Application of Biostatistics in Pharmacy

Course Objectives: Provides students with an understanding of probability concepts, distributions of random variables, nonparametric methods, and other statistical methods HSEH in biousedcal, pharmaceutical, and health care research. Two hours of lecture per week. Prerequisite: First professional year standing in the College of Pharmacy and Health Sciences or consent of the instructor.
Statistics and distributions in samples. Probability theory. Random variables and probability distributions. Variables, continuous random variables, parameters of probability distributions. Application of distributions in medicine.

Course Description
This is the Biostatistics core course. Students obtain an understanding of the concepts of statistical reasoning as applied to the study of clinical pharmacy problems. This includes learning basic terminology and its meaning, the calculations of various statistical measures and indices, quantification of health relationships and the interpretation of inferential statistical techniques.

Presents practical sampling methods and their theoretical background. Covers simple random, stratified, systematic, and simple stage cluster sampling techniques; also, ratio, regression, and difference estimation. Emphasizes sampling human populations in large communities. Introduces current health problems in biostatistics methods and theory.

At the end of the course the student will be able to: 1) recognize the advantages and disadvantages of different experimental designs and be able to select the appropriate design to conduct a study; and 2) properly analyze complex experiments in public health and practice.

Introduction to Statistical Methods 1

This course is an introductory applied biostatistical course for students needing a more comprehensive approach than provided in the Core Course (BIOS 2011). Topics covered include probability, confidence intervals, estimation and hypothesis testing. Statistical procedures covered include t-test, contingency tables, analysis of variance, linear regression and basic nonparametric procedures.

BIOST 2042: Introduction to Statistical Methods 2

This course constitutes the second part of the basic sequence of applied statistical methods. The course covers nonparametric methods, multiple linear regression, odds ratios, relative risk, logistic regression, methods in survival analysis (Kaplan-Meier, lifetable analyses, Cox proportional hazards models), multiple comparisons procedures, the general linear contrast, multi-way ANOVA (general fixed effects model, factorial design, qualitative and quantitative interactions, randomized blocks, random effects models, repeated measures) and analysis of covariance.

Introduction to Statistical Theory 1

Basic introduction to statistical theory. Topics covered include joint, marginal and conditional probabilities; moment generating and characteristic functions; transformation of variables; convergence of random variables; law of large numbers; and the central limit theorem..

Introduction to Statistical Theory 2

Continuation of the introduction to statistical theory introduced in BIOS 2043. Topics covered include sufficiency, completeness, Rao-Cramer's inequality, fundamentals of hypothesis testing, Neyman-Pearson Lemma, and likelihood ratio tests.

Analysis of Case-Control Studies

Teaches methods to study health problems in community population groups. Covers measures of disease occurrence and association for various study designs; classical analysis of grouped and matched case-control studies. Both conditional and unconditional logistic regressions are covered. Methods are given for analyzing a variable number of controls for each case, assessing the effect of multiple expansive levels, and assessing model fit.

Analysis of Cohort Studies

This introductory applied course in statistical modeling focuses on regression methods for the analysis of cohort data. Topics include the generalized linear model and generalized estimating equations (with emphasis on logistic and Poisson regression), and Cox regression with timedependent covariates. Students analyze several cohort data sets, assess the adequacy of their models, and interpret their results.

Introduction to Biological Assay

Teaches statistical techniques in biological assay, including direct and indirect assays, quantitative and quantal responses, estimation of median effective dose, and comparisons of effectiveness

Occupational Biostatistics
Topics covered include nested case control studies, design and analysis of historical prospective studies, the statistical package OCMAP, evaluation of disease clusters, and the multistage model. The course considers the practical problems of exposure assessment, data collection, and adjustment for confounders in addition to the selection of the appropriate statistical method.

