ABSTRACT
Traditionally, the design of phase I trials has been seen as a clinical objective in the sense of quantifying and understanding the safety profile of a new agent or combination of agents when given in a first-in-man trial or in a new patient population. The goal is to escalate and de-escalate until we find a safe and tolerable dose with the additional constraints that are present in any clinical trial that we have to accomplish as efficiently as possible. This means that we need to minimize the number of patients enrolled in order to answer the study’s objective, minimize cost and resources by minimizing trial duration, while at the same time try to get the right dose which is the maximum tolerated dose (MTD) or the vicinity of the MTD as fast as possible so that patients enrolled in this trial can be treated at and around the MTD. The initial questions that clinical investigators need to address are as follows:
How many dose levels will we explore?
What is the actual amount of dosage increase between adjacent dose levels?
How many patients are needed to complete the study?
How long will the trial take to complete?
What is the definition of dose-limiting toxicity (DLT)?
