Supporting clinical research in the NHS in England: the National Institute for Health Research Dementias and Neurodegenerative Diseases Research Network
© BioMed Central Ltd 2012
Published: 6 July 2012
Clinical research is best done when aligned with clinical care - that is, when the patient can be identified, recruited and, in many instances, researched in parallel with the delivery of clinical service. However, to achieve this effectively requires identification of the additional cost to the National Health Service clinical support services and the development of an appropriately skilled workforce. The National Institute for Health Research (NIHR) Cancer Research Network demonstrated the value of dedicated research support in terms of the number of patients recruited into clinical trials. Building on this model, the NIHR in England funded the Dementias and Neurodegenerative Diseases Research Network (DeNDRoN). DeNDRoN is now in its sixth year and has established a geographically widespread network of research support staff and research leadership managed by a central coordinating centre. Success can already be measured by a significant increase in the number of patients entering studies and the speed with which both commercial and noncommercial studies are completed. There are also early indications that the network will result in improved patient outcomes.
DeNDRoN: background, context and purpose
During 2007 and 2008 approximately £500 million ($780 million) of research support funding was withdrawn from NHS trusts in England and replaced with new mechanisms to support the delivery of clinical research (see Box 1). The NIHR Clinical Research Net-work is the largest part of this new research infrastructure in England.
As part of the NIHR Clinical Research Network, DeNDRoN has five key aims: to ensure that patients and healthcare professionals from all parts of England are able to participate in and benefit from clinical research in dementia, Parkinson's disease, motor neurone disease, Huntington's disease and other neurodegenerative diseases; to integrate health research and patient care in these conditions; to improve the quality, speed and coordination of clinical research in these conditions; to streamline and performance-manage NHS support (see Box 1) for eligible studies  (see Box 2) to ensure that the NHS Support Costs are met in a timely and efficient manner; and to strengthen research collaboration with life-sciences industries and ensure that the NHS can meet the health research needs of industry.
Box 1. How clinical research is funded in England
Clinical research studies comprise a number of component activities, which, for the purpose of agreeing funding arrangements, are attributed to one of three broad cost categories:
Research Costs are the costs of the R&D itself that end when the research ends. They relate to activities that are being undertaken to answer the research questions. These costs are met by research funding bodies such as the Medical Research Council or Alzheimer's Research UK.
NHS Treatment Costs are the patient care costs, which would continue to be incurred if the patient care service in question continued to be provided after the R&D study had stopped. These costs are met by the NHS through its clinical commissioning systems.
NHS Support Costs are the additional patient care costs associated with the research, which would end once the R&D study in question had stopped, even if the patient care involved continued to be provided. Until 2006 these costs were funded by the government directly to NHS trusts under the Culyer system. Following a period of transition, since 2008 the NHS support costs have been met through the NIHR infrastructure.
Box 2. Eligibility for inclusion in the NIHR Clinical Research Network Portfolio
For a research study to qualify for receiving NHS Support Costs (see Box 1) from the NIHR Clinical Research Network it must meet certain criteria. In summary, studies must be of clear value to the NHS and must have full research funding that has been awarded as a result of open competition across England with high-quality peer review.
Studies funded by the NIHR, other areas of central government, and NIHR noncommercial partners are automatically eligible for the portfolio. NIHR noncommercial partners are organisations that meet predefined conditions in their funding processes. Other studies - such as commercial contract research, investigator-initiated, commercial-collaborative studies or academic studies funded by overseas governments or charities - require formal consideration via an adoption process. The NIHR Clinical Research Network manages the adoption process for both commercial and noncommercial studies on behalf of the Department of Health.
In addition to Clinical Research Network-wide aims, DeNDRoN has two further goals. Despite the scale of the social, health and economic burden of dementia and neuro-degenerative diseases, there has historically been relatively little investment in research into these conditions in the UK compared with other diseases [3–5]. Notwithstanding this, there are a number of internationally recognised centres of excellence in dementia and neurodegenerative diseases research, and the UK ranks second in the world on both research output and citation impact in dementia research . DeNDRoN aims to build on this existing expertise to increase the dementia and neurodegenerative diseases clinical research leadership capability in England.
The clinical service pathways for people with dementias and neurodegenerative diseases in England are highly complex. People are diagnosed and treated across a combination of primary and secondary NHS settings, and by a number of specialists including old-age psychiatrists, neurologists and geriatricians. These specialists have different training paths, professional bodies and research traditions, and operate in different NHS settings, leading to relatively little collaboration between specialties. DeNDRoN aims to increase collaboration between these specialties to develop and deliver dementia and neurodegenerative diseases research.
