Dose titration becomes more and more common in improving drug tolerability as well as determining individualized treatment doses, thereby maximizing the benefit to patients. Dose titration starting from a lower dose and gradually increasing to a higher dose enables improved tolerability in patients as the human body may gradually adapt to adverse gastrointestinal effects. Current statistical analyses mostly focus on the outcome at the end-of-study follow-up without considering the longitudinal impact of dose titration on the outcome. Better understanding of the dynamic effect of dose titration over time is important in early-phase clinical development as it could allow to model the longitudinal trend and predict the longer term outcome more accurately. We propose a parametric model with two empirical methods of modeling the error terms for a continuous outcome with dose titrations. Simulations show that both approaches of modeling the error terms work well. We applied this method to analyze data from a few clinical studies and achieved satisfactory results.
Keywords: Dose response; integrated two-component prediction model; nonlinear mixed model.