Assessing the impact of risk-based data monitoring on outcomes for a paediatric multicentre randomised controlled trial.

BACKGROUND/AIMS: Regulatory guidelines recommend that sponsors develop a risk-based approach to monitoring clinical trials. However, there is a lack of evidence to guide the effective implementation of monitoring activities encompassed in this approach. The aim of this study was to assess the efficiency and impact of the risk-based monitoring approach used for a multicentre randomised controlled trial comparing treatments in paediatric patients undergoing cardiac bypass surgery. METHODS: This is a secondary analysis of data from a randomised controlled trial that implemented targeted source data verification as part of the risk-based monitoring approach. Monitoring duration and source to database error rates were calculated across the monitored trial dataset. The monitored and unmonitored trial dataset, and simulated trial datasets with differing degrees of source data verification and cohort sizes were compared for their effect on trial outcomes. RESULTS: In total, 106,749 critical data points across 1,282 participants were verified from source data either remotely or on-site during the trial. The total time spent monitoring was 365 hours, with a median (interquartile range) of 10 (7, 16) minutes per participant. An overall source to database error rate of 3.1% was found, and this did not differ between treatment groups. A low rate of error was found for all outcomes undergoing 100% source data verification, with the exception of two secondary outcomes with error rates >10%. Minimal variation in trial outcomes were found between the unmonitored and monitored datasets. Reduced degrees of source data verification and reduced cohort sizes assessed using simulated trial datasets had minimal impact on trial outcomes. CONCLUSIONS: Targeted source data verification of data critical to trial outcomes, which carried with it a substantial time investment, did not have an impact on study outcomes in this trial. This evaluation of the cost-effectiveness of targeted source data verification contributes to the evidence-base regarding the context where reduced emphasis should be placed on source data verification as the foremost monitoring activity.

Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol.

INTRODUCTION: Despite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile and the emergence of specific impairments in children with CHD entering school. The performance of standardised screening tools to predict neurodevelopmental outcomes at school age in this high-risk population remains poorly understood. The NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial randomised 1371 children <2 years of age, investigating the effect of gaseous nitric oxide applied into the cardiopulmonary bypass oxygenator during heart surgery. The NITRIC follow-up study will follow this cohort annually until 5 years of age to assess outcomes related to cognition and socioemotional behaviour at school entry, identify risk factors for adverse outcomes and evaluate the performance of screening tools. METHODS AND ANALYSIS: Approximately 1150 children from the NITRIC trial across five sites in Australia and New Zealand will be eligible. Follow-up assessments will occur in two stages: (1) annual online screening of global neurodevelopment, socioemotional and executive functioning, health-related quality of life and parenting stress at ages 2-5 years; and (2) face-to-face assessment at age 5 years assessing intellectual ability, attention, memory and processing speed; fine motor skills; language and communication; and socioemotional outcomes. Cognitive and socioemotional outcomes and trajectories of neurodevelopment will be described and demographic, clinical, genetic and environmental predictors of these outcomes will be explored. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Children's Health Queensland (HREC/20/QCHQ/70626) and New Zealand Health and Disability (21/NTA/83) Research Ethics Committees. The findings will inform the development of clinical decision tools and improve preventative and intervention strategies in children with CHD. Dissemination of the outcomes of the study is expected via publications in peer-reviewed journals, presentation at conferences, via social media, podcast presentations and medical education resources, and through CHD family partners. TRIAL REGISTRATION NUMBER: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as 'Gene Expression to Predict Long-Term Neurodevelopmental Outcome in Infants from the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) Study - A Multicentre Prospective Trial'. TRIAL REGISTRATION: ACTRN12621000904875.

Job satisfaction and symptoms of depression, anxiety, stress, and burnout: A survey of Australian and New Zealand intensive care research coordinators.

INTRODUCTION: Intensive care unit clinical research is often implemented by specialised research coordinators (RCs). Clinical research activity within Australian and New Zealand intensive care units has escalated, particularly during the COVID-19 pandemic. Growth of the intensive care RC workforce to match research demand is poorly understood. AIM: The aim of this study was to repeat an Intensive Care Research Coordinator Interest Group workforce survey conducted in 2004 and 2009 to describe the current workforce and role satisfaction and also to determine reported symptoms of depression, anxiety, stress, and burnout in Australian and New Zealand intensive care RCs. METHODS: In April 2021, an online anonymised survey was distributed to intensive care RCs to complete demographic and workforce questions, the McCloskey/Mueller Satisfaction Scale, the Depression Anxiety Stress Scales-21, and the Maslach Burnout Inventory-Human Services Survey for Medical Personnel. RESULTS: Of 128 Intensive Care Research Coordinator Interest Group eligible members, 98 (77%) completed the survey. Respondents were mainly women (91%), the median age was 47 years, 37% have a postgraduate qualification, and a third have over 10 years of RCC experience (31%). Half do not have permanent employment (52%). The mean Depression Anxiety Stress Scales-21 scores were within the normal range, and respondents reported symptoms of depression (21 [21%]), anxiety (23 [23%]), and stress (26 [27%]). Nearly half of the respondents (44%) exhibited an early symptom of burnout by reporting problematic experiences of work. The overall role satisfaction score was 3.5/5 (neutral; neither satisfied nor dissatisfied). CONCLUSIONS: Intensive care RCs are an experienced group of professionals with limited satisfaction in the role. One-fifth of the ICU RCs experienced depression, anxiety, or stress symptoms, with close to half reporting signs of burnout. These results highlight the need to address areas of concern to ensure retention of this specialised intensive care workforce.

