Origins of the tool kit (editorial)

The origin of the Tool Kit

The Joint Project on the EU Clinical Trials Directive

The EU Clinical Trials Directive
The MRC-led Impact Assessment
Aims of the Joint MRC/DH Project
Membership of the Steering Group
Working Groups Themes and Membership
Impact of the Joint Project
Acknowledgements

The EU Clinical Trials Directive

The European Union adopted the Clinical Trials Directive in 2001.  Under the Directive, member states were required to have implementing national legislation in place by 1 May 2004.  In February 2003, the Medicines Control Agency (now the Medicines & Healthcare products Regulator Agency, MHRA) consulted widely on the UK draft regulations.

The MRC-led Impact Assessment

The potential impact of the Directive on academic clinical trials had been raised with the MCA and the European Commission by individual trialists and organisations such as the MRC, Cancer Research UK (CRUK), the Association of Medical Research Charities (AMRC) and the Academy of Medical Sciences and, at a European level, by the European Organisation for Research and Treatment of Cancer (EORTC) and by the European Science Foundation.  
The MCA consultation provided new impetus to this activity.  MRC, CRUK and the National Co-ordinating Centre for the Health Technology Assessment Programme (NCCHTA) worked together to assess the impact of the Directive.  They consulted academic clinical trialists and trial managers and published their report in May 2003.  The assessment highlighted the benefits of clinical trials to the public, and a number of concerns, namely:

  • the scope of the Directive which extends to a range of research far beyond that which the MCA then regulated
  • the apparent requirement for a single sponsor which would not fit the collaborative approach to sharing of responsibilities in multi-centre publicly funded trials
  • the increase in burdensome and potentially damaging red tape 
  • duplicative processes and controls resulting from the multiple organisations involved in publicly funded trials attempting to limit their risks 
  • lack of clarity about many of the requirements. The increased costs of conducting trials which in conjunction with the limited public funds available would inevitably result in fewer trials being funded.

Aims of the Joint MRC/DH Project

In July 2004, at the initiative of the DH, the MRC and DH agreed to collaborate on a joint project to document best practice in publicly and charitably-funded clinical trials of medicines, for the benefit of the trials and R&D management communities and the MHRA. 
The specific aims were to 

  • work with the MHRA to assist the agency by clarifying the concerns that the publicly funded trial community had raised 
  • identify and document the range of good practice that already existed in managing and monitoring quality and risks in clinical trials
  • provide guidance on adapting the approaches used in publicly-funded trials to meet the new requirements 
  • identify issues to be taken up in related guidance or that needed further attention.

Membership of the Steering Group

The joint project was overseen by a Steering Group chaired until January 2004 by Professor Kent Woods (Leicester University), and then by Professor Janet Darbyshire (MRC Clinical Trials Unit).
Other members of the Steering Group were
Professor Rory Collins, MRC/CRUK/BHF Clinical Trial Service Unit
Dr Chris Counsell, NHS R&D Forum
Professor Sally Davies and then Professor Russell Hamilton, Department of Health
Dr Brian Davis,MHRA
Professor Stephen Evans, London School of Hygiene & Tropical Medicine
Dr Joe McNamara and then Dr Chris Watkins MRC Head Office
Professor Peter Sandercock, Edinburgh University
Dr Gillian Shepherd, MHRA
Dr Jim Smith, Chief Pharmaceutical Officer, DH
Professor Robert Souhami, Cancer Research UK
Professor Tom Walley, Liverpool University

Working Groups Themes and Membership

Seven Working Groups were set up during the lifetime of the project.  The resources you find listed under the stations of the three route-maps were developed and validated by these Groups.  Most were placed on the Joint Project website, hosted by the NCCHTA, until August 2004.  They were updated and incorporated into the Clinical Trials Tool Kit in September 2004. 

