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Real-world evidence of emerging therapies in headache

Edited by: Shuu-Jiun Wang and Michel Lanteri-Minet

Randomized controlled trials (RCTs) top the hierarchy of evidence for the assessment of new health technologies due to their high internal validity and reduction of confounding. However, RCTs have limited external validity with respect to the generalizability of results to a real-world setting. A particular limitation is the weak representativeness of a RCT population related to inclusion/exclusion criteria, restricted sample size and non-consideration of special populations (children and adolescents, elderly, pregnant and breastfeeding females, patients with comorbidities, patients belonging to particular ethnic groups). Other elements limit the use of RCTs data in daily practice, such as the duration of RCTs, which is often too short, and the lack of identification of predictive markers for therapeutic response. To improve the external validity of RCTs, it is recommended a supplementation with Real-World Evidence (RWE).

RWE is derived from analysis of Real-World data (RWD) collected from a variety of sources (registries, collections of electronic health records, administrative and medical claims databases…). RWD sources can be used for data collection but also to develop RWE randomized trials (large simple trials, pragmatic clinical trials) and observational studies (prospective and retrospective).

RWE providing clinical evidence plays an increasing role in health care decisions but, to be relevant and useful, it is essential that RWE be of high quality. In this perspective, many initiatives have been developed. In 2016, after the promulgation of the Cures Act designed to accelerate medical product development and bring new innovations and advances faster and more efficiently to the patients who need them in United States, the Food and Drug Administration (FDA) developed a framework for evaluating the potential use of RWE. More recently, European Medicines Agency (EMA) initiated the Data Analysis and Real Word Interrogation Network (DARWIN EU®) project with the vision to give EMA and national competent authorities in European Union Members States access to valid and trustworthy RWE.

In this context, The Journal of Headache and Pain has started a thematic series on Real-World Evidence of Emerging Therapies in Headache with the aim to collect high quality RWD dedicated to headache field. 

In this collection, both review articles and original contributions are welcome.  


  1. Many migraine patients do not respond adequately to conventional preventive treatments and are therefore described as treatment/medically resistant or difficult to treat cases. Calcitonin gene-related peptide ...

    Authors: Emma Troy, Arif A. Shrukalla, Alina Buture, Katie Conaty, Esther Macken, Roisin Lonergan, Jane Melling, Niamh Long, Eamonn Shaikh, Kieran Birrane, Esther M. Tomkins, Peter J. Goadsby and Martin H. Ruttledge
    Citation: The Journal of Headache and Pain 2023 24:5
  2. Controlled and real-world evidence have demonstrated the efficacy of calcitonin gene related peptide (CGRP) monoclonal antibodies (MABs) in migraine. However, data on the over-one-year sustained effectiveness ...

    Authors: Anna P. Andreou, Matteo Fuccaro, Bethany Hill, Madeleine Murphy, Valeria Caponnetto, Rachael Kilner and Giorgio Lambru
    Citation: The Journal of Headache and Pain 2022 23:139
  3. The identification of predictors of response to antiCGRP mAbs could favor tailored therapies and personalized treatment plans. This study is aimed at investigating predictors of ≥ 50%, ≥ 75% and 100% response ...

    Authors: Piero Barbanti, Gabriella Egeo, Cinzia Aurilia, Claudia Altamura, Florindo d’Onofrio, Cinzia Finocchi, Maria Albanese, Marco Aguggia, Renata Rao, Maurizio Zucco, Fabio Frediani, Massimo Filippi, Roberta Messina, Sabina Cevoli, Antonio Carnevale, Giulia Fiorentini…
    Citation: The Journal of Headache and Pain 2022 23:138
  4. Galcanezumab of 300 mg monthly is the FDA approved preventive medication for cluster headache (CH) during the cluster period. Compared to the 120 mg galcanezumab syringe for the treatment of migraines, the 100...

    Authors: Heejung Mo, Byung-Kun Kim, Heui-Soo Moon and Soo-Jin Cho
    Citation: The Journal of Headache and Pain 2022 23:132
  5. In Italy, monoclonal antibodies targeting the CGRP pathway are subsidized for the preventive treatment of high frequency and chronic migraine (CM) in patients with a MIgraine Disability ASsessment (MIDAS) scor...

    Authors: Roberto De Icco, Gloria Vaghi, Marta Allena, Natascia Ghiotto, Elena Guaschino, Daniele Martinelli, Lara Ahmad, Michele Corrado, Federico Bighiani, Federica Tanganelli, Sara Bottiroli, Francescantonio Cammarota, Grazia Sances and Cristina Tassorelli
    Citation: The Journal of Headache and Pain 2022 23:123
  6. Migraine is responsible for significant disability and societal burden. Recently, drugs targeting the calcitonin gene-related peptide (CGRP) pathway raised new hopes. CGRP, a potent vasodilator, plays a key ro...

    Authors: Alexandre O. Gérard, Diane Merino, Elise K. Van Obberghen, Fanny Rocher, Alexandre Destere, Michel Lantéri-Minet and Milou-Daniel Drici
    Citation: The Journal of Headache and Pain 2022 23:53