46: Robust semi-parametric dose-response model for early phase trials

Music City Center 

Dose-response modeling (DRM) is essential in early-stage clinical trials, where the interest is in estimating the relationship between the dose of a drug and its response. Clinically meaningful parametric forms are routinely proposed to model effects of response as a function of dose. However, if such models are mis-specified, the resulting inferences may be unreliable. To mitigate misspecification, a non-parametric DRM approach may be used. While it provides reliable inference, it may reduce inferential efficiency, even when a simpler parametric model is largely correct. To that end, as a compromise between fully parametric and fully non-parametric approaches, we propose a novel non-parametric Bayesian DRM, formulated around a pre-specified parametric DRM. This strategy will produce a dose-response curve that closely resembles the pre-specified parametric form in most regions, while allowing for deviations where necessary. We perform simulations to assess the performance of this approach including the robustness to model misspecifications, and compare with other approaches such as a fully parametric or a fully non-parametric models, model-averaging etc.

Dose response modeling

Semi parametric inference

Robustness

Interpretability 

Biopharmaceutical Section