John J. Crowley - US grants

This proposal describes how the Southwest Oncology Group Statistical Center would be organized and operated to provide data management and evaluation, statistical analysis, and input on design of protocols for clinical trials in cancer. It is proposed to locate the Statistical Center at the Fred Hutchinson Cancer Research Center in Seattle, Washington, under the direction of Dr. John Crowley, with Dr. Brent Blumenstein as Deputy Director. The application concentrates on the role of the Statistical Center in developing and monitoring protocols, including eligibility criteria, registration and randomization procedures, endpoint and sample size determination, trial monitoring, and analysis strategies. Data management and database management strategies are described in detail. Transition plans and plans for the future are also discussed.

DESCRIPTION (provided by applicant): The Southwest Oncology Group is a major multi-disease, multi-disciplinary, multi-institution group engaged in cooperative cancer research. This organization now consists of 35 Member Institutions, 29 Community Clinical Oncology Programs (CCOPs), 230 Affiliates, and 26 Urologic Cancer Outreach Programs (UCOPs), who together accrue 5,000 patients to clinical trials each year. Currently there are 96 studies open for accrual in 14 committees. The Statistical Center is essential to the design, conduct, and analysis of the cancer research in the Southwest Oncology Group. Its main functions are: (1) to participate in the review of proposed protocols, particularly as regards experimental design, sample size, and feasibility; (2) to provide for registration of all patients on all studies, and for randomization where appropriate; (3) to develop Web and software technology for paperless submission of data; (4) to provide for review and quality control of data collected during studies; (5) to provide for data entry and for computer processing and storage and retrieval of data; (6) to work with the Group chair and other investigators in the Group to improve the quality of clinical trials through improved forms, more uniform and reproducible data definitions, and more economical flow of data; (7) to assist the Group chair in the administration of the Group; (8) to analyze and publish the results of studies in conjunction with the study coordinators; (9) to use the data collected to try to find new leads regarding prognostic factors and late effects; (10) to perform statistical research on the efficient design, conduct, and analysis of cancer clinical trials and cancer control research; and (11) to educate investigators, nurse oncologists and CRAs in statistical analysis, research design and the utilization of the most advanced scientific and data management strategies.

The Southwest Oncology Group is a major multi-disease, multi- disciplinary, multi-institution group engaged in cooperative cancer research. This organization now consists of 34 Member Institutions, 26 Community Clinical Oncology Programs (CCOPs), 291 Cooperative Group outreach Programs (CGOPs), 23 Urologic Cancer Outreach Programs (UCOPs) and 26 High Priority affiliates, who accrue approximately 8700 patients to clinical trials each year. Currently there are approximately 100 studies open for accrual in 14 committees. The Statistical Center is essential to the design, conduct, and analysis of the cancer research in the Southwest oncology Group. Its main functions are: to participate in the review of proposed protocols, particularly as regards experimental design, sample size, and feasibility; to provide for central registration of all patients on all studies, and for randomization where appropriate; to provide for review and quality control of data collected during studies; to provide for data entry and for computer processing, storage and retrieval of data; to work with the Group chair and other investigators in the Group to improve the quality of clinical trials through improved forms, more uniform and reproducible data definitions, and more economical flow of data; to help the Group chair in the administration of the Group; to analyze and publish the results of studies in conjunction with the study coordinator; to use the data being collected to try to find new leads regarding prognostic factors and late effects; and to perform statistical research on the efficient design, conduct and analysis of cancer clinical trials and cancer control research.

The overall goal of this project continues to be the development and investigation of methods for the efficient design and analysis of clinical studies. A major specific aim will be on the development of methods appropriate for phase III cancer clinical trials, especially multi-arm phase III trials. We will continue to work on statistics appropriate for ordered alternatives, and will develop designs appropriate for situations when the alternatives can be assumed to have such an order restriction. Practical approaches for factorial designs, making explicit allowance for the possibility of interactions, will be developed. We will also continue our work in exploratory methods for survival analysis, emphasizing smoothed regression functions and extensions of the regression tree methodology. We will also continue to work on methods for use with multistate and multivariate survival data, starting with multistate situations which can be summarized by the probability of being in a given state over time (possibly conditional on being alive), and with bivariate survival data subject to univariate censoring. Extensions will be explored as the project proceeds. Other topics that arise in our work on clinical studies will also be explored. Group sequential ideas will be extended to the problem of developing a batted of prognostic factors over time, and small sample distributions for the logrank test will be investigated. Taken as a whole, the project will contribute to improvements in cancer mortality through better methods for design, conduct and analysis of clinical studies.