Chemotherapy is a method used to treat cancer but it has a number of side-effects. Research conducted by the Department of Chemical Engineering at BYU involves a new method of administering chemotherapy using ultrasound waves and water-soluble capsules. The goal is to reduce the side-effects by localizing the delivery of the medication. As part of this research, a two-factor experiment was conducted on rats to test if the water-soluble capsules and ultrasound waves by themselves have an effect on tumor growth or patient survival. Our project emphasizes the usage of Bayesian Hierarchical Models and Win-BUGS to jointly model the survival data and the longitudinal data—mass. The results of the joint analysis indicate that the use of ultrasound and water-soluble microcapsules have no negative effect on survival. In fact, there appears to be a positive effect on the survival since the rats in the ultrasound-capsule group had higher survival rates than the rats in other treatment groups. From these results, it does appear that the new technology involving ultrasound waves and microcapsules is a promising way to reduce the side-effects of chemotherapy. It is strongly advocated that the formulation of a joint model for any longitudinal and survival data be performed. For future work for the ultrasound-microcapsule data it is recommended that joint modeling of the mass, tumor volume, and survival data be conducted to obtain additional information.

Joint modeling of longitudinal and survival data has received much attention and is becoming increasingly useful. In clinical studies, longitudinal biomarkers are used to monitor disease progression and to predict survival. These longitudinal measures are often missing at failure times and may be prone to measurement errors. In previous studies these two types of data are frequently analyzed separately where a mixed effects model is used for longitudinal data and a survival model is applied to event outcomes. The argument in favor of a joint model has been the efficient use of the data as the survival information goes into modeling the longitudinal process and vice versa. In this thesis, we present joint maximum likelihood methods, a two stage approach and time dependent covariate methods that link longitudinal data to survival data. First, we use simulation studies to explore and assess the performance of these methods with bias, accuracy and coverage probabilities. Then, we focus on four time dependent methods considering models that are unadjusted and adjusted for time. Finally, we consider mediation analysis for longitudinal and survival data. Mediation analysis is introduced and applied in a research framework based on genetic variants, longitudinal measures and disease risk. We implement accelerated failure time regression using the joint maximum likelihood approach (AFT-joint) and an accelerated failure time regression model using the observed longitudinal measures as time dependent covariates (AFT-observed) to assess the mediated effect. We found that the two stage approach (TSA) performed best at estimating the link parameter. The joint maximum likelihood methods that used the predicted values of the longitudinal measures, similar to the TSA, provided larger estimates. The time dependent covariate methods that used the observed longitudinal measures in the survival analysis underestimated the true estimates. The mediation results showed that the AFT-joint and the AFT-observed underestimated the mediated effect. Comparison of the methods in Framingham Heart Study data revealed similar patterns. We recommend adjusting for time when estimating the association parameter in time dependent Cox and logistic models. Additional work is needed for estimating the mediated effect with longitudinal and survival data.