@article{54d976bbec2148dfab4c91b75b5def3a,
title = "A dose finding design for seizure reduction in neonates",
abstract = "Clinical trials in vulnerable populations are extremely difficult to conduct. A sequential phase I–II trial aimed at finding the appropriate dose of levetiracetam for treating neonatal seizures was planned with a maximum sample size of 50 newborns. Three primary outcomes are considered: efficacy and two types of toxicity that occur at the same time but are measured at different time points. In the case of failure, physicians could add a second agent as a rescue medication. The primary outcomes were modelled via a logistic model for efficacy and a weighted likelihood with pseudo-outcomes for the two toxicities taking into account the dependences under Bayesian inference. Simulations were conducted to assess the design properties.",
keywords = "Efficacy, Newborns, Phase I–II, Time to event, Toxicity constraints",
author = "Moreno Ursino and Ying Yuan and Corinne Alberti and Emmanuelle Comets and Geraldine Favrais and Tim Friede and Frederike Lentz and Nigel Stallard and Sarah Zohar",
note = "Funding Information: This work was conducted as part of the {\textquoteleft}Innovative methodology for small populations research{\textquoteright} project funded by the European Union{\textquoteright}s seventh framework programme for research, Funding Information: We should like to show our gratitude to Estelle Boivin, Bruno Giraudeau, Julie Leger, Elie Saliba and Elsa Tavernier, who are involved in the LEVNEONAT clinical trial, for sharing their opinions and being ready to help and give information to adapt the model for this trial. We also thank two reviewers for their suggestions. This work was conducted as part of the ?Innovative methodology for small populations research? project funded by the European Union's seventh framework programme for research, technological development and demonstration under grant agreement FP HEALTH 2013-602144. Funding Information: technological development and demonstration under grant agreement FP HEALTH 2013-602144. Publisher Copyright: {\textcopyright} 2018 The Authors Journal of the Royal Statistical Society: Series C (Applied Statistics) Published by John Wiley & Sons Ltd on behalf of the Royal Statistical Society.",
year = "2019",
month = feb,
day = "1",
doi = "10.1111/rssc.12289",
language = "English (US)",
volume = "68",
pages = "427--444",
journal = "Journal of the Royal Statistical Society. Series C: Applied Statistics",
issn = "0035-9254",
publisher = "Wiley-Blackwell",
number = "2",
}