Francisco J. Diaz, Ph.D.
Associate Professor, Department of Biostatistics & Data Science
B.S., Mathematics, National University of Colombia, Medellin, Colombia
M.S., Statistics, National University of Colombia, Medellin, Colombia
Ph.D., Statistics, University of Kentucky, Lexington, KY
1996, Meritorious M.S. Thesis Award, given by the School of Sciences of the Universidad Nacional de Colombia
1999, Graduate School Fellowship, Awarded by the Graduate School of the University of Kentucky
2000, Graduate School Fellowship, Awarded by the Graduate School of the University of Kentucky
2000-2001, Raymond W. Rishel Prize for Best Student in Applied Probability, Awarded by the Department of Statistics of the University of Kentucky
Mixed models and Longitudinal data analysis, Bayesian feedback in drug dosage individualization, Statistical methods in pharmacological and medical research, Clinical epidemiology, Clinical trials, Bioequivalence studies.
Personal Mission Statement
I am an experienced biostatistician who has participated in a substantial number of collaborative research projects concerning physiologic, medical and pharmacological issues, and also the author or co-author of a substantial number of articles published in prestigious medical, pharmacological and methodological journals. Thus, my extensive methodological expertise, and my experience in the application of statistical methods to a wide range of medical and pharmacological research guarantees an appropriate design, and an appropriate analysis of the data generated in medical, pharmacological and biomedical research. Also, I have many years of experience teaching undergraduate and graduate courses in statistics and biostatistics programs. A goal of my methodological research is to develop statistical models applicable to personalized medicine. In particular, I am currently developing methods based on statistical mixed models. I am also involved in the development of statistical models for the analysis of toxicological data obtained in high throughput screening studies.
Contributions to Science and Research Methodology
My methodological research has been published in highly regarded statistical journals including Statistics in Medicine, Journal of Biopharmaceutical Statistics, and Journal of Computational and Graphical Statistics, as well as in prestigious pharmacological journals including Clinical Pharmacokinetics, Therapeutic Drug Monitoring, Pharmacopsychiatry, and Combinatorial Chemistry & High Throughput Screening. In particular, I have developed applications of random effects linear models to drug dose individualization and personalized medicine. My research demonstrates that these models may provide more accurate predictions of blood drug levels than the models traditionally used in therapeutic drug monitoring. I believe that random effects statistical models will revolutionize the mathematical theory and practical applications of pharmacology and personalized medicine.
Examples of publications:
Diaz, F.J., Berg, M.J., Krebill, R., Welty, T., Gidal, B.E., Alloway, R., Privitera, M. (2013). Random-effects linear modeling and sample size tables for two special cross-over designs of average bioequivalence studies: the 4-period, 2-sequence, 2-formulation and 6-period, 3-sequence, 3-formulation designs. Clinical Pharmacokinetics, 52:1033-1043. PMID: 24085600.
Diaz, F.J., de Leon, J. (2013). The mathematics of drug dose individualization should be built with random effects linear models (Letter to the Editor). Therapeutic Drug Monitoring, Vol. 35: 276-277.
Diaz, F.J., Yeh, H-W., de Leon, J. (2012). Role of statistical random-effects linear models in personalized medicine. Current Pharmacogenomics and Personalized Medicine, 10, 22-32. PMCID: PMC3580802.
Diaz, F.J., Cogollo, M., Spina, E., Santoro, V., Rendon, D.M., de Leon, J. (2012). Drug Dosage Individualization Based on a Random-Effects Linear Model. Journal of Biopharmaceutical Statistics, 22, 463-484. PMID: 22416835.
Diaz, F.J., Rivera, T.E., Josiassen, R.C., de Leon, J. (2007). Individualizing drug dosage by using a random intercept linear model. Statistics in Medicine, 26, 2052-2073. PMID: 16847902.
Diaz, F. J. (1999). "Identifying Tail Behavior by Means of Residual Quantile Functions", Journal of Computational and Graphical Statistics, Vol. 8, Number 3, 493-509. A SAS program to compute Bundles.
As a result of my work in the High Throughput Screening (HTS) laboratory of the University of Kansas, I developed statistical methods for testing toxic and dose-response effects of chemical compounds using cell based assays. This work was motivated by the need of statistical methods for selecting effective compounds from big libraries of chemicals in order to support both drug repurposing and combinatorial chemistry research, and ultimately to expedite the finding of pharmacological cures. Part of this work (Diaz et al. 2013) was featured in the August, 2013 issue of Global Medical Discovery. These methods are published in:
Diaz, F.J., McDonald, P.R., Roy, A., Taylor, B., Price, A., Hall, J., Blagg, B.S.J., Chaguturu, R. (2013) Compound ranking based on a new mathematical measure of effectiveness using time course data from cell-based assays. Combinatorial Chemistry & High Throughput Screening, 16:168-179. PMCID: PMC3655799.
Hendricks, P., Diaz, F.J., Schmitt. S., Sittampalam, G.S., Nirmalanandhana, V.S. (2012) Effects of respiratory mechanical forces on the pharmacological response of lung cancer cells to chemotherapeutic agents. Fundamental & Clinical Pharmacology, 26: 632-643. PMID: 21718364.
Diaz, F.J., McDonald, P.R., Pinter, A., Chaguturu, R. (2015) Measuring and statistically testing the size of the effect of a chemical compound on a continuous in-vitro pharmacological response through a new statistical model of response detection limit. Journal of Biopharmaceutical Statistics, 25: 757-780. PMID: 24905187.
