Positions
Professor , Dept. of Medicine
Director of Biostatistics ,Chao Family Comprehensive Cancer Center
Degrees
Ph.D., Case Western Reserve University
Distinctions
Fellow, American Statistical Association;
Fellow, Royal Statistical Society/Institute of Statistics;
Member, NSF Division of Mathematical Sciences, Statistics and Probability Panel;
Phi Kappa Phi Honor Society
Research Summary
Overview of Research Interests
Statistical models provide insight into the structure of data. Models of biological processes can assist with distinguishing between health and disease. Dr. McLaren's statistical modeling research has concentrated on mixture distribution analysis, goodness-of-fit testing, and hierarchical regression modeling of longitudinal data. Medical applications including disease prevalence and estimation of iron overload and hemochromatosis, analysis of distributions of red blood cell volume and hemoglobin concentration in iron deficiency anemia, detection of cisplatin-induced anemia in patients undergoing cancer chemotherapy, and screening for hepatocelluar carcinoma. As a result of her experience with statistical modeling and collaborative medical research, in January of 2000, Dr. McLaren received a $4 million 5-year contract awarded by NIH/NHLBI, Screening for Iron Overload and Hereditary Hemochromatosis Field Center.
Current and Recent Research Projects
IRON OVERLOAD AND HEMOCHROMATOSIS
Prevalence Estimation:
There is now incontrovertible evidence that early diagnosis and therapy of hereditary hemochromatosis prevents virtually all manifestations of the disease and results in normal life expectancy. In contrast, unrecognized and untreated disease leads to cirrhosis, hepatocellular carcinoma and other lethal complications. We analyzed the distribution of transferrin saturation values in the second National Health and Nutrition Examination Survey to estimate the prevalence of hemochromatosis homozygotes and heterozygotes in the United States population. The gene frequencies for hemochromatosis were estimated to be 0.081 for males and 0.070 for females corresponding to prevalences of homozygotes of 6.6 and 4.8 per thousand. Our results confirm that the gene for hemochromatosis is common in the white population of the United States.
Disease Screening:
Cost-effectiveness analyses indicate that the cost of screening and treatment for hemochromatosis is far less than the medical cost of treating chronic disabilities resulting from the secondary disease conditions such as cirrhosis and diabetes due to iron overload. In population screening, the number and proportion of individuals identified as having hemochromatosis will depend, in part, upon the specific initial screening criteria applied. Our research efforts have concentrated on identifying appropriate screening values for transferrin saturation to identify hemochromatosis heterozygotes and homozytoges.
MIXTURE DISTRIBUTION ANALYSIS
Maximum likelihood estimation of finite mixture models using the EM algorithm: Another primary research interest has been in finite mixture distributions and their applications in medicine. After examining the theoretical basis for the statistical evaluation of red blood cell volume distributions we developed a mathematical model of the distribution of the volumes of circulating red cells and verified predictions in healthy individuals and patients with anemia. Analysis of the empirical data required development of a method for log normal parameter estimation appropriate to grouped truncated distributions. We then developed statistical methods for detection of mixtures of two log normal distri-butions in doubly-truncated data when the sample size is large. Alterations in erythrocyte subpopulations were quantified in untransfused patients with refractory anemia, sideroblastic anemia, and patients treated for iron deficiency anemia.
Hierarchical models for screening of iron deficiency anemia: In this joint work with Dr. Padhraic Smyth, UCI Department of Information and Computer Science, we developed a model of the bivariate distribution of hemoglobin concentration and red blood cell volume. A new mixture fitting algorithm was devised to analyze data measured using an automated blood cell analyzer. A two-level classification technique of model parameters achieved accurate discrimination between healthy individuals and patients with disorders of anemia.
SEQUENTIAL ANALYSIS OF LABORATORY DATA
Patient-specific Sequential Analysis of Laboratory Data: For this area of concentration, our research group developed statistical methods to sequentially analyze laboratory test results and identify departures from past values. These methods include hierarchical multiple regression modeling, with a weighted minimum risk criteria for model selection, to choose models indicating changes in mean values over time. Clinical applications have included detection of developing iron deficiency anemia, identification of anemia due to cisplatin-based chemotherapy, regulation of T cells numbers in Gaucher disease, and screening for hepatocelluar carcinoma. These methods promise to provide more sensitive techniques for improved diagnostic evaluation of diseases and serial monitoring of response to therapy.
Publications - McLaren CE, Barton JC, Adams PC, et al. Hemochromatosis and iron overload screening (HERIS) study design for an evaluation of 100,000 primary care-based adults. Am J Med Sci 2003;325:53-62.
- McLaren CE, Li K-T, Gordeuk VR, Hasseblad V, McLaren GD. Relationship between transferrin saturation and iron stores in the African American and US Caucasian populations: analysis of the third National Health and Nutrition Examination Survey data. Blood 2001;98:2345-2351.
- McLaren CE, Kambour EL, McLachlan GJ, Lukaski HC, Li X, Brittenham GM,McLaren GD. Patient-specific analysis of sequential haematological data by multiple linear regression and mixture distribution modelling. Statistics in Medicine 19:83-98,2000.
- Olivieri NF, Brittenham GM, McLaren CE, Templeton DM, Cameron RG, McClelland RA, Burt AD, Fleming KA. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. New England Journal of Medicine 339:417-23, 1999.
- McLaren CE, McLachlan GJ, Halliday JW, Webb SI, Leggett BA, Jazwinska EC, Crawford DH, Gordeuk VR, McLaren GD, Powell LW. Distribution of transferrin saturation in an Australian population: relevance to the early diagnosis of hemochromatosis. Gastroenterology 114:543-9, 1998.
- McLaren CE. Mixture models in haematology: a series of case studies. Statistical Methods in Medical Research 5:129-53, 1996.
- McLaren CE, Gordeuk VR, Looker AC, Hasselblad V, Edwards CQ, Griffen LM, Kushner JP, Brittenham GM. Prevalence of heterozygotes for hemochromatosis in the white population of the United States. Blood 86:2021-7, 1995.
Professional Society
American Statistical Association
International Biometrics Society |