Applied Regression Analysis

Covers the basics of classical and modern regression techniques. Topics covered include multiple regression, indicator variables, multicolinearity, selection of a best model, influence .diagnostics, and nonlinear regression

Statistical Estimation Theory

This course covers selected topics in classical estimation and builds on some of the estimation topics covered in Biostatistics 2044. Topics covered include comparisons of different methods of estimation, properties of maximum likelihood estimations, brief overview of measure theory, and the decision theoretic framework work for estimation. Although this course is primarily theoretical practical issues are discussed such as convergence problems when obtaining ,maximum likelihood estimations, impact of missing data, and the role of some of the recent computationally .intensive methods

Multivariate Analysis
Topics covered include the multivariate normal distribution, estimation of the mean vector and covariance matrix, distributions and uses of simple, partial and multiple conclation coefficients, the generalized T2 statistic, the distribution of the sample generalized variance, multivariate analysis of variance. Multivariate methods will be applied to repeated measures analysis, factor analysis, and discriminant analysis. The beginning of the course emphasizes theory. Later applications and computational methods are emphasized.

Nonparametric Methods in Statistics

Order statistics and quantiles: the U statistic and Hoeffding's theorem; ranks and mid-ranks; Kendall's and Spearman's rank correlation coefficients; the sign test; Kolmogorov-Smirnov and Cramer-Von Mises tests of goodness of fit; rank (order) test; Mann-Whitney (Wilcoxon) rank test; the several-sample problem; the Mood Brown median test; Mood's median test; the Kruska-Wallis .H test; Friedman's test; efficiency of nonparametric tests; Pitman efficiency of tests

Survival Analysis
Covers the basic theoretical aspects of various models to analyze "time to event" data. Introduces basic concepts such as the survival function, hazard function, left and right hand censoring, and common parametric models for analyzing survival data. Also includes the proportional hazards model with fixed and time dependent covariates, the stratified PH model, regression diagnostics for survival models, additive hazards regression models and multivariate survival models.

Likelihood Theory & Application

The purpose of this course is to introduce the student to modern likelihood theory and its applications. The course will cover maximum likelihood theory, profile likelihood theory, pseudo likelihood theory and generalized estimating equations. The course is taught at the doctoral level and much of the theory is illustrated through applications.

Clinical Trials: Methods and Practice

Course consists of two weekly lectures, posted on the web in advance, and two in-class sessions which consist of questions and answers related to the web-based information, problem-solving, or discussion of case studies. It covers fundamental concepts in the design and conduct of modern clinical trials. Topics include: experimental designs for safety and efficacy trials, quantitative methods for design, interim monitoring, and analysis of randomized comparative clinical trials including crossover, factorial and equivalence designs. Ethical, organizational, and practical considerations of design and conduct of single and multicenter studies are integrated in lectures and case studies. The course also covers international guidelines on statistical considerations for drug development, guidelines adopted for publication of trials in major medical journals, and recommended approaches for meta-analyses.

Bayesian and Empirical Bayes Statistical Methods

Teaches how to use Bayesian and empirical Bayes statistical methods in data analysis. Gives examples and includes discussion of common data-analysis issues. Compares and contrasts Bayesian, empirical Bayesian, and classical methods. Topics covered include Savage axioms, conjugate priors, the likelihood principle, noninformative priors, Empirical Bayes and hierarchal Bayes approaches

Bayesian and Empirical Bayes Statistical Methods

This course provides the students with an understanding of both the theory and practice with regard to the EM algorithm, Markov-chain, sampling techniques, importance sampling, and the solution of decision trees. Students gain hands-on experience programming with S-Plus. The .course is designed to complement BIOS 2063

Mathematical Methods for Statistics

This course is designed to bridge the gap between students with an undergraduate mathematics background and the mathematics required for the mathematical statistics courses. It is recommended for students who meet only the minimum requirement of one year of calculus at the time of entry into the program. It covers selected topics in advanced calculus and linear .algebra

Linear Models
Teaches linear model techniques for analyzing balanced and unbalanced data. Basic topics covered include properties of quadratic forms, noncentral chi-square and F distributions, best linear unbiased estimations, and likelihood ratio test. Also covers generalized inverses, models not of full rank, orthogonal contrasts with unbalanced data, regression on dummy variables, .analysis of covariance; and analysis of variance components

