Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis
Abstract Background Natalizumab and fingolimod are used as high-efficacy treatments in relapsing–remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The o...
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| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Medical Research Methodology |
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| Online Access: | https://doi.org/10.1186/s12874-022-01623-8 |
| _version_ | 1818238443440832512 |
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| author | M. Lefort S. Sharmin J. B. Andersen S. Vukusic R. Casey M. Debouverie G. Edan J. Ciron A. Ruet J. De Sèze E. Maillart H. Zephir P. Labauge G. Defer C. Lebrun-Frenay T. Moreau E. Berger P. Clavelou J. Pelletier B. Stankoff O. Gout E. Thouvenot O. Heinzlef A. Al-Khedr B. Bourre O. Casez P. Cabre A. Montcuquet A. Wahab J. P. Camdessanché A. Maurousset H. Ben Nasr K. Hankiewicz C. Pottier N. Maubeuge D. Dimitri-Boulos C. Nifle D. A. Laplaud D. Horakova E. K. Havrdova R. Alroughani G. Izquierdo S. Eichau S. Ozakbas F. Patti M. Onofrj A. Lugaresi M. Terzi P. Grammond F. Grand’Maison B. Yamout A. Prat M. Girard P. Duquette C. Boz M. Trojano P. McCombe M. Slee J. Lechner-Scott R. Turkoglu P. Sola D. Ferraro F. Granella V. Shaygannejad J. Prevost D. Maimone O. Skibina K. Buzzard A. Van der Walt R. Karabudak B. Van Wijmeersch T. Csepany D. Spitaleri S. Vucic N. Koch-Henriksen F. Sellebjerg P. S. Soerensen C. C. Hilt Christensen P. V. Rasmussen M. B. Jensen J. L. Frederiksen S. Bramow H. K. Mathiesen K. I. Schreiber H. Butzkueven M. Magyari T. Kalincik E. Leray |
| author_facet | M. Lefort S. Sharmin J. B. Andersen S. Vukusic R. Casey M. Debouverie G. Edan J. Ciron A. Ruet J. De Sèze E. Maillart H. Zephir P. Labauge G. Defer C. Lebrun-Frenay T. Moreau E. Berger P. Clavelou J. Pelletier B. Stankoff O. Gout E. Thouvenot O. Heinzlef A. Al-Khedr B. Bourre O. Casez P. Cabre A. Montcuquet A. Wahab J. P. Camdessanché A. Maurousset H. Ben Nasr K. Hankiewicz C. Pottier N. Maubeuge D. Dimitri-Boulos C. Nifle D. A. Laplaud D. Horakova E. K. Havrdova R. Alroughani G. Izquierdo S. Eichau S. Ozakbas F. Patti M. Onofrj A. Lugaresi M. Terzi P. Grammond F. Grand’Maison B. Yamout A. Prat M. Girard P. Duquette C. Boz M. Trojano P. McCombe M. Slee J. Lechner-Scott R. Turkoglu P. Sola D. Ferraro F. Granella V. Shaygannejad J. Prevost D. Maimone O. Skibina K. Buzzard A. Van der Walt R. Karabudak B. Van Wijmeersch T. Csepany D. Spitaleri S. Vucic N. Koch-Henriksen F. Sellebjerg P. S. Soerensen C. C. Hilt Christensen P. V. Rasmussen M. B. Jensen J. L. Frederiksen S. Bramow H. K. Mathiesen K. I. Schreiber H. Butzkueven M. Magyari T. Kalincik E. Leray |
| author_sort | M. Lefort |
| collection | DOAJ |
| description | Abstract Background Natalizumab and fingolimod are used as high-efficacy treatments in relapsing–remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. Methods Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. Results Overall, 5,148 relapsing–remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. Conclusions This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled. |
| first_indexed | 2024-12-12T12:41:44Z |
| format | Article |
| id | doaj.art-84c3797631444a10b4fb616e78d4bf21 |
| institution | Directory Open Access Journal |
| issn | 1471-2288 |
| language | English |
| last_indexed | 2024-12-12T12:41:44Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Research Methodology |
| spelling | doaj.art-84c3797631444a10b4fb616e78d4bf212022-12-22T00:24:12ZengBMCBMC Medical Research Methodology1471-22882022-05-0122111410.1186/s12874-022-01623-8Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosisM. Lefort0S. Sharmin1J. B. Andersen2S. Vukusic3R. Casey4M. Debouverie5G. Edan6J. Ciron7A. Ruet8J. De Sèze9E. Maillart10H. Zephir11P. Labauge12G. Defer13C. Lebrun-Frenay14T. Moreau15E. Berger16P. Clavelou17J. Pelletier18B. Stankoff19O. Gout20E. Thouvenot21O. Heinzlef22A. Al-Khedr23B. Bourre24O. Casez25P. Cabre26A. Montcuquet27A. Wahab28J. P. Camdessanché29A. Maurousset30H. Ben Nasr31K. Hankiewicz32C. Pottier33N. Maubeuge34D. Dimitri-Boulos35C. Nifle36D. A. Laplaud37D. Horakova38E. K. Havrdova39R. Alroughani40G. Izquierdo41S. Eichau42S. Ozakbas43F. Patti44M. Onofrj45A. Lugaresi46M. Terzi47P. Grammond48F. Grand’Maison49B. Yamout50A. Prat51M. Girard52P. Duquette53C. Boz54M. Trojano55P. McCombe56M. Slee57J. Lechner-Scott58R. Turkoglu59P. Sola60D. Ferraro61F. Granella62V. Shaygannejad63J. Prevost64D. Maimone65O. Skibina66K. Buzzard67A. Van der Walt68R. Karabudak69B. Van Wijmeersch70T. Csepany71D. Spitaleri72S. Vucic73N. Koch-Henriksen74F. Sellebjerg75P. S. Soerensen76C. C. Hilt Christensen77P. V. Rasmussen78M. B. Jensen79J. L. Frederiksen80S. Bramow81H. K. Mathiesen82K. I. Schreiber83H. Butzkueven84M. Magyari85T. Kalincik86E. Leray87Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U 1309, Univ Rennes, EHESP, CNRS, InsermDepartment of Medicine, University of MelbourneDepartment of Neurology, The Danish Multiple Sclerosis Registry, Copenhagen University HospitalService de Neurologie, Sclérose en Plaques, Pathologies de La Myéline Et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de LyonService de Neurologie, Sclérose en Plaques, Pathologies de La Myéline Et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de LyonCentre Hospitalier Régional Universitaire de Nancy, Hôpital CentralCentre Hospitalier Universitaire de Rennes, Hôpital PontchaillouCentre Hospitalier Universitaire de Toulouse, Hôpital Purpan, CRC-SEPCentre Hospitalier Universitaire de Bordeaux, Hôpital PellegrinService des maladies inflammatoires du système nerveux – neurologie, centre d’investigation clinique de Strasbourg, Hôpitaux Universitaire de Strasbourg, Hôpital de HautepierreAssistance Publique Des Hôpitaux de Paris, Hôpital de La Pitié-SalpêtrièreCentre Hospitalier Universitaire de Lille, Hôpital SalengroCentre Hospitalier Universitaire de Montpellier, Hôpital Gui de ChauliacCentre Hospitalier Universitaire de Caen Normandie, Hôpital Côte de NacreCentre Hospitalier Universitaire de Nice, UR2CA-URRIS,, Université Nice Côte d’Azur, HôpitalCentre Hospitalier Universitaire Dijon Bourgogne, Hôpital François Mitterrand, Maladies Inflammatoires du Système Nerveux Et Neurologie GénéraleCentre Hospitalier Régional Universitaire de Besançon, Hôpital Jean MinjozCentre Hospitalier Universitaire de Clermont-Ferrand, Hôpital Gabriel-MontpiedService de Neurologie, Aix Marseille Univ, APHM, Hôpital de La TimoneAssistance Publique Des Hôpitaux de Paris, Hôpital Saint-AntoineFondation Adolphe de Rothschild de L’œil Et du CerveauCentre Hospitalier Universitaire de Nîmes, Hôpital CarémeauCentre Hospitalier Intercommunal de Poissy Saint-Germain-en-LayeCentre Hospitalier Universitaire d’Amiens PicardieRouen University HospitalCentre Hospitalier Universitaire Grenoble-AlpesCentre Hospitalier Universitaire de Martinique, Hôpital Pierre Zobda-QuitmanCentre Hospitalier Universitaire Limoges, Hôpital DupuytrenAssistance Publique Des Hôpitaux de Paris, Hôpital Henri MondorCentre Hospitalier Universitaire de Saint-Étienne, Hôpital NordCentre Hospitalier Régional Universitaire de Tours, Hôpital BretonneauCentre Hospitalier Sud FrancilienCentre Hospitalier de Saint-Denis, Hôpital CasanovaCentre Hospitalier de PontoiseCentre Hospitalier Universitaire de Poitiers, Site de La MilétrieAssistance Publique Des Hôpitaux de Paris, Hôpital BicêtreCentre Hospitalier de Versailles, Hôpital André-MignotCHU de NantesDepartment of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University HospitalDepartment of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University HospitalDivision of Neurology, Department of Medicine, Amiri HospitalHospital Universitario Virgen MacarenaHospital Universitario Virgen MacarenaDokuz Eylul UniversityGF Ingrassia Department, University of CataniaDepartment of Neuroscience, Imaging, and Clinical Sciences, University G. d’AnnunzioDipartimento Di Scienze Biomediche E Neuromotorie, Università Di BolognaMedical Faculty, 19 Mayis UniversityCISSS Chaudiere-AppalacheNeuro Rive-SudNehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical CenterHopital Notre DameHopital Notre DameHopital Notre DameKTU Medical Faculty Farabi HospitalDepartment of Basic Medical Sciences, Neuroscience and