Stockholm university logo, link to start page

Dissertation defence - Renata Tsirpitzi


Date: Friday 17 December 2021

Time: 13.00 – 16.00

Location: Hörsal 11, Frescati. Zoom:

Due to new advice and recommendations to limit the spread of covid-19: Before entering the auditorium, we recommend that you wash your hands with soap and water or use hand disinfectant. Inside the auditorium, do not sit too close to each other in larger gatherings / groups.


Optimal design for dose-finding studies



One of the most complex tasks during the clinical development of a new drug is to find a correct dose. Optimal experimental design has as a goal to find the best ways to perform an experiment considering the available resources and the statistical model. Optimal designs have already been used to determine the design of dose-finding studies.  In this thesis, optimal designs are considered for the simultaneous response of efficacy and safety in a bivariate model, for the drug combination trials, and for general regression problems, including but not limited to dose-finding analysis.

The thesis consists of four papers:  In Paper I, the dose that maximizes the clinical utility index based on an efficacy-safety Emax model gives us the desirable balance between effects and side effects. In order to make use of a symmetry property, we use a log-transformed dose scale. The geometric characterization of the multivariate Elfving method is used to derive c-optimal points and weights for arbitrary c-vectors.  The second paper is an extension of the first one.  We still use the log-transformed dose scale bivariate model and consider now also the placebo effect and side-effect.  Fedorov’s exchange algorithm is applied in order to derive locally D-optimal designs numerically.