Open AccessModel‐Based Assessment of Alternative Study Designs in Pediatric Trials. Part I: Frequentist Approaches
Author(s) -
Smania G,
Baiardi P,
Ceci A,
Magni P,
Cella M
Publication year - 2016
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12083
Subject(s) - frequentist inference , crossover , crossover study , sample size determination , placebo , clinical study design , statistics , adaptive design , clinical trial , computer science , medicine , mathematics , machine learning , bayesian probability , bayesian inference , alternative medicine , pathology
Alternative designs can increase the feasibility of pediatric trials when compared to classical parallel designs (PaD). In this work we present a model‐based approach based on clinical trial simulations for the comparison of PaD with the alternative sequential, crossover, and randomized withdrawal (RWD) designs. Study designs were evaluated in terms of: type I and II errors, sample size per arm (SS), trial duration (TD), treatment exposures, and parameter estimate precision (EP). The crossover requires the lowest SS and TD, although it implies higher placebo and no treatment exposures. RWD maximizes exposure to active treatment while minimizing that to placebo, but requires the largest SS. SS of sequential designs can sometimes be smaller than the crossover one, although with poorer EP. This pharmacometric framework allows a multiscale comparison of alternative study designs that can be used for design selection in future pediatric trials.