In this chapter we address the design and statistical considerations for the development of “middle phase” clinical trials, especially those associated with phase II cancer trials. Here the focus shifts from toxicity to efficacy, and trials are run on much larger groups of patients (say, 40 to 200). We also delve more deeply into the subject of adaptive designs, a subject of greatly increasing interest and utility in middle-phase studies. After obtaining preliminary information about the safety profile, dose,
and administration schedule of a drug in early (phase I) development, the next issue is to examine whether a drug has sufficient efficacy to warrant further development. Phase II studies can be further divided into two parts. The initial assessment of the drug’s efficacy is the primary goal for phase IIA trials. Typically, phase IIA trials are conducted as single-arm studies to assess the efficacy of new drugs, with the goal of screening out those that are ineffective. Subsequently, phase IIB trials are multi-arm studies to compare the efficacy of the new drug versus the standard treatment or other experimental drugs, so that the most promising one can be selected for large scale evaluation in late phase studies. The toxicity profile of the new agents may also be further evaluated in phase II studies. Phase II studies provide important intermediate steps for a successful
drug development. In today’s post-genomic and high-throughput era, the number of new candidate agents is growing by leaps and bounds. Since late phase studies are large, time consuming, and expensive, middle phase trials play a critical role in eliminating the “chaff” from our drug collection, so that only the most promising treatments are funneled through to late phase development, thus ensuring a higher overall success rate.