Title: Improving outcomes through development and implementation of Core Outcome Sets in paediatric surgical research
Funder: Department of Health and Social Care

Abstract: Objectives The ability of paediatric surgeons to counsel parents, obtain informed consent and develop evidence-based management guidelines for key conditions is limited by the paucity of research that has sufficient statistical power and methodological quality to address the impact of interventions on outcomes of interest to patients, parents and service providers(Allin 2014). The objective of this fellowship is to investigate methods for addressing these deficiencies, and in doing so, develop an evidence base for best clinical practice in paediatric surgery in the UK. Key objectives: Increase patient relevance and improve synthesisability in Hirschsprung's disease (HD) and gastroschisis research through development of core outcome sets (COS) to assess surgical treatment of these conditions. Perform a nationwide, multi-centre cohort study investigating the impact of choice of surgical intervention on core outcomes at six years of age in infants with HD. Perform an international, multi-centre cohort study exploring which patient and operative factors affect core outcomes in infants with gastroschisis at initial discharge and one year of age. Wider benefits: Development of transferrable methodology for creation of COS in paediatric surgical conditions, including: Recruitment of patients and parents Incorporation of outcomes from clinicians with priorities varying dependent on age they encounter the patient Development of the collaborations required for conducting large-scale observational and interventional studies in paediatric surgical research.Design Four work packages (WP) will be developed to achieve these aims. WP1 and WP3 COS development Based upon best practice from the COMET initiative(Williamson 2011), three phase Delphi processes will be conducted to generate COS for infants with HD and gastroschisis. The methodology used in WP3 will be refined based upon feedback from WP1. WP2: Impact of surgical intervention on core outcomes at six years of age for infants with HD The British Association of Paediatric Surgeons Congenital Anomalies Surveillance System dataset will be used to identify a cohort of infants with HD who will turn six years of age, and start school, during the period of the fellowship. Operative factors affecting core outcomes in this group of infants will be investigated. WP4 Impact of pre-operative and operative factors on core outcomes in infants with gastroschisis: an International, multi-centre cohort study By combining UK and Canadian data, I will investigate a cohort of 1300 infants with gastroschisis. Secondary analysis of prospectively collected data will be performed using multi-variable regression analyses in order to establish infant characteristics and operative factors that affect core outcomes at initial discharge and one year of age. Expected outcomes and anticipated benefits Development of COS for HD and gastroschisis will increase the relevance of studies to patients, reduce reporting bias, and increase synthesisability of data(Clarke 2007, Williamson 2011). Doing so will reduce waste(Chan 2014) and improve the ability of clinicians to counsel and consent parents. WP2 and WP4 will investigate current management practices in order to inform generation of evidence-based guidelines for HD and gastroschisis in the UK. Standardisation of management will improve outcomes, make financial savings for the NHS, and reduce the impact of these long-term conditions on infants and their families. With the average in-patient stay for an infant with gastroschisis costing over 90,000(Robbins 2007), and a major operation in an infant less than one year old costing 25,000, these financial savings have the potential to be large(Team 2012). By forging the collaborations required for successful completion of this fellowship, interactions between academic institutions, major paediatric surgical centres, and the British Association of Paediatric Surgeons will have been enhanced, thereby improving the co-ordination of research, and increasing the ease with which new findings are translated into clinical practice.

Lay abstract: How can research be improved to help paediatric surgeons deliver the best treatments for children they care for? Paediatric surgeons treat children from birth to age 16 who have a problem that may need an operation, e.g. appendicitis or a hernia. Many of the conditions that they treat however, like Gastroschisis (where the babies are born with their bowels outside their body), and Hirschsprung's disease (where the infants' bowels do not work properly) are rare, and there has been little high-quality research trying to determine the best treatments. Using these conditions as examples, I plan to investigate methods for improving the quality of paediatric surgical research, and in doing so, make sure that every child receives the best possible treatment for their condition. Most research in surgery tries to work out whether one type of treatment is better than another. One way of doing this is to compare children who have had the two different treatments, and look at different things that happen to them, such as whether they get complications from the treatment, or how long they stay in hospital. Each of the things you could look at it is called an outcome measure. Because there are many different outcome measures, different researchers use different ones in their studies. This means that it is difficult to compare or combine results from different studies. Researchers often use a certain outcome measure because it is easy to gather information about, such as how quickly children leave hospital, rather than one that is important to patients, like whether they have long-term pain. This means that the results of the research are often not actually relevant to patients with the condition. On top of this, researchers will sometimes measure many different outcome measures, but only publish the ones that support their argument. This is called reporting bias.A tool called a core outcome set has been developed to address these problems. Core outcome sets are a list of outcome measures that should be reported in every study looking at a particular condition. A group of experts for each condition, usually consisting of doctors, researchers, and patients/parents, has come up with this list by a series of steps called a Delphi process, where the group come to a decision they all agree with. The first half of this fellowship will conduct Delphi processes to create core outcome sets for use in Hirschsprung's Disease and gastroschisis. Developing these core outcome sets will ensure that all gastroschisis and Hirschsprung's Disease research is relevant to patients, is not affected by reporting bias, and is easy to combine with other pieces of research. This will significantly increase the quality of research into these conditions in the future. Currently, many researchers investigating treatments for Hirschsprung's Disease and gastroschisis try to determine which treatment is best by looking at a limited number of patients they have previously treated. It is difficult to draw conclusions from these studies because the small number of studied patients means it is very difficult to tell if differences between the treatments are occurring because one treatment is better than the other, because of chance, or because of differences between the groups of children who received each treatment. For studies to include larger numbers of patients, there need to be collaborations developed between different groups of researchers. The second half of this fellowship will develop these collaborations and use them to run larger studies aiming to determine which the best treatments are for Hirschsprung's Disease and gastroschisis. In order to make sure that these studies answers are relevant to patients, and not affected by reporting bias, we will use the core outcome sets that were developed in the first half of the fellowship. Results from this fellowship can help develop treatment guidelines. Developing these guidelines will ensure that all infants with Hirschsprung's Disease and gastroschisis get the best treatments available. We will work with groups of parents of infants with these conditions to make sure that the results of this fellowship are published in a way that is understandable and accessible by affected members of the public, not just doctors and researchers. Methods we have used to develop core outcome sets and collaborations in this fellowship can be used again in research for other paediatric surgical conditions. Therefore, as well as making sure infants with Hirschsprung's Disease and gastroschisis get the best care, this fellowship will also create a longer-lasting improvement in the quality of research in other paediatric surgical conditions.

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