Title: Individualising in centre haemodialysis therapy to reduce the harm caused by the two day break in the three times a week treatment schedule
Funder: Department of Health and Social Care

Abstract: Background In the UK, 24,000 patients receive haemodialysis (HD) for kidney failure at a total cost of 636 million per year. An average patient survives less than five years on dialysis. The HD treatment itself causes cardiovascular disease and dementia. Most attend for their HD treatment three times a week, meaning that patients are exposed on a weekly basis to a period of two days without HD. Patients eat and drink less over this period and feel more unwell at the end of it. I have shown that after this 2 day break there is a 69% increase in hospital admissions, primarily due to fluid overload and falls, and a 22% increase in deaths. This increase in deaths is purely in patients dying before they attend for their HD session. Changes to HD treatment may impact on this problem, but are complex, potentially expensive and could cause harm if applied to the wrong patients. AimTo individualise HD to reduce the adverse impact on patients of the two day break between dialysis sessions that occurs in the widely utilised three times weekly dialysis schedule. To become expert in the skills necessary to perform this research: comparative effectiveness methods, evaluation and translation of observational findings to clinical trial design. Plan of Investigation Having received the appropriate training, I will systematically review of the existing literature to identify potential modifiable practices which influence mortality and hospitalisation. I will begin developing an evaluation theory to aid my understanding of which patients benefit from therapies in what context and begin identifying barriers to implementation. Using high quality observational study data I will identify the characteristics of patients experiencing the long gap problem and exclude the confounding effect of non-adherence with HD therapy. Using data from a UK registry of patients on HD linked to hospitalisation data, and data from an international observational study of patients on HD, I will evaluate a range of possible interventions. These will include: longer HD treatment three times a week, more frequent HD (e.g. 4 times a week), reactive practices (scheduling extra sessions when fluid or biochemistry accumulates), and non-dialysis interventions like increased patient involvement, targeting blood pressure etc. I will be trained in a technique that uses the variation in attitudes and provision of these practices across centres in the UK to reduce confounding by indication and generate real world measures of effect size called instrumental variable analysis. Using these findings I will conduct a discrete choice experiment, where patients choose an intervention balancing the acceptability of greater time receiving HD treatment against potential health benefits. Obtaining opinions from experts through a modified Delphi consultation and discussion with a patient panel, I will design a pilot or feasibility clinical trial of the appropriate HD treatment if appropriate. This design will utilise the preceding work. Benefits Patients will benefit from the development of person-centred HD treatment, tailored according to individual preferences and risk. They will experience an improvement in wellbeing through a reduction in breathlessness, cardiac morbidity, fewer falls, better recovery time following HD, reduced hospitalisation and improved survival. Healthcare providers will improve the quality of their care, satisfaction and cost effectiveness, with a reduction in adverse events.

Lay abstract: When someone develops kidney failure, water and body toxins build up. Haemodialysis (HD) is a treatment which uses a machine to remove this build up, otherwise eventually the person would die. At this moment in the UK, 24,000 patients receive HD for kidney failure. Despite attending for their HD treatment three times a week an average HD patient lives less than five years. Three times a week HD means that once a week patients have a period of two days where they don't receive any HD. Patients have to reduce how much they eat and drink over these two days and often feel tired and sick at the end of this time. After this two day break (for instance Monday in patients dialysing Monday/Wednesday/Friday) there is an increase in admissions due to difficulty breathing caused by water on the lungs. More patients die after the two day break, mostly before getting to the dialysis unit.Doing more HD (being on the machine for longer, or more times a week) might be a solution. Clinical trials have explored more HD but only in patients who are generally healthier than average. More HD is a burden for patients and can be difficult to organise. As a result it has been difficult to apply what we have learned from previous trials to large numbers of patients, a common problem in medical research. My aim is to tailor HD to the individual patient in order to reduce the harm caused by the two day break. Before I can do this I will use existing information collected on patients receiving HD in the UK, and collected as part of larger studies internationally, to get a better understanding of who is at risk of being admitted or dying after the two day break. This will ensure I only explore giving extra dialysis to people who need it. Again using existing information I will then evaluate the impact of giving more HD to these at risk patients. I will specifically look at longer time on the HD machine, four times a week HD and organising extra HD treatments when needed. I will give HD patients a questionnaire to assess if patients would be willing to have extra HD compared to their current treatment. By offering the possible benefits of extra HD from my previous work, patients will be able to make an informed decision about the problem and how changing their HD may help. At this point I should have an understanding of who is at risk from the long gap, what are the potential treatments, the benefits from these and who would accept these treatments. I will bring together patients, doctors and nurses, and relevant managers to explain these findings with the aim of deciding if it is appropriate to issue guidance on managing patients at risk of problems from the long gap, or do a small well designed clinical trial of extra HD compared to normal three times a week HD. By doing this study I will begin the important process of changing HD to reduce the harm the three times a week pattern causes. I will develop tools to design HD specifically for a patient, and avoid extra HD being given to patients in whom it has no benefit or does harm. I will learn important skills that can be used to evaluate the benefits of treatments and their acceptability in a range of other diseases.

Research activity codes: 6.3 MEDICAL DEVICES;7.1 INDIVIDUAL CARE NEEDS
Health categories: RENAL AND UROGENITAL