Research

The Biostatistics Shared Resource program contributes to a range of research conducted at UC Irvine's Chao Family Comprehensive Cancer Clinic (CFCCC). Some collaborations require the application of standard statistical methods when addressing the scientific goals of interest.

Others require the development and application of novel statistical methods for a proper data analysis and, ultimately, a valid scientific inference.

Two research highlights are given below. Our first illustrates the fruits of a close scientific collaboration between Dr. Dan Gillen and former CFCCC member Dr. Susan Neuhausen in the development of novel methods of survival analysis in the presence of unknown genetic haplotypes. The second describes methods and software as used by BSR faculty for the efficient design and analysis of sequential clinical trials.

Scientific Collaboration

Dr. Gillen recently collaborated with Dr. Susan Neuhausen on the analysis of genetic modifiers of the risk of breast cancer among BRCA1 and BRCA2 carriers. This research involved the analysis of censored survival data stemming from a complex sampling design as well as the imputation of unknown genetic haplotypes.

As no existing methodology or software for these data existed at the time, Dr. Gillen received a NCI R03 grant to develop new methodology as well as software for applying the proposed methods.

Figure 1 depicts a subset of results in a forthcoming publication by Drs. Neuhausen and Gillen (among others) illustrating the relationship between SNPs on the MMP7 gene and the relative risk of breast cancer diagnosis among BRCA1/2 carriers. In addition, Dr. Gillen presented this new methodology during a talk at the 2010 International Biometrics Conference held in Flioronopolis, Brazil.

Figure 1: Association between the MMP7 gene and the risk of breast cancer diagnosis among BRCA1 carriers.

Statistical Methodology

Group sequential methods provide more efficient and hence more ethical design options for later stage clinical trials by allowing for interim testing of accruing trial data. Such methods allow for early stopping when confidence in a decision is reached while controlling statistical operating characteristics such as type I and II error rates. Dr. Gillen is a collaborator in the development of RCTDesign, a software package for the R statistical programming language. RCTDesign is a comprehensive package for the design, monitoring, and reporting of group sequential clinical trials.

Figure 2 displays example plots that are produced by this research endeavor. Specifically, these are the 95% confidence intervals that would be observed at each stopping time for a symmetric 5%-level O’Brien-Fleming group sequential boundary. This software is freely available and used by BSR faculty.

Figure 2: Output produced by RCTDesign. Inference (corrected point estimates and 95% confidence intervals) that corresponds to stopping at each interim analysis time.

Selected BSR Publications

Examples of other notable research highlights from BSR faculty include:

Acton RT, Barton JC, Leiendecker-Foster C, Zaun C, McLaren CE, Eckfeldt JH. Tumor necrosis factor-alpha promoter variants and iron phenotypes in 785 hemochromatosis and iron overload screening (HEIRS) study participants. Blood Cells Mol Dis 2010;44(4):252-6.
Brown SM, Culver JO, Osann KE, Macdonald DJ, Sand S, Thornton AA, Grant M, Bowen DJ, Metcalfe KA, Burke HB, Robson ME, Friedman S, Weitzel JN. Health literacy, numeracy, and interpretation of graphical breast cancer risk estimates. Patient Educ Couns 2010;[Epub ahead of print].
Garner C. A statistical method for scanning the genome for regions with rare disease alleles. Genet Epidemiol 2010;34(5):386-95.
Thompson PA, Wertheim BC, Zell JA, Chen W-P, McLaren CE, LaFleur BJ, Meyskens FL, Gerner EW. Levels of Rectal Mucosal Polyamines and Prostaglandin E2 Predict Ability of DFMO and Sulindac to Prevent Colorectal Adenoma. Gastroenterology 2010;139(3):797-805.e1.
Kamell J, Rietkerk W, Lam K, Phillips J, Wu J, McCullough J, Linden K, Osann K. Medical Students Educate Teens About Skin Cancer: What Have We Learned? J Cancer Educ 2010:1-3.

Seminar and Lecture Notes

3D-Tissue Microsystems for Tumor Microenvironments: Designs for Basic and Translational Research, Michael Phelan, November 28, 2012. Slides