I have authored or co-authored a significant number of articles investigating the pharmacokinetics and side effects of psychotropic drugs. As a first author, my collaborative research has made substantial contributions to the literature on clozapine and valproic acid metabolism. Also, I conducted the statistical analyses of eight studies investigating different aspects of the metabolic syndrome in psychiatric patients, including studies of the effects of antipsychotics on lipid levels; all these studies have been successfully published in prestigious journals. My participation in pharmacological research has allowed me to develop collaborations with worldwide experts in psychopharmacology at the University of Messina, Italy, Lausanne University, Switzerland, and the University of Kentucky at Lexington. Some examples from this work are:
Diaz, F.J., Eap, C.B., Ansermot, N., Crettol, S., Spina, E., de Leon, J. (2014) Can valproic acid be an inducer of clozapine metabolism? Pharmacopsychiatry, 47, 89-96. PMID: 24764199.
Diaz, F.J., Perez-Iglesias, R. Mata, I. Martínez-Garcia, O. Vázquez-Barquero, J.L., de Leon, J., Crespo-Facorro, B. (2011). Using structural equations to test for a direct effect of some antipsychotics on triglyceride levels in drug-naïve first-episode psychosis patients. Schizophrenia Research, 131, 82-89. PMID: 21726981
Diaz, F.J., Santoro, V., Spina, E., Cogollo, M., Rivera, T.E., Botts, S., de Leon, J. (2008). Estimating the size of the effects of co-medications on plasma clozapine concentrations using a model that controls for clozapine doses and confounding variables. Pharmacopsychiatry, 41, 81-91. PMID: 18484549.
Diaz, F. J., de Leon, J. (2002). Excessive Antipsychotic Dosing in 2 U.S. State Hospitals. Journal of Clinical Psychiatry, 63, 998-1002. PMID: 12444813.
A significant part of my collaborative research career has been dedicated to the study of addictions, including legal and illegal substance abuse, and their relationship with the occurrence and symptoms of psychiatric illnesses. In particular, I have conducted the statistical analyses of more than 20 published studies investigating different aspects of smoking behavior and nicotine addiction in mentally ill patients and/or the general population, including the psychometric problems involved in measuring nicotine addiction. One of my most important articles in this area is a meta-analysis demonstrating that the association between schizophrenia and smoking is consistent all over the world (Schizophrenia Research 2005;76:135-157); this article has already been cited 378 times in the medical literature according to the Web of Science Core Collections. All this research demonstrates the need of understanding the socio-biological vulnerability of mentally ill people for developing addictions, and the need of developing anti-addiction therapies specific for this population.
Diaz, F.J., James, D., Botts, S., Maw, L., Susce, M.T., de Leon, J. (2009). Tobacco Smoking Behaviors in Bipolar Disorder: A Comparison of the General Population, Schizophrenia and Major Depression. Bipolar Disorders, 11, 154-165. PMID: 19267698.
Diaz, F.J., Velásquez, D.M., Susce, M.T., de Leon, J. (2008). The association between schizophrenia and smoking: Unexplained by either the illness or the prodromal period. Schizophrenia Research, 104, 214-219. PMID: 18650069.
de Leon, J., Diaz, F. J. (2005) A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophrenia Research, 76, 135-157. PMID: 15949648.
Diaz, F. J., Jané, M., Saltó, E., Pardell, H., Salleras, Ll., Pinet, C., de Leon, J. (2005). A Brief Measure of High Nicotine Dependence for Busy Clinicians and Large Epidemiological Surveys. Australian and New Zealand Journal of Psychiatry, 39, 161-168. PMID: 15701065.
Other publications reflecting my extensive collaborative experience in medical and epidemiological research.
Diaz, F. J., Baca-Garcia, E., Diaz-Sastre, C., García Resa, E., Blasco, H., Braquehais Conesa, D., Saiz-Ruiz, J., de Leon, J. (2003) "Dimensions of suicidal behavior according to patient reports." European Archives of Psychiatry and Clinical Neurosciences, 253, 197-202.
Diaz, F. J., Jané, M., Saltó, E., Pardell, H., Salleras, Ll., Pinet, C., de Leon, J. (2005) "A Brief Measure of High Nicotine Dependence for Busy Clinicians and Large Epidemiological Surveys." Australian and New Zealand Journal of Psychiatry, 39, 161-168.
Diaz, F.J., Meary, A., Arranz, M.J., Ruaño, G., Windemuth, A., de Leon, J. (2009). "Acetyl-coenzyme A carboxylase α gene variations may be associated with the direct effects of some antipsychotics on triglyceride levels." Schizophrenia Research, 115; 136-140.
Diaz, F.J., Perez-Iglesias, R., Mata, I., Martinez-Garcia, O., Vazquez-Barquero, J.L., de Leon, J., Crespo-Facorro, B. (2010) "Possible effects of some antipsychotic drugs on C-reactive protein in a drug-naïve psychotic sample." Schizophrenia Research, Vol. 121; pp. 207-212.
Diaz, F.J., Rojas-Villarraga, A., Salazar, J.C., Iglesias-Gamarra, A., Mantilla, R.D., Anaya, J-M. (2011) "Anti-CCP antibodies are associated with early age at onset in patients with rheumatoid arthritis." Joint Bone Spine, Vol. 78; pp. 175-178.
de Leon, J., Diaz, F.J. (2012) "Genetics of schizophrenia and smoking: An approach to studying their comorbidity based on epidemiological findings". Human Genetics, Vol. 131:877-901.
The following URL has a full list of my published works: