Statistical analysis plan for the Petal trial: the effects of parental touch on relieving acute procedural pain in neonates

Abstract

Background: Infants undergo multiple clinically-required painful procedures during their time in hospital, and there is an increasing desire from both parents and clinical staff to have parents directly involved in their newborn’s pain relief. The Petal trial is a multicentre randomised controlled trial to investigate the effect of parental touch prior to a clinically-required heel lance on neonatal pain responses and parental anxiety. To avoid biases due to selective analysis and reporting, a clinical trial’s statistical analysis plan (SAP) should be finalised and registered prior to dataset lock and unblinding. Here, we outline the SAP for the Petal trial, which was registered on the ISRCTN registry prior to dataset lock and unblinding. The SAP is written in line with best practice guidelines to provide sufficient detail for reproducibility. Methods: The primary outcome is the neonate’s brain activity recorded using electroencephalography (EEG) in response to a heel lance blood sampling procedure. In this superiority trial, the primary objective is to investigate the potential efficacy of a parent-led non-pharmacological analgesic intervention on reducing the magnitude of neonates’ noxious stimulus-evoked brain activity. Secondary outcomes include neonatal clinical pain scores and tachycardia, and parental anxiety. Conclusions: Paediatric pain trials have been highlighted by regulatory bodies as an important and challenging topic, with interest increasing in brain imaging outcomes. The Petal trial, to which this SAP relates, is part of a larger effort of establishing a brain-based EEG outcome measure of infant pain for use in clinical trials. This SAP is thus likely to be of interest to those in academia, pharmaceutical companies, and regulatory bodies. We hope this SAP will help establish a foundation for the use of brain imaging outcomes in neonatal pain clinical trials, on which best practices can be built. Trial registration: ClinicalTrials.gov: NCT04901611, 25/05/2021; ISRCTN: ISRCTN14135962, 23/08/2021).