Establishing the dose–response relationship is one of the most important activities

in developing a new drug. A clinical development program for a new drug

can be broadly divided into four phases – namely Phases I, II, III, and IV. Phase

I clinical trials are designed to study the clinical pharmacology. Information obtained

from these studies will help in designing Phase II studies. Dose–response

relationships are usually studied in Phase II. Phase III clinical trials are large-scale,

long-term studies. These studies serve to confirm findings from Phases I and II.

Results obtained from Phases I, II, and III clinical trials would then be documented

and submitted to regulatory agencies for drug approval. In the United States, reviewers

from Food and Drug Administration (FDA) review these documents and

make a decision to approve or to reject this New Drug Application (NDA). If the

new drug is approved, then Phase IV studies can be started. Phase IV clinical trials

are also known as postmarketing studies.

This book introduces the drug development process and the design and analysis

of clinical trials. Much of the material in the book is based on applications of

statistical methods in the design and analysis of dose-response studies. In general,

there are two major types of dose-response concerns in drug development—

concerns regarding drugs developed for nonlife-threatening diseases and those for

life-threatening diseases. Most of the drug development programs in the pharmaceutical

industry and the ICH E4 consider issues of nonlife-threatening diseases.

On the other hand, many of the NIH/NCI sponsored studies and some of the pharmaceutical

industry-sponsored studies deal with life-threatening diseases. Statistical

and medical concerns in designing and analyzing these two types of studies can

be very different. In this book, both types of clinical trials will be covered to a certain

depth.