A dose finding design for seizure reduction in neonates

Moreno Ursino, Ying Yuan, Corinne Alberti, Emmanuelle Comets, Geraldine Favrais, Tim Friede, Frederike Lentz, Nigel Stallard, Sarah Zohar

Research output: Contribution to journalArticle

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.

LanguageEnglish (US)
Pages427-444
Number of pages18
JournalJournal of the Royal Statistical Society. Series C: Applied Statistics
Volume68
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Dose Finding
Toxicity
Efficacy
Weighted Likelihood
Logistic Model
Bayesian inference
Clinical Trials
Dose
Sample Size
Design
Simulation
Sample size
Logistic model
Clinical trials
Vulnerable populations
Physicians
Medication

Keywords

  • Efficacy
  • Newborns
  • Phase I–II
  • Time to event
  • Toxicity constraints

ASJC Scopus subject areas

  • Statistics and Probability
  • Statistics, Probability and Uncertainty

Cite this

A dose finding design for seizure reduction in neonates. / Ursino, Moreno; Yuan, Ying; Alberti, Corinne; Comets, Emmanuelle; Favrais, Geraldine; Friede, Tim; Lentz, Frederike; Stallard, Nigel; Zohar, Sarah.

In: Journal of the Royal Statistical Society. Series C: Applied Statistics, Vol. 68, No. 2, 01.02.2019, p. 427-444.

Research output: Contribution to journalArticle

Ursino, M, Yuan, Y, Alberti, C, Comets, E, Favrais, G, Friede, T, Lentz, F, Stallard, N & Zohar, S 2019, 'A dose finding design for seizure reduction in neonates', Journal of the Royal Statistical Society. Series C: Applied Statistics, vol. 68, no. 2, pp. 427-444. https://doi.org/10.1111/rssc.12289
Ursino, Moreno ; Yuan, Ying ; Alberti, Corinne ; Comets, Emmanuelle ; Favrais, Geraldine ; Friede, Tim ; Lentz, Frederike ; Stallard, Nigel ; Zohar, Sarah. / A dose finding design for seizure reduction in neonates. In: Journal of the Royal Statistical Society. Series C: Applied Statistics. 2019 ; Vol. 68, No. 2. pp. 427-444.
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