BMC Medical Research Methodology (May 2022)
Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis
- 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
Affiliations
- M. Lefort
- Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U 1309, Univ Rennes, EHESP, CNRS, Inserm
- S. Sharmin
- Department of Medicine, University of Melbourne
- J. B. Andersen
- Department of Neurology, The Danish Multiple Sclerosis Registry, Copenhagen University Hospital
- S. Vukusic
- Service de Neurologie, Sclérose en Plaques, Pathologies de La Myéline Et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon
- R. Casey
- Service de Neurologie, Sclérose en Plaques, Pathologies de La Myéline Et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon
- M. Debouverie
- Centre Hospitalier Régional Universitaire de Nancy, Hôpital Central
- G. Edan
- Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou
- J. Ciron
- Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, CRC-SEP
- A. Ruet
- Centre Hospitalier Universitaire de Bordeaux, Hôpital Pellegrin
- J. De Sèze
- Service des maladies inflammatoires du système nerveux – neurologie, centre d’investigation clinique de Strasbourg, Hôpitaux Universitaire de Strasbourg, Hôpital de Hautepierre
- E. Maillart
- Assistance Publique Des Hôpitaux de Paris, Hôpital de La Pitié-Salpêtrière
- H. Zephir
- Centre Hospitalier Universitaire de Lille, Hôpital Salengro
- P. Labauge
- Centre Hospitalier Universitaire de Montpellier, Hôpital Gui de Chauliac
- G. Defer
- Centre Hospitalier Universitaire de Caen Normandie, Hôpital Côte de Nacre
- C. Lebrun-Frenay
- Centre Hospitalier Universitaire de Nice, UR2CA-URRIS,, Université Nice Côte d’Azur, Hôpital
- T. Moreau
- Centre Hospitalier Universitaire Dijon Bourgogne, Hôpital François Mitterrand, Maladies Inflammatoires du Système Nerveux Et Neurologie Générale
- E. Berger
- Centre Hospitalier Régional Universitaire de Besançon, Hôpital Jean Minjoz
- P. Clavelou
- Centre Hospitalier Universitaire de Clermont-Ferrand, Hôpital Gabriel-Montpied
- J. Pelletier
- Service de Neurologie, Aix Marseille Univ, APHM, Hôpital de La Timone
- B. Stankoff
- Assistance Publique Des Hôpitaux de Paris, Hôpital Saint-Antoine
- O. Gout
- Fondation Adolphe de Rothschild de L’œil Et du Cerveau
- E. Thouvenot
- Centre Hospitalier Universitaire de Nîmes, Hôpital Carémeau
- O. Heinzlef
- Centre Hospitalier Intercommunal de Poissy Saint-Germain-en-Laye
- A. Al-Khedr
- Centre Hospitalier Universitaire d’Amiens Picardie
- B. Bourre
- Rouen University Hospital
- O. Casez
- Centre Hospitalier Universitaire Grenoble-Alpes
- P. Cabre
- Centre Hospitalier Universitaire de Martinique, Hôpital Pierre Zobda-Quitman
- A. Montcuquet
- Centre Hospitalier Universitaire Limoges, Hôpital Dupuytren
- A. Wahab
- Assistance Publique Des Hôpitaux de Paris, Hôpital Henri Mondor
- J. P. Camdessanché
- Centre Hospitalier Universitaire de Saint-Étienne, Hôpital Nord
- A. Maurousset
- Centre Hospitalier Régional Universitaire de Tours, Hôpital Bretonneau
- H. Ben Nasr
- Centre Hospitalier Sud Francilien
- K. Hankiewicz
- Centre Hospitalier de Saint-Denis, Hôpital Casanova
- C. Pottier
- Centre Hospitalier de Pontoise
- N. Maubeuge
- Centre Hospitalier Universitaire de Poitiers, Site de La Milétrie
- D. Dimitri-Boulos
- Assistance Publique Des Hôpitaux de Paris, Hôpital Bicêtre
- C. Nifle
- Centre Hospitalier de Versailles, Hôpital André-Mignot
- D. A. Laplaud
- CHU de Nantes
- D. Horakova
- Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital
- E. K. Havrdova
- Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital
- R. Alroughani
- Division of Neurology, Department of Medicine, Amiri Hospital
- G. Izquierdo
- Hospital Universitario Virgen Macarena
- S. Eichau
- Hospital Universitario Virgen Macarena
- S. Ozakbas
- Dokuz Eylul University
- F. Patti
- GF Ingrassia Department, University of Catania
- M. Onofrj
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. d’Annunzio
- A. Lugaresi
- Dipartimento Di Scienze Biomediche E Neuromotorie, Università Di Bologna
- M. Terzi
- Medical Faculty, 19 Mayis University
- P. Grammond
- CISSS Chaudiere-Appalache
- F. Grand’Maison
- Neuro Rive-Sud
- B. Yamout
- Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center
- A. Prat
- Hopital Notre Dame
- M. Girard
- Hopital Notre Dame
- P. Duquette
- Hopital Notre Dame
- C. Boz
- KTU Medical Faculty Farabi Hospital
- M. Trojano
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari
- P. McCombe
- University of Queensland
- M. Slee
- Flinders University
- J. Lechner-Scott
- School of Medicine and Public Health, University Newcastle
- R. Turkoglu
- Haydarpasa Numune Training and Research Hospital
- P. Sola
- Department of Neuroscience, Azienda Ospedaliera Universitaria
- D. Ferraro
- Department of Neuroscience, Azienda Ospedaliera Universitaria
- F. Granella
- Department of Medicine and Surgery, University of Parma
- V. Shaygannejad
- Isfahan University of Medical Sciences
- J. Prevost
- CSSS Saint-Jérôme
- D. Maimone
- Garibaldi Hospital
- O. Skibina
- Monash University
- K. Buzzard
- Monash University
- A. Van der Walt
- Monash University
- R. Karabudak
- Hacettepe University
- B. Van Wijmeersch
- Rehabilitation and MS-Centre Overpelt and Hasselt University
- T. Csepany
- Department of Neurology, Faculty of Medicine, University of Debrecen
- D. Spitaleri
- Azienda Ospedaliera Di Rilievo Nazionale San Giuseppe Moscati Avellino
- S. Vucic
- Westmead Hospital
- N. Koch-Henriksen
- Department of Clinical Epidemiology, Aarhus University Hospital Aarhus
- F. Sellebjerg
- Danish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup
- P. S. Soerensen
- Danish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup
- C. C. Hilt Christensen
- Department of Neurology, Aalborg University Hospital, Multiple Sclerosis Unit
- P. V. Rasmussen
- Aarhus University Hospital, Neurology, PJJ Boulevard
- M. B. Jensen
- Department of Neurology, University Hospital of Northern Sealand
- J. L. Frederiksen
- Department of Clinical Medicine, University of Copenhagen
- S. Bramow
- Danish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup
- H. K. Mathiesen
- Department of Neurology, Copenhagen University Hospital Herlev
- K. I. Schreiber
- Danish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup
- H. Butzkueven
- Central Clinical School, Monash University
- M. Magyari
- Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital
- T. Kalincik
- Department of Medicine, University of Melbourne
- E. Leray
- Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U 1309, Univ Rennes, EHESP, CNRS, Inserm
- DOI
- https://doi.org