Research registries and biobanks present an efficient way of doing research. In the UK the life sciences industry, charities and academia are collaborating to maximise this new approach and open up a wealth of new opportunities to accelerate new advances that will benefit kidney disease patients.
Published: 04 October 2019
The NIHR research infrastructure supports the delivery of complex and innovative clinical trials.
Using a biorepository to investigate disease progression
Clinical Need: Stratification of chronic kidney disease (CKD)
Most diseases and conditions progress over time, but some diseases progress faster in some patients than they do in others. For example, chronic kidney disease (CKD) affects around 10 percent of the adult population and is associated with an increased risk of heart attack, stroke and end stage kidney disease (ESKD). However, the majority of people affected by CKD are at relatively low risk of these outcomes.
By learning which patients are at a higher risk we can adopt a stratified treatment approach. This means resources can be directed to those patients who are most at risk of disease progression, while those at lower risk can be offered less frequent monitoring, requiring less hospital visits.
Better risk prediction is one of the primary aims of the NURTuRE biobank initiative. Maarten Taal, Professor of Medicine at the Centre for Kidney Research and Innovation, University of Nottingham, is the Chief Investigator for the NURTuRE CKD study. He explains what NURTuRE is, and why it was established:
“NURTuRE - the National Unified Renal Translational Research Enterprise - is a unique kidney biorepository for chronic kidney disease (CKD) and idiopathic nephrotic syndrome (INS) covering England, Scotland and Wales. It is the first of its kind and will soon contain patient tissue, samples and linked clinical data from 3000 patients with CKD and 800 patients with INS.
It is the first of its kind and will soon contain patient tissue, samples and linked clinical data from 3000 patients with CKD and 800 patients with INS.
“The samples are being collected initially for two separate studies: NURTuRE CKD and NURTuRE INS. These studies have the same primary aims: firstly to increase understanding of disease mechanisms and improve our ability to predict which patients are more likely to progress to end stage kidney disease (in the case of CKD); and secondly to enable better targeting of treatments and resources. In addition, we hope that by identifying novel biomarkers we can help accelerate the development of new treatments for CKD and INS.
“These two studies are running in parallel and for each patient recruited we are collecting over 90 plasma and serum samples and over 30 urine samples. Plus each participant in the CKD cohort has agreed to a one year follow up appointment where we will collect the same number of samples a second time. This combined collection of samples forms the NURTuRE biobank.”
Once the second appointment is complete, follow up of NURTuRE CKD participants will continue for 15 years and will be done automatically by the UK Renal Registry. Professor Taal feels that having a low burden of participation is a key benefit:
“Patients with chronic Kidney disease will be visiting hospital regularly for monitoring purposes. When we conduct research we have to be mindful of that, and we don’t want to make too many extra demands on their time. Working through the registry and biorepository enables multiple researchers to ask multiple, different research questions at the same time using the same patients, but without those patients having multiple visits to the hospital, or having to provide multiple samples. It is a very efficient way of doing research.”
Recruitment to NURTuRE CKD is now complete with 3004 patients enrolled, and NURTuRE INS is on track with more than 500 patients recruited (as of 19 September 2019), despite being a rarer condition. Topping the leader board for CKD recruitment are two sites: Derby and Nottingham. At both sites the East Midlands branch of the NIHR Clinical Research Network has supported the study. Professor Taal acknowledges that this support has been a major factor in the high recruitment levels:
“The Clinical Research Network team at the site where I am based in Derby have certainly contributed to the study. They allocated research nurse resource to help recruit and consent patients, and take samples. Sixteen sites in total have contributed to the study; fourteen sites in England, one in Wales and one in Scotland.
“It has been a fantastic collaborative effort, which is very satisfying to see. When I began doing research over 20 years ago, investigators predominantly conducted single centre studies. All that has changed. The NIHR research infrastructure in England has made multi-centre studies much easier to do and collaboration is now commonplace. If we want to progress and advance treatments, we have to be able to collaborate.”
The NIHR research infrastructure in England has made multi-centre studies much easier to do and collaboration is now commonplace.
Collaborating to boost UK renal research
The vision and ambition behind NURTuRE extends beyond the two studies: NURTuRE CKD and NURTuRE INS. The creation of NURTuRE fulfils one of the key objectives set out in the UK Renal Research Strategy, published in 2016, which provides a blueprint for renal research in the UK. The strategy recognised the need for a kidney biobank to provide a resource for fundamental and translational research.
A number of companies were already having conversations with different clinical academics about setting up kidney biorepositories, and clinical academics were approaching both companies and charities for support. Combining resources into one national CKD biorepository quickly became a viable prospect and Kidney Research UK was in a unique position to bring everyone together. Professor Taal describes the collaborative approach which paved the way for NURTuRE:
“NURTuRE is a unique partnership between: academic investigators; the universities of Bristol, Birmingham, Nottingham and Geneva; Kidney Research UK; NIHR-funded biocentres; and five pharmaceutical companies - Abbvie, Evotec, UCB, Astrazeneca and Retrophin. Following the UK Renal Research Strategy these five companies agreed to provide funding via Kidney Research UK to set-up the biobank.
“Around the same time myself and Professor Moin Saleem had, independently of each other, both conceived the ideas behind NURTuRE CKD and NURTuRE INS and approached Kidney Research UK for support in obtaining funding. Both studies are unique but have similarities and we were brought together by Kidney Research UK. The charity agreed to support both studies as part of a wider collaborative initiative to develop the new renal biobank. It presented a unique opportunity to share resources and infrastructure to recruit patients to the two studies, while simultaneously creating this important research resource. This is how NURTuRE was born.
