Module 1: Introduction to Clinical Trials
Instructor: Scott Emerson
This module provides an overview of the clinical and scientific issues that must be considered by the many disciplines that collaborate on a clinical trial. The material of this module is presumed for Modules 4 and 5. In this module, we consider the clinical, scientific, and regulatory setting of clinical trials, describing the phased approach to “treatment discovery” in which the safety, efficacy, and effectiveness of candidate treatments is investigated. In particular, we discuss the issues surrounding identification of the target population, definition of the treatment, choice of clinical outcomes, choice of comparators, choice of randomization strategies, blinding, conduct and monitoring of the study, and plans for reporting of the result. The importance of a well-defined study protocol is emphasized.
Module 2: Longitudinal Data
Instructors: Patrick Heagerty
Longitudinal studies follow individual subjects over time and repeatedly measure health status. This module will introduce and illustrate methods of analysis for longitudinal data. An introduction to pre-post data will be followed by detailed description of regression methods such as linear mixed models and generalized estimating equations. Examples from randomized clinical trials and observational studies will be used to illustrate key approaches. Computing examples will be given in R, STATA, and SAS.
Module 3: Introduction to Survival Analysis
Instructors: Susanne May and Barbara McKnight
This module covers survival analysis methods with emphasis on applications in the context of clinical trials. We will introduce standard univariable descriptive functions including the Kaplan-Meier curve, two-sample tests and multivariable methods including the Cox regression model. Topics such as censoring assumptions, informative censoring and competing risks, will be covered. Other topics will include time-dependent covariates, checking for departure from proportional hazards, and identification of influential observations. In addition, sample size estimation and power will be discussed. The course will focus on understanding the concepts; mathematical details will be kept to a minimum.
Module 4: Advanced Topics in Design of Clinical Trials
Instructors: Tom Fleming and Scott Emerson
This module provides detailed discussion of a number of topics that are currently receiving special emphasis in the community of clinical trialists. As such, this module presumes the material of Module 1. Included in this module are presentations on the important distinctions between confirmatory and exploratory studies; the use of biomarkers and surrogate endpoints in clinical trials; the handling of missing data in clinical trials; issues surrounding the conduct of noninferiority trials; the role of adaptive randomization schemes; role of data monitoring committees (DMCs) in monitoring the conduct of the clinical trial; an overview of strategies for adaptive clinical trials; and requirements for study protocols, study monitoring plans, and statistical analysis plans.
Module 5: Sequential Monitoring of Clinical Trials
Instructors: Dan Gillen and John Kittelson
Increasingly, clinical trials are conducted using group sequential methods in order to address the ethical and efficiency requirements for performing experiments with human volunteers. The design, conduct, and analysis of a sequential clinical trial is necessarily more involved than that for a clinical trial in which the data would only be analyzed at the end of the study. In this module we provide an introduction to methodology for the design, monitoring and analysis of group sequential trials. The module will present and illustrate methods for adaptive trial design that maintain pre-specified trial operating characteristics. Methodology will presented using case studies and examples of clinical trials with continuous, binary, and survival endpoints. The sequential methods will be illustrated using RCTdesign, an R module for the design, monitoring, and analysis of clinical trials. Emphasis will be placed on both the scientific and statistical impact of group sequential trial design. This module presumes knowledge of the material in Module 1.
Module 6: Design of Clinical Trials in Oncology
Instructors: John Crowley and Antje Hoering
Topics in all phases of oncology clinical trials (phase I-III) will be covered. The first half of the course will review basic concepts of oncology clinical trials including safety, efficacy and endpoint considerations. The most common phase I trial designs will be discussed. Single stage and two-stage phase II trial designs as well as randomized phase II trial designs, as well as pros and cons of these designs in various clinical settings, will be covered. Superiority and non-inferiority phase III trials will be reviewed. Real world examples of recent SWOG and CRAB clinical trials will be given and trial designs will be demonstrated using our on-line calculators. The third edition of the Handbook of Statistics in Clinical Oncology edited by the instructors has just been published. The second half of the course will cover current topics in oncology clinical trial designs based on this Handbook, including trial designs for cytostatic or targeted agents in all phases of development. Variations with targeted agents include dose exploration in seamless phase I/II trials; multiple strata phase II trials; phase II/III trials; and phase III designs for joint biomarker and drug development.