Issues Impacting Adverse Event Frequency and Severity

We explore factors that may have contributed to differences in treatment-emergent adverse events in the phase 2 and phase 3 lasmiditan clinical trials. Phase 2 and phase 3 trials showed that the centrally penetrant 5-HT agonist, lasmiditan, was effective; higher frequency and severity of adverse eve...

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Autores: Kudrow, David, Krege, John H., Hundemer, Hans P., Berg, Paul H., Khanna, Rashna, Ossipov, Michael H., Pozo-Rosich, Patricia|||0000-0003-0796-4702
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:226199
Acceso en línea:https://ddd.uab.cat/record/226199
https://dx.doi.org/urn:doi:10.1111/head.13731
Access Level:acceso abierto
Palabra clave:Episodic migraine
Migraine headache
Lasmiditan
Adverse events
Treatment-emergent adverse event
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spelling Issues Impacting Adverse Event Frequency and SeverityDifferences Between Randomized Phase 2 and Phase 3 Clinical Trials for LasmiditanKudrow, DavidKrege, John H.Hundemer, Hans P.Berg, Paul H.Khanna, RashnaOssipov, Michael H.Pozo-Rosich, Patricia|||0000-0003-0796-4702Episodic migraineMigraine headacheLasmiditanAdverse eventsTreatment-emergent adverse eventWe explore factors that may have contributed to differences in treatment-emergent adverse events in the phase 2 and phase 3 lasmiditan clinical trials. Phase 2 and phase 3 trials showed that the centrally penetrant 5-HT agonist, lasmiditan, was effective; higher frequency and severity of adverse events (AEs) were seen in phase 2. This work represents a hybrid of a review of primary documents and study reports with additional post hoc analyses. Protocols, informed consents, data collection forms, and methodologies were reviewed. This information was supplemented by results from the clinical study reports and post hoc analyses of individual patient data from each trial. For lasmiditan 100 and 200 mg, in phase 2, the incidence of ≥1 AE was 72-86% (26% severe), while in phase 3 was 36-43% (2% severe). The most common AEs in all studies were CNS-related. The phase 2 consent form was more descriptive of AEs than phase 3. In phase 2, patients recorded AEs and severity in a paper diary that warned about drowsiness and dizziness. In phase 3, patients recorded in electronic diaries whether they experienced unusual feelings after dosing with lasmiditan that they had not felt with a migraine before, and were contacted to determine if an AE had occurred. In phase 2, the AE Schwindel was variably translated from German as "vertigo" or "dizziness," while phase 3 vertigo cases were queried to ensure there was a sensation of rotation or movement. History of recurrent dizziness and/or vertigo was exclusionary in phase 3. This work illustrates how informed consent wording, AE collection methods, translation, exclusion criteria, and other factors may be important determinants for reporting of the frequency and severity of AEs in clinical trials.Universitat Autònoma de Barcelona 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/226199https://dx.doi.org/urn:doi:10.1111/head.13731reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2261992026-06-06T12:50:31Z
dc.title.none.fl_str_mv Issues Impacting Adverse Event Frequency and Severity
Differences Between Randomized Phase 2 and Phase 3 Clinical Trials for Lasmiditan
title Issues Impacting Adverse Event Frequency and Severity
spellingShingle Issues Impacting Adverse Event Frequency and Severity
Kudrow, David
Episodic migraine
Migraine headache
Lasmiditan
Adverse events
Treatment-emergent adverse event
title_short Issues Impacting Adverse Event Frequency and Severity
title_full Issues Impacting Adverse Event Frequency and Severity
title_fullStr Issues Impacting Adverse Event Frequency and Severity
title_full_unstemmed Issues Impacting Adverse Event Frequency and Severity
title_sort Issues Impacting Adverse Event Frequency and Severity
dc.creator.none.fl_str_mv Kudrow, David
Krege, John H.
Hundemer, Hans P.
Berg, Paul H.
Khanna, Rashna
Ossipov, Michael H.
Pozo-Rosich, Patricia|||0000-0003-0796-4702
author Kudrow, David
author_facet Kudrow, David
Krege, John H.
Hundemer, Hans P.
Berg, Paul H.
Khanna, Rashna
Ossipov, Michael H.
Pozo-Rosich, Patricia|||0000-0003-0796-4702
author_role author
author2 Krege, John H.
Hundemer, Hans P.
Berg, Paul H.
Khanna, Rashna
Ossipov, Michael H.
Pozo-Rosich, Patricia|||0000-0003-0796-4702
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Episodic migraine
Migraine headache
Lasmiditan
Adverse events
Treatment-emergent adverse event
topic Episodic migraine
Migraine headache
Lasmiditan
Adverse events
Treatment-emergent adverse event
description We explore factors that may have contributed to differences in treatment-emergent adverse events in the phase 2 and phase 3 lasmiditan clinical trials. Phase 2 and phase 3 trials showed that the centrally penetrant 5-HT agonist, lasmiditan, was effective; higher frequency and severity of adverse events (AEs) were seen in phase 2. This work represents a hybrid of a review of primary documents and study reports with additional post hoc analyses. Protocols, informed consents, data collection forms, and methodologies were reviewed. This information was supplemented by results from the clinical study reports and post hoc analyses of individual patient data from each trial. For lasmiditan 100 and 200 mg, in phase 2, the incidence of ≥1 AE was 72-86% (26% severe), while in phase 3 was 36-43% (2% severe). The most common AEs in all studies were CNS-related. The phase 2 consent form was more descriptive of AEs than phase 3. In phase 2, patients recorded AEs and severity in a paper diary that warned about drowsiness and dizziness. In phase 3, patients recorded in electronic diaries whether they experienced unusual feelings after dosing with lasmiditan that they had not felt with a migraine before, and were contacted to determine if an AE had occurred. In phase 2, the AE Schwindel was variably translated from German as "vertigo" or "dizziness," while phase 3 vertigo cases were queried to ensure there was a sensation of rotation or movement. History of recurrent dizziness and/or vertigo was exclusionary in phase 3. This work illustrates how informed consent wording, AE collection methods, translation, exclusion criteria, and other factors may be important determinants for reporting of the frequency and severity of AEs in clinical trials.
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/226199
https://dx.doi.org/urn:doi:10.1111/head.13731
url https://ddd.uab.cat/record/226199
https://dx.doi.org/urn:doi:10.1111/head.13731
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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