Defense Date

2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biostatistics

First Advisor

Nitai Mukhopadhyay

Second Advisor

Roy Sabo

Third Advisor

Donna McClish

Fourth Advisor

Amy Pakyz

Fifth Advisor

Shuxian Sinks

Abstract

In recent years, adaptive designs in clinical trials have been attractive due to their efficiency and flexibility. Response adaptive randomization procedures in phase II or III clinical trials are proposed to appeal ethical concerns by skewing the probability of patient assignments based on the responses obtained thus far, so that more patients will be assigned to a superior treatment group. General response-adaptive randomizations usually assume that the primary endpoint can be obtained quickly after the treatment. However, in real clinical trials, the primary outcome is delayed, making it unusable for adaptation. Therefore, we utilize surrogate and primary endpoints simultaneously to adaptively assign subjects between treatment groups for clinical trials with continuous responses. We explore two types of primary endpoints commonly used in clinical tirials: normally distributed outcome and time-to-event outcome. We establish a connection between the surrogate and primary endpoints through a Bayesian model, and then update the allocation ratio based on the accumulated data. Through simulation studies, we find that our proposed response adaptive randomization is more effective in assigning patients to better treatments as compared with equal allocation randomization and standard response adaptive randomization which is solely based on the primary endpoint.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-30-2016

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