Title: Statistical Methods In Surgical Trials Evaluation and Research
Funder: Department of Health and Social Care

Abstract: Research question: What are the best statistical methods to improve the quality and quantity of clinical trials of surgical interventions? Background: Clinical trials are the gold standard research method for providing the evidence to change clinical practice but the number of trials of surgical interventions is low.There are efficient statistical designs used in the evaluation of drug treatments to identify active treatments early. These include single stage studies of real world evidence and emerging simulation methods used in engineering for device development. These statistical methods are rarely used in the evaluation of surgical interventions. Effective surgical interventions need to be assessed better and earlier in the research pathway to accelerate to late phase effectiveness trials more quickly. Surgical interventions are complex interventions made up of multiple interacting components. There are novel statistical designs used in behavioural sciences that statistically optimise interventions for late stage evaluation by investigating the component parts. Robust evidence of component parts ensures i) effective interventions are not dropped inappropriately ii) understanding of why interventions are ineffective. These statistical methods are rarely used in the evaluation of surgical interventions. This programme will develop and make recommendations for the statistical evaluation of complex surgical interventions through a new statistical framework. Aims: 1. To improve the health of patients by increasing the quality and quantity of clinical trials of surgical interventions 2. Develop and disseminate a new statistical framework for surgical trials research embedding early phase, novel and efficient designs not currently being used 3. To create an international statistical network dedicated to surgical trials research 4. To become an international leader in the statistical methodology for surgical trials researchObjectives: 1. Create an international statistical network for surgical trials research 2. Streamline the research pathway using early phase methodologies and in silico computer simulated evidence 3. Use novel and efficient statistical designs to optimise interventions 4. Develop and make recommendations for the statistical evaluation of complex surgical interventions 5. Undertake a bespoke leadership development programme to develop my international leadership role Methods: WP1: International Statistical Network Bring together existing networks and collaborations to develop an international network of statisticians dedicated to the design and analysis of clinical trials of surgical interventions. WP2: Early Phase Research Identify and redesign early stage surgical trials adopting and adapting early phase methodologies, considering single stage designs of real world evidence, early phase randomised designs, simulation methods incorporating Bayesian designs. Identify potential barriers to uptake, make recommendations for adoption. WP3: Optimised Interventions Identify and redesign surgical trials using novel multiphase optimization strategy (MOST) and sequential multiple assignment randomised trial (SMART) designs to statistically screen for active components simulating design properties. Identify potential barriers to uptake, make recommendations for adoption. Timelines for delivery: I will compete the research and my development programme in 60 months. Anticipated impact and dissemination: Disseminate framework to methodologists, clinicians, public, funders, intervention developers, industry partners and commissioners; enhanced surgical trials portfolios with improved opportunities for patient participation and evidence for rollout of optimised surgical interventions.

Lay abstract: Background: Clinical trials provide the evidence to make sure that patients get the best possible care. The best way to do this is to compare a new treatment with an existing treatment. However, surgery is a more complex treatment. Having surgery involves a number of different parts; equipment, anaesthetic, the surgery itself. The clinical trials research is therefore a lot more complicated, can take longer and be more expensive. This means there is less surgical research than other research, just at a time when the number of people needing surgery is increasing. Conventional trial designs do not provide answers to the additional questions about the specific parts of the treatment. This means that different surgeons may not perform the surgery in the best way which can lead to inequalities in the care that patients receive. To provide answers about specific parts of the treatment we need novel designs that use statistics to find out which components works best for the medical team and has the best outcome for patients. There are designs that quickly show how well a drug treatment works. These designs are hardly ever used to find out how well a new operation works. These designs could make research faster so that treatments can be given to patients sooner. Overall the aim of this application in to improve surgery for patients by having more efficient and informative clinical trials research. We can then share this with the teams of medical staff who carry out operations both in the UK and internationally. This would provide reliable evidence to reduce variability in patient care. Aims: 1. To improve the health of patients by increasing the quality and quantity of surgical research 2. To write new guidance to improve the design of surgical research 3. To work with an international group of statisticians to review and share findings worldwidePatient and Public Involvement: I talked to the NIHR Surgical MedTech Cooperative PPI group about the need for more surgical research, the stages of research and the need to find out more quickly which components of surgery work best. They thought this would be cost-effective for the NHS. The discussion helped me write and focus the ideas behind my project. I plan to form a PPI group that will be involved in every stage of my project. Impact: More surgical research with better designs Find out more quickly which components work best to improve health and reduce inequality in patient care Easier opportunities for patients to take part in surgical research

Research activity codes: 6.4 SURGERY;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE