Improve outcomes for infants following surgery in the first year of life by enhancing the evidence base for choice of surgical strategies

(i) Proposed Research and Leadership Programme AIMS 1. To improve outcomes for infants following surgery in the first year of life by improving the evidence base for choice of surgical strategies 2. To further enhance the quality of maternity care through additional work to inform the evidence base for policy, service provision and management strategies 3. To enhance research capacity and capability through developing academic skills amongst practising paediatric surgeons, midwives, obstetricians and obstetric anaesthetists 4. To establish the use of emerging technologies to allow for rapid data capture and analysis VISION The UKOSS, set up by Dr Knight, has proved an extremely effective system to generate high quality research evidence to inform the management of, and service provision for, women with severe and uncommon complications of pregnancy. This work has established her group within the NPEU as a national centre of excellence for evidence-based observational studies, bringing together collaborative groups of clinicians and researchers to enhance the quality of maternity care. In collaboration with members of the British Association of Paediatric Surgeons Research and Clinical Outcomes Committee, she has developed similar methodology within the field of neonatal surgery. This NIHR research professorship, through enabling Dr Knight to develop research capacity within the NPEU as well as her collaborating network of paediatric surgical centres will allow her to develop an embedded national programme of evidence-based observational and interventional research into interventions within paediatric surgery, thus establishing her group at the NPEU, inpartnership with BAPS and the Nuffield Department of Surgery at Oxford Radcliffe Hospitals, as a centre of excellence for research to inform evidencebased paediatric surgery. By developing research capability and capacity within the paediatric surgical setting, Dr Knight will facilitate ongoing appropriate evidence-based assessment of interventions beyond the life of the Professorship. Furthermore, taking advantage of the Professorship to develop the use of emerging technologies for data capture will minimise future administrative costs of these programmes, enhancing sustainability in the future, whilst potentially allowing development of a model which can be used in other NHS contexts. CONTEXT Randomised controlled trials are challenging in emergency situations, as well as where the management strategies involved are surgical and also during pregnancy. The reasons for this are several. In emergency situations, the ethical issues surrounding informed consent are complex, raising issues of capability to consent and assent by proxy alongside the challenges of a rapidly evolving clinical situation and the need for urgent action. Recruitment to trials in the emergency situation can thus be difficult. Where interventions are surgical, individual surgeons are likely to develop expertise in, and therefore preference for, one particular technique. Establishing clinical equipoise, a prerequisite for a randomised trial, can be very difficult since evidence of effectiveness is usually based on case series from individual centres, therefore multicentre randomised controlled trials of surgical interventions are more difficult to set up. In pregnancy also, concerns for both mother and fetus, and the potential for catastrophic adverse outcomes for infants can make clinicians reluctant to recruit for clinical trials. There are thus many clinical management decisions in these situations which cannot be informed by this the highest quality of research evidence, simply because it does not exist. Robust, population-based prospective observational studies can provide an alternative form of high quality evidence to inform policy and practice. Retrospective studies using data collected foradministrative purposes, for example hospital admissions databases, cannot provide this quality of evidence, since they do not provide sufficient detail of the timing and type of management strategies used or the additional clinical characteristics of each individual which may impact on the outcomes of the intervention used. The UK NHS, however, with its universality of health care provision, is an ideal environment in which high quality prospective observational studies can be conducted with minimal biases. The UK Obstetric Surveillance System (UKOSS) and the British Association of Paediatric Surgeons Congenital Anomalies Surveillance System (BAPS-CASS) are established systems through which to conduct robust prospective observational studies. This Professorship provides the opportunity to enhance the utility of the information for clinical practice, specifically through (i) enhancing research capability in paediatric surgery, allowing the future development of interventional, qualitative and economic studies alongside the observational studies and (ii) the use of emerging data capture technologies (Apple and Android apps), facilitating rapid data analysis and enhanced utility to quickly inform clinical practice. PROPOSED PROGRAMME THEMES THEME 1 DEVELOPING A CENTRE OF RESEARCH EXCELLENCE TO IMPROVE CARE RELATED TO EARLY PAEDIATRIC SURGERY Crosscutting theme: Research capacity development The appointment of a clinical lecturer, under the leadership of Dr Knight, would allow further development of the BAPS-CASS collaboration between public health and paediatric surgical staff to enhance the evidence base for quality paediatric surgical care. The ultimate goal would be for the clinical lecturer to take forward an independent research programme in this area, for example through a subsequent NIHR clinician scientist fellowship. Leadership of individual studies from different paediatric surgical centres would further enhance research capability within the specialty. Dr Knight also proposes, within the Professorship programme, to include a PhD studentship to additionally develop research capability within this underdeveloped area. Stream 1: Clinical effectiveness of paediatric surgical interventions National cohort studies (anorectal disorders, exomphalmos, duodenal atresia, posterior urethral valves) will be conducted using the BAPS-CASS methodology. Cases of specific morbidities will be ascertained through the monthly card mailing of BAPS-CASS to all paediatric surgical units in the UK. In response to a case report, clinicians will be sent a questionnaire requesting information to confirm the case definition together with additional information regarding diagnosis, established prognostic factors, management and outcomes, allowing comparisons to be made between infants managed with different surgical strategies whilst adjusting for known prognostic factors. The following questions will be addressed in all studies: What is the incidence and what are the outcomes of the condition for babies? Are any factors (e.g. gestation, birthweight, type of anomaly, condition of infant at diagnosis, timing of diagnosis) associated with a poor outcome (death, severe additional morbidity) for infants? How is the condition managed in the UK? Is