Defining future research priorities: Results of the UK Kidney Transplant Priority Setting Partnership Simon Knight Academic Clinical Lecturer Nuffield Department of Surgical Sciences, University of Oxford On behalf of the Kidney Transplant PSP Steering Group

Background Importance of involving patients in research is increasingly recognised Increasing evidence that research priorities differ between stakeholders 1 – Clinicians – Patients and carers – Researchers – Funders Research agendas are often driven by the interests of individual researchers and/or of the pharmaceutical industry – Over half of RCTs in transplantation relate to immunosuppression – Over one third RCTs in transplantation receive industry funding 2 1 Manns B et al. Clin J Am Soc Nephrol. 2014; 9(10): Pengel LHM et al. Transplant International 2009; 22: 377

Priority Setting Partnerships (PSPs) The James Lind Alliance have pioneered the development of PSPs These projects aim to bring together healthcare professionals, patients and their carers The aim is to identify unanswered research questions, and prioritise these for future research This list can then be used to prioritise allocation of funding Over 35 JLA PSPs completed in many areas of medicine

Aims To conduct a Priority Setting Partnership in kidney transplantation, using JLA methodology To identify and prioritise unanswered research questions in kidney transplantation To promote these questions for funding for future research

The JLA Process 1.Gain the support of key partner organisations 2.Form a steering group of clinicians, patients and carers representing these organisations 3.Create a survey to gather unanswered research questions 4.Refine these questions 5.Second survey for interim prioritisation 6.Final priorities setting workshop 7.Publication and dissemination

Initial survey “What unanswered questions about kidney transplantation would you like to see answered by research?” Electronic survey Paper survey Results from previous surveys (KRUK, BTS)

Initial survey 183 respondents – Mix of ages, location and roles – Approx 50/50 professional/non-professionals Two previous surveys Total of 497 research questions – 440 from PSP survey – 57 from previous surveys Mixture of questions from all points along the transplant pathway, from assessment and listing to the failing transplant

497 Questions 365 Questions 97 “Indicative” Questions 132 Out of scope 7 Already answered 90 “Indicative” Questions 45 Submitted by more than two people Prioritisation Survey Grouping Literature search

Interim prioritisation survey “Score the importance of each question to you” 5-point Likert scale: – Not at all important – Slightly important – Moderately Important – Very Important – Extremely Important

Interim prioritisation survey 265 responses to the survey Good mix of patients, donors and professionals Questions ranked by mean score Top 25 questions taken through to the final workshop

Final prioritisation workshop Held at the Royal College of Surgeons in Feb 2016 Modified nominal group technique 20 participants – Patients (7), Donors (4), Professionals (9) Using small group discussions and voting, agreed a top ten priorities for future research

The Top Ten How can immunosuppression be personalised to the individual patients to improve the results of transplantation? What is the best combination of immunosuppressive drugs following kidney transplantation? (e.g. azathioprine or mycophenolate, belatacept, generic or proprietary (brand-name) drugs) Can we improve monitoring of the level of immunosuppression to achieve better balance between risk of rejection and side effects? (e.g. T-cell or B- cell ELISPOT, point-of-care tacrolimus monitoring, MMF monitoring) How can we prevent sensitisation in patients with a failing transplant, to improve their chances of another successful transplant (e.g. removal of the transplant, withdrawal of immunosuppressive medicines or continuation of these medicines?) How can we improve transplant rates in highly sensitised patients?

The Top Ten What is the best way to treat vascular or antibody-mediated acute rejection? What are the long-term health risks to the living kidney donor? What techniques to preserve, condition and transport the kidney before transplantation allow increased preservation times and/or improve results? (e.g. machine perfusion, normothermic reconditioning, addition of agents to the perfusate) How can we encourage tolerance to the transplant to prevent or reduce the need for immunosuppression? (e.g. by use of T-regulatory cells, induction of haemoxygenase 1) Can bioengineered organs be developed to be as safe as human-to-human transplants? How can this be achieved?

Dissemination/impact The results will be publicised so that researchers and funders can use them to prioritise research and funding – Published papers – Conference presentations – Presentations to charities/funding bodies The results have already been discussed with representatives from the NIHR and are being considered for future funding calls

Conclusions The PSP process has bought together patients, carers and healthcare professionals to prioritise areas for research in kidney transplantation Prioritised questions include short and long-term aims, and all points along the transplant pathway Patient involvement played a big part in the shape of the final priorities These priorities will help researchers and funders to direct research activity to areas that will make the greatest difference to patients

Acknowledgements Project steering group Simon Knight (Lead) Leanne Metcalf (Chair) Katriona O’Donoghue Simon Ball Angela Beale William Beale Rachel Hilton Keith Hodkinson Graham Lipkin Fiona Loud Lorna Marson Peter Morris Workshop participants Karen Casey Rebecca Farwell Sue Lyon Nick Palmer Alistair Reid Tracey Rose Chris Walton David Wilson Lisa Wynn Rasheed Ahmad Pippa Bailey Chris Ide Steven Sachs Bynvant Sandhu Michelle Willicombe Funder Oxford Biomedical Research Centre All healthcare professionals, patients, donors and carers who responded to the PSP surveys All partner organisations who helped to promote the surveys and PSP process