• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

About FDA

  • Print
  • Share
  • E-mail

Center for Drug Evaluation and Research (CDER)

2012 Preceptors


Picture of Ram Tiwari

Ram C. Tiwari, Ph.D.
Associate Director, Office of Biostatistics
Center for Drug Evaluation & Research, FDA
10903 New Hampshire Ave., WO Bldg. 21, Rm. 3524
Silver Spring, MD 20993-0002
 

Background:
M.S. & Ph.D. (Mathematical Statistics), Florida State University
Fellow, American Statistical Association
Member, International Statistical Institute
Previous Employment: Mathematical Statistician and Program Director, Surveillance
Research program, NCI/NIH (2000-2008);
Professor & Chairman, Department of Mathematics, University
of North Carolina, Charlotte, NC (1994-2000);
Asst./Assoc./Professor, Department of Mathematics, University
of North Carolina, Charlotte, NC (1986-1994);
Asst. Professor, Indian Institute of Technology, Bombay (2002-
2006); Visiting Lecturer, UC Santa Barbara (1981-1982, 1985-1986).
 

Current Research Interests:

Development of statistical methods for i) clinical trials; and ii) signal detection in drug safety surveillance
Proposed Research Project for FDA Fellow:

Statistical methods for signal detection in FDA’s AERS data and their extension to signal detection in longitudinal observational safety databases

Background Material: Basic understanding of likelihood theory, Bayesian methodology and Markov chain Monte Carlo (MCMC) simulation techniques is required. The project would also require basic understanding of the standard univariate and multivariate distributions.

Research Plan:

Project would require review of existing methods for signal detection including PRR, ROR, MGPS, BCPNN, and a newly developed method based on Likelihood Ratio Test; familiarity with AERS database; and an understanding of signal detection methods in Observational Medical Outcomes Partnership (OMOP) and Sentinel Initiatives. Fellow would spend considerable time in understanding the nonparametric Bayesian literature including the Dirichlet process as a prior for the class of nonparametric distributions. MCMC simulation techniques, using WinBUGS and R, for sampling from a Dirichlet process are needed. The objective is to assume that the counts on the drug-adverse events are distributed as Poisson random variables with mean modeled by a Dirichlet process. The posterior distribution of the mean will be derived, and the posterior expectation of the mean will be obtained. A decision criterion that will compare the observed counts with the expected counts, along the lines of MGPS, would be developed for the signal detection.
Applicant Project Requirements:

Ph.D. in Biostatistics, with SAS, R and WinBUGS experience

Selected Recent Publications (from over 150 papers):

1. Cook, A.J., Tiwari, R.C., Wellman, E.D., Heckbert, S.R., Li, L., Heagerty, P., Marsh, T., and Nelson, J. Statistical approaches to group sequential monitoring of postmarket safety surveillance data: Current state of the art for use in the Mini-Sentinel pilot, accepted for publication in Phramacoepidemiology and Drug Safety for the Mini-Sentinel special addition.

2. Huang, L., Zalkikar, J., and Tiwari, R.C., A likelihood ratio test based method for signal detection with application to FDA’s drug safety data, accepted for publication in Jour. Amer. Statist. Assoc. (available online: http://pubs.amstat.org/doi/abs/10.1198/jasa.2011.ap10243)

3. Cook, A.J., Li, Y., Arterburn, D., and Tiwari, R.C. Spatial cluster detection for weighted outcomes using cumulative geographic residuals, Biometircs , 66 (2010), 783- 792.

4. Huang, L., Tiwari, R.C., Zou, Z., Kulldorff, M., and Feuer, E.J. Weighted normal spatial scan statistic for heterogeneous population data, Jour. Amer. Statist. Assoc., 104 (2009), 886-898.
5. Ghosh, P., Basu, S., Tiwari, R.C. Bayesian analysis of cancer rates from SEER Program using parametric and semiparametric joinpoint regression models, Jour. Amer. Statist. Assoc., 104 (2009), 439-452.
 