Discrete Multivariate Analysis

This more advanced course on modeling multivariate categorical data focuses on the theory and methods underlying both asymptotic and exact inference. Log-linear models, models for ordinal and multinomial data, exact logistic regression, and extensions of generalized linear models to .correlated discrete data are emphasized

Applied Time Series Analysis

Covers time series, estimation in the time domain, forecasting, and spectral analysis. Stresses .computer application with real data sets

Biostatistics Consulting Practicum

For second-year master's and doctoral students. Provides exposure and experience in consulting on the biostatistical aspects of research problems in biomedical or allied fields. Students have discussions with investigators, leading to the design or analysis of a current research problem. .Includes weekly group discussions with instructor

Introduction to Computing
Gives basic computer skills on the VAX/VMS mainframe. Emphasizes developing the basics for data process and analysis using MINITAB, an interactive statistical program. Also covers computerized library searching techniques.

Data Management and Analysis

Emphasizes data and file management, and data description aspects of statistical packages .BMDP, SAS, and SPSS. Covers VAX/VMS system utilities for editing and sorting

Introduction to Database Management Systems

Gives database techniques used in a formal database management system. Applications are in .VAX/VMS and PC microcomputer environments

Applied Statistical Computing in the Health Sciences

Teaches fundamentals of good programming techniques and procedures, strengths and limitations of computational approaches. Integrates programming techniques with biostatistical and health sciences problems

Research and Dissertation for the Doctoral Degree

Variable number of credits assigned for work on student research dissertation.

CLINICAL RESEARCH TRAINING PROGRAM

CLRES 2005: Computer-based Data Analysis(1 Credit) Provides instruction on the use of computerized methods for clinical research. Dataset manipulation, descriptive statistics and the graphical presentation of data will be presented using a standard statistical package. To read the syllabus please click here

CLRES 2010: Clinical Research Methods(3 Credits) Provides an overview of the basic research strategies, methods, and goals of clinical research. Topics include study design, data analysis and interpretation, and determination of appropriate methodologies to answer different research questions. Participants will learn about bias and confounding in observational research, the clinical value of diagnostic tests, the use of cross-sectional, case-control and cohort study designs, and various statistical modeling used in clinical research. The course will emphasize research design and measurement. Standard epidemiological measurements (incidence, prevalence, rates, and risk ratios) will be presented, and tools and techniques to understand the value of clinical information (Bayes theorem, diagnostic test performance, and ROC analysis) will be developed. The design of Phase I, II, and III clinical studies, as well as randomized non-pharmacological clinical trials will be discussed. Criteria for internal and external validity, randomization methods, unbiased outcomes determination, sample size estimation and power calculations will be presented. The implementation of clinical studies will be presented including recruitment, informed consent, enhancement and monitoring adherence, and terminating a clinical trial. Issues in the analysis of clinical trials, including intention-to-treat

and meta analyses will be introduced. To read the syllabus please click here

CLRES 2020: Biostatistics: Statistical Approaches in Clinical Research (4 Credits) Focuses on basic concepts and statistical methods and their application to problems in the health and biomedical sciences. Topics include data description and summarization, basic probability theory, estimation, and hypothesis testing with emphasis on one- and twosample comparisons involving continuous and categorical data. Linear regression and analysis of variance will be introduced. Students will develop their analytic skills through the analysis and discussion of large clinical studies.

CLRES 2021: Regression and ANOVA(1 Credit) Designed for medical researchers who are non-Biostatistics majors. The course will focus on the basic concepts of analysis of variance, analysis of covariance, linear regressions and some useful experimental designs. At the completion of the course, the student should: understand the skills to appropriately use ANOVA and linear regressions; develop the skills to appropriately use ANOVA and/or linear regressions; understand the basic concepts behind an experimental design for the existing medical research; possibly build up the ability to design an experiment for future medical research; and recognize situations that require more advanced knowledge and methods.

