Title: The BRaveR Study - Methods to develop and deliver Better ReseArch to improVe outcomes and inform practice in brEast Reconstruction
Funder: Department of Health and Social Care

Abstract: Background Breast reconstruction (BR) may improve outcomes for women following mastectomy for breast cancer, but there is currently a lack of high-quality evidence of the clinical or cost-effectiveness of different procedures to inform decision-making for patients or policy-makers. Randomised clinical trials (RCTs) are ideally-needed, but BR trials are challenging. In addition to the methodological difficulties, reconstructive surgeons are generally unfamiliar with evidence-based practice and often sceptical about RCTs. Recent methodological advances and changes in surgical research culture as evidenced by the success of collaborative projects such as the NIHR-funded iBRA study in implant-based breast reconstruction (IBBR), suggest that RCTs in BR may now be possible. Before a large-scale BR trial can be proposed, however, further work is needed to develop better methods for assessing the clinical and cost-effectiveness of BR and to explore whether randomisation to different techniques is acceptable to patients and professionals. Aims and objectives The aim of this Fellowship is inform the design of a definitive RCT in BR by developing methods to optimally measure the outcomes and costs of reconstructive breast surgery and determine whether it is possible to randomise patients into a trial comparing two types of implant-based BR. Specific objectives are to Improve the quality and consistency of outcome-reporting in BR by developing a core measurement set and consensus regarding standardised time-points when key outcomes should be measured Improve the use and value of economic evaluation of BR by developing a novel micro-costing framework for use in future studies Determine the feasibility of conducting an RCT in IBBR by conducting an external pilot-RCT. Engage and work with breast and plastic surgeons to design a multi-centre pragmatic RCT. Plan of investigation Work package 1 will build on my core outcome set work to develop and implement a core measurement set (CMS) for BR. This will involve systematic reviews (SRs), Delphi surveys with patients and healthcare professionals and consensus meetings to determine the final CMS. Uptake of the CMS will be promoted through active dissemination to funding-bodies, journal editors and patient advocacy groups. Work package 2 will use a SR of micro-costing in economic evaluations of surgical interventions and a real-time micro-costing study of the three main types of BR to identify the main cost-drivers for surgical procedures. These will be used to develop a framework for the use of micro-costing as a preferred method for resource-use assessment in future surgical RCTs. Work package 3 will determine the feasibility of undertaking a pragmatic large-scale RCT comparing the effectiveness and cost-effectiveness of two approaches to IBBR. This will build on the non-randomised feasibility work in iBRA to determine whether randomisation is acceptable to patients and professionals and whether the interventions identified by iBRA are sufficiently stable for formal evaluation in the context of an RCT. The pilot-RCT will take place in three centres and will include the Quintet recruitment intervention to allow anticipated issues around recruitment to be explored, understood and addressed to optimise participation. Consensus among professionals and patients will be used to establish the feasibility of a large-scale RCT and key aspects of study design.Summary of potential benefits to patients and the NHS This Fellowship will inform high-quality collaborative research in BR and educate, engage and empower the reconstructive community in the need for the creation of evidence such that future practice will be based on the results of well-designed and delivered trials. This will benefit patients and the NHS by promoting evidence-based practice, improving outcomes through more informed decision-making and supporting commissioners in making high-quality decisions about the provision of BR in a financially-constrained NHS.

Lay abstract: Aim To work out how to do a research study in breast reconstruction that will fairly compare two new types of operation using implants (i.e a randomised trial) by establishing: Effective methods to assess the outcomes and costs of breast reconstruction Whether patients and surgeons will be willing to take part in such a study Background Breast cancer affects 54,000 women each year of whom 40% may require a mastectomy (removal of the breast). The loss of a breast may dramatically affect a woman's well-being and in the UK, breast reconstruction (BR) is routinely-offered to improve quality of life. There are, however, several types of BR-operation that may be performed. These include simple procedures using an implant and more advanced techniques involving transferring tissue from the women's back or abdomen. It is important to be able to compare different types of surgery in research-studies that are properly-designed and conducted to allow future patients and surgeons make informed choices. Detailed analyses of literature have shown that there is little well-designed research in BR and few studies have considered whether BR is value-for-money' (cost-effective). There is no agreed-way to measure the outcomes or costs of BR-surgery so studies of different operations cannot be compared. Research that includes randomisation (i.e. the patient has a similar chance of receiving either of the operations being studied) is the best way to compare two procedures. In BR, however, such studies are difficult because patients and surgeons often have strong preferences about surgery (even though there is a lack of scientific data to support these choices). Recent research and changes in the surgical culture suggest that studies that involve randomisation may now be possible if careful planning is undertaken to work out how to do the trial so it is acceptable to patients and surgeons.Design and methods Firstly, I will develop a standardised way in which the outcomes of BR are measured (a core measurement set, CMS). I have already worked with patients and healthcare professionals to determine what outcomes should be measured in all research-studies in BR (the core outcome set). This next step is to determine how and when these 11 key-outcomes should be measured. I will use detailed analyses of the literature, surveys and meetings with patients and professionals to agree the CMS. I will then work with funding-bodies, journal editors and patient groups to encourage researchers to use the CMS in future BR-studies.Secondly, I will develop methods to improve how accurately healthcare costs are measured. This approach (called micro-costing) involves looking in detail and valuing all elements of a patient's care including staff-costs, operating-theatre time and consumables such as dressings. I will review the literature and go into the operating-theatre to micro-cost' different BR-procedures. I will use the review and micro-costing study to identify the elements of care that are the most expensive (cost-drivers). These cost-drivers' will be used to develop a more accurate way of measuring the costs of surgical procedures for use in other surgical trials. Finally, I will determine whether it is possible to gain patients' consent to participate in randomised studies of types of implant-based BR. During a randomised study, two groups of patients with similar characteristics are scientifically-created which means it is possible to make a fair comparison of the outcomes of surgery. The study will take place in three centres and will include special training of surgeons to help them work out the best way to explain the study to patients so that they consent to take part.Patient and public involvement Patient involvement is central to this project. Patients have been involved at all stages of the application and fully-support the need for high-quality evidence in BR. Patients will be involved on the steering groups of each proposed-project and will benefit the research by bringing their rich experiences and ensuring that the work remains patient-focused. Patients will play a particularly important role optimising the design of the randomised study and a patient advisory group will be convened to advise on key design-features, progress and the ultimate feasibility of a large-scale trial. Dissemination The work will be presented at national and international conferences and published in peer-reviewed journals. We will engage funding-bodies, journal editors and patient advocacy groups to promote adoption of the core measurement set and work with patients, the professional associations and the reconstructive community to establish the need for and desire to produce high-quality research and randomised studies in BR which will ultimately improve outcomes for patients.

Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: CANCER AND NEOPLASMS