Title: What is the comparative clinical and cost- effectiveness of pharmacological treatments for adults with chronic migraine?
Funder: Department of Health and Social Care

Abstract: What is the problem?_x000D_ Chronic migraine is a very disabling condition that can destroy work and family life. People with chronic migraine have headaches on at least 15 days of each month. On at least eight of those days they have other migraine symptoms (such as severe headache, feeling or being sick, sensitivity to light). Many people also have other symptoms, like fatigue, in between headaches. Certain drugs, taken every day, can make headache days less frequent and improve quality of life. These include cheap tablets that have been available for many years and new expensive, injected drugs. _x000D_ _x000D_ There are three problems with the research to date which we would like to address:_x000D_ 1. There is no overall summary of how these drugs compare with placebo (fake) drugs, or with each other, when they are used to prevent chronic migraine. An overall summary could allow doctors to prescribe the most appropriate drugs and let researchers know which drugs need more testing._x000D_ 2. These drugs can cause unpleasant side-effects. Typically, researchers have only measured their effect on the number of headache days and not enough attention has been given to how these drugs may affect a person’s quality of life._x000D_ 3. There has been little research done to find out which of these drugs are best value for money to the NHS._x000D_ _x000D_ What do we want to find out?_x000D_ We want to find out how these drugs compare with each other, and with placebo (fake) drugs. We will look at the benefits and risks of using them. We also want to find out which drugs need new research to decide if they help people with chronic migraine and are good value to the NHS. _x000D_ _x000D_ How will we do this?_x000D_ We will start by looking at what research has already been done on the use of regular drugs to prevent chronic migraine and report the findings. We will look at clinical trials of these drugs. We will also look at research about their side-effects and whether they are value for money. Using this information, we will estimate which drug(s) are better at improving people’s quality of life and are the best value for money. _x000D_ _x000D_ At the end, we will provide an overall picture of which drugs are most useful. We will bring patients and healthcare professionals together to share our findings and discuss how best to use them._x000D_ _x000D_ Sharing the findings_x000D_ We will publish results in scientific journals and present at national and international meetings. With the help of our patient-partners we will also share the results on social media and patient websites. We will continue to work with the National Migraine Centre and to share our findings with people with chronic migraine._x000D_ _x000D_ Patient and Public Involvement (PPI)_x000D_ We have two patient representatives on the team, both of whom have experience of chronic migraine and tried medications to help prevent migraines. They will be part of the study management team, which means they will be invited to meetings and provide their input on the study as it progresses in the same way as our clinical expert team members will. This includes helping us interpret our findings in terms of what they mean for patients. They will also be involved in the final work package, where we will bring patients and health care professionals together to decide on the priorities for future research at a one-day workshop.

Lay abstract: Research question_x000D_ To review and compare the clinical and cost-effectiveness of prophylactic drug treatments for adults with chronic migraine._x000D_ _x000D_ Background_x000D_ Migraine affects 15% of UK adults, most commonly young adults with work and family commitments. Chronic migraine is a profoundly disabling condition and affects 2-4% of the UK adult population and is defined as headaches on 15 days or more a month with features of migraine on at least eight of those days. With the advent of expensive calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs), it is timely to compare the clinical- and cost-effectiveness of drugs to treat chronic migraine._x000D_ _x000D_ Aims and objectives_x000D_ Our overall aim is to produce evidence needed for people with chronic migraines and their doctors to make more informed decisions about prophylactic treatment of chronic migraine._x000D_ _x000D_ Our research objectives seek to determine:_x000D_ 1. What is the comparative effectiveness of prophylactic drugs for chronic migraine?_x000D_ 2. What are the comparative incidences of adverse events of prophylactic drugs used for migraine?_x000D_ 3. What is known about the cost-effectiveness of prophylactic drugs for chronic migraine?_x000D_ 4. Which prophylactic drugs for the management of chronic migraine are the most cost-effective?_x000D_ 5. Based on our findings what should the research recommendations be?_x000D_ _x000D_ Methods_x000D_ We propose five work packages (WP):_x000D_ WP1: Systematic review and network meta-analysis (NMA) of the clinical effectiveness of prophylactic medications; primary analyses include headache days, migraine days, and headache-related quality of life._x000D_ WP2: Systematic review to identify the comparative incidence of adverse events of prophylactic drugs used for migraine._x000D_ WP3: Systematic review of cost-effectiveness studies of prophylactic drugs used for treatment of chronic migraine._x000D_ WP4: Development of an economic model comparing prophylactic drugs for chronic migraine. _x000D_ WP5: Will bring together people with chronic migraine and clinicians in order to feedback the findings of our reviews and identify and prioritise research recommendations._x000D_ _x000D_ Patient and Public Involvement_x000D_ Working closely with two patient representatives who have experience of chronic migraine, we will discuss our results with them at regular intervals via teleconference or face-to-face meetings, where appropriate and feasible. Their involvement will primarily be in WP5 and interpretation of the results and translation to research recommendations and, also dissemination of findings. Both of our PPI representatives felt that it would make most sense to have one meeting rather than separating the two groups. This avoids having two separate debates and potentially coming up with two ‘consensuses’, which would not achieve our goal of a single overall consensus._x000D_ _x000D_ Timelines for delivery_x000D_ We will complete the project within the 18-month timeframe._x000D_ _x000D_ Anticipated impact and dissemination_x000D_ Our findings from our evidence synthesis and economic model will feed directly into recommendations on prophylactic medications for chronic migraine.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: NEUROLOGICAL