of history in clinical research
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The UK as a site for clinical trials

• Former reputation based on
• Excellent clinical and research facilities
• Easy access to diagnostic testing
• Highly qualified staff
• Structure of Primary Care system
• Investigator agreements
• Informal financial accounting
• But .. environmental changes in late 90s
• Clinical and Research Governance
• NHS performance targets
• Management of Primary Care
• Result poor performance in commercial trials

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UKs continuing assets and advantages

• Strategic alignment of government charity
  funders
• RD infrastructure with a high degree of
  coordination
• National forums for strategic planning
• Highest rate of cancer trials accrual of any
  country
• Potential for large scale clinically annotated
  specimen resources
• Potential for comprehensive epidemiological,
  demographic, outcomes, resource utilisation
  data
• The base on which we build

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The economic importance of the pharmaceutical
industry in the UK
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Pharma industry contribution to UK

• Major balance of payments contribution
• Leading industrial provider of research base in
  the UK
• 3.3b spent in 2004
• 40 (gt1.25b) on clinical research
• but in 2000
• Serious problems recognised with UK
  competitiveness
• Initiation of PICTF process

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Overview of PICTF including the Clinical Research
Working Group

• The Pharmaceutical Industry Competitiveness Task
  Force (PICTF) a joint UK Government and
  Industry body
• PICTF Working Groups reviewed and made
  recommendations on
• The UK Market for Pharmaceuticals
• Intellectual Property Rights
• Licensing of Medicines
• The UK Science Base
• Clinical Research
• - A major influence on the Governments RD
  strategy for health

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PICTF Working Group on Clinical Research (March
2001) reported

• How the UK must adapt to international
  developments (ICH GCP, EUD, wider geographical
  distribution of good research capacity)
• On the UKs problems in
• speed of clinical trial initiation,
• patient recruitment,
• data quality and
• site costs
• These observations connected by the Resource
  Spiral

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The Resource Spiral

• Inefficient research management results in
• delayed trial initiation
• lowered patient recruitment
• reduced investigator fee income,
• lost trial site personnel
  
• incomplete data
• slow resolution of data queries but
• higher trial costs

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Implications of the Resource Spiral hypothesis

• Effective Sponsor/Site liaison and efficient
  negotiations are key
• Poor research management prejudices trial
  performance
• The roles of NHS Trusts and Universities needed
  clarification
• NHS, University (and Industry) research managers
  needed training in trial site negotiations
• Standardised contracts would speed up trial
  initiation
• Resulted in the model Clinical Trial Agreement
  2003

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Negotiations for the NHS-ABPI-BIA model Clinical
Trial Agreement in 2005 and 2006

• 11 discussions with companies, trusts etc
• briefing papers on themes
• shuttle diplomacy to identify routes to
  resolution
• briefed plenary discussions
• teleconference
• modifications for Devolved Administrations and
  production of guidance
• final versions endorsed by coordinating bodies
• adoption

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Revision of mCTA Industry issues

• Single agreement with site
• Clarity about insurance/indemnity
• Clarity about FOIA
• Liaison with RD and Investigator as appropriate
• Site commitment to contracted level of
  recruitment
• Simplify dispute resolution procedure

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Revision of mCTA NHS issues

• Less onerous liabilities and indemnities clause
• More equitable treatment of IP and KH
• Data Protection and FOIA provisions
• Sign-off and protocol amendments
• Simplification of dispute resolution
• Corporate governance concerns for Foundation
  Trusts
• Ensure trial registration and data publication
• Delete foreign law provisions
• Clarify universities positions

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Revision of mCTA What everyone wanted

• Practical, agreed and robust in format and
  content

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Revision of mCTA adoption process

• Agreement signed off by
• ABPI Legal and Medical Committees
• Health Departments in Scotland, Wales and
  Northern Ireland (tartanized etc versions)
• Monitor, NHS Confederation
• UK Clinical Research Collaboration
• Council of Heads of Medical Schools
• Trusts
• Companies
• For mCTA see http//www.nihr.ac.uk/industry.aspx

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Legal status of the mCTA

• The mCTA is a template in which the specific
  features of individual trials have to be
  accommodated.
• Use of the mCTA is
• commended to NHS trusts by DH
• commended to pharma companies by ABPI
• No statutory requirement to use the template as
  published, but companies or trusts choosing to
  modify it have to accept the likelihood of severe
  time and cost penalties

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Questions about the interpretation and use of the
new mCTA

• Already almost universal adoption by pharma
  operating in the UK
• Some questions raised about non-inclusion of CFR
  provisions and treatment of liabilities and IPR.
  In the UK context these should be regarded as
  non-negotiable

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What lessons can be learned from the UK
experience?

