Assessing the Cumulative Exposure Response in Alzheimer’s Disease Studies

To assess long-term cumulative benefit of a treatment, relationship betwe en cumulative drug exposure and outcomes could be explored to understand the dose response. However, cumulative exposure corresponds to the longitudinal profile of an outcome, which is often heavily confounded with natural disease progression and missing data. A model-based approach is developed to account for the confounding factors. In particular, the observed measures are adjusted by the projected disease progression at the corresponding time points before exposure response is assessed. The proposed approach introduces new insights to the interpretation of exposure data. In the presented case study, the proposed method identified various degrees of potential efficacy trend favoring higher level of cumulative exposure in active drug.