A dose finding design for seizure reduction in neonates

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...

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Bibliographic Details
Published in:Journal of the Royal Statistical Society Series C: Applied Statistics 2019-02, Vol.68 (2), p.427-444
Main Authors: Ursino, Moreno, Yuan, Ying, Alberti, Corinne, Comets, Emmanuelle, Favrais, Geraldine, Friede, Tim, Lentz, Frederike, Stallard, Nigel, Zohar, Sarah
Format: Article
Language:English
Subjects:
Bayesian analysis
Clinical research
Clinical trials
Computer simulation
Convulsions & seizures
Drug dosages
Drugs
Efficacy
Life Sciences
Medical research
Newborn babies
Newborns
Phase I–II
Physicians
Seizures
Statistical inference
Statistics
Time to event
Toxicity
Toxicity constraints
Vulnerability
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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.
ISSN:0035-9254
1467-9876
DOI:10.1111/rssc.12289