“As a collaboration, we were also able to use the existing data collection infrastructure which underpins the UK Renal Registry and the National Registry of Rare Kidney Diseases (RaDaR). This is a huge advantage because it means that all our systems are interconnected. So as well as biosamples, we can also access the routinely collected clinical data linked to that patient. Plus, for the majority of patients, we also have the ability to contact them about taking part in interventional trials. It is a truly unique and extremely valuable resource.”
for the majority of patients, we also have the ability to contact them about taking part in interventional trials. It is a truly unique and extremely valuable resource.
Currently the NURTuRE resource is only available to the partnership organisations, including the five life science companies. Each partner has an allocation of samples with which to conduct research. But the partnership approach extends further than just sharing the samples. Partners are also duty-bound to share their findings. Professor Taal continues:
“One of the unique things about the partnership is that we have resolved IP [Intellectual Property] issues so that each partner retains ownership of their research, but we all have an obligation to publish our results and to share the information from our investigations. Contributing that knowledge back into the central data set is another example of the willingness to collaborate. We all have the same long term goal - to develop new treatments for patients with kidney disease.”
From 2020 approximately half of the NURTuRE samples will be made available to external researchers (non-partners), thus fulfilling the need identified in the UK Renal Research Strategy. Access will be regulated by an independent committee and fees will be charged on a cost-recovery basis for academic applicants and slightly more for commercial organisations (life science companies). The ambition is for NURTuRE to be self-sustainable in the long term and Professor Taal reveals that there are already new studies in the pipeline:
“There is a comprehensive plasma and urine biomarker analysis project planned for the autumn. In addition we will be conducting GWAS study - a genome-wide association study. This is an observational study of genetic variants in different individuals to see if any variant is associated with a disease trait. The project will also include exome sequencing of DNA from all participants. The goal of this approach is to identify genetic variants that alter protein sequences that are associated with disease pathways.”
Commercial perspective: Giving the UK a leading edge
NURTuRE has certainly sparked interest in the renal research world. But biorepositories are not a new concept. So what sets NURTuRE apart from existing biorepositories? Professor Taal sums up the benefits:
“There are biobanks in other countries, and some are quite mature. But ours is unique for two reasons; firstly because the samples can be connected to the routinely collected clinical data; and secondly because we will soon be allowing access to external investigators (non-partners).
“This creates a fantastic platform for multiple new research projects to examine the mechanism of kidney disease and help us identify new targets for therapeutic intervention. It will open up a wealth of new opportunities for all researchers and industry to accelerate new advances that will benefit kidney patients, their treatment and care.”
UCB Biopharma is one of NURTuRE’s five commercial partners. Professor Tim Johnson, fibrosis lead at UCB Biopharma is also keen to convey the value of this collaborative initiative:
“The biggest hurdle to bringing new medicines for patients with CKD is the size and the length of the clinical trials, which makes them prohibitively expensive to run. Identifying patients with more progressive disease, and understanding if a new medicine was having an effect before we see changes in kidney function itself, would shorten this process considerably while reducing patient numbers in the studies.
“NURTuRE gives us a unique opportunity to obtain high quality samples from these patients matched to detailed clinical data and outcomes. From these samples we can use platform biology approaches to identify protein fingerprints of patient status associated with both progressive and stable populations. This not only allows us to stratify patients better for inclusion in clinical studies, but a switch from a progressive to stable fingerprint tells us about drug effectiveness early in the study”.
While this is a key reason for companies supporting NURTuRE Professor Johnson added:
One of the other major challenges the pharmaceutical industry faces is understanding which diseases a new therapeutic may be most effective in.
“One of the other major challenges the pharmaceutical industry faces is understanding which diseases a new therapeutic may be most effective in. One of the best ways to understand this is to look at levels of the drug target in various patient populations. The breadth of different chronic kidney diseases collected under NURTuRE, the quality of the sample collections in a range of biofluids and the detailed clinical data provide a fantastic resource for building the translational data package required to enable clinical studies.”
“Finally, let us not forget the value of NURTuRE for identifying new pathological mechanisms in CKD we can develop new medicines against. Each of the industry partners is using a different approach to identify new drug targets such that genomic, transcriptomic and proteomic data sets will be developed. A core strategy of NURTuRE is that all data generated by the industrial partners and academics will be returned to the central database and made available to all. This will generate an unparalleled data set in CKD for bioinformatic identification of key disease pathways. This pre-competitive cooperation and combining of resources is a great model of how we should be working together to help bring benefit for patients”.
More about biobanks and research registries
A research registry is a database of clinical data from patients with a particular disease or condition. When a patient consents to become part of a research registry, they are allowing their electronic health record to be anonymised and added to the database, and giving permission for it to be accessed by investigators for observational research purposes. The patient may also give their consent to be contacted about participating in interventional studies and trials, which means that some registries can be used for identifying and pre-screening potential participants. Biorepositories (also called biobanks) are similar, but in addition to data they collect biological samples such as plasma (blood), serum, urine, DNA and tissue from biopsies, again for research purposes.
For investigators seeking to analyse the progression of a particular disease over time, registries and biobanks present a very efficient way of doing research. Registries negate the need to recruit patients for each new study. Instead investigators have instant access to historical patient records, including routine test results, alongside information about which treatments were given and how patients responded. Similarly, biorepositories provide instant access to biological samples for laboratory analysis. In effect, the recruitment is already done.
For the patient there are also advantages. The burden of participating in multiple studies is reduced as there are few, if any, extra hospital visits required over and above routine clinical appointments.
The NURTuRE Biobank is a unique collaboration which combines the benefits of both research registries and biobanks.
Find out more
- Read a case study about the RaDaR (National Registry of Rare Kidney Diseases).
- Watch related videos on our NIHRtv channel on YouTube: Complex and innovative trial design and delivery playlist.
- Visit our Delivering complex and innovative research web page to learn more about how we support these types of trials.