Clinical trials of acute treatments for migraine including multiple attack studies of pain, disability, and health-related quality of life

Because migraine has features in common with episodic monophasic pain disorders (such as postoperative or posttraumatic pain) and with chronic pain disorders (such as osteoarthritis or painful neuropathy), it is often considered an episodic-chronic disorder. In clinical practice, the chronic aspects of migraine are addressed using preventive treatment strategies, while the episodic attacks are addressed by acute treatment strategies. Acute treatment strategies have generally been supported by clinical trial designs that focus on single attacks, whereas preventive treatment strategies evaluate multiple attacks over a period of time. Recently, long-term acute treatment clinical designs have emerged that may inform the design of clinical trials for other episodic-chronic disorders. After reviewing traditional acute treatment clinical trials, we focus here on study methods designed to evaluate treatment and management strategies for migraine over multiple attacks, including outcomes that assess the chronic-episodic nature of migraine (such as headache recurrence and consistency of relief), rather than relief from single attacks. We also discuss end points that reflect the treatment needs of patients, such as disability and health-related quality of life. The traditional randomized controlled trial designed to assess treatment efficacy for a single attack is insufficient to address the broader set of issues that arise in clinical practice. We consider clinical trials strategies designed to address the more complex clinical and policy requirements for meeting the needs of those with migraine.