DeNDRoN: increasing the NHS leadership and workforce capacity to deliver dementia research in England
National coordination of the network
Following an open, peer-reviewed competition, a contract was awarded in September 2005 by the Department of Health in England to the Institute of Neurology at University College London (UCL) to run DeNDRoN in collaboration with Newcastle University. A national Co-ordinating Centre was established by collaborators from UCL, Newcastle University, Manchester University, Sheffield University and Cardiff University. The contract was extended for a further 5 years in 2010 following successful international peer review. The Coordinating Centre is led by Directors Martin Rossor at UCL and Ian McKeith at Newcastle University, supported by Associate Directors David Burn at Newcastle University (lead for Parkinson's disease), Steve Iliffe at UCL (primary care, and patient and public involvement), John O'Brien at Newcastle University (dementia), Anne Rosser at Cardiff University (Huntington's disease) and Pamela Shaw at Sheffield University (motor neurone disease).
The DeNDRoN Coordinating Centre provides leadership to the network and manages it on behalf of the NIHR. It is responsible for developing and quality assuring local and national infrastructure, systems and processes to meet the aims of the network. It coordinates network participation in NIHR Clinical Research Network portfolio studies and promotes the active involvement of patients and the public in research.
Local research infrastructure
Each of the seven DeNDRoN LRNs is hosted by an NHS trust, either an acute hospital or mental health trust, which manages the approximately £500,000 ($780,000) government funding for local NHS infrastructure to support relevant clinical research. The core operational activities of each of the DeNDRoN LRNs are: supporting site selection and feasibility assessment for future studies; supporting local research management and governance processes and facilitating study set-up; recruiting patients to participate in portfolio studies (see Box 2 and the 'DeNDRoN research portfolio' section below); managing the progress of patients through the research process; carrying out investigations, assessments and tests attributed as NHS Support activities (see Box 1); collecting, collating and submitting research performance management data; and promoting the active involvement of patients and the public in research. In addition, the LRNs undertake a number of activities to support the development of the network, such as: delivering service improvement projects; raising awareness of research in patient, carer and clinical communities; and workforce development and training, including developing new investigators.
Under the overall guidance of the DeNDRoN Coordinating Centre, LRNs have invested their resources according to local requirements, leading to variability. Factors influencing the development of LRN infrastructure include local research interests and expertise, existing research infrastructure and the clinical pathways in the local NHS. The LRNs can be characterised by the relative centralisation or decentralisation of their resources. For example, in the North Thames region where existing research activity and expertise was focused in central London and transport links are good, research support staff were employed in the host trust and travelled to outlying locations as required. In the South West, the largest geographical region, resources were invested in two hubs from which support was offered to neighbouring sites. In the South Coast region, where there are a number of sites with equivalent populations spread across the region, staff were employed and worked locally at each site. As the network has developed and the number of sites actively recruiting patients has increased, each of the LRNs has evolved and adapted its resourcing model. Today the networks increasingly run mixed models with some centralised staff and some decentralised staff, with the general trend towards decentralisation. This new infrastructure represents a significant move towards integration of clinical care and research compared with the largely university-based research teams that delivered dementia research prior to DeNDRoN.
The development of local network infrastructure was slow in the first year while contracts were negotiated and key management staff employed. During the second year the numbers of staff grew rapidly, but this period was also characterised by high staff turnover at almost 20%. Turnover remained high compared with the average NHS turnover rate of 13%  during this period. Evidence from exit interviews suggests three main reasons for this: a lack of understanding or clarity about job descriptions and roles; insufficient research activity (see the 'Portfolio growth' section below); and lack of workforce stability itself. Since April 2009, with increasing understanding of the role requirements and sufficient portfolio activity, the workforce has become stable (turnover <10%) and increasingly experienced and sophisticated.
Total staffing establishment of DeNDRoN Local Research Networks, 2011
Number of posts
Percentage of whole-time equivalent
Clinical research leads
Research support staff
Percentage of front-line staff time spent on different activities, 2008
Staff time (%)
Screening and consenting
Completing case report forms
Training and development
Patient and public involvement
Supporting dementia research in the remainder of England
Prior to the establishment of DeNDRoN, an NIHR Mental Health Research Network (MHRN), led from King's College London and Manchester University, had been established in 2003. As many of the clinical services for dementia and mental health are provided by the same NHS trusts, the MHRN has also been able to support dementia research. In particular, the MHRN has supported major multicentre trials in regions without DeNDRoN LRNs - which has meant that the active dementia research centres in the East and West Midlands and in south London have received equivalent network support.
Much of DeNDRoN's focus has been and remains on improving the capacity and performance of clinical research performance in the UK. To date there has been little international collaboration with other similar networks, except through delivery of international studies. The exception to this is the UK Huntington's Disease Network, part of DeNDRoN, which plays a major role in the European and global Huntington's disease networks.