• Process can be as important as content
• Identify corporate drivers
• The development of model agreements is a
  worthwhile and effective tactic for accelerating
  commercial clinical research site initiation
• Model agreements alone are not a panacea for the
  ills affecting clinical research
• The strong clinical and research governance
  arrangements embedded in the UKs NHS are
  important assets for clinical research
• Lessons translate overseas and are positively
  reinforced

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Next steps

• Modify CRO mCTA and launch (Q1 2007)
• Develop medical device agreement (mCIA) in Q2
  2007
• Revise the NHS RD Partnership with the
  Pharmaceutical Industry (Q2 2007?). Some issues
  outstanding.
• Devise contracting arrangements for the UK
  Clinical Research Networks bipartite agreements
  between trust and sponsor facilitated by CRNs

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Developments are within the context of the
Governments strategy Best Research for Best
Health, launched in January 2006
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UK Clinical Research Collaboration (UKCRC)

• Established 2004 to re-engineer environment
• Partnership between public sector, private sector
  and patients
• Vision
• to establish the position of the UK as a world
  leader in clinical research by harnessing the
  power of the NHS
• to benefit the public and patients by improving
  national health and increasing national wealth

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Industry Involvement in UKCRC All Levels
UKCRC Board
Industry Reference Group
Meetings of Industry Board Members
Subgroup on UKCRN
Other initiatives eg public engagement
Workstreams
Industry Road Map Group
Feedback via Trade Associations
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National Institute for Health Research

• Structure
• UKCRN Co-ordinating Centre
• Six topic-specific Research Networks (Cancer
  Mental Health Medicines for Children Diabetes
  Stroke Dementias Neurodegenerative Diseases)
  each with a National Co-ordinating Centre and
  local research networks
• One Primary Care Research Network (PCRN-E),
• One Comprehensive NHS Research Network,
  comprising local research networks covering
  England, to address all areas of disease/need and
  to play a key role in RD management and
  governance.

Infrastructure
Research Networks
Experimental Medicine Facilities
Technology Platforms
National Schools for Research
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UKCRN Services to Industry

• One stop shop for access to experts and
  specialist experience
• Standing Confidentiality Agreements covering
  company and UKCRN networks to expedite
  consultation
• Rapid response mode initial feasibility opinion
• Highly detailed site specific capability
  assessment
• Routine use of model Clinical Trial Agreement

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UKCRN Coordinating Centre

• National coordination of UKCRN activities
• Conduit for addressing barriers to trials at
  national level
• Development provision of national systems
  approaches to trial development management
• Central team of 30-35 staff with leads for the
  different workstreams
• Performance management of Topic-Specific
  Coordinating Centres
• Financial management of UKCRN
• Provides direct link with UKCRC Board/Partners
• NB not coordination of scientific
  plans/portfolios

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UKCRN Services to Industry

• Single costing template for multi-centre studies.
  Using RD Forum ICR model http//www.rdforum.nhs.
  uk/docs/commercial_research_guidance_2005.pdf
• Central sign off for RD at a national level for
  multi-centre trials
• Research Passport for honorary research
  contract agreements
• Network monitoring of recruitment and
  performance management

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Adoptions to Feb 2007

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Comprehensive Clinical Research Network (CRN)

• Build on UKCRN developments across the full
  spectrum of disease and clinical need
• Coordination, support and performance management
  to be provided by the UKCRN Coordinating Centre
• Establishment will be incremental over the 3 year
  RD transition period starting 2007
• Purpose of Clinical Research Network for England
  is
• to provide the NHS infrastructure to support
  clinical research
• provide funding for NHS support costs
• help streamline the research management function

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UKCRC Industry Roadmap Group goals -
facilitating industry trials in networks

• Focus on
• Better feasibility data
• Speed of commitment
• Speed of trial set-up
• Speed of delivery
• Quality of data
• Consistency of agreements
• arrangements
• Cost of service
• Building up the basis for partnership working
• Metrics

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The improved environment for clinical research in
the UK

• Best Research for Best Health the Governments
  health research strategy
• Importance of UKCRN
• Partnership
• Coordinating structures
• Channels of communication
• Tools of the trade
• Expertise in research and management
• Commitment

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mark.lewis_at_nwlondon.nhs.ukmark_at_measlewis.plus.co
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