PROJECT SUMMARY (See instructions): The purpose of the Biostatistics Core is to support the dinical and laboratory-based projects of this program project so that research studies are efficiently designed, conducted, monitored, and analyzed. To ensure that scientifically valid conclusions can be drawn from these experiments, this includes statistical modeling, hypothesis formalization, design of laboratory experiments, clinical trial design, and data analysis. These activities in tum may require development of innovative statistical methods as needed to address new statistical problems as they arise, and accompanying development of appropriate new computer programs to implement these methods. All of these activities are carried out in collaboration with the laboratory and clinical investigators. The specific objectives are: Aim 1 To provide biostatistical consultation and collaboration in the planning, conduct, analysis and reporting of clinical trials in CML, including phase I trials to determine safe dose combinations, phase II trials to assess therapeutic efficacy, randomized trials to compare competing treatments, and hybrid trials having multiple goals. Trials involving biologic agents or specific types of lymphocytes or stem cells are especially relevant. These statistical designs accommodate multiple patient outcomes, including toxicity, regimen-related death, complete remission (CR), graft-versus-host disease (GVHD) in allogeneic transplantation (allotx) trials, and times to disease remission, progression, onset of CML accelerated phase, blast crisis, and death. Many of the designs accommodate patient heterogeneity by stratification or regression models.that account for patient prognostic characteristics, to help develop individualized treatments when treat-prognosis interactions exist. Aim 2. To consult and collaborate with researchers evaluating the cellular and molecular basis of response. Aim 3.T0 develop novel statistical methods for clinical trial design and data analysis as required to address special goals and needs of the projects. Aim 4. To evaluate prognostic significance of innovative treatments and possible synergistic effects with specific biological and molecular markers. This includes regression, data analysis, and hypothesis formulation.

The statistical methods applied in this program project will ensure that the laboratory experiments and clinical trials are designed reliably and efficiently in order to conserve resources and ensure that valid inferences may be drawn from the resulting data. This also will ensure that the clinical trials meet high ethical standards. In tum, this will enhance the likelihood of achieving the ultimate goal of this research, which is to improve the diagnosis and treatment of CML