Education

Ph.D. Statistics (1991), University of Connecticut, Storrs, CT.

M.S. Statistics (1987), University of Connecticut, Storrs, CT.

Research

          Methodological interests

Application-motivated research in diagnostic test validation, sequential models, clinical-trial design and Bayesian methods.

          Main areas of collaboration

                   HIV/AIDS

·         Read a presentation about data-driven search for changes in risk after initiation of antiretroviral therapy in Africa based on piece-wise Weibull models. Both the one and two-parameter maximization were performed with the STATA ML procedures. Also, read LJ Jiwanis MSc thesis from Simon Fraser University on piece-wise Weibull models and Germán Rodríguez’s treatment of the piece-wise exponential model.

·         Read detailed analyses of weight changes after ARV initiation in Kenya (from Wools-Kaloustian et al., AIDS, 2006).

                   Oncology

·         Read an analysis about PSA doubling time and change point mixed models of PSA growth.

·         Read an presentation of various estimates of the LD50 in animal experiments.

Publications

     Here is a list of selected publications. For a comprehensive list of publications click here.

1.      Hall CD, Dafni U, Simpson D, Clifford D, Wetherill P, Cohen B, McArthur JC, Hollander H, Yiannoutsos CT,Major E,Millar L, Timpone J: Failure of Cytosine Arabinoside Therapy of Human Immunodeficiency Virus-I Associated Progressive Multifocal Leucoencephalopathy. New England Journal of Medicine, 1998; 338:19, 1345-51. Get the NEJM citation. See also comment by J.E. Greenlee.

2.      Chen, MH, Ibrahim, JG, and Yiannoutsos, C. Prior Elicitation, Variable Selection and Bayesian Computation for Logistic Regression Models, Journal of the Royal Statistical Society, Series B, 1999; 61(1) 223-242. Get the article.

3.      Yiannoutsos CT, Major EO, Curfman B, Jensen PN, Gravell M, Hou J, Clifford DB, Hall CD. Relation of JC virus DNA in the CSF to survival in AIDS patients with biopsy-proven Progressive Multifocal Leukoencephalopathy. Annals of Neurology, 1999; 45(6) 816-820.

4.      Price RW, Yiannoutsos CT, Clifford DB, Zaborski L, Tselis A, Sidtis JJ, Cohen B, Hall CD, Erice A, and Henry K. Neurological outcomes in late-stage HIV-1 infection: adverse influence of neurological impairment on Survival and protective effect of antiviral therapy. AIDS, 1999; 13: 1677-1686. Get the article.

5.      Simpson DM, Haidich AB, Schifitto G, Yiannoutsos CT, Geraci AP, McArthur JC, Katzenstein DA. Severity of HIV-associated Neuropathy is Associated with Plasma HIV-1 RNA Levels. AIDS, 2002; 16(3): 407-412. Get the article.

6.      Polydefkis M, Yiannoutsos CT, Shriver S, Simpson DM, Cohen BA, Adornato BT, Hollander H, Marra CM, Clifford DB and McArthur JC. Intraepidermal nerve fiber density in HIV-associated sensory neuropathy. Neurology, 2002; 58(1): 115-119. Get the article.

7.     Nakas C, Yiannoutsos CT, Bosch RJ, Moyssiadis C. Assessment of diagnostic markers by goodness-of-fit tests. Statist Med; 2003; 22(15): 2503-2513. Get the article.

9.     Nakas CT, Yiannoutsos CT. Ordered multiple class ROC analysis with continuous measurements. Statist Med 2004; 23: 3437-3449. Get the article.

10.  Yiannoutsos CT, Ernst T, Chang L, Lee PL, Richards T, Marra C, Meyerhoff DJ, Jarvic J, Kolson D, Schifitto G, Ellis RJ, Swindells, Simpson DM, Miller EN, Gonzalez RG, Navia BA. Patterns of regional brain metabolism and diagnostic utility of proton MRS in AIDS Dementia Complex. Neuroimage 2004; 23(3): 928:935. Get the article.

11.  Li L, Shi H, Yiannoutsos CT, Huang T-H-M, Nephew KP. Epigenetic hypothesis tests for methylation and acetylation in a triple microarray system. J Comp Biol, 2005; 12(3):270-390. Get the article.

12.  Sweeney C, Liu G, Yiannoutsos CT, Kolesar J, Horvath D, Staab MJ, Fife K, Armstrong V, Treston A, Sidor C, Wilding G. A Phase II multicenter, randomized, double-blind, safety, PK, PD, and efficacy study of oral 2-methoxyestradiol in hormone refractory prostate cancer. Clin Cancer Res, 2005; 11(18): 6625-6633. Get the article. See more details of the changepoint model.

13. Wools-Kaloustian K, Kimaiyo S, Diero L, Siika AM, Sidle J, Yiannoutsos CT, Musick BS, Einterz RM, Fife KH, Tierney, WM The clinical and immunologic outcomes of an antiretroviral treatment program in western Kenya: retrospective cohort study. AIDS, 2006; 20:41-48. Get the article. Read detailed analyses of weight changes after ARV initiation in Kenya.

14.     Wruck LM, Yiannoutsos CT, Hughes, MD. A sequential design to estimate sensitivity and specificity of a diagnostic test. Stat Med, 2006; 25:3458-3473. Get the article.

15.     An M-W, Frangakis CE, Musick BS, Yiannoutsos CT. The need for double-sampling designs in survival studies: An application to monitor PEPFAR. Biometrics, 2009; 65:301-306. Get the article.

16.     Yiannoutsos CT, An M-W, Frangakis CE, Musick BS, Braitstein P, Wools-Kaloustian K, Ocheng D, Martin JN, Bacon M, Kimaiyo S.  Sampling-Based Approaches to Improve Estimation of Mortality among Patient Dropouts: Experience from a Large PEPFAR-Funded Program in Western Kenya. PLoS ONE, 2009; 3(12): e3843 doi:10.1371/journal.pone.0003843. Get the article.

17.     Yiannoutsos CT. Modeling AIDS survival after initiation of antiretroviral treatment using Weibull models with change points. JIAS, 2009; 12:9. Get the article.

Monitoring and evaluation (M&E) of HIV care and treatment programs is impacted by losses to follow-up (LTFU) in the patient population. The severity of this effect is undeniable but its extent unknown. Tracing all lost patients addresses this but census methods are not feasible in programs involving rapid scale-up of HIV treatment in the developing world. Sampling-based approaches and statistical adjustment are the only scaleable methods permitting accurate estimation of M&E indices.

In a large antiretroviral therapy (ART) program in western Kenya, we assessed the impact of LTFU on estimating patient mortality among 8,977 adult clients of whom, 3,624 were LTFU. Overall, dropouts were more likely male (36.8% versus 33.7%; p = 0.003), and younger than non-dropouts (35.3 versus 35.7 years old; p = 0.020), with lower median CD4 count at enrollment (160 versus 189 cells/ml; p<0.001) and WHO stage 3–4 disease (47.5% versus 41.1%; p<0.001). Urban clinic clients were 75.0% of non-dropouts but 70.3% of dropouts (p<0.001). Of the 3,624 dropouts, 1,143 were sought and 621 had their vital status ascertained. Statistical techniques were used to adjust mortality estimates based on information obtained from located LTFU patients. Observed mortality estimates one year after enrollment were 1.7% (95% CI 1.3%–2.0%), revised to 2.8% (2.3%–3.1%) when deaths discovered through outreach were added and adjusted to 9.2% (7.8%–10.6%) and 9.9% (8.4%–11.5%) through statistical modeling depending on the method used. The estimates 12 months after ART initiation were 1.7% (1.3%–2.2%), 3.4% (2.9%–4.0%), 10.5% (8.7%–12.3%) and 10.7% (8.9%–12.6%) respectively.

Assessment of the impact of LTFU is critical in program M&E as estimated mortality based on passive monitoring may underestimate true mortality by up to 80%. This bias can be ameliorated by tracing a sample of dropouts and statistically adjust the mortality estimates to properly evaluate and guide large HIV care and treatment programs.

Teaching

I have taught a number of courses at a number of institutions both in the US and around the world. In addition to the Division of Biostatistics at Indiana University, these include Harvard University Extension School, in Cambridge, MA, the University of Athens Medical School in Athens, Greece, and, more recently, the Moi University School of Public, in Eldoret, Kenya.

Here are notes from classes I have taught in the past.

·         Introduction to Biostatistics I (taught with STATA)

o       Lectures (book format)

o       Labs

·         Introduction to Biostatistics II (taught with STATA)

o       Lectures (book format)

o       Labs

·         Introduction to Biostatistics II (taught with SAS)

o       Lectures (book format)

o       Labs

·         Introduction to Biostatistics II (taught with SPSS; includes video)

·         Generalized Linear Models (taught with STATA) also see the excellent presentation by Germán Rodríguez at Princeton University from where many of the ideas for these notes were taken.

o       Lectures (book format)

o       Labs

·         Applied Survival Analysis (taught with STATA)

o       Lectures (book format)

o       Labs (stata)

o       Labs (SAS)