Chapter 33 - Design of Clinical Development Programs

Abstract

This chapter provides an overview of the clinical drug development process, which includes the clinical proof of mechanism, the clinical proof of concept, and the characterization of clinical safety. Phase I includes first-in-human trials that provide information about the safety (tolerability) and pharmacokinetics (PK) of a new drug. Phase II consists of small trials in individuals with the illness to be treated. The goals of Phase II trials are to provide either a proof of mechanism or a proof of the hypothesized therapeutic concept, identify the patient population in which the new drug appears to work, and determine an appropriate dose regimen for subsequent large-scale trials. Two key resources for input into the design of a successful clinical development program are the corresponding therapeutic Food and Drug Administration (FDA) Guidance and the publicly available reviews by FDA reviewers for previously approved drugs. Objective 1 of clinical development focuses on understanding the factors that influence the absorption, distribution, metabolism, and elimination (ADME) of a new drug, as well as the relationship between drug concentrations in various body fluids or organs and the observed pharmacological effects. Objective 2 entails the assessment of a new drug to determine what types of clinical side effects can be expected and in which patient populations, at what doses and dose durations, and whether the side effects are reversible and, if so, after how long. The critical clinical drug development decision points are also elaborated in the chapter.