Learning About New Therapies: Phase 3 Clinical Studies—And Beyond

Abstract

All new therapeutic agents, and updated versions of older ones, must be submitted for review by regulatory agencies. While this process is complex, its goals as stated by the U.S. Food and Drug Administration (FDA) are straightforward. The main aim is to determine “whether the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks” (1). Additional concerns are the information provided in the package insert and assurance of quality and consistency of the manufacturing process. Phase 3 trials, which test the safety and efficacy of candidate drugs in moderately large cohorts of human subjects, lie at the center of the process. Properly done studies of this kind help determine whether a new product should be approved for clinical use and also provide some guidance regarding how best to use it in daily practice. However, phase 3 studies—as essential as they are to the regulatory process—have important limitations, which are the topic of this commentary. Appearing in this issue of Diabetes Care is a good example of such a study. Gough et al. (2) report a comparison of a 200 units/mL (U200) formulation of degludec, a long-acting insulin analog, with U100 insulin glargine (Lantus). The study was well designed and well conducted. The investigators enrolled 457 participants with type 2 diabetes no longer well controlled with oral therapies alone (mean A1C ∼8.2%), and randomized them to begin and titrate dosage of once-daily U200 degludec or U100 glargine using a typical treat-to-target scheme for 26 weeks. Efficacy of the new agent was assessed by the reduction of A1C from baseline, and its safety by, among other measurements, the frequency of hypoglycemic events. As in many studies, the main end point was noninferiority of glycemic improvement versus a well-known active comparator. The results …