Title: The iBRA (implant Breast Reconstruction evAluation) study – A prospective multicentre cohort study to inform the feasibility and conduct a pragmatic randomised clinical trial comparing new techniques of implant-based breast reconstruction
Funder: Department of Health and Social Care

Abstract: Background Breast cancer affects 45,000 women each year, of whom up to 40% will require a mastectomy. The loss of a breast may profoundly affect women s self-esteem and immediate breast reconstruction is offered to improve outcomes. The most frequently-performed reconstruction in the UK is implant-based breast reconstruction (IBBR). Traditional subpectoral IBBR is performed in two operations. This is necessary because the subpectoral pocket is too small to accommodate a definitive implant and expansion with a tissue-expander is required as a first-stage. Several expansions with saline are then needed before the final implant can be inserted. Recently, new techniques have been introduced which involve augmentation of the lower-aspect of the subpectoral pocket with mesh. The mesh enlarges the pocket sufficiently to accommodate the implant in a single operation, avoiding the need for a tissue-expander and expansions which are time-consuming and uncomfortable. Numerous biological (e.g.Strattice) and synthetic (e.g.TiLOOP) meshes are available. These vary widely in cost, with product selection based on surgeon preference. Many poorly-designed and conducted non-randomised studies of IBBR have been undertaken and summarised in systematic reviews, but only one RCT has been attempted. This aimed to compare IBBR with and without mesh, but failed to recruit. Decision-making in IBBR is therefore based purely on surgeon preference. There is an urgent need for evidence of the effectiveness and cost-effectiveness of novel techniques of IBBR, but there are well-known methodological and cultural challenges of performing RCTs in surgery which need to be addressed before a main trial can be undertaken Aims To establish the feasibility and design of a multi-centre RCT to examine the effectiveness and cost-effectiveness of novel approaches to IBBR. Plan of investigation The study will have four phases: Phase 1&ndash;A national practice survey Phase 2&ndash;A 12-month prospective cohort study of consecutive patients undergoing IBBR to evaluate the clinical and patient-reported outcomes of surgery Phase 3&ndash;An IBBR-RCT acceptability survey to explore patients and surgeons views of proposed trial designs and outcomes. Phase 4&ndash;The design of the main trial for submission for future funding. All centres offering IBBR will be encouraged to participate by the breast and plastic surgical professional associations (ABS and BAPRAS). Data collected will inform the feasibility of undertaking a definitive pragmatic RCT by defining current practice and exploring issues surrounding recruitment; selection of comparator arms; choice of primary outcome; sample-size; selection criteria; trial conduct; methods of data collection and feasibility of working with the National Trainee Research Collaborative (NTRC) to recruit patients and collect data. The study will be conducted by the NTRC with the expert methodological support from the Liverpool Clinical Trials Research Centre and the Bristol Surgical Trials Centre. Potential benefits to patients and the NHS For patients If this work informs the main trial, this will provide high-quality evidence to inform clinical decision-making in IBBR. If a full trial is not feasible, the outcomes from this research will still benefit patients and the NHS as it will generate prospective multicentre observational data regarding the outcomes of IBBR which may still be used to inform patients of outcomes of surgery and aid decision-making. Identification of variations in practice and outcomes may also promote better standardisation of care and improve outcomes for patients considering surgery in the future. For the NHS If this feasibility work shows that a main trial is possible this will provide evidence to inform health-policy and how investment in the most effective methods of IBBR can be achieved. In addition, the study will create a network of research-active surgical trainees, supported by consultants. This will create an infrastructure for the effective future delivery of breast reconstruction research.

Lay abstract: Implant-based breast reconstruction (IBBR) is the most frequently-performed breast reconstruction operation following mastectomy (removal of the breast) for breast cancer in the UK. The standard approach involves two operations, but new techniques have recently been introduced that allow a one-stage reconstruction to be performed. While this is attractive, there is currently a lack of high-quality evidence to compare the outcomes of these procedures with the standard two-stage approach. Randomised controlled trials(RCTs) are the best way of comparing treatments but surgical RCTs are challenging and breast surgeons have not participated in multi-centre breast reconstruction RCTs before. This study will determine the feasibility of conducting a main RCT which will examine the effectiveness and cost-effectiveness of different IBBR techniques. The study will have four phases: Phase 1&ndash;A national practice survey Phase 2&ndash;A 12-month prospective cohort study of consecutive patients undergoing IBBR to evaluate the clinical and patient-reported outcomes of surgery Phase 3&ndash;An IBBR-RCT acceptability survey to explore patients and surgeons views of proposed trial designs and outcomes for a trial. Phase 4&ndash;The design of the main RCT for submission for future funding. The study will document current practice, explore potential comparators, identify relevant outcome measures, inform selection criteria, trial conduct and the size of a future trial to determine whether it is feasible. No ethical issues are anticipated. The study will be conducted by the National Trainee Research Collaborative with the support of expert methodologists from the Liverpool Clinical Trials Research Centre and the Bristol Surgical Trials Centre. This study will benefit patients and surgeons not only by determining trial feasibility, but also by generating the best current evidence regarding the outcomes of new approaches to IBBR. Demonstrating variations in the provision and outcomes of care will improve standardisation of practice and outcomes for future patients undergoing surgery.

Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS