Periodic Reporting for period 2 - BETTER-B (BETTER TREATMENTS FOR BREATHLESSNESS IN PALLIATIVE AND END OF LIFE CARE) Reporting period: 2020-07-01 to 2021-12-31 Summary of the context and overall objectives of the project The BETTER-B project focuses on breathlessness that persists despite optimal treatment of the underlying disease, usually referred to as chronic or refractory. This type of breathlessness is burdensome, neglected and yet one of the most common symptoms of advanced disease, estimated to affect 15 million people in Europe. Breathlessness can have a devastating impact on patients’ lives, and that of their family, friends and caregivers. Further, chronic breathlessness results in high health, social and informal care costs. New treatments for breathlessness are urgently needed as there is currently no licensed drug for the management of chronic breathlessness. An existing antidepressant, mirtazapine, has the potential to decrease chronic or refractory breathlessness in patients with advanced respiratory disease, in palliative care and at end of life. However, currently there is not robust evidence for mirtazapine’s use for this purpose. The overall objective of the BETTER-B project is to test whether mirtazapine is an effective and cost-effective medicine for the relief of patient-reported chronic or refractory breathlessness in patients with chronic obstructive pulmonary disease (COPD) or interstitial lung diseases (ILD). This is a patient-centred trial that could result in reduced symptom burden and significant improvements in quality of life for patients and their family and friends. Concurrently, the project maps and compare views, usual practice and experiences of palliative and respiratory clinicians across Europe on the main medications to alleviate breathlessness in COPD and ILD. This informs understanding of the feasibility of integrating mirtazapine in current clinical management, palliative and/or end of life and/or survivorship care regimes and healthcare systems across Europe. We actively engage with those affected by breathlessness across Europe to inform our plans and produce and disseminate European wide easily accessible multi-lingual guidance on the management of breathlessness in supportive, palliative and end of life care with wide-reaching impacts. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far In months 1-36 of the BETTER-B project, substantial work has been undertaken across work packages. As part of Work Package (WP) 1, we conducted an online multinational survey exploring the current attitudes and practices of respiratory and palliative care physicians for managing chronic breathlessness. 450 responses were included in the analysis. The responses revealed substantial differences in current approaches to clinical management of chronic refractory breathlessness between specialties, and across malignant and non-malignant lung diseases. Survey findings are helping to inform future components of the BETTER-B project, and have been disseminated at international conferences, and further results published in BMC Pulmonary Medicine in January 2022. The setup of the main trial (WP2) has progressed with nine of our 11 sites now recruiting participants. Recruitment is accelerating, though behind our target. The effect of COVID-19 is particularly acute in respiratory care, because staff working in these areas (e.g. respiratory medicine, palliative care) are often diverted to work in COVID, and are not available to provide services or identify patients. We aim to meet our recruitment target with the multifaceted contingency plans, including opening additional sites, and likely lengthening recruitment period beyond July 2022. Our projections indicate we aim to achieve 50% recruitment of 162 participants in June 2022 and our target of 324 participants in December 2022. Trial progress is kept under weekly review. We are in the process of setting up our sites in Poland and Rome to open in April 2022. In addition to the COVID-19 pandemic, delays have occurred because of local issues in Poland and Rome. In the UK and EU sites (except Poland), Clinical Trial Authorisation have been obtained. Ethical approval from all countries are in place. As a result of WP7, BETTER-B is developing a strong public presence. We have produced a series of press releases, launched the BETTER-B project website (www.betterbreathe.eu) shared five project newsletters and disseminated Better-B information on social media. For WP8, the BETTER-B consortium have produced key project documents including the project handbook, and data and risk management plans. We have held meetings with the consortium, Executive Board, Ethics Advisory Board and trial oversight committees. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) There is currently a paucity of evidence-based treatments for breathlessness in palliative and end of life care. BETTER-B will transform our understanding and management of breathlessness. Our findings will also have increased relevance globally, with breathlessness being a symptom of SARS-CoV-2 infection. Our work package 1 survey explored usual practice and experiences of palliative and respiratory clinicians on management of chronic breathlessness. We found varied approach to breathlessness management across specialties, and across and within diseases. Our findings suggest a need for improved dissemination and uptake of jointly developed breathlessness management guidelines in order to encourage appropriate use of existing, evidence-based therapies. Advances BETTER-B will bring about include:• Timely testing of a new therapeutic option for a common symptom in palliative and end of life care, with robust data on its effectiveness and cost effectiveness;• If mirtazapine is found to be effective, the potential to be of benefit to patients with many advanced conditions, and their families. It is available in all European countries at low cost. Equally, if mirtazapine is not cost-effective in patients with breathlessness, the findings will save resources as the results will enable decision makers to recommend that mirtazapine should not routinely be used for this patient group; • Understanding whether mirtazapine is clinically and cost effective, will help to develop further interventions for breathlessness;• The health economic components of our study will test methods of measuring cost effectiveness in this group, which will aid future studies, improving care;• The largest randomised trial on breathlessness in palliative and end of life care in the world to date;• The potential to merge data with major trials in breathlessness being conducted by members of the consortium. Such a meta-analysis will provide unparalleled understanding of breathlessness and allow better comparisons of potential treatments;• The development of a European wide collaborative between respiratory and palliative care that will be a platform for future studiesWe have assembled a unique collaboration of diverse clinicians, researchers, health professionals and social scientists in five European countries to lead the BETTER-B project. Through our nine work packages, we expect our findings to have the following impacts: • Reduced symptom burden and suffering or improved well-being of patients in need of palliative, end of life or survivorship care and of their formal and informal caregivers;• Improved clinical guidance and policy recommendations;• Improved quality, effectiveness and cost-effectiveness of palliative, end of life or survivorship care services as well as access to care;• Reduced economic and wider societal burden arising from increased numbers of patients in need of palliative, end of life or survivorship care. better-b-transparent4-large.gif