Picture of Ping Zhao

Ping Zhao, Ph.D.
Office of Clinical Pharmacology (OCP)
Office of Translational Sciences (OTS)
Center for Drug Evaluation and Research (CDER)
Silver Spring, MD

Background:
Ph.D. – Drug Metabolism and Pharmacokinetics
Pharmaceutical industry experience – 6 years
FDA Experience – 3.5 years
 

Research Interests:
Use of population-based, physiologically-based pharmacokinetic (PBPK) modeling and simulations to facilitate regulatory review of clinical pharmacology issues.

Proposed Research Project for FDA Fellow:
The short term objective of this project is to set up a workflow to utilize population-based, physiologically-based pharmacokinetic (PBPK) modeling and simulations in regulatory review of clinical pharmacology issues. The long term objective is to provide regulatory recommendations on the use of PBPK models in drug development and regulation. The intrinsic (e.g., age, gender, organ function, genetics) and extrinsic factors (e.g., food, concomitant medications) affecting drug exposure are often separately evaluated in clinical pharmacology studies. The results have been listed in the drug labeling with recommendations for dosing adjustment for a particular factor when appropriate. However, concurrent multiple affecting factors are clinically more relevant. Population PBPK models incorporate in vitro and in vivo drug disposition, drug interaction information, and physiological information of target population in a systems biology manner. These models are suitable for mechanistically evaluating clinical events of multiple affecting factors, which is often impractical to study experimentally. The results may be used to prioritize the clinical trial design or for risk assessment.

Applicant Requirements:
Required: Ph.D., Pharm.D., or M.D. with training and work experience in general clinical pharmacology, drug metabolism, drug transport, pharmacokinetics and pharamcokinetics-pharmacodynamics modeling, and simulations, and skills in PK, PBPK and statistical modeling tools.
Optional: Systems biology, bioengineering

Selected Recent Publications:
1. Vieira MLT, Zhao P, Gil Berglund E, Reynolds KS, Zhang L, Lesko LJ, Huang S-M (2011) Case Study of Telithromycin, a Time-Dependent CYP3A Inhibitor. Clin Pharmacol Ther, (In press)
2. Zhao P, Vieira MLT, Grillo JA, Song P, Wu T-C, Zheng JH, Arya V, Gil Berglund E, Atkinson AJ Jr, Sugiyama Y, Pang KS, Reynolds KS, Abernethy DR, Zhang L, Lesko LJ, Huang S-M (2011) Utility of Physiologically-based Pharmacokinetic Modeling and Simulation (PBPK) in Evaluating Comparative Exposures of Non-renally Eliminated Drugs in Subjects with Normal Renal Functions versus Subjects with Renal Impairment. J Clin Pharmcol, (In press)
3. Zhao P, Zhang L, Grillo JA, Liu Q, Bullock J, Moon YJ, Song P, Brar S, Madabushi R, Wu T-C, Booth BP, Rahman NA, Reynolds KS, Gil Berglund E, Lesko LJ, Huang S-M (2011) Applications of Physiologically-based Pharmacokinetic (PBPK) Modeling and Simulation During Regulatory Review. Clin Pharmacol Ther. 89:259-67
4. Duan JZ, Jackson AJ, Zhao P (2011) Bioavailability Considerations in Evaluating Drug-Drug Interactions Using the Population Pharmacokinetic Approach. J Clin Pharmacol, 51: 1087-1100
5. Zhao P, Ragueneau-Majlessi I, Zhang L, Strong JM, Reynolds KS, Levy RH, Thummel KE, Huang SM (2009). Quantitative evaluation of pharmacokinetic inhibition of CYP3A substrates by ketoconazole: a simulation study. J Clin Pharmacol. 49:351-9.
 


Picture of Lei Zhang

Lei Zhang, Ph.D.