Hypothermia for Traumatic Brain Injury in Children-A Phase II Randomized Controlled Trial.

OBJECTIVES: To perform a pilot study to assess the feasibility of performing a phase III trial of therapeutic hypothermia started early and continued for at least 72 hours in children with severe traumatic brain injury. DESIGN: Multicenter prospective randomized controlled phase II trial. SETTING: All eight of the PICUs in Australia and New Zealand and one in Canada. PATIENTS: Children 1-15 years old with severe traumatic brain injury and who could be randomized within 6 hours of injury. INTERVENTIONS: The control group had strict normothermia to a temperature of 36-37°C for 72 hours. The intervention group had therapeutic hypothermia to a temperature of 32-33°C for 72 hours followed by slow rewarming at a rate compatible with maintaining intracranial pressure and cerebral perfusion pressure. MEASUREMENTS AND MAIN RESULTS: Of 764 children admitted to PICU with traumatic brain injury, 92 (12%) were eligible and 55 (7.2%) were recruited. There were five major protocol violations (9%): three related to recruitment and consent processes and two to incorrect temperature management. Rewarming took a median of 21.5 hours (16-35 hr) and was performed without compromise in the cerebral perfusion pressure. There was no increase in any complications, including infections, bleeding, and arrhythmias. There was no difference in outcomes 12 months after injury; in the therapeutic hypothermia group, four (17%) had a bad outcome (pediatric cerebral performance category, 4-6) and three (13%) died, whereas in the normothermia group, three (12%) had a bad outcome and one (4%) died. CONCLUSIONS: Early therapeutic hypothermia in children with severe traumatic brain injury does not improve outcome and should not be used outside a clinical trial. Recruitment rates were lower and outcomes were better than expected. Conventional randomized controlled trials in children with severe traumatic brain injury are unlikely to be feasible. A large international trials group and alternative approaches to trial design will be required to further inform practice.

Local experience with the use of sustained low efficiency dialysis for acute renal failure.

Renal replacement therapy (RRT) is a common therapy used to treat critically ill patients in acute renal failure. Currently a number of dialysis modalities are used such as haemodialysis, continuous renal replacement therapy (CRRT), and sustained low efficiency dialysis (SLED). As SLED is a recently implemented RRT, very little literature is available on the nursing aspects of SLED. This paper shares the local nursing experience of using SLED, thus providing a nursing perspective. Between 2002 and 2006, 103 patients were treated with SLED resulting in 307 SLED treatments. Early problems encountered involved patient hypotension, dialysis catheter patency and water quality; all of which were overcome by initially commencing dialysis at a lower prescribed blood pump rate, using larger catheters and improving water quality. Nursing advantages of SLED over CRRT included being able to release the patient for nursing activities and patient transfer out of the ICU for investigations and procedures; reduced nursing workload related to less machine and patient monitoring during the dialysis procedure; and cost reduction. Disadvantages of SLED are related to poor water quality, accessibility of water supply and limited space to house the two machines required. SLED has proven to be a nurse friendly dialysis modality for critically ill patients with acute renal failure.

Local experience with the use of nasal bubble CPAP in infants with bronchiolitis admitted to a combined adult/paediatric intensive care unit.

Bronchiolitis is an acute inflammatory disease of the lower small airways predominantly occurring in infants younger than 1 year of age. As a result of the respiratory distress associated with bronchiolitis, infants frequently require admission to an intensive care unit for respiratory support. Thirty-five infants diagnosed with bronchiolitis were admitted to a combined adult/paediatric tertiary intensive care unit over a 2-year period for nasal bubble continuous positive airway pressure (CPAP). Following this therapy, 20 (57.14%) of these infants could be transferred to the medical ward of the onsite paediatric hospital. The remainder required transfer to the national paediatric intensive care unit (PICU) for ongoing observation and/or positive pressure ventilation. Nasal bubble CPAP is a simple therapy that can be easily set up at the bedside. The use of nasal bubble CPAP enabled infants to remain in their geographical area, thus improving family visiting access and reducing the demand for paediatric beds in the national PICU.