Incorporation of healthy volunteers data on receptor occupancy into a phase II proof-of-concept trial using a Bayesian dynamic borrowing design.

Receptor occupancy in targeted tissues measures the proportion of receptors occupied by a drug at equilibrium and is sometimes used as a surrogate of drug efficacy to inform dose selection in clinical trials. We propose to incorporate data on receptor occupancy from a phase I study in healthy volunteers into a phase II proof-of-concept study in patients, with the objective of using all the available evidence to make informed decisions. A minimal physiologically based pharmacokinetic modeling is used to model receptor occupancy in healthy volunteers and to predict it in the patients of a phase II proof-of-concept study, taking into account the variability of the population parameters and the specific differences arising from the pathological condition compared to healthy volunteers.

A comparison of estimation methods adjusting for selection bias in adaptive enrichment designs with time-to-event endpoints.

Adaptive enrichment designs in clinical trials have been developed to enhance drug developments. They permit, at interim analyses during the trial, to select the sub-populations that benefits the most from the treatment. Because of this selection, the naive maximum likelihood estimation of the treatment effect, commonly used in classical randomized controlled trials, is biased.