Supplementary memorandum by Sir Liam Donaldson
DEPARTMENT OF HEALTH AND RESEARCH COUNCIL
FUNDED RESEARCH
DEPARTMENT OF
HEALTH
The Department's goals for NHS research and
development are set out in Best Research for Best Health—a
new national health research strategy. The strategy document was
published in January 2006 and its implementation is well underway.
That implementation includes the strengthening of pre-existing
research programmes, and the introduction of new funding streams.
The first of the two clusters of research activity concerned with
organ donation and transplantation described below belongs to
an established research programme (the Health Technology Assessment
programme). The second is a product of the new Biomedical Research
Centres set up to drive the development, testing and uptake of
new and better ways to prevent, diagnose and treat ill health.
1. Health Technology Assessment Programme
1.1 An evaluation of the costs, effectiveness
and quality of renal replacement therapy provision in renal satellite
units in England and Wales (Roderick) 178 pages, Volume 9, number
24.
Original project title: An evaluation of the
cost-effectiveness and quality of care of renal replacement therapy
provision in satellite units.
Chief Investigator: Dr Paul J Roderick, Reader
in Public Health, Public Health Sciences and Medical Statistics,
University of Southampton.
Publication date: July 2005
1.2 A systematic review and economic model
of the clinical and cost-effectiveness of immunosuppressive therapy
for renal transplantation in children (Yao) 178 pages, Volume
10, number 49.
Original project title: A systematic review
and economic model of the clinical and cost-effectiveness of immunosuppressive
therapy for renal transplantation in children.
Chief Investigator: West Midlands Health Technology
Assessment Collaboration (WMHTAC), University of Birmingham
Publication date: December 2006
1.3 Clinical and cost-effectiveness of newer
immunosuppressive regimens in renal transplantation: a systematic
review and modelling study (Woodroffe) 194 pages, Volume 9, number
21.
Original project title: Clinical and cost-effectiveness
of newer immunosuppressive regimens in renal transplantation:
a systematic review and modelling study.
Chief Investigator: West Midlands Health Technology
Assessment Collaboration (WMHTAC), University of Birmingham
Publication date: May 2005
1.4 The clinical and cost effectiveness
of pulsatile machine perfusion vs. cold storage of kidneys for
transplantation retrieved from heart-beating and non-heart-beating
donors (Wight) 94 pages, Volume 7, number 25.
Original project title: The clinical effectiveness
and cost effectiveness of preservation systems for retrieving
kidneys from beating and non-heart beating donors.
Chief Investigator: School of Health and Related
Research (ScHARR-TAG), University of Sheffield.
Publication date: September 2003
1.5 Evaluation of molecular techniques in
prediction and diagnosis of cytomegalovirus disease in immunocompromised
patients (Szczepura) 176 pages, Volume 10, number 10.
Original project title: Evaluation of molecular
techniques in prediction and diagnosis of cytomegalovirus (CMV)
disease in immunocompromised individuals.
Chief Investigator: Dr Diana Westmoreland, Consultant
Virologist, Department of Medical Microbiology and Public Health
Laboratory, University Hospital of Wales
Publication date: April 2006
2. Biomedical Research Centres
2.1 Cambridge BRC: Improving Outcome in
Transplantation Research Theme.
This theme is aligned to the internationally
renowned multi-organ transplant unit based at Cambridge University
Hospitals NHS Foundation Trust (CUHNFT). The two major problems
in transplantation are a severe shortage of human organs and tissues
for transplantation and graft rejection along with the side effects
of non-specific immunosuppression. The overall aim of this theme
is to address these two problems. We aim to maximise patient access
to organ and tissue transplantation and to improve outcome after
transplantation by reducing post-transplant morbidity and graft
loss.