Special Assistant to Office Director
Immediate Office
Office of Clinical Pharmacology (OCP)
Office of Translational Sciences (OTS)
Center for Drug Evaluation and Research (CDER)
Silver Spring, MD
 

Background:

Ph.D. in Biopharmaceutical Sciences, University of California, San Francisco
Pharmaceutical Industry Experience – 4 years
FDA Experience – 9.5 years
 

Research Interests:

My research interests include role of transporters in drug interactions, pharmacogenomics of metabolizing enzymes and transporters, interplay of drug metabolizing enzymes and transporters, effect of renal or hepatic impairment on enzymes and transporters, and pharmacokinetics/pharmacodynamics.

Membrane transporters represent ~15% of the human genome of approximately 30K genes. These transporters are expressed in many tissues such as the intestine, liver, kidney and brain, and play key roles in drug absorption, distribution and excretion. As such, transporters can affect the pharmacokinetics and pharmacodynamics of a drug whether acting alone or in concert with drug metabolizing enzymes. Increasing number of examples in the literature and regulatory reviews have demonstrated that drug interactions and polymorphisms involving transporters can affect safety or efficacy of therapeutics, e.g., organic cation transporting polypeptides (OATPs) and cholesterol lowering statin drugs. Transporters represent an emerging area for regulatory research. I lead a Transporter Scientific Interest Group (SIG) in the Office of Clinical Pharmacology/Office of Translational Sciences to conduct regulatory research projects in the transporter area and we have generated data to support regulatory guidance development, e.g., FDA’s recently published draft drug interaction guidance (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM292362.pdf, February 2012).

Proposed Research Project for FDA Fellow:

The Commissioner’s Fellow would perform the following research projects involving transporters to enhance regulatory science: 1) Build an internal transporter database based on recent NDA and IND review cases; 2) Collect information to support “best practice” of in vitro transport assays; 3) Understand the effect of organ impairment and disease states in transporter function; 4) Understand the regulation of transporters; and 5) Explore physiologically-based pharmacokinetic (PBPK) modeling and simulations involving transporters. The research will enable us to develop better evaluation tools for drug interaction assessment.

Applicant Requirements:

Ph.D., Pharm.D., or M.D. with training and work experience in clinical pharmacology, drug transport, drug metabolism, and pharmacokinetics/pharmacodynamics. Skills in physiologically-based pharmacokinetic modeling and statistical modeling tools are a plus.

Selected Recent Publications:

1. Agarwal S, Arya V, Zhang L. Review of P-gp Inhibition Data in Recently Approved New Drug Applications: Utility of the Proposed [I1]/IC50 and [I2]/IC50 Criteria in the P-gp Decision Tree. J Clin Pharmacol. 2012 Feb 7. [Epub ahead of print].
2. Zhang L, Huang S-M, Lesko LJ. Transporter-Mediated Drug-Drug Interactions. Clin Pharmacol Ther. 89(2):259-267, 2011.
3. Zhao P, Zhang L, Grillo JA, Liu Q, Bullock J, Moon YJ, Song P, Brar S, Madabushi R, Wu T-C, Booth BP, Rahman NA, Reynolds KS, Gil Berglund E, Lesko LJ, Huang S-M. Applications of Physiologically-based Pharmacokinetic (PBPK) Modeling and Simulation During Regulatory Review. Clin Pharmacol Ther. 89:259-267, 2011.
4. Zhang L, Reynolds KS, Zhao P, Huang S-M. Drug Interactions Evaluation: An Integrated Part of Risk Assessment of Therapeutics. Toxicol and Appl Pharmacol. 243:134–145, 2010.
5. Zhang L, Zhang Y, Huang S-M. Scientific and Regulatory Perspectives on Metabolizing Enzyme-Transporter Interplay and its Role in Drug Interactions - Challenges in Predicting Drug Interactions. Mol Pharmaceutics. 6(6):1766–1774, 2009.