BAYESIAN PHASE I DOSE FINDING IN CANCER TRIALS

This dissertation explores phase I dose-finding designs in cancer trials from three perspectives: the alternative Bayesian dose-escalation rules, a design based on a time-to-dose-limiting toxicity (DLT) model, and a design based on a discrete-time multi-state (DTMS) model. We list alternative Bayesian dose-escalation rules and perform a simulation study for the intra-rule and inter-rule comparisons based on two statistical models to identify the most appropriate rule under certain scenarios. We provide evidence that all the Bayesian rules outperform the traditional ``3+3'' design in the allocation of patients and selection of the maximum tolerated dose. The design based on a time-to-DLT model uses patients' DLT information over multiple treatment cycles in estimating the probability of DLT at the end of treatment cycle 1. Dose-escalation decisions are made whenever a cycle-1 DLT occurs, or two months after the previous check point. Compared to the design based on a logistic regression model, the new design shows more safety benefits for trials in which more late-onset toxicities are expected. As a trade-off, the new design requires more patients on average. The design based on a discrete-time multi-state (DTMS) model has three important attributes: (1) Toxicities are categorized over a distribution of severity levels, (2) Early toxicity may inform dose escalation, and (3) No suspension is required between accrual cohorts. The proposed model accounts for the difference in the importance of the toxicity severity levels and for transitions between toxicity levels. We compare the operating characteristics of the proposed design with those from a similar design based on a fully-evaluated model that directly models the maximum observed toxicity level within the patients' entire assessment window. We describe settings in which, under comparable power, the proposed design shortens the trial. The proposed design offers more benefit compared to the alternative design as patient accrual becomes slower.

Homeless mortality in Harris County in 2008

Little research has been on homeless mortality, but what has been done indicates that homeless people have higher mortality rates than the general population. Homeless decedents in Harris County in 2008 who were referred to the Harris County Medical Examiner's Office (HCMEO) were described by age, race/ethnicity, sex, and marital status and compared to the homeless population as enumerated by the Coalition of the Homeless (COH) in 2007. Of the 47 decedents, eight (17%) were female and 39 (83%) were male, 24 (51.1%) were non-Hispanic white, 11 (23.4%) were black, and 12 (25.5%) were Hispanic, none of the decedents were listed as married, however, a large number (29, 61.5%) were listed as “unknown,” and the average age of decedents was 50 years, six years older than the average of 44 years in the general homeless population. Most common causes of death were injuries, which included motor vehicle accidents, homicides and suicides and poisonings, (acute overdose and chronic substance use). Homeless decedents were representative to the larger Harris County homeless population. ^