Research Ethics Committee decision-making in relation to an efficient neonatal trial

Objective Randomised controlled trials, a gold-standard approach to reduce uncertainties in clinical practice, are growing in cost and are often slow to recruit. We determined the acceptability to United Kingdom (UK) Research Ethics Committees (REC) of approaches to facilitate large, efficient clinical trials. Design We developed a protocol in collaboration with parents, for a comparative-effectiveness, randomised controlled trial comparing two widely used blood transfusion practices in preterm infants. We incorporated four approaches to improve recruitment and efficiency: i) point-of-care design using Electronic Patient Records for patient identification, randomisation and data acquisition, ii) short two-page information sheet; iii) explicit mention of possible inclusion benefit; iv) opt-out consent with enrollment as the default. With the support of the UK Health Research Authority, we submitted an identical protocol to 12 UK REC. Setting Research Ethics Committees in the UK Main outcome Number of REC granting favourable opinions. Results The use of Electronic Patient Records was acceptable to all REC; one REC raised concerns about the short parent information sheet, 10 about inclusion benefit and 9 about opt-out consent. Following responses to queries 9 REC granted a favourable final opinion; 3 rejected the application because they considered the opt-out consent process invalid. Conclusions A majority of REC in this study consider the use of Electronic Patient Record data, short information sheets, opt-out consent and mention of possible inclusion benefit to be acceptable in neonatal comparative-effectiveness research. We identified a need for guidance for REC in relation to opt-out consent processes. These methods provide opportunity to facilitate large randomised controlled trials

Optimising nutrition during therapeutic hypothermia

There is little evidence to inform provision of enteral or parenteral nutrition to infants with hypoxic ischaemic encephalopathy (HIE) during and soon after therapeutic hypothermia; as a consequence, clinical practice is both variable and changing. A 2014 UK survey found that 79% (33 of 42) of responding neonatal units routinely withheld enteral nutrition during cooling; 3 years later, a similar survey found that 41% (20 of 49) of responding units reported withholding enteral nutrition.1 The latter study also reports wide variation in how, when and how much to feed, and in the use of parenteral nutrition. Internationally, practice is even more variable: withholding enteral feeds is practised almost universally2 in some countries, while in others, milk feeding during hypothermia is routine.3 Here we discuss the limited evidence available to inform enteral and parenteral nutrition during therapeutic hypothermia

Body composition following necrotising enterocolitis in preterm infants

Background: The optimal nutritional regimen for preterm infants, including those that develop necrotising enterocolitis (NEC), is unknown. Objective: The objective here was to evaluate body composition at term in infants following NEC, in comparison with healthy infants. The primary outcome measure was non-adipose tissue mass (non-ATM). Methods: We compared body composition assessed by magnetic resonance imaging at term in infants born <31 weeks of gestational age that participated in NEON, a trial comparing incremental versus immediate delivery of parenteral amino acids on non-ATM, and SMOF versus intralipid on intrahepatocellular lipid content. There were no differences in the primary outcomes. We compared infants that received surgery for NEC (NEC-surgical), infants with medically managed NEC (NEC-medical), and infants without NEC (reference). Results: A total of 133 infants were included (8 NEC-surgical; 15 NEC-medical; 110 reference). In comparison with the reference group, infants in the NEC-surgical and NEC-medical groups were significantly lighter [adjusted mean difference (95% CI) NEC-surgical: –630 g (–1,010, –210), p = 0.003; NEC-medical: –440 g (–760, –110), p = 0.009] and the total adipose tissue volume (ATV) was significantly lower [NEC-surgical: –360 cm3 (–516, –204), p < 0.001; NEC-medical: –127 cm3 (–251, –4); p = 0.043]. There were no significant differences in non-ATM [adjusted mean difference (95% CI) NEC-surgical: –46 g (–281, 189), p = 0.70; NEC-medical: –122 g (–308, 63), p = 0.20]. Conclusion: The lower weight at term in preterm infants following surgically and medically managed NEC, in comparison to preterm infants that did not develop the disease, was secondary to a reduction in ATV. This suggests that the nutritional regimen received was adequate to preserve non-ATM but not to support the normal third-trimester deposition of adipose tissue in preterm infants

Developing, implementing and disseminating a core outcome set for neonatal medicine

Background In high resource settings, 1 in 10 newborn babies require admission to a neonatal unit. Research evaluating neonatal care involves recording and reporting many different outcomes and outcome measures. Such variation limits the usefulness of research as studies cannot be compared or combined. To address these limitations, we aim to develop, disseminate and implement a core outcome set for neonatal medicine. Methods A steering group that includes parents and former patients, healthcare professionals and researchers has been formed to guide the development of the core outcome set. We will review neonatal trials systematically to identify previously reported outcomes. Additionally, we will specifically identify outcomes of importance to parents, former patients and healthcare professionals through a systematic review of qualitative studies. Outcomes identified will be entered into an international, multi-perspective eDelphi survey. All key stakeholders will be invited to participate. The Delphi method will encourage individual and group stakeholder consensus to identify a core outcome set. The core outcome set will be mapped to existing, routinely recorded data where these exist. Discussion Use of a core set will ensure outcomes of importance to key stakeholders, including former patients and parents, are recorded and reported in a standard fashion in future research. Embedding the core outcome set within future clinical studies will extend the usefulness of research to inform practice, enhance patient care and ultimately improve outcomes. Using routinely recorded electronic data will facilitate implementation with minimal addition burden. Trial registration number Core Outcome Measures in Effectiveness Trials (COMET) database: 842 (www.comet-initiative.org/studies/details/842)

Study Protocol: Optimising newborn nutrition during and after neonatal therapeutic hypothermia in the United Kingdom: Observational study of routinely collected data using propensity matching

ntroduction Therapeutic hypothermia is standard of care for infants born ≥36 weeks gestation with hypoxic ischaemic encephalopathy (HIE); consensus on optimum nutrition during therapeutic hypothermia is lacking. This results in variation in enteral feeding and parenteral nutrition (PN) for these infants. In this study, we aim to determine the optimum enteral nutrition and PN strategy for newborns with HIE during therapeutic hypothermia. Methods and analysis We will undertake a retrospective cohort study using routinely recorded electronic patient data held on the United Kingdom (UK) National Neonatal Research Database (NNRD). We will extract data from infants born ≥36 weeks gestational age between 1 January 2008 and 31 December 2016, who received therapeutic hypothermia for at least 72 hours or died during therapeutic hypothermia, in neonatal units in England, Wales and Scotland. We will form matched groups in order to perform two comparisons examining: (1) the risk of NEC between infants enterally fed and infants not enterally fed, during therapeutic hypothermia; (2) the risk of late-onset blood stream infections between infants who received intravenous dextrose without any PN and infants who received PN, during therapeutic hypothermia. The following secondary outcomes will also be examined: survival, length of stay, breast feeding at discharge, hypoglycaemia, time to full enteral feeds and growth. Comparison groups will be matched on demographic, maternal, infant and organisational factors using propensity score matching. Ethics and dissemination In this study, we will use deidentifed data held in the NNRD, an established national population database; parents can opt out of their baby’s data being held in the NNRD. This study holds study-specific Research Ethics Committee approval (East Midlands Leicester Central, 17/EM/0307). These results will help inform optimum nutritional management in infants with HIE receiving therapeutic hypothermia; results will be disseminated through conferences, scientific publications and parent-centred information produced in partnership with parents