CLRES 2022: Logistic Regression(1 Credit) Introductory course in logistic regression modeling. This course is intended for physicians in fellowship training programs and other researchers with a limited background in statistics. The course focuses on regression methods for binary data, and the basics of maximum likelihood inference. At the completion of the course the student should: understand how logistic regression can be used to address a variety of epidemiological and clinical questions, interpret the models, and assess their appropriateness and adequacy; develop analytic skills through the analysis of data sets taken from the fields of medicine and

public health; and, develop oral and written communication skills through the description of analytic strategies and the summarization and interpretation of results.

CLRES 2023: Cox Regression(1 Credit) Introductory course in regression modeling of time-to-event data. This course is intended for physicians in fellowship training programs and other researchers with a limited background in statistics. The course focuses on descriptive methods for survival data, Cox regression, and the issues pertaining to time-dependent covariates. At the completion of the course the student should: recognize when it is necessary to account for time in the analysis yes/no outcomes, and appropriately summarize time-to-event data; interpret the Cox regression model, and assess the appropriateness and adequacy of the model; understand issues in the design, analysis, and interpretation of studies involving time-dependent covariates; develop analytic skills through the analysis of data sets taken from the fields of medicine and public health; and develop oral and written communication skills through the description of analytic strategies and the summarization and interpretation of results.

CLRES 2024: Applied Nonparametric Statistics(1 Credit) Introductory course is intended for physicians in fellowship training programs and other researchers with a limited background in statistics. This course focuses on statistical methods that are applicable when research outcomes follow diverse probability distributions, normal and non-normal. Specific attention will be given to bootstrap and rankbased methods. Trainees will develop analytic skills through the analysis of data sets taken from the fields of medicine and public health and develop oral and written communication skills through the description of analytic strategies and the summarization and interpretation of results.

CLRES 2040: Measurement in Clinical Research(1 Credit) Focuses on the properties of good measurement integral to the research process. Specific objectives are to: 1) analyze methods for testing psychometric properties (reliability and validity) of both

psychological and physiological instruments; 2) evaluate the adequacy of selected scaling methodologies used in research; 3) apply knowledge of instrumentation in description of a psychosocial and a physiological instrument for a research proposal; and 4) synthesize course content with statistical criteria for scale evaluation and make decisions regarding scale revision. The domain sampling model is presented as the major theory of measurement error with the parallel test model presented as a special case of domain sampling model. The construct, criterion and content validity of psychosocial instruments are explored and methods for evaluating each of these relative to specific instruments are presented. A variety of scaling methodologies will be discussed as well as the principles involved in the design and formatting of questionnaires. To read the syllabus please click here

CLRES 2050: Ethics and Regulation of Clinical Research(1 Credit) Presents an in-depth examination of ethical issues in the conduct of clinical research. Topics include issues related to privacy, confidentiality, protection of human and animal subjects, and informed consent as well as the role of the IRB in ensuring the responsible conduct of research. Special consideration will be given to regulatory issues (from OMB, NIH, IRB, and others) pertaining to the conduct of clinical trials and health service research. Other topics will include: potential conflicts between research and clinical priorities; subject selection; plagiarism and scientific misconduct; responsibilities of sponsors, monitors, and investigators; research with vulnerable populations; clinical equipose; authorship; compassionate use of investigational drugs; orphan drugs; research integrity; and, quality control. The longitudinal component of the ethics module will be structured to complement the content of the Integrated Methods Seminar and the Grantsmanship and Biomedical Writing course. The trainees will use their NIH style proposal to create an Institutional Review Board (IRB) submission. This will be reviewed and critiqued by the other trainees and selected faculty. (Taken simultaneously with CLRES 2070) To read the syllabus please click here

CLRES 2070: Research Design and Development Seminar(5 Credits)

The purpose of the integrated methods seminar series is to build upon the skills learned in the intensive summer session and provide a hands-on research experience. Trainees will learn the phases of the research process from conception, to design, and ultimately, implementation of the research. Through a combination of group seminars and independent work, using a topic of their own research choice, trainees will develop their own research proposal in the form of an NIH grant application. This will include specific aims, background and significance, prior work and methods sections. In addition, trainees will review and critique the work of their peers. (Prerequisite: Mentor must be identified prior to class; CLRES 2050 is taken simultaneously) To read the syllabus please click here

