A dose finding design for seizure reduction in neonates. Issue 2 (18th May 2018)

• Record Type: Journal Article
• Authors: Ursino, Moreno; Yuan, Ying; Alberti, Corinne; Comets, Emmanuelle; Favrais, Geraldine; Friede, Tim; Lentz, Frederike; Stallard, Nigel; Zohar, Sarah
• Is Part Of: Journal of the Royal Statistical Society. Volume 68:Issue 2(2019)
• Page Start: 427
• Page End: 444
• Publication Date: 2018-05-18
• Subjects: Efficacy -- Newborns -- Phase I–II -- Time to event -- Toxicity constraints; Statistics -- Periodicals; 519.5
• DOI: 10.1111/rssc.12289
• Languages: English
• ISSNs: 0035-9254

Abstract

Summary: 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.