Doctoral candidate in Biostatistics, Jennifer Proper, will present:
“Innovations in Early Phase Drug Development Aimed at Reducing Exposure to Ineffective Treatments”
PhD Adviser: Tom Murray
Abstract: This dissertation focuses on innovations in early phase drug development aimed at reducing exposure to ineffective treatments. The first half of this presentation concerns response-adaptive randomization (RAR), which alters the allocation ratio based on accruing data in favor of the empirically superior treatment. In contrast to fixed 1:1 allocation, RAR gives participants a greater chance of receiving the superior treatment during the trial but is commonly criticized for reducing power and engendering nontrivial probabilities of allocating more participants to the inferior arm. To address these issues, we develop a novel probability model and randomization strategy for implementing Bayesian RAR in a binary outcome setting. We also introduce a patient benefit metric for comparing group sequential designs that improves on existing metrics by holding error rates constant across designs and measuring the expected number of failures in the fixed group of individuals who are directly impacted by the design choice.
The second half of this presentation concerns drug repurposing, which is the process of discovering new therapeutic uses for existing treatments. Compared to traditional drug discovery, drug repurposing is attractive for its speed, cost, and reduced risk of failure. However, existing approaches for drug repurposing involve complex, computationally-intensive analytical methods that are not widely used in practice. Instead, repurposing decisions are often based on subjective judgements from limited empirical evidence. In this talk, we develop a novel Bayesian network meta-analysis (NMA) framework that can predict the efficacy of an approved treatment in a new indication. We evaluate the predictive performance of the proposed methods using a simulation study and conclude by discussing an illustrative example in psoriasis and psoriatic arthritis.
