Establishing an infrastructure to support the development and delivery of clinical research in patients with kidney disease

Establishment of the UK Kidney Research Consortium

The need to provide a structure to facilitate the best research, foster translational research and promote excellence in kidney research was recognised by the renal community. An inclusive consortium (the UK Kidney Research Consortium (UKKRC)) was therefore established in 2007 comprising key stakeholders in renal research from across the UK. The current membership of the consortium is shown in Box 1. The consortium is hosted by the Renal Association, the British Renal Society and Kidney Research UK, with the chair rotating biennially. The key core subgroups of UKKRC are the 12 clinical study groups (CSGs) listed in Box 2. The membership and reporting lines of UKKRC are shown in Fig 1; this includes the NIHR CRN represented by the chair of the national renal disorders speciality group. It was agreed that membership of the CSGs should be inclusive with representation from the multiprofessional team and wherever possible include trainees and patient/carer representatives. The CSGs are responsible for identifying areas where there is a clear need for more evidence, designing studies to address these areas and developing appropriate grant applications. Thus UKKRC fulfils the portfolio-generating role not covered by the CLRNs or in their successor the NIHR CRN. So far this role has resulted in the development and successful funding of 13 studies to a total value of £13443648. In total, 7 have been funded by NIHR, 3 by Kidney Research UK, 2 by the British Heart Foundation and 1 by the Medical Research Council. A list of these studies is shown in Table 1.

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Fig 1.

Organogram showing the membership and reporting lines of UKKRC. CGCs = clinical study groups; NIHR = National Institute for Health Research; UKKRC = UK Kidney Research Consortium.

While the delivery of NIHR portfolio studies is primarily the remit of the NIHR CRN and its renal disorders speciality group, CSGs have also assumed responsibility for identifying and then supporting studies that are not recruiting to time and target. This strengthens the synergy between UKKRC and the renal disorders speciality group. To promote this synergy the two organisations meet ‘back-to-back’ on the same day twice a year and many key researchers have roles in both groups. We are not aware of other specialty groups where there is a similar synergistic relationship.

As can be seen from Box 1, UKKRC has representatives from the research networks of Scotland, Northern Ireland and Wales. Studies that are developed by the CSGs are open to patients in all of the countries of the UK.

Establishment of an infrastructure for the study of rare renal diseases

In 2010 the Renal Association and the British Association for Paediatric Nephrology published Rare kidney diseases: an integrated strategy for patients in the UK.⁶ Implementation of this strategy required the introduction of disease-specific working groups, development of care pathways and introduction of a UK registry for rare kidney diseases. Funded by Kidney Research UK and the British Kidney Patient Association, disease-specific working groups (rare disease groups (RDGs)) have now been established for 12 diseases and are listed in Box 3. Like the UKKRC, CSG membership of the RDGs is inclusive with representation from the multiprofessional team, trainees and patient/carer representatives. There is, however, a greater emphasis on patient/carer involvement with many of the groups organising information days. Out of these, independent patient–family support groups, such as those for atypical haemolytic uraemic syndrome (aHUSUK) and membranoproliferative glomerulonephritis/dense deposit disease (the membranoproliferative glomerulonephritis (MPGN)/dense deposit disease (DDD) support group), have evolved. The RDGs are responsible for providing information about their respective diseases for both clinicians and patients. This information is available at www.rarenal.org and includes care pathways. A registry for each of these diseases has been established at www.renalradar.org and so far information from over 1500 patients has been entered. The RDGs, like the CSGs, have a substantial role in both the generation of new studies and their delivery. For example, both the steroid resistant nephrotic syndrome (SRNS) and MPGN/DDD groups have developed NIHR portfolio studies. These are ‘RaDaR; the SRNS Study’ and the ‘National Study of Membranoproliferative Glomerulonephritis’. The target for recruitment to both has been exceeded. The RDGs therefore sit alongside the CSGs within the UKKRC and fulfil a role in both generation and delivery of portfolio studies.