The Coordinators and membership of the Working Groups was as follows:

Whole Systems
Coordinator: Peter Dukes (until May 2004) then Sarah Dickson, MRC Head Office

Quality Partnerships
Coordinator: Marc Taylor, Department of Health

Institutional Trials Portfolio Management
Coordinator: Noreen Caine, Papworth NHS Trust
Gill Dale (Institute of Psychiatry/SLAM), Sarah Dickson (MRC), Dr David Langley (Imperial College), Lynne Kerridge (NCCHTA), Susan Kerrison (UCLH), Richard Liwicki (Oxford University), Tony Soteriou (Avon & Wiltshire Mental Health Partnership NHS Trust)

Trial Initiation to Commencement
Coordinator: Barbara Farrell, MRC Clinical Trials Unit
Sarah Meredith (MRC CTU), Maxine Stead (NCRN), Elaine Godfrey (MHRA); Jane Armitage (CTSU); Janet Wisely (COREC); Janet Boothroyd (NHS R&D Forum); Sally Burtles (CRUK); Assistant:  Angela Meade (MRC CTU)

Trial Management
Coordinator: Sarah Meredith, MRC Clinical Trials Unit
Noreen Caine (NHS R&D Forum), Barbara Farrell (UK TMN), Martin Landray (CTSU), Cathy McDowell (CRUK), Jane Robertson (NCCHTA), Maxine Stead (NCRN); Assistant Yolanda Collaco-Moraes;
Expert Panel: Prof Peter Brocklehurst (NPEU), Dr Marion Campbell (University of Aberdeen), Prof Rory Collins (CTSU), Prof Janet Darbyshire (MRC CTU), Prof Stephen Evans (LSHTM), Mr Ian Oulsnam (MHRA), Prof Peter Sandercock (Edinburgh University), Dr Tony Soteriou (NHS R&D Forum), Prof Tom Walley (NCC HTA), and Prof Simon Wessely (Institute of Psychiatry)

Trial Supplies
Coordinator: Keith Preece, Department of Health
Angela Ball (Christie Hospital NHS Trust), Roger Brooks (Sheffield Hospitals NHS Trust), John Farrell (Royal Free Hospital Trust), V’lain Fenton-May (Wales Quality Control), Helen Johnson (Bristol-Myers Squib), GH Halbert (University of Strathclyde), Margaret McFarland (Royal Hospitals Trust), Bronwyn Phillips (MRHA), Rebecca Prowse (Glaxo Smith Kline), Keith Wheatley (University of Birmingham).

Pharmacovigilance
Coordinator: Simon Dyer, Department of Health
Rory Collins (CTSU), Tom Barnes (London West MH R&D Consortium), Helen Foster (NCRN), Susan Kerrison (UCLH), Gus MacConnachie (Ninewells Hospital), Christos Pagonis / Sally Burtles (CRUK), Richard Sullivan / Judith Bliss (CRUK), Ann Marie Swart (MRC CTU), Philip Harrison, (MHRA), Maria Palmer (NHS R&D Forum)

Impact of the Joint Project

Several partnership events and activities involving the Joint Project working groups and other partners contributed to a number of important developments in the UK and at the EU Commission.  Some of these are as follows:

  • The role of the sponsor was clarified through a series of meetings, some organised by the Joint Project, and others by the Academy of Medical Sciences and Universities.
  • Controls that are proportionate to the risks was emphasised in a number of fora, including meetings organised by the European Science Foundation and EUGCP Forum.  The draft Directive on Good Clinical Practice of Commission issued for consultation in July 2004 appeared to recognise many of the concerns that trialists on the one hand and the MHRA on the other had raised with the Commission.
  • Improving the “user friendliness” of procedures has been achieved to some extent, through working with the MHRA and the EMEA.
  • Dissemination of information about the new requirements has been promoted through a joint MRHA/Joint project seminar, meetings organised with or by the NHS R&D Forum, the UK Trial Managers’ Network, the ABPI and COREC, and commercial conference organisers.  The Clinical Trials Tool Kit brings together and disseminates the work of the Joint Project.

Acknowledgements

The MRC and Department of Health wish to acknowledge the commitment and expertise of the many individuals and organisations without which the Clinical Trials Tool Kit could not have been constructed.  We wish to thank the Steering Group, the Working Group co-ordinators and members; the UK Trial Managers’ Network; and NCCHTA for hosting the initial Joint Project web site.