The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression

The Journal of Headache and Pain

Research

Julie M. Tweedie¹  Jessica Cirillo¹  Edward Kim¹  Gil L’Italien¹  Kunal Lodaya²  Nicholas Antaki²  Farah Pathan²  Dushon Riley²  Stewart J. Tepper³  Peter McAllister⁴  Brian H. Nathanson⁵ 

[1] Biohaven Pharmaceuticals, New Haven, CT, USA;Boston Strategic Partners Inc, 4 Wellington St., Suite 3, Boston, MA, USA;Geisel School of Medicine at Dartmouth, Dartmouth Headache Clinic, Hanover, NH, USA;New England Institute for Neurology and Headache, Stamford, CT, USA;OptiStatim, LLC, PO Box 60844, Longmeadow, MA, USA;

关键词: Migraine;    Placebo response;    Preventive treatment;    Temporal trend;    Meta-analysis;    Systematic literature review;   

DOI  :  10.1186/s10194-023-01587-0

 received in 2023-01-09, accepted in 2023-04-26,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMigraine affects 1.1 billion people globally and is the second leading cause of disability worldwide. In clinical trials, treatment efficacy is evaluated by comparing the differential responses in the treatment and placebo arms. Although placebo response in preventive migraine trials has been studied, there is limited research examining temporal trends. This study evaluates the trend of placebo response over thirty years in migraine prevention trials and investigates the association of potential confounders, such as patient, treatment, and study characteristics on placebo response using meta-analysis with regression.MethodsWe conducted literature searches from January 1990 to August 2021 in bibliographical databases (PubMed, Cochrane Library, and EMBASE). Studies were selected according to PICOS criteria and included randomized, double-blind, placebo-controlled trials evaluating preventive migraine treatments in adult patients diagnosed with episodic or chronic migraine, with or without aura. The protocol was registered with PROSPERO (CRD42021271732). Migraine efficacy outcomes included were either continuous (e.g., monthly migraine days) or dichotomous (e.g., ≥ 50% responder rate (yes/no)). We assessed the correlation of the change in outcome from baseline in the placebo arm, with the year of publication. The relationship between placebo response and year of publication was also assessed after accounting to confounders.ResultsA total of 907 studies were identified, and 83 were found eligible. For the continuous outcomes, the change from baseline in mean placebo response showed an increase over the years (rho = 0.32, p = 0.006). The multivariable regression analysis also showed an overall increase in placebo response over the years. The correlation analysis of dichotomous responses showed no significant linear trend between publication year and mean placebo response (rho = 0.08, p = 0.596). Placebo response also varied by route of administration.ConclusionPlacebo response increased over the past 30 years in migraine preventive trials. This phenomenon should be considered when designing clinical trials and conducting meta-analyses.

【 授权许可】

CC BY   
© The Author(s) 2023

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