Patient, carer and public involvement and engagement in UKKRC

The importance of patient, carer and public involvement and engagement (PCPIE) in the design and delivery of studies has been emphasised by a recent report from the Mental Health Research Network showing an association between the extent of patient involvement in studies and recruitment to target.⁷ PCPIE representation within the UKKRC is achieved at multiple levels. Membership of the UKKRC includes patients and carers proposed by Kidney Research UK. These include both trustees and members of the charity's lay advisory committee. In addition the chair of the National Kidney Federation is a member of UKKRC. There are also patient/carer representatives within most of the CSGs and RDGs.

Industry and UKKRC

A priority for the NIHR CRN is to help the life-sciences industry undertake high-quality research within the NHS. This includes support for undertaking feasibility, set-up and performance management of studies. This initiative has been very successful with industry studies adopted to the NIHR portfolio accounting for over 50% of all commercial phase II–IV studies. Through the CSGs, UKKRC has provided extra support for the life-sciences industry by identifying areas where there is a clear need for high-quality studies which would best be provided by a collaboration between a CSG (or multiple CSGs) and industry. A good example of this is the PIVOTAL study (Proactive IV irOn Therapy in haemodiALysis patients). One of the key questions the anaemia CSG identified as a high priority concerned what the optimal dose of intravenous iron should be in haemodialysis patients. This was because publication of several randomised controlled trials (RCTs) of erythropoiesis stimulating agents (ESAs) in chronic kidney disease had shown harm associated with high doses, and consequently intravenous iron dosing had increased corresponding with reduced ESA use. It seemed appropriate to seek an industry partner for such a study and the pharmaceutical companies that market intravenous iron were approached. Vifor Pharmaceuticals markets two IV iron preparations, Venofer® and Ferinject®, and responded enthusiastically, providing an unrestricted award to Kidney Research UK that was sufficient to enable the study to be undertaken. The company is also providing all the iron for the study for free. Using the governance structures of Kidney Research UK, including full external peer review, a protocol for an open-label RCT comparing a high dose of intravenous iron with a standard low dose was developed. With a sample size of 2080 the study started in September 2013 and is recruiting well. This model of trial development benefits both the pharmaceutical industry and the renal research community. The funding of this large RCT is extremely modest at £2.5 million; if the study was sponsored exclusively by industry it would cost significantly more than this. Performing this trial with such limited resources relies on the infrastructure support of the NIHR LCRNs, which had been geared up to anticipate PIVOTAL in advance of its inception.

One of the main impediments to industry bringing forward new medicines for renal patients is the lack of validated end points and patient reported outcomes. In the future, UKKRC could extend its role to work with regulatory agencies and industry to agree how new medicines could be supported through the development pathway.

UKKRC and the translational gaps

The Cooksey review⁸ identified two key gaps in the translation of health research – ‘translating ideas from basic and clinical research into the development of new products and approaches to treatment of disease and illness’ and ‘implementing those new products and approaches into clinical practice’. Table 1 shows that the CSGs have successfully developed studies (such as the EMPIRIKAL study) within the first translational gap. Cooksey identified four organisations involved in addressing the second translational gap – the Health Technology Assessment (HTA) programme, the Service Delivery and Organisation programme, the National Institute for Health and Care Excellence and NHS Connecting for Health. Table 1 shows that the CSGs have developed four studies which have been funded by the HTA. From this it is apparent that the UKKRC has successfully covered the full spectrum of the pathway for translation of health research into healthcare improvement.

A national strategy for renal research

In October 2013, Kidney health: delivering excellence, a report on kidney health, was published under the auspices of Kidney Research UK, the Renal Association, the British Kidney Patient Association, the British Renal Society, the British Association for Paediatric Nephrology and the British Transplantation Society.⁹ This report documents the future ambitions of the renal community for the kidney care pathway. Research is an integral part of this pathway and the stated ambition was that ‘a research strategy for kidney disease is developed, supported by the funding required to design and conduct high quality studies, and used to further understanding of the mechanisms of disease, and improve healthcare quality and outcomes’. The renal community have responded to meeting this ambition. Coordinated by the UKKRC, a steering group has been established with representation from the renal community to provide a roadmap leading to the publication of a national renal research strategy in 2015.