Bayesian doubly optimal group sequential designs for randomized clinical trials

When conducting a randomized comparative clinical trial, ethical, scientific or economic considerations often motivate the use of interim decision rules after successive groups of patients have been treated. These decisions may pertain to the comparative efficacy or safety of the treatments under study, cost considerations, the desire to accelerate the drug evaluation process, or the likelihood of therapeutic benefit for future patients. At the time of each interim decision, an important question is whether patient enrollment should continue or be terminated; either due to a high probability that one treatment is superior to the other, or a low probability that the experimental treatment will ultimately prove to be superior. The use of frequentist group sequential decision rules has become routine in the conduct of phase III clinical trials. In this dissertation, we will present a new Bayesian decision-theoretic approach to the problem of designing a randomized group sequential clinical trial, focusing on two-arm trials with time-to-failure outcomes. Forward simulation is used to obtain optimal decision boundaries for each of a set of possible models. At each interim analysis, we use Bayesian model selection to adaptively choose the model having the largest posterior probability of being correct, and we then make the interim decision based on the boundaries that are optimal under the chosen model. We provide a simulation study to compare this method, which we call Bayesian Doubly Optimal Group Sequential (BDOGS), to corresponding frequentist designs using either O'Brien-Fleming (OF) or Pocock boundaries, as obtained from EaSt 2000. Our simulation results show that, over a wide variety of different cases, BDOGS either performs at least as well as both OF and Pocock, or on average provides a much smaller trial. ^

The prevalence of periodontal disease in Mexican American vs European American elderly in three distinct socio-economic communities in San Antonio, Texas

Purpose of the Study: This study evaluated the prevalence of periodontal disease between Mexican American elderly and European American elderly residing in three socio-economically distinct neighborhoods in San Antonio, Texas. ^ Study Group: Subjects for the original protocol were participants of the Oral Health: San Antonio Longitudinal Study of Aging (OH: SALSA), which began with National Institutes of Health (NIH) funding in 1993 (M.J. Saunders, PI). The cohort in the study was the individuals who had been enrolled in Phases I and III of the San Antonio Heart Study (SAHS). This SAHS/SALSA sample is a community-based probability sample of Mexican American and European American residents from three socio-economically distinct San Antonio neighborhoods: low-income barrio, middle-income transitional, and upper-income suburban. The OH: SALSA cohort was established between July 1993 and May 1998 by sampling two subsets of the San Antonio Heart Study (SAHS) cohort. These subsets included the San Antonio Longitudinal Study of Aging (SALSA) cohort, comprised of the oldest members of the SAHS (age 65+ yrs. old), and a younger set of controls (age 35-64 yrs. old) sampled from the remainder of the SAHS cohort. ^ Methods: The study used simple descriptive statistics to describe the sociodemographic characteristics and periodontal disease indicators of the OH: SALSA participants. Means and standard deviations were used to summarize continuous measures. Proportions were used to summarize categorical measures. Simple m x n chi square statistics was used to compare ethnic differences. A multivariable ordered logit regression was used to estimate the prevalence of periodontal disease and test ethnic group and neighborhood differences in the prevalence of periodontal disease. A multivariable model adjustment for socio-economic status (income and education), gender, and age (treated as confounders) was applied. ^ Summary: In the unadjusted and adjusted model, Mexican American elderly demonstrated the greatest prevalence for periodontitis, p < 0.05. Mexican American elderly in barrio neighborhoods demonstrated the greatest prevalence for severe periodontitis, with unadjusted prevalence rates of 31.7%, 22.3%, and 22.4% for Mexican American elderly barrio, transitional, and suburban neighborhoods, respectively. Also, Mexican American elderly had adjusted prevalence rates of 29.4%, 23.7%, and 20.4% for barrio, transitional, and suburban neighborhoods, respectively. ^ Conclusion: This study indicates that the prevalence of periodontal disease is an important oral health issue among the Mexican American elderly. The results suggest that the socioeconomic status of the residential neighborhood increased the risk for severe periodontal disease among the Mexican American elderly when compared to European American elderly. A viable approach to recognizing oral health disparities in our growing population of Mexican American elderly is imperative for the provision of special care programs that will help increase the quality of care in this minority population.^