Quan Hui, Mao Xuezhou, Wei Lynn, Wang Lin
a Biostatistics and Programming, Sanofi, Bridgewater , New Jersey , USA.
J Biopharm Stat. 2014;24(5):1073-90. doi: 10.1080/10543406.2014.929584.
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.
