Trial Designs for Evaluating Migraine Treatment

The study aims to estimate treatment effects in randomized controlled trials (RCT) and a balanced placebo design (BPD) to specify how contextual and psychological factors interact in acute migraine treatment and influence adverse event occurrence. Using a clinical within-subjects design, patients with episodic migraine will receive six treatment conditions in a randomized order.

The existing paradigm for testing the effect of treatments is the double-blind RCT comparing an active drug to an inactive placebo. This comparison is done in order to control for contextual and psychological factors such as the patients' treatment expectations - a key factor in placebo responses. However, recent study results have indicated that some assumptions underlying the RCT may be incorrect and may lower the assay sensitivity and miscalculate the actual drug response. The so-called balanced placebo design targets the shortcomings of the RCT by balancing the information given to the patients (correct or false) with the actual treatment administered (active treatment or placebo). In this project, the aim is to examine if the magnitude of the drug effect differs when estimated based on the RCT design and when based on BPD, conditioning on the information provided to the recipient. Additionally, it will also be tested if active drug response and the placebo response interact in acute migraine treatment. Patients suffering from episodic migraine will go through six treatment conditions in randomized order. They will receive acute migraine treatment (a sumatriptan pill) or inactive treatment (a placebo pill) in the event of a developing migraine attack. Using a clinical within-subjects design, the patients receive 1) sumatriptan or 2) placebo and are told that they receive a) sumatriptan or placebo, b) sumatriptan , or c) placebo. All treatments and accompanying treatment descriptions will be administered at home.