Optimal design of a population pharmacodynamic experiment for ivabradine

Purpose. To design a parsimonious population pharmacodynamic experiment tha t has the same or greater efficiency than that provided by two phase I stud ies. Methods. The design was based on optimization of the population Fisher info rmation matrix. Options for optimization were (1) determination of the opti mal sampling times for each group ("group" represents a group of subjects t hat have identical design characteristics), (2) determination of the optima l doses for each group, and (3) determination of the optimal group structur e. Results. (1) Optimizing the sampling times, while retaining only four uniqu e times per group, provided a more parsimonious experiment with the same ef ficiency as the original "study" that involved on average 10 samples per su bject. Splitting sampling times between the first dose and a steady-state d ose gave the most informative design. (2) The optimal dose was the same in all groups and was the upper bound of the dose range. (3) The optimal popul ation design consisted of only one group with four unique sampling times th at are the same for all subjects. Conclusion. A population pharmacodynamic trial design is presented that is more parsimonious than the original study and would be appropriate for incl usion in a premarketing clinical study.