Organ transplantation saves thousands of lives every year and is the treatment of choice for end stage organ failure. Despite awareness of importance of transplantation, a gulf remains between the supply and need for life-saving organs. This is predicted to worsen over the next decade, making this disparity a key challenge facing the transplant community today. Due to this shortage, nowadays older and higher risk donors are accepted. However, uncertainty as regards transplantability often results in decline and sometimes discard of scarce organs. Between April 2015 and March 2016, 479 patients died waiting for a lifesaving transplant. A further 3,452 patients were temporarily suspended from the waiting list because they were unfit for transplant. The Quality in Organ Donation (QUOD) Biobank was established in 2012. This unique resource combines collection of detailed clinical information from virtually all organ donors in the UK with blood and urine samples taken around the time of donation and carefully collected small biopsies from a range of organs stored within a central 'bank'. This has been invaluable in research focused on understanding how stress associated with becoming an organ donor around the time of death affects control of important whole body systems such as blood pressure and glucose levels in addition to impact on specific organs. This has already enabled otherwise impossible research focused on better selection and optimisation of organs enhancing successful transplantation. The pancreas, heart and lungs work in concert to maintain glucose levels, blood pressure and effective oxygenation throughout life. The extreme stress around the time of death has a major impact on these control systems. Despite a huge unmet clinical need, 'conversion' of these organs into successful transplants is much lower than in kidney transplantation. Impairment and failure of these organs is also central to many of the most common and challenging chronic diseases, including diabetes, heart failure; and lung disease. We propose to expand QUOD to include samples from pancreas, heart and lungs and will work closely with MRC Units to ensure provision to the research community of highest quality state-of-the-art clinical pathology and molecular techniques as well as single cell analysis platforms, in addition to facilities expert in processing organs to retrieve live functioning cells. This will allow us to create detailed atlases and a data library representing the range of normal, acutely stressed and chronically diseased tissues from these organs that can be seldom accessed in life which has severely limited true understanding of mechanisms driving damage and failure. This type of resource linked to such high quality clinical information and a library of new markers associated with these processes and easily monitored from blood samples does not currently exist. The QUOD remit and proposed expansion will be made accessible to the widest possible scientific and clinical community. It will enable new understanding of causes of organ stress, facilitating new treatments to maximise transplant success and ultimately help to prevent / reverse chronic diseases without need for transplantation. In type 1 and 2 diabetes it is becoming clear that insulin-producing cells are not completely destroyed, offering exciting new possibilities for reactivating function which may ultimately lead to a cure for this burdensome and dangerous disease. Deeper understanding of mechanisms underlying heart pump failure will facilitate increased numbers of heart transplants but also new treatments for all with chronic heart failure targeting specific processes damaging the muscle. Elucidation of the causes of scarring lung disease will be accelerated through this resource. Moreover, previously impossible parallel research exploring pathological interplay between pancreas, heart and lungs with already collected data on liver and kidney will be enabled.

Information governance background: Important health and social science research is limited by the capacity of individual researchers to adhere to the necessary safeguards which are put in place to protect the privacy of individuals. Universities, as publicly funded organisations, have a legal basis to use data for research (Article 6(1) of the Data Protection Act 2018); however, research that seeks to combine information for individuals from different datasets requires the sharing of more sensitive information - such as name and date of birth - between organisations, which has a higher threshold of confidentiality (common law duty of confidentiality). One way to share such confidential data is to seek consent from the individuals represented in the data. However, when considering administrative datasets containing entire populations, it becomes infeasible, and bias due to self-selection into a study diminishes the value of a population-based approach. This is particularly important in health studies, where those individuals of most concern may not be attending clinics and so cannot even be approached for the option to be included. The Health Research Authority offer an alternative set of approvals to share confidential information where consent cannot be obtained (known as 'Section 251', part of the National Health Service Act 2006). Typically, researchers seek such an exemption to answer a specific set of research questions (known as 'Project Specific Section 251'), as we did in our current project linking the diabetes audits to education datasets for Wales. However, in this proposal we extend this to a special case of the exemption known as 'Research Database Section 251'. Substantive background: Evidence on how children with chronic conditions such as diabetes, epilepsy, and asthma fare in spheres beyond health is limited, in part due to the challenges in combining administrative data described above. To tackle this for diabetes we worked with the national paediatric and adult diabetes audits, together with HESA and Welsh Government, to flow and link these health and education datasets for Wales. This was a gruelling process involving working with data providers, the Health Research Authority, and the Medical Research Council Regulatory Support Centre to ensure the information governance was of the highest standard and was well understood and supported by the data providers and other parties. Objective 1 Information governance framework: The central task of our project is to set up the information governance framework (with the Research Database Section 251 approval as the backbone) for the linkage of paediatric health data to education data for England and Wales. This includes drafting linkage protocols, planning and drafting an application process for external researchers that wish to use the linked datasets, publishing the application process for researchers to use our Research Database approvals to link their own disease specific datasets into the research database; publishing all fair processing documentation for patients including modified versions specifically for children, for parents, in other languages etc. Objective 2 Proof of concept linkages: To demonstrate the efficacy of the framework we will link the paediatric (aged 0 to 16) and adult (aged 16 to 30) diabetes audits to the schools (NPD) and university (HESA) data for England using DfE as the processor for the identifiers and ONS-SRS as the secure repository. Objective 3 Extensions to other conditions: While the potential to use the governance framework to add data for other health conditions is a fundamental part of objective 1, we will work with other researchers, primarily for epilepsy, to ensure they are able to use the framework to add their data.