CLRES 2080: Masters Thesis Research(3 Credits) Trainees may register for this course with approval from the mentor and selected faculty of the CRTP Curriculum Committee. CLRES 2080 is designed for trainees who are prepared to undertake their substantive research project or thesis. -

CLRES 2100: Outcomes and Effectiveness Research Methods(2 Credits) Provides a survey of effectiveness research. The curriculum will deal with conceptualization, design, sampling, modeling, data collection and analysis used in outcomes and effectiveness studies. The emphasis of the course will be largely on research methodology and study design. The course will be interactive and will extensively use studies published in the literature as a teaching tool. At the completion of the course the student should: understand how to design an effectiveness study; have an understanding of how to control for severity and comorbidity in the studies of effectiveness; know the wide range of outcomes used in this research; and learn important examples of effectiveness studies. To read the syllabus please click here

CLRES 2110: Quality Improvement for Health Care(1 Credit)

Provides an introduction to concepts and techniques used to measure and improve the quality of health care. The causes of the apparent prominence of health care quality in the current debate about HMOs and managed care will be developed, and an understanding of the methodologies that can be applied to the process of health care delivery to improve the quality of care will be presented. The application of the basic techniques used in quality assessment and process improvement, including statistical process control, process management and variations analysis will be presented. To read the syllabus please click here

CLRES 2120/HPM 2220: Cost-Effectiveness Analysis(1 Credit) Provides an introduction to the methods used in the economic analysis of health care programs. It will teach the economic principles that provide the foundation of cost-effectiveness analysis, describe the various methods, ratios and methodologies used in cost-effectiveness studies, and highlight the current controversies in cost-benefit analysis. Additional topics include the appropriate use of costeffectiveness in making medical decisions in patients and populations and concepts of perspective, utility analysis, discounting, and the definition of various costs and benefits. To read the syllabus please click here

CLRES 2121/HPM 2217: Clinical Decision Analysis(1 Credit) Presents an overview of the theory of medical decision-making, the incorporation of uncertainty and risk into medical decision-making, and describe the use of these techniques in both population and individual patient settings. The design, structure, and evaluation of decision tree-using software packages will be presented, and trainees will become skilled in structuring and analyzing decision problems. Sensitivity analysis and the stability of model outputs will be presented. Controversies such as perspective of the analysis, discounting of costs and benefits will be discussed. To read the syllabus please click here

CLRES 2122: Advanced Methods for Decision and Costeffectiveness Analysis(1 Credit)

Expands upon topics introduced in CLRES 2120 (Cost Effectiveness Analysis) and CLRES 2121 (Clinical Decision Analysis) and provides additional guidelines for using decision sciences in larger, more complex applications. Topics include modeling clinical processes and systems; discrete event simulation; advanced sensitivity analysis and confidence limits; controversies surrounding the use of costeffectiveness analyses; and multi-attribute utility theory. (Prerequisites: CLRES 2120 and CLRES 2121.) To read the syllabus please click here

CLRES2130: Health Services Research Using Secondary Data: A Didactic Course(1 Credit) Health services researchers and epidemiologists rely on many publicly and privately available secondary databases, ranging from those collected primarily for research and surveillance (the National Health Interview Survey) to those collected for administrative or billing purposes but which have research utility (Medicare claims). CLRES 2130 provides an introduction to many of the large databases that are frequently used by health services researchers. (Prerequisite for CLRES 2131)

CLRES 2131: Health Services Research Using Secondary Data: Project Course(3 Credit) Provides students with an opportunity to complete a mentored research project using one of theses large secondary databases. Over a nine-month period of time, Trainees will revise their research projects from CLRES 2130, acquire necessary data files to conduct their study, perform essential data cleaning, manipulation, and analyses, and develop an abstract for submission to a professional meeting. (Prerequisite: CLRES 2130)

CLRES 2140: The Practice of Research: Project Implementation and Operation(1 Credit) Covers the basic operations of conducting a health services research project, from developing realistic timelines and schedules to building

tracking databases, training interviewers and data collectors, monitoring data collection and budgets, to reporting, and closing out a study.