This document provides an introduction to the course "Design and Analysis of Clinical Trials". It discusses how clinical research uses statistics to investigate medical treatments and assess benefits of therapies. Statistics allow for reasonable inferences from collected data despite variability in patient responses. The course covers fundamental concepts of clinical trial design and analysis including phases of trials, randomization, sample size, treatment allocation, and ethical considerations. It aims to teach students how to generalize trial results to populations and combine empirical evidence with medical theory using statistical methods.

1. Design and Analysis of Clinical Trials
Stat 6202
Introduction to the course
Clinical Research
Role of statistics in clinical research
Course description

2. Clinical Research
• Clinical research involves:
– investigating proposed medical treatments,
– assessing the relative benefits of competing therapies,
– and establishing optimal treatment combinations.
• Clinical research attempts to answer questions such as:
– Is the incidence of serious adverse effects among patients
receiving a new therapy greater than the patients
receiving the standard therapy?
• Before the widespread use of experimental trials, clinicians
attempted to answer such questions by generalizing from the
experiences of individual patients to the population at large.

3. The role o statistics in clinical
research
• In the twentieth century, the field of statistics developed
and was applied to clinical research.
• Statistics is the “ theoretical science or formal study of the
inferential process, especially the planning and analysis of
experiments, surveys, and observational studies.”
• Statistical methods provide formal accounting for sources
of variability in patients’ responses to treatment.
• The use of statistics allows the clinical researcher to form
reasonable and accurate inferences from collected
information and to make sound decisions in the presence
of uncertainty.

4. Statistical reasoning components
1. Establishing an objective framework for conducting
an investigation
2. Placing data and theory on an equal scientific
footing
3. Designing data production through experimentation
4. Quantifying the influence of chance
5. Estimating systematic and random effects
6. Combining theory and data using formal methods

5. In summary
• Clinical researchers must generalize from the few to
many and combine empirical evidence with theory..
• In both medical and statistical sciences, empirical
knowledge is generated from observations and data.
• Medical theory is based upon established biology and
hypotheses.
• Statistical theory is derived from mathematical and
probabilistic models.
• To establish a hypothesis requires both a theoretical
basis in biology and statistical support for the
hypothesis, based on the observed data and the
theoretical statistical model.

6. Course Description
• Chapter 1: Introduction to Clinical Trials
– Fundamental Points
– Definition of a Clinical Trials
– Clinical Trial Phases
– Why Are Clinical Trials Needed?
– Problems in the Timing of a Trial
• Chapter two: Design of clinical Trials
– Basic Design Considerations
– Experimental Design
– Randomization
– Introduction to Parallel and Crossover Designs
– Crossover Design
• Chapter 3: Study participants & Treatment allocations
– The study population
– Biases in Clinical trials
– Sample size
– Treatment allocation
– End points

7. • Chapter 4: Data analysis in clinical trials
– Introduction to Statistical Methods
– Hypothesis testing
– Confidence Interval Approach
– Intention to treat (ITT)
– Subgroup analysis
– Meta analysis
• Chapter 5: Ethical issues in Clinical Trials
– Ethical principles
– Regulatory bodies
– Data safety & monitoring
– Interim decision making

8. References
1. Chow S.C. and Liu J.P. (2004), Design and Analysis of Clinical
Trials, 2nd Edition, Marcel Dekkar.
2. Friedman L. M., Furburg C., and Demets D. L. (1998),
Fundamentals of Clinical Trials, Springer Verlang.
3. Fleiss J. L. (1989), The Design and Analysis of Clinical
Experiments, Wiley and Sons.
4. Steven Piantadosi, ( 2005), Clinical Trials: A Methodologic
Perspective, 2nd edition, Wiley-Interscience;
• Lecture Slides