Clarification Regarding “Phase II Trials Published in 2002: A Cross-Specialty Comparison Showing Significant Design Differences between Oncology Trials and Other Medical Specialties” and the Accompanying Commentary, “Phase II Cancer Trials: Out of Control?”

To the Editors: We would like to clarify our comments about the use of placebos in phase II cancer clinical trials, as discussed in the article by Michaelis and Ratain, “Phase II Trials Published in 2002: A Cross-Specialty Comparison Showing Significant Design Differences between Oncology Trials and Other Medical Specialties” (1), and the accompanying commentary, “Phase II Cancer Trials: Out of Control” by Chabner (2).

In particular, the commentary addressed the “problematic” inclusion of a control group treated only with placebo as one arm of a randomized phase II evaluation of an experimental compound. Although many oncologists would find it difficult to offer such a trial to patients with progressive and potentially fatal disease, we both strongly endorse certain “innovative” trial designs that use placebos. Such designs might include either a limited period of placebo treatment versus initial therapy with experimental drug, a trial of a standard agent plus placebo versus the same standard agent plus an experimental agent, or a randomized discontinuation design in which all patients receive experimental drug, and, thereafter, stable patients receive either continued experimental drug or placebo, until disease progression. These and other designs might provide valuable information regarding the effect of the experimental drug on disease progression, and at the same time provide an opportunity to assess the effect of drug on biomarkers. In these and other trial designs, periods of placebo treatment are not likely to adversely affect patient outcomes compared with “standard” treatment. Other novel designs using placebos are certainly possible.