Colon Cancer Risk Modification by PPI and HRI Therapy

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DESCRIPTION (provided by applicant): The candidate is a junior faculty member in Gastroenterology and a faculty-fellow in Clinical Epidemiology at the Center for Clinical Epidemiology and Biostatistic (CCEB) of the University of Pennsylvania. He is applying for this Mentored Clinical Scientist Development Award under the sponsorship of Dr. Brian L. Strom, an authority on clinical pharmacoepidemiology and a pioneer in the use of computerized medical data in biomedical research. The candidate's principal career goal is to become an independent clinical investigator in the field of gastroenterology, with a primary focus on acid peptic disease, gastrointestinal malignancies and pharmacoepidemiology. The candidate is also interested in utilizing large computerized data sources to answer patient focused research questions. During the proposed training period, the candidate will use the proven "90% research / 10% clinical" career model, which will provide a source of clinical research questions as well as the infrastructure to conduct patient-oriented research. He will complete advanced courses in epidemiology and biostatistics. He will also conduct a case-control study nested within a large computerized medical research database. In the last phase of the award, the candidate will develop additional research ideas, perform pilot studies, and apply for federal research (e.g., R01) funding. The proposed nested case-control study will investigate whether long-term (> 5 years) proton pump inhibitor (PPI) therapy increases the risk of colorectal cancer, and whether long-term (> 5 years) HMG-CoA reductase inhibitor (HRI) therapy reduces the risk of colorectal cancer. Data for the study will come from the General Practice Research Database (GPRD), a large population-representative computerized system of medical records from the United Kingdom. The cases will consist of all colorectal cancer patients in the GPRD who have > 5 years of follow-up in the GPRD prior to their initial colorectal cancer diagnoses. The controls will be selected through incidence density sampling from all patients with > 5 years of follow-up in the GPRD. The primary exposure of interest is > 5 years of PPI or HRI exposure. The candidate will, with the assistance of the Biostatistical Analysis Center at the CCEB, extract and survey the raw data and create analytical datasets. The candidate will perform the analysis of the data using conditional logistic regression. This award will enable the candidate to complete the development of the skills and experience necessary to evolve into an independent academic investigator.