Title: Evaluating the benefits for patients and the NHS of new and existing biological fluid biomarkers in liver and renal disease
Funder: Department of Health (England)

Abstract: Aims and Objectives: to develop a stringent approach to protein biomarkers to evaluate potential benefits for patients and the NHS, focusing on liver and renal disease, but with generalisable outputs. We will develop a methodological framework for monitoring disease with protein biomarkers; a system to rapidly and robustly select biomarkers good enough to formally evaluate in the NHS and determine if our existing biomarker panel can improve care for patients with chronic liver disease. Background: protein biomarkers in body fluids which have demonstrable associations with the activity and outcome of a wide range of diseases are now being identified by modern proteomic technologies. They may be simple, accessible, cheap and safe tests which can inform diagnosis, prognosis, treatment selection, monitoring of disease activity and therapy. They may substitute for or augment more complex, invasive and expensive tests. However, their substantial potential to improve patient care and health service provision is not yet being realised because the pathway linking biomarker research to health services research is still quite poorly defined. Liver and renal diseases generate huge and growing patient and service burdens, are amenable to biomarker application. Plan: an integrated programme of research with three workstreams - 1) Methodological work to define current best practice and explore innovations particularly in relation to the use of biomarkers to monitor disease activity issuing guidance for investigators and updates in years 1, 3 and 5. 2) A clinical biochemistry workstream to rapidly identify protein biomarkers with the appropriate clinical characteristics to justify evaluation in the health service in liver and renal diseases. 3) A randomised trial on an established panel of 3 biomarkers for liver fibrosis and cirrhosis for which clinical evidence for potential value in chronic liver disease is excellent. We will determine whether they will sufficiently alter the diagnostic timing and subsequent management of cirrhosis of the liver in order to reduce serious complications and improve outcomes for patients and service provision. Our programme will add value through the interaction between these workstreams The methodological work will inform the whole field, and our work to select biomarkers relevant to the NHS and the design of our trial, will inform the development of future research strategies and trials to ensure rapid and robust indications that new biomarkers, alone or in panels, will genuinely improve the quality of health care. Team: we have assembled an outstanding internationally recognised multi-disciplinary team of methodologists, clinicians and marker scientists all of whom hold major programme funding from other funding bodies. Outputs, outcomes and impacts: 1) methodological guidance for our own and related fields for linking biomarker research with health service research 2) a system with clinical data and samples which can rapidly select and evaluate new markers of genuine promise for the health service in chronic liver disease, renal transplantation and renal cancer 3) a robust evaluation of whether three biomarkers (the ELF panel) can diagnose cirrhosis early enough to reduce the major morbidities associated with progressive cirrhosis including hepatocellular carcinoma and variceal bleeding. These will collectively significantly improve survival and quality of life and health service provision for patients with chronic liver disease and present a framework for which biomarker monitoring research could produce benefits of a similar magnitude and quality for patients with renal diseases. Our work will provide a flexible prototype for evaluating protein biomarkers for a wide range of major health care problems which are amenable to diagnosis, prognosis, prediction of therapy and particularly by protein biomarkers. Public involvement and ethics: Our application involves patients in its development and its conduct and will be subject to rigorous ethical approval. Resources: we provide a cost effective programme with the minimum essential resources necessary for the knowledge and impacts which we will generate. Collaborations with investigators of NIHR and its Partners will be cost recovered; collaboration with industry will involve full economic costing.? ??


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: RENAL AND UROGENITAL;ORAL AND GASTROINTESTINAL