Title: The Role of Fibrin Sealants in Reducing Surgical Complications in Patients Undergoing Neck Dissection for Head and Neck Cancer: A Randomised External Pilot Study
Funder: Department of Health and Social Care

Abstract: Background Neck dissections are one of the most commonly performed major Head and Neck surgical procedures and can carry a complication rate of up to 40% in certain high-risk patients. These complications are a significant cause of morbidity and mortality. Ongoing qualitative research in Head and Neck Cancer has demonstrated that avoidance of complications and the further invasive treatment is very important' to patients. Fibrin Sealants (FS) are commercially available products that provide an adjunct to haemostasis and represent an interesting means to mitigate these complications.As preparatory work for this project, I undertook a systematic review and meta-analysis on the role of FS in soft-tissue Head and Neck Surgery has been completed. In doing so I have shown that FS may potentially reduce surgical complications as well as reduce the retention time of surgical drains and hospital length of stay. However, the studies included in the review were of variable quality and differed significantly in their findings. The substantial statistical heterogeneity in the meta-analysis impaired the ability to draw definitive conclusions. There was also a paucity of randomised data on the role of FS in neck dissections specifically.Based on the current evidence a surgical trial to determine the effectiveness of FS in reducing complications after neck dissection is warranted. However, it is necessary to conduct a randomised external pilot study in preparation for this future trial as there are key uncertainties regarding deliverability and how the components of the study design work together.Aims The aims of this randomised external pilot study are to address the following key uncertainties: Recruitment and retention. Effectiveness of the blinding strategy. The administrative processes of intra-operative randomisation and data management. Provision of adequate out-patient clinic resources. Assess the ability of nurses and patients to adhere to the conditions of the protocol. Estimate the required quantities for reliable sample size calculation for a future study.Plan of investigation The study will be divided into three key stages:Stage 1. Pre-recruitment preparation: During this period essential preparation will be completed including application for ethical approval and registration of the study protocol. Surgeon training and credentialing' days will also be developed and delivered to participating centres.Stage 2. Recruitment to pilot study: This will take place over 12 months in each of the two centres, with the second site opening 3 months later. Stage 3. Analysis and dissemination: During this final period the pilot study outcomes will be analysed and disseminated. Key stakeholders will make an assessment of the deliverability of the future trial. Benefits to patients & NHS Positive findings regarding deliverability from the pilot study will encourage development of a larger phase III trial quantifying patient benefit in terms of complications and broader health economic assessment. If the future trial demonstrated positive outcomes, these would potentially have far reaching and immediate implications on UK and international practice. Furthermore, this study dovetails with a national drive to improve outcomes by encouraging more patients and surgeons to participate in health research through recruitment to surgical trials.

Lay abstract: Background As a trainee surgeon I have managed many surgical complications and witnessed the misery they cause to my patients. Complications after major surgery are a significant problem for patients and are known to have a detrimental effect on quality of life. The neck dissection is one of the most commonly performed major operations for patients with head and neck cancer. A neck dissection is an operation that involves removing the lymph nodes (glands) deep in the neck either because they have cancer within them or they are at risk of cancer spreading to them. When the surgeon performs the operation the lymph nodes are very close to important nerves and large blood vessels with potential for significant bleeding. Complications can occur in up to 40% of patients depending on their health and whether they have had previous surgery or radiotherapy to the area.Ongoing research on understanding the thoughts and feelings of patients having head and neck cancer treatment, has highlighted that avoiding complications is very important to them. I have conducted a thorough review of the available evidence on the role of tissue sealants in head and neck surgery and found that they may protect patients from complications. This is because they can seal areas of bleeding and stick the raw surfaces of the wound together, reducing the potential space for blood to collect within. Tissue sealants are natural products derived from blood that copy the clotting process and are absorbed by the body a few days after the operation. There are very few high quality studies that have specifically assessed the role of tissue sealants in neck dissection and the results have been variable. Therefore a future clinical trial has been designed to address this deficiency in evidence. However, before this can be started there is a need to conduct a miniature version of the study (pilot study) to make sure all the components of the main trial will work together.Aims The aims of this research are: To successfully complete a pilot study that addresses the following issues: Ensuring sufficient patients can be recruited to the study. Ensuring that the process of randomly deciding whether the patient receives the sealant or not works without problems. Determining if the nurses and the patient have detected whether they (the patient) received the sealant or not during the study. Making sure the day-to-day administration and running of the trial can be done without problems. Once the pilot study is completed, the data will help calculate how many patients are needed in the full trial. To provide me with a comprehensive and practical training in designing and delivering clinical trials so that I may successfully carry out the full trial in the future. Patient and public involvement Patients have been integral to the inception of this project and will have a central role in all future stages of the research process: A patient representative as a collaborator on the study with ongoing influence on the research. An active role in the Trial Steering Committee to ensure the study retains a patient-centred focus. Assistance in the development of the patient information packs and consent forms. Role-playing within the teaching day for surgeons to guide them towards the best consent practice. Publicising the results within support & recruited patient groups. Publicising the Results Good publicity of the results is key to the success of the future trial. Strategies will include: A summary of the key findings to each patient that participated in the trial included with letters of thanks. Presentation of the results to patient support groups with publication of results on patient support websites. Publication of results in a surgical journal. Presentation of results at national/international conferences and surgical trainee meetings. Benefits to Patients & NHS This pilot study represents a vital step towards showing whether the use of tissue sealants at the end of neck dissection operations can benefit patients. If successful, a full trial (phase III) would follow with the aim of seeing how much impact tissue sealants have on preventing complications.Furthermore, this proposal will fit well with national initiatives to increase the number of patients who participate in high quality surgical research. I feel strongly that this research proposal will lay essential foundations for me to fulfill my ambition of delivering high quality surgical research and most importantly improve patient care.

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