title: A case study of modeling and exposure-response prediction for count data.
abstract: Even with two doses of an experimental drug in Phase III studies, with the commonly used approach for assessing treatment effects of individual doses, it may still be difficult to determine the final commercial dose. In such a scenario, with plasma concentration data collected in the studies, a modeling approach can be applied to predict treatment effects at different plasma concentration levels. Through an established relationship between plasma concentration and dose, the treatment effects of doses not studied in the Phase III studies can then be predicted. The results can further be applied to justify the final dose confirmation or selection. In this article, a Phase III program example with count data as the primary endpoint in the multiple sclerosis area is used to illustrate the application of such a technique for dose confirmation. Several models, such as the overdispersion Poisson model, negative binomial model, and recurrent event models, are considered. The negative binomial model is preferable due to better data fitting and the capability of within-treatment assessment and between-treatment comparison.
authors.affiliation: a Biostatistics and Programming, Sanofi, Bridgewater , New Jersey , USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Quan
authors.forename: Xuezhou
authors.initials: X
authors.lastname: Mao
authors.forename: Lynn
authors.initials: L
authors.lastname: Wei
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
mesh_terms: D017326:Clinical Trials, Phase III as Topic / Q000379:methods* / Q000706:statistics & numerical data; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood; D016012:Poisson Distribution; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D012107:Research Design; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D004364:Pharmaceutical Preparations
keywords: Annualized relapse rate; Negative binomial; Plasma concentration; Recurrent event; Risk ratio; Trial simulation