Sense Organs, University of BariUniversity of QueenslandFlinders UniversitySchool of Medicine and Public Health, University NewcastleHaydarpasa Numune Training and Research HospitalDepartment of Neuroscience, Azienda Ospedaliera UniversitariaDepartment of Neuroscience, Azienda Ospedaliera UniversitariaDepartment of Medicine and Surgery, University of ParmaIsfahan University of Medical SciencesCSSS Saint-JérômeGaribaldi HospitalMonash UniversityMonash UniversityMonash UniversityHacettepe UniversityRehabilitation and MS-Centre Overpelt and Hasselt UniversityDepartment of Neurology, Faculty of Medicine, University of DebrecenAzienda Ospedaliera Di Rilievo Nazionale San Giuseppe Moscati AvellinoWestmead HospitalDepartment of Clinical Epidemiology, Aarhus University Hospital AarhusDanish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet GlostrupDanish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet GlostrupDepartment of Neurology, Aalborg University Hospital, Multiple Sclerosis UnitAarhus University Hospital, Neurology, PJJ BoulevardDepartment of Neurology, University Hospital of Northern SealandDepartment of Clinical Medicine, University of CopenhagenDanish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet GlostrupDepartment of Neurology, Copenhagen University Hospital HerlevDanish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet GlostrupCentral Clinical School, Monash UniversityMelbourne MS Centre, Department of Neurology, Royal Melbourne HospitalDepartment of Medicine, University of MelbourneArènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U 1309, Univ Rennes, EHESP, CNRS, InsermAbstract Background Natalizumab and fingolimod are used as high-efficacy treatments in relapsing–remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. Methods Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. Results Overall, 5,148 relapsing–remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. Conclusions This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.https://doi.org/10.1186/s12874-022-01623-8EffectivenessMultiple sclerosisPropensity scoreIndication biasCausal contrastsCensoring |
| spellingShingle | M. Lefort S. Sharmin J. B. Andersen S. Vukusic R. Casey M. Debouverie G. Edan J. Ciron A. Ruet J. De Sèze E. Maillart H. Zephir P. Labauge G. Defer C. Lebrun-Frenay T. Moreau E. Berger P. Clavelou J. Pelletier B. Stankoff O. Gout E. Thouvenot O. Heinzlef A. Al-Khedr B. Bourre O. Casez P. Cabre A. Montcuquet A. Wahab J. P. Camdessanché A. Maurousset H. Ben Nasr K. Hankiewicz C. Pottier N. Maubeuge D. Dimitri-Boulos C. Nifle D. A. Laplaud D. Horakova E. K. Havrdova R. Alroughani G. Izquierdo S. Eichau S. Ozakbas F. Patti M. Onofrj A. Lugaresi M. Terzi P. Grammond F. Grand’Maison B. Yamout A. Prat M. Girard P. Duquette C. Boz M. Trojano P. McCombe M. Slee J. Lechner-Scott R. Turkoglu P. Sola D. Ferraro F. Granella V. Shaygannejad J. Prevost D. Maimone O. Skibina K. Buzzard A. Van der Walt R. Karabudak B. Van Wijmeersch T. Csepany D. Spitaleri S. Vucic N. Koch-Henriksen F. Sellebjerg P. S. Soerensen C. C. Hilt Christensen P. V. Rasmussen M. B. Jensen J. L. Frederiksen S. Bramow H. K. Mathiesen K. I. Schreiber H. Butzkueven M. Magyari T. Kalincik E. Leray Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis BMC Medical Research Methodology Effectiveness Multiple sclerosis Propensity score Indication bias Causal contrasts Censoring |
| title | Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis |
| title_full | Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis |
| title_fullStr | Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis |
| title_full_unstemmed | Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis |
| title_short | Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis |
| title_sort | impact of methodological choices in comparative effectiveness studies application in natalizumab versus fingolimod comparison among patients with multiple sclerosis |
| topic | Effectiveness Multiple sclerosis Propensity score Indication bias Causal contrasts Censoring |
| url | https://doi.org/10.1186/s12874-022-01623-8 |
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