6a.1 - Treatment Mechanism and Dose Finding Studies

For many treatment mechanism (TM) studies, sample size is not an important issue because usually only a few subjects are enrolled to investigate treatment mechanisms. Here you are taking a lot of measurements on a few subjects in order to find out what might be going on with your treatment.

As presented last week, dose-finding (DF) and dose-ranging studies typically involve a design scheme, such as a modified Fibonacci design or continual reassessment. An example of phase I cytotoxic drug trials is as follows. A set of doses is determined a priori, such as 100 mg, 200 mg, 300 mg, 500 mg, 800 mg, etc. Subjects are recruited into the DF study in groups of three. The first group receives the lowest dose of 100 mg. If none of the subjects experience the effect (toxicity, side effect, etc.), then the next group of three subjects is escalated to the next dose of 200 mg. If one of the three subjects at 100 mg experiences the effect, however, then the next group of three subjects will receive the same dose of 100 mg. Whenever six subjects at the same dose reveal at least two subjects that experience the effect, then the study is terminated and the chosen dose for a safety and efficacy study is the previous dose level.

With such mechanisms in place to determine initial dosage levels, selection of. the study sample size is not a major consideration. In fact, the final sample size is dependent on patient outcomes.