The specific aims are to:
— improve organ allocation through
better understanding the influence of MHC gene products on transplant
outcome;
— evaluate novel targets for therapeutic
intervention in vascular injury associated with transplantation;
— test new immunosuppressive agents
for their ability to modulate alloimmunity and improve transplant
outcome;
— evaluate novel approaches for optimising
organ preservation and assessing organ function and viability
before and following transplantation; and
— develop the use of human embryonic
stem cells as a source of cells and tissue for clinical transplantation.
2.2 Guy's & St Thomas' Hospitals NHS
Foundation Trust / King's College London BRC: Emerging Diagnostic
and Therapeutic Approaches in Organ and Cell Transplantation Research
Theme.
The number of life-saving or life-enhancing
solid organ transplants (heart, lung, kidney, liver, and pancreas)
exceeds 25,000/year in the US and UK. However the success of transplantation
is plagued by a shortage of donor organs (enough for one in four
eligible patients) and high rates of graft failure (4-10% per
annum) beyond the first year of transplantation. Moreover, intensive
use of therapy to prevent rejection is associated with life-threatening
complications, including a 20% risk of cancer. Advances are thus
needed to reduce the burden of failures, in particular to prevent
reperfusion damage and early rejection episodes, which together
reduce the half-life of kidney transplants by about 50%. Given
the high initial (£54,000/patient) and maintenance (£10,000/year)
costs of transplantation, the current failure rate of 2,700 transplants
(out of 9,000) over five years in the UK equates to an estimated
waste of £250 million for kidney transplantation alone.
Based on several outstanding programmes of pre-clinical
and clinical research and one of the largest patient cohorts in
Europe (eg 150 kidney and 150 liver transplants/year, largest
living donor programme in UK, hepatocyte and islet transplant
programmes), we propose to deliver improvement in graft half-life
though better control of the inflammatory and immune response,
aided by application of genetic markers that predict and interpret
the outcomes of transplantation and development of new imaging
techniques for visualising the inflammatory response in transplant
organs. Specifically we propose the following aims:
— to apply membrane targeted inhibitors
of complement to the prevention of reperfusion damage, and so
reduce the burden of graft failure through non inflammatory injury
and immune stimulation;
— to promote long term graft acceptance
through tolerance induction protocols using cell-based therapy;
— to develop new imaging techniques
that enable complement inflammatory activity and the cellular
immune response to be visualised in whole organs; and
— to develop biomarkers in the innate
and adaptive immune system that help to predict and interpret
the outcome of transplantation.
2.3 Imperial College Healthcare NHS Trust
Imperial College London: Renal Medicine and Transplantation Research
Theme.
The overall aim of our programme is to pursue
translational and clinical research in key areas of renal medicine
and transplantation. We run a renal laboratory group of around
40 clinical and non-clinical researchers, whose work is integrated
with the Imperial College London broad strategic research theme
of Immunity and Inflammation. We work closely with researchers
in the Immunology Department. Our basic research is directly linked
to our translational research programme through six multidisciplinary
clinical research groups. These are based at the West London Renal
and Transplant Centre (WLRTC) at Hammersmith, which is the largest
centre for renal disease in Europe. This gives us a tremendous
opportunity to develop our translational research over the next
five years. Our specific objectives include the following:
— to understand disease mechanisms
and develop diagnostic and therapeutic approaches in glomerulonephritis
and diabetic nephropathy;
— to investigate the causes and development
treatment for renal cystic disease and renal carcinoma;
— to increase the donor pool and improve
the outcome in renal transplantation; and
— to improve the outcome and quality
of life in patients on dialysis.
MEDICAL RESEARCH
COUNCIL
The Medical Research Council (MRC) is one of
the main agencies though which the Government supports medical
and clinical research. The MRC is an independent body funded by
the Department for Innovation, Universities and Skills, via the
Science and Innovation Group.
The MRC's portfolio of transplantation research
is largely addressed through the Infections and Immunity Board
and focuses primarily on mechanisms of rejection and tolerance.
The MRC has recently funded the new MRC Centre for Transplantation
at King's College London, directed by Professor Steven Sacks.
The Centre, one of six new translation research centres, has been
awarded £2 million over five years to investigate a range
of issues in transplantation including better preservation of
donated organs. Although this award is not directly linked to
DH activity, the Centre is embedded within one of the NIHRs Biomedical
Research Centres and has significant clinical links. Prof Sacks
also holds an MRC Research Grant which has recently been renewed
at a level of £1.4 million for a further five years.
Current grants relating to transplantation total
£7,872,875, comprising nine awards with an annualised spend
of £1.9 million.
Relevant projects are as follows:
— Dr M Cobbold, University of Birmingham—The
development of cellular therapy for the correction of CMV-specific
immunodeficiency after stem cell transplantation (1/7/03-30/6/08
£550k)
— Dr K Suzuki, Heart Science Centre,
London—Role of cell transplantation in treating heart failure
(August 03-July 08 £775k)
— Dr A Dorling, Imperial College, London—Targeted
inhibition of coagulation—an anti inflammatory approach
to prolonging organ graft survival (3/10/07-2/10/08 £171k)
— Dr S Nicholls, University of Bristol—Corneal
graft rejection in the inbred minipig (1/3/07-28/2/09 £250k)
— Professor P Moss, University of Birmingham—Adoptive
T cell immunotherapy therapy for adenovirus infection in transplant
patients (1/9/06-31/8/09 £160k)
— Dr K Y Shiu, Imperial College, London—Defining
the pathophysiological role of B cells and the therapeutic potential
of anti-CD20 in chronic renal allograft rejection (1/9/06-31/8/09
£64k)
— Professor H Waldmann, University
of Oxford—Therapeutic Immunoregulation (1/1/05-31/12/09
£2.0 million)
— Professor S Sacks, Kings College,
London—Targeting the complement system in transplantation
(1/1/07-31/12/11 £1.4 million)
— Professor S Sacks, Kings College,
London—Emerging diagnostic and treatment approaches in organ
and stem cell transplantation (1/4/07-31/3/12 £2.08 million)
In addition, the MRC funds a large ongoing programme
of transplantation biology research (£854k in 05/06) led
by Professor Elizabeth Simpson at the MRC's Clinical Sciences
Centre in London.
ECONOMIC AND
SOCIAL RESEARCH
COUNCIL
The Economic and Social Research Council funds
research and training in social and economic issues. The ESRC
is an independent organisation that receives most of its funding
through the Department for Innovation, Universities and Skills.
A budget of £181 million (2007-08) funds over 2,500 researchers
in academic institutions and policy research institutes throughout
the UK and supports more than 2,000 postgraduate students.
ESRC research in the area of organ donation
and transplantation includes:
Transplantation and the organ deficit in the
UK
Xenotransplantation: risk identities and the
human/nonhuman interface
Medical device governance
Childhood cancer tissue donations
Professor Mary Dixon-Woods
Using simulation modelling in the management
of liver transplantation
Spaces of stem cell science: exploring processes
of transnational research
Professor Stephen Wainwright
Processes, dynamics and problems in translation:
a comparative study of stem cell innovation in the UK
Haemotopoietic stem cells: the dynamics of expectations
in innovation
Quality of life as an innovative health technology
Measuring preferences regarding equity and variations
in health
Mapping stem cell innovation in action
UK Transplant—part of NHS Blood and Transplant—also
commission research.
"Barriers to organ donation within the
general public"—published March 2003, conducted by
RBA Research
"NHS staff attitudes to organ donation"—published
Dec 2004, by Research Quorum
"Attitudes and barriers to organ donation,
and best communications routes to reach black and minority ethnic
communities (BME)"—published May 2006, by Connect Research
& Consultancy Ltd.
NHS Blood and Transplant have also conducted
a number of short polls, including "How well do you know
your partner's wishes", and "The value of sight"
survey, The results of both these surveys have been used to help
develop news releases for specific public relations activity for
example the 10th anniversary campaign and the 100th anniversary
of the first successful cornea transplant.
December 2007
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