there any association between specific surgical strategies and outcomes, taking into account known prognostic factors? Are there any local departures from recommended management according to national guidelines (if these exist) and do these have any impact on the outcomes for babies? Stream 2: Patient/Parent experiences of early paediatric surgical care Experiences of parents of infants who require surgery in the first year of life are rarely recorded. Even after discharge from hospital, infants may require multiple outpatient visits to differentspecialist clinics and the ongoing care requirements can have significant effects on the quality of life of parents and existing children, as well as economic effects through lost work days for parents attending with their infants. This work stream will address this gap in the evidence through a qualitative study of parents’ experiences, working in partnership with the established Health Experiences Research Group at the University of Oxford. Focussing initially on parents of infants with congenital diaphragmatic hernia, parents will be invited to participate in a qualitative interview to describe their experiences. Between 40 and 50 parents will be purposively sampled. Semi-structured interviews, comprising a narrative element followed by a series of prompts informed by the literature and the input of the advisory group, will be conducted by a single researcher and video or audio recorded for analysis. Analysis will be undertaken by two researchers using the thematic approach based on constant comparison. Stream 3: Long term follow-up after paediatric surgery Most studies of surgical strategies, because of their retrospective hospital-based nature, report relatively short-term outcomes for infants, for example, length of hospital stay, time to establishment of full oral feeding. However, neonatal morbidities requiring surgery may have significant long-term impacts, both physical and psychological, for parents, their infants and other children. Exploration of these wider impacts is important to inform both service provision and economic evaluation of different surgical management strategies (stream 4). This work stream will investigate the feasibility of long-term follow-up of two cohorts of infants previously prospectively identified through BAPS-CASS (infants with gastroschisis and Hirschsprung’s disease) through a parental questionnaire describing current functional and cosmetic outcomes at age 5. Stream 4: Cost effectiveness of paediatric surgical interventions Due to the difficulty of conducting clinical trials and thus obtaining effectiveness data, studies of cost-effectiveness are rarely undertaken in paediatric surgery. In the absence of randomised controlled trial data, national observational data, such as that obtained through BAPS-CASS, may be used to assess effectiveness of different current treatments for conditions requiring neonatal surgery. A national observational study collecting information on health outcomes in infants with Hirschsprung’s disease has recently been completed. This workstream will explore the use of these and other data obtained through literature review or from other workstreams in the programme to conduct an economic evaluation of the main alternative surgical management strategies for early-diagnosed Hirschsprung’s disease. Stream 5: Configuration of paediatric surgical services Evidence-based configuration of services is as important as evidence-based management. This work stream will explore the use of previously collected data, as well as data from work stream 2 to develop an evidence-based model of care for infants born with congenital diaphragmatic hernia. Stream 6: Moving from observational to interventional Whilst national observational data can be used to generate the evidence base for intervention, the ultimate gold standard remains the randomised controlled trial. In order to realise the vision of developing a centre for excellence in evidence-based paediatric surgery, it is clearly important to move forward to conducting national multi-centre trials. The NPEU already has an established clinical trials unit, which has successfully conducted obstetric and neonatal trials for many years. Dr Knight and her clinical collaborators will therefore work with Dr Ed Juszczak, Head of Trials at the NPEU to develop a trial of management of uncomplicated gastroschisis. This work stream will investigate the use of BAPS-CASS as a network through which to conduct this trial, comparing management with operative primary fascial closure with the use of a preformed silo. We will investigate the feasibility of different randomisation strategies, including surgical “buddy” systemsor cluster randomisation, as well as appropriate inclusion criteria through a survey of BAPS members and a consultation meeting at the annual BAPS congress. Development of a widely acceptable randomisation strategy and inclusion criteria will lead to a funding application for a full trial. The overall aim is to use this as a springboard for future trials of surgical strategies. THEME 2 ENHANCING THE EVIDENCE BASE TO INFORM PRIORITISATION DECISIONS IN MATERNITY CARE Crosscutting theme: Research capacity development This NIHR Professorship would release the NIHR funds which currently cover Dr Knight’s salary to employ a senior and junior health economist to develop further the use of national observational data to inform prioritisation decisions in maternity care. The economic as well as clinical evaluation of management and service strategies is becoming increasingly important in the context of limited resources and a rising birth rate. Developing research capacity in the specific area of economic evaluation in maternity care is therefore essential. Using evidence previously or currently being collected through UKOSS, studies evaluating the clinical and cost effectiveness of different management strategies for HELLP syndrome (a syndrome of Haemolysis, Elevated Liver enzymes, Low Platelets, part of the spectrum of pre-eclamptic disorders) and obstetric cholestasis, and of antenatal screening for fetomaternal/neonatal alloimmune thrombocytopenia (FMAIT/NAIT) will be undertaken. All of these disorders are associated with severe long-term maternal and/or fetal morbidity and mortality. THEME 3 DEVELOPING THE USE OF EMERGING TECHNOLOGIES Smartphone and tablet computer technologies have developed rapidly in recent years, allowing for the development of applications to allow secure and rapid electronic data capture. Currently both the UKOSS and BAPS-CASS systems rely on paper-based completing of data collection forms and subsequent data entry by designated administrative staff. Dr Knight proposes, as part of the Professorship programme, to develop smartphone and tablet computer applications, in both Android and iPhone/iPad formats for future data capture in the BAPS-CASS programme. This will facilitate more rapid data capture, analysis and hence more rapid use of results, will enhance both the sustainability and cost-effectiveness of the systems for clinical use, by reducing the administrative costs, and will potentially provide a patentable system which could be adapted for use in other clinical fields within the NHS. LaySummary>