This application proposes renewal of a novel, integrated program for predoctoral training in biostatistics focused on preparing trainees for careers in cardiovascular disease research.  The critical shortage of skilled biostatisticians equipped to address ongoing and emerging challenges in this exciting era of cardiovascular disease research calls for training that formally integrates deep and sustained experience in collaboration in a multidisciplinary environment, mastery of the theoretical underpinnings of statistics required for valid application of sophisticated biostatistical techniques and for research on development of new methodology, and strong emphasis on communication and leadership skills.  The program will be a joint effort of the Department of Statistics at North Carolina State University (NCSU) and the Duke Clinical Research Institute (DCRI), capitalizing on an existing partnership between one of the largest graduate programs in statistics in the world and a research institution that is the largest of its kind and home to internationally-known researchers at the forefront of cardiovascular disease research.  The five-year program will support five (5) trainees slots in each year and will involve rigorous study at NCSU of statistical theory, including probability, inference, linear and other statistical models, measure theory and advanced probability, and advanced statistical inference, and statistical methods, including clinical trials design/analysis, longitudinal data analysis, survival analysis, and cutting-edge special topics;training in fundamental aspects of biology and cardiovascular medicine;course work in research responsibility and ethics;and extensive formal and experiential training in communication and leadership skills.  Trainees will be introduced to DCRI cardiovascular disease research gradually, evolving to a full collaborative apprenticeship in which they are integrated as functioning members of DCRI project teams.  Through both this apprenticeship and formal courses and seminars, trainees will develop extensive working knowledge and expertise in cardiovascular medicine that will position them to make immediate contributions to cardiovascular disease research upon completion of the program.  Trainees will be assigned an inter- institutional mentorship team consisting of primary and secondary biostatistician mentors at each site and a secondary clinician mentor at DCRI, who will collaborate in guiding them through all aspects.  Dissertation research will involve development and evaluation of novel statistical methodology inspired by challenges encountered in trainees'cardiovascular disease research collaborations.