Quantifying individual nociceptive sensitivity to optimise analgesic trials in infants

Despite the high burden of pain experienced by hospitalised infants there are few analgesics with proven efficacy. Testing analgesics in infants is experimentally and ethically challenging and minimising the number of infants required to demonstrate efficacy is essential. EEG-derived measures of noxious-evoked brain activity can be used to assess analgesic efficacy, however, as variability exists in infant’s responses to painful procedures, large sample sizes are often required. Here we present a novel experimental paradigm to account for individual differences in baseline nociceptive sensitivity which can be used to improve the design of analgesic trials in infants. The paradigm is developed and tested across four studies using clinical, experimental and simulated data (99 infants). We provide evidence of the efficacy of both gentle brushing and paracetamol, substantiating the need for randomised controlled trials of these interventions. This work provides an important step towards safe, cost-effective clinical trials of analgesics in infants. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was funded by the Wellcome Trust via a Senior Fellowship awarded to Rebeccah Slater (Grant number 207457/Z/17/Z). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from the National Research Ethics Service (reference 12/SC/0447) and informed written parental consent was obtained prior to each study. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data that support the findings of this study, including data to produce [figures 1][1], [3][2], [4][3], [5][4] and supplementary figures 1 to 5, are available from the corresponding author upon reasonable request. Data sharing requests should be directed to rebeccah.slater{at}paediatrics.ox.ac.uk. [1]: #F1 [2]: #F3 [3]: #F4 [4]: #F5