Design considerations in migraine with aura trials: Learning from experience

Abstract

In this issue of the journal, Hauge and colleagues (1) discuss the challenges they faced, and the lessons they learned, while studying the effects of the drug tonabersat. Tonabersat is ineffective for migraine without aura, but may work against aura. Hauge and colleagues have participated in five tonabersat trials and have additional experience studying the epidemiology and diagnosis of aura (2). Based on their knowledge, these researchers make a number of recommendations about the design of trials in migraine with aura, which are summarised in Box 1. They remind us that the design and interpretation of such trials presents methodological challenges. These include the variability of aura occurrence and duration, selection and measurement of outcomes, and the need for precise techniques of data collection. Experienced headache specialists have always known that for some migraine sufferers it is aura, rather than headache, that is disabling. Over time, scientific knowledge of the mechanisms underlying aura has increased. Recent epidemiological research provides reason to suspect that repeated attacks of aura – even in the absence of headache – may be undesirable rather than harmless. Animal models now allow the identification of candidate drugs that block cortical spreading depression and might be expected to work against aura in humans. All of these things have increased interest in treatments that target aura, not just headache, and the tonabersat trials highlight aspects of migraine treatment trial design that may need modification.