Author ORCID Identifier

Defense Date


Document Type


Degree Name

Doctor of Philosophy



First Advisor

Adam P. Sima


Dropout is a common issue in randomized controlled clinical trials and can negatively impact the internal validity of a study and potentially bias the treatment effect. When subjects discontinue study participation, they are not being given the opportunity to gain from the investigational therapy as if they had remained in the study, defeating one of the main purposes of clinical trials, providing treatment. Specifically in unblinded studies, such as the wait-list control (WLC) design, dropout is often due to group membership. Subjects allocated to the control group often dropout at higher rates than in the treatment group. Adaptive designs have the flexibility to account for this differential dropout in clinical trials. The proposed methods build upon existing adaptive methods in randomized controlled trials by adjusting them for dropout. We propose a dropout adjusted response adaptive (DARA) allocation ratio that incorporates group specific dropout rates into the randomization ratio to skew allocation away from groups with high dropout rates in both the two arm and WLC clinical trial. Utilization of the DARA method results in more subjects receiving the better performing treatment, improved total expected response, and a larger effective sample size in the study compared to the existing randomization methods. Additional methodology was developed that adjusts current adaptive methods for assigning wait times to control subjects in the WLC design for dropout occurring in the treatment group, resulting in more comparable group distributions and stronger internal validity. This research fills the void in the literature regarding accounting for dropout in adaptive designs and leads to more ethical and statistically sound clinical trials.


© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission


Available for download on Sunday, May 11, 2025

Included in

Biostatistics Commons