The Placebo Responder Rate in Children and Adolescents

The key issue facing clinicians conducting clinical trials for the acute treatment of migraine in the pediatric and adolescent patients has been the high placebo responder rate. While adult studies have been able to predictably yield a placebo-response rate about 35%, pediatric trials typically have demonstrated rates to be 50% or higher. Even the most novice student of statistics can appreciate the challenge to designing a study with an anticipated placebo response of greater than 50% to 60%. To demonstrate efficacy with a 50+% placebo-response rate, the differential between active and placebo must be large. Unfortunately, reported studies have typical “active” responder rate has been between 60% to 85%. The burden then falls to the attainment of an “n” sufficient to detect a significant difference. This becomes discouraging, cost-ineffective, and, quite frankly, ponderous. The purpose of this review is to survey the available literature regarding acute treatment trials, to critically assess the design flaws that have become increasingly apparent and, finally, to comment on “trench” experiences that may be useful in the development of future trials. How can we affect the placebo responder rates?