Title: Transforming treatment of immune-mediated inflammatory diseases through better trials and evaluations
Funder: Department of Health and Social Care

Abstract: Research question How can treatment for patients with immune-mediated inflammatory diseases (IMIDs) be improved through making trials and evaluations more efficient, informative and patient-centric? Background IMIDs are a group of conditions that share common inflammatory and immunity pathways. They affect >5% of the population and cause serious impact on patients and healthcare services. Clinical trials are essential for improving treatment of IMID patients but are expensive, often non-generalisable, and difficult to do for rare IMIDs. They often focus on short-term efficacy of a treatment and not how a chronic IMID should be treated over the long-term. To address these issues, there is a need for improved methods that are tailored to the nature of IMIDs together with overcoming barriers of their use in practice. Objectives 1. Develop innovative statistical methods tailored to IMID trials. 2. Develop methods for using additional sources of patient data to improve informativeness and generalisability of IMID trials. 3. Develop methods for identifying and evaluating the best long-term IMID treatment strategies. 4. Promote wide application of the new methods in practice.Methods Each objective links to an associated work package (WP). WP1: My team will develop statistical methods for improving the efficiency and patient-benefit of IMID trials. This includes methods for: better analysing complex trial outcomes that are used in many IMID settings; designing 'basket trials' that combine trials testing a drug that targets symptoms or biological mechanisms which are shared by several IMIDs, including rare ones; improved adaptive designs for chronic IMID settings that allow patients to switch to more effective treatments. These methods will be applied to several ongoing IMID trials. WP2: We will access cohort data from IMID-Bio-UK and routinely collected data from patients in North-East England. Methods will be developed for using these data to improve generalisability of IMID trials to under-served patient groups and patients with co-occurring autoimmune diseases. We will also investigate whether these other data sources can replace a control arm for rare IMID trials, thus reducing the sample size required. The developed methods will be applied to an ongoing trial in primary biliary cholangitis. WP3: We will consider how distinct sources of data can be used to identify the best long-term IMID treatment strategies. Methods will be developed to design an efficient and robust evaluation of these strategies. The developed methods will be illustrated using rheumatoid arthritis, with data available from cohorts, routinely collected data and trials. WP4: We will work with UK and international IMID clinical researchers to apply the developed methods in current and future trials. We will also develop free, high-quality, software and training materials to promote more widespread use of the developed methods. Anticipated impact Short-term: improved availability of better methods, and training of researchers in their use; proof-of-concept analyses of trials to improve interpretation of trial results; innovative design methods used in grant applications. Long-term: training materials and dissemination leading to widespread use of methods; changing practice leading to improved treatment of IMID patients.

Lay abstract: Background to researchOver three million people in the UK have one or more diseases where the body's immune system incorrectly attacks itself and causes damage through swelling (inflammation). The damage from inflammation leads to serious symptoms. These diseases are called immune-mediated inflammatory diseases (IMIDs), which include rheumatoid arthritis, psoriasis, inflammatory bowel disease, and many others. IMIDs harm the activities, health, and wellbeing of affected individuals. They also impact the NHS, which spends billions of pounds per year on treating patients with IMIDs. Clinical trials are vital for improving the health of IMID patients. They are used to test if new drugs are beneficial and the best ways of using existing treatments. There are challenges with IMID trials. Firstly, they are very expensive and time-consuming. Secondly, patients in trials are not always representative of all patients, meaning results are not relevant to everyone. Thirdly, trials are hard to do for rare IMIDs, meaning a lack of evidence to inform their treatment. Fourthly, trials do not usually answer how best to treat IMID patients in the long-term. Aim of research This Professorship programme will fund researchers to work with me to develop new methods to address these challenges and improve IMID research. These new methods will benefit: 1) patients who take part in trials; 2) other patients, who will benefit from improved treatment; 3) the NHS, by providing better evidence about which treatments are best.The new methods will be used in current and future IMID studies. Summary of planned research We will fulfil the aim through the following research: 1) We will develop methods for designing and analysing trials that are best for patients with IMIDs. The methods will mean trials are cheaper to do, better for trial patients, and give more information about whether the treatment is beneficial. The methods will mean more trials testing treatments for rare IMIDs can be done. 2) Healthcare systems record which treatments are given and how they affect patients' health. We will investigate how this Information can be used to make trial results more relevant to patients who are not included in the trial. We will investigate how this data can increase evidence about the best treatments for rare IMIDs. 3) We will research methods for improving the long-term care of IMID patients. We will use data from trials and healthcare systems to find the best treatment strategies for different IMIDs. This will help doctors know which treatments should be used for their patient at different points of the disease. Several IMID trials that are currently underway will provide opportunities for using the methods. This project has the support of many experienced IMID clinical researchers (in rheumatoid arthritis, liver disease, inflammatory bowel disease and rare IMIDs in children) and patients. We will work with these researchers and patients to implement the research in current and future IMID research. We will train other researchers to allow widespread use of the methods Dissemination We will create free, high-quality training materials and tools to help researchers use our new methods. Research will be published in journals and clear summaries of the research will be made available on our website. Research will be disseminated through disease-specific networks, including patient groups, that we have connections with.Patient and public involvement Three different public and patient groups have provided invaluable input to developing this programme. The research will be supported by a Public Advisory Group, which will meet twice a year. They will support researchers in the goal to clearly communicate the research to the public. They will also ensure the research remains focused on improving IMID patient outcomes.

Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: INFLAMMATORY AND IMMUNE SYSTEM