DeNDRoN: supporting the development of dementia research in England
DeNDRoN is predominantly a delivery organisation, providing the infrastructure described above to support the delivery of clinical research studies in the NHS. However, DeNDRoN also has a mandate to support the development of its academic research portfolio to increase the quantity and quality of dementia and neurodegenerative diseases research in England, which it does through development activities focused in three main areas.
DeNDRoN academic portfolio activities
What are they?
How were/are they established?
Clinical Studies Groups
Ongoing national multidisciplinary groups undertaking horizon scanning, idea generation, prioritisation, and so forth, in a disease area
Through open national competition during 2006. Annual open calls for new membership. Approximately 100 members in total
Motor neurone disease
Time-limited multidisciplinary groups focused on idea generation in specific topic area(s)
Topics identified through CSGs or in discussion with partner organisations. Run in collaboration with specific partners
Vascular dementia (with Stroke Association and Alzheimer's Society)
End-of-life care (with Alzheimer's Society)
Assistive technology (with Alzheimer's Society)
Group of research collaborators working together to submit a multicentre grant application to an NIHR-eligible funding body
Through CSGs; as outputs from task forces; through open calls for expressions of interest; or in response to application from researchers
25 groups were supported in 2011. Approximately one-half have already submitted grant applications
The second area is to improve the feasibility and deliverability of studies. The network has supported the delivery of more than 130 dementia studies since 2006. Increasingly sophisticated processes are being developed to enable researchers to draw on data and experience from this activity to support them in developing feasible protocols - in particular, drawing on the knowledge of LRN staff responsible for delivery.
The final area is to support active patient and public involvement in protocol development. DeNDRoN provides researchers with two levels of support with involving patients and carers in protocol development. Guidance and advice is provided via an online toolkit and in person by the DeNDRoN Patient and Public Involvement Coordinator. A managed service is provided for DeNDRoN Writing Groups, through which DeNDRoN provides: expert advice in developing a patient and public involvement plan to support the application; administrative support to arrange specific patient and public involvement activities; management support with conducting specific patient and public involvement activities; and funding to cover the costs of coordination of specific patient and public involvement activities.
DeNDRoN research portfolio
Widening the scope from dementia to neurodegenerative diseases allows greater interdisciplinarity and reflects the way that the research community is beginning to organise itself. Huntington's disease is a prototypic dementia and the other neurodegenerative diseases all share cognitive impairment to a variable extent. There is now greater engagement across neurology, psychiatry and geriatric medicine than any single disease network could achieve. This does generate specialism and service delivery boundary issues, but tackling these is important for research as they reflect service delivery issues in the clinical setting.
Impact of DeNDRoN
During 2011 the NIHR issued its first ever Themed Call for Dementia Research across most of its clinical research funding programmes. DeNDRoN supported the community to respond to the call through its Clinical Studies Groups, Writing Groups and more generally through providing input into deliverability and patient and public involvement. Approximately £17 million will be committed to 18 new research projects through the call, exceeding original expectations . DeNDRoN appears to have been effective in supporting the development of more successful applications than might have occurred without network involvement. However, as the network matures and with the increase in funding for dementia research announced in March 2012 , could DeNDRoN support even greater output from existing researchers by taking a more strategic role in portfolio development? This is primarily a question for researchers and research funders.
Participation in research
Performance of studies
In addition to increasing NHS capacity to deliver dementia research, DeNDRoN has also improved the performance of individual studies. In the 24 months to 31 December 2010, the average time taken to recruit first subject into academic portfolio studies was 126 days with a median of 50 days. Since the introduction of a dedicated Portfolio Delivery Manager and Portfolio Management Groups in January 2011, the average is 91 days with a median of 29 days. Although reliable baseline data are not available about delivery of studies on time to target, it is estimated that the proportion of academic and commercial studies completing on target within predefined timelines in 2006 was 30% and 40%, respectively, which is in line with published data . In the current year (2011/12) this proportion is 73% (n = 15) and 87% (n = 8), respectively. Comparative performance between regions with and without DeNDRoN LRNs cannot be assessed for academic dementia studies as multicentre studies have received equivalent support from the MHRN in non-DeNDRoN LRN regions. In the Parkinson's disease portfolio where there has been no alternative support outside DeNDRoN LRNs until the CLRN infrastructure developed, sites in DeNDRoN LRN regions have been shown to recruit participants twice as quickly as those outside [11, 12].
Of perhaps more interest in assessing the network model is the fact that the rate of growth of recruitment in DeNDRoN regions is 13 times higher than that outside the network. One of the key benefits for commercial sponsors working with the network is the additional coordination of the NHS sites participating in their studies. The impact of this is an increased ability to share learning across sites and intervene to ensure successful delivery. The LRNs also provide a flexible workforce that can be deployed as required to support peaks in activity, provide cover for absent staff or even open new sites if required. In the most recently completed commercially sponsored study, all 16 DeNDRoN LRN sites completed on target within the agreed timeframe, compared with three out of eight sites outside DeNDRoN LRNs. Of the DeNDRoN sites, 12 of the 16 had become active in commercial research with the support of the network - for six of these sites, this was their first commercial study.
Registers of interest in research
In addition to increasing capacity, the network is also identifying, piloting and implementing new ways of delivering clinical research in the NHS. For example, DeNDRoN has been piloting the use of research registers - lists of people with dementia who have given their consent to be contacted about future research activity - across a number of its LRNs.
Initial findings from the North Thames Dementia Register (DemReg) pilot suggest that using these lists greatly increases rates of recruitment and reduces the costs [13, 14]. During the first 6 months of the EVIDEM-E project, recruitment was via the clinical services of the local NHS Mental Health Trust . One person was recruited to the study for every 75 people screened and sent information packs (n = 300). Subsequently the study started recruiting by writing to people who had already registered their interest in studies through DemReg. This approach more than doubled recruitment rates, with one person recruited per 29 people screened (n = 88). When the research team contacted people on DemReg in person (either by telephone or face to face in the clinic), the recruitment rate was one person per two people screened (n = 30). In addition to the increase in recruitment rates, the use of DemReg significantly reduced the resources required in the research team to recruit patients. During the original recruitment phase, 130 hours of research team time were spent explaining the trial to the clinical teams, compared with 3 hours working with the DemReg coordinators to run the relevant queries.
In 2012 DeNDRoN will be leading another of the projects of the Ministerial Advisory Group on Dementia Research (Recruitment and Feasibility Tools Project), assisting with the development and use of registers to support dementia research across England, and developing a nationally consistent system to support participation in research as announced by the Prime Minister in his challenge on dementia .
Impact on patient outcomes
At present, as this analysis suggests, much of the impact of DeNDRoN can only be evaluated in terms of the level of research activity and the performance of clinical studies in England. However, the key success measure for the network will be in the impact of this research activity on people with dementia and their carers. Owing to the long timescale between the delivery of research and the evaluation of the impact of the implementation of research findings, it will be some years before the impact of DeNDRoN on patient outcomes and experience will be known. Indications from the early studies supported by DeNDRoN are encouraging [16–19], however, and there are several areas that might usefully be evaluated in the shorter term.
One such area is the impact on patient experience of being involved in research; and the impact of research activity on the quality of care. Evidence from cancer suggests that participation in clinical trials may benefit an individual over another receiving equivalent treatment outside a trial  and that research-active healthcare systems deliver better outcomes for patients than research-inactive systems . DeNDRoN has an impact on levels of research activity in NHS providers, so it would be valuable to understand the impact of that activity on patient outcomes.
A second area is the impact of DeNDRoN's patient and public involvement activities on patient awareness and involvement in the research process, which have been suggested to be major factors in increasing recruitment to clinical trials .
Another area for evaluation is the extent to which research is becoming part of the culture of dementia services in England, and the role of DeNDRoN in supporting cultural change.
A final area for evaluation is the development of working relationships between researchers and clinicians from different backgrounds, specialties and interests; and their impact on dementia research.
There has been a fundamental change in the way clinical research is supported in England over the past 5 years. During this period a new network to support clinical research in dementias and neurodegenerative diseases has been established. As a result there is a significantly larger and more experienced workforce in England to support the delivery of dementia studies. The workforce is more embedded in NHS clinical services than before the networks and has increased the capacity of the NHS in England to deliver dementia research. There is increasing collaboration across the dementia research community and a growing number of clinical services are involved in research. There is also more interaction between old-age psychiatrists, geriatricians and neurologists, and between the different NHS trusts in which these specialists work.
The network is increasing the number of dementia studies developed in England and the capacity of the NHS to deliver them. This is increasing access to research for patients and improving the performance of studies. The development of dedicated infrastructure, systems and processes to support dementia and neurodegenerative diseases research in England has already had a significant impact and provides a platform for future developments. With the prioritisation of dementia research by the UK Government - and in particular the recent investment in dementia translational research facilities, including the establishment of a dementia translational research collaboration - there is an exciting opportunity for the dementia research community in England to collaborate towards answering further key research questions more quickly.
DeNDRoN should consider extending its role in leadership and coordination of research development to support the community in responding to this opportunity, focusing on pulling through research from translational medicine to implementation into clinical practice. DeNDRoN also offers the international research community and commercial research sponsors better access to researchers and patients in England to support international efforts to alleviate the suffering caused by dementia and neurodegenerative diseases.
Comprehensive Local Research Network
North Thames Dementia Register
Dementias and Neurodegenerative Diseases Research Network
Integrating Networks and Embedding Research in Clinical Services Project
Local Research Network
Mental Health Research Network
National Health Service
National Institute for Health Research
research and development
University College London.
DeNDRoN is funded by the Department of Health in England via the NIHR.
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