The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression
Abstract Background Migraine 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 tr...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10194-023-01587-0 |
| _version_ | 1797822726437601280 |
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| author | Stewart J. Tepper Jessica Cirillo Edward Kim Gil L’Italien Julie M. Tweedie Kunal Lodaya Dushon Riley Farah Pathan Nicholas Antaki Brian H. Nathanson Peter McAllister |
| author_facet | Stewart J. Tepper Jessica Cirillo Edward Kim Gil L’Italien Julie M. Tweedie Kunal Lodaya Dushon Riley Farah Pathan Nicholas Antaki Brian H. Nathanson Peter McAllister |
| author_sort | Stewart J. Tepper |
| collection | DOAJ |
| description | Abstract Background Migraine 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. Methods We 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. Results A 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. Conclusion Placebo response increased over the past 30 years in migraine preventive trials. This phenomenon should be considered when designing clinical trials and conducting meta-analyses. |
| first_indexed | 2024-03-13T10:13:23Z |
| format | Article |
| id | doaj.art-3e58907b2f604a08a99a67903cab2933 |
| institution | Directory Open Access Journal |
| issn | 1129-2377 |
| language | English |
| last_indexed | 2024-03-13T10:13:23Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-3e58907b2f604a08a99a67903cab29332023-05-21T11:22:03ZengBMCThe Journal of Headache and Pain1129-23772023-05-0124111810.1186/s10194-023-01587-0The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regressionStewart J. Tepper0Jessica Cirillo1Edward Kim2Gil L’Italien3Julie M. Tweedie4Kunal Lodaya5Dushon Riley6Farah Pathan7Nicholas Antaki8Brian H. Nathanson9Peter McAllister10Geisel School of Medicine at Dartmouth, Dartmouth Headache ClinicBiohaven PharmaceuticalsBiohaven PharmaceuticalsBiohaven PharmaceuticalsBiohaven PharmaceuticalsBoston Strategic Partners IncBoston Strategic Partners IncBoston Strategic Partners IncBoston Strategic Partners IncOptiStatim, LLCNew England Institute for Neurology and HeadacheAbstract Background Migraine 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. Methods We 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. Results A 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. Conclusion Placebo response increased over the past 30 years in migraine preventive trials. This phenomenon should be considered when designing clinical trials and conducting meta-analyses.https://doi.org/10.1186/s10194-023-01587-0MigrainePlacebo responsePreventive treatmentTemporal trendMeta-analysisSystematic literature review |
| spellingShingle | Stewart J. Tepper Jessica Cirillo Edward Kim Gil L’Italien Julie M. Tweedie Kunal Lodaya Dushon Riley Farah Pathan Nicholas Antaki Brian H. Nathanson Peter McAllister 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 Migraine Placebo response Preventive treatment Temporal trend Meta-analysis Systematic literature review |
| title | The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression |
| title_full | The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression |
| title_fullStr | The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression |
| title_full_unstemmed | The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression |
| title_short | The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression |
| title_sort | temporal trend of placebo response in migraine prevention from 1990 to 2021 a systematic literature review and meta analysis with regression |
| topic | Migraine Placebo response Preventive treatment Temporal trend Meta-analysis Systematic literature review |
| url | https://doi.org/10.1186/s10194-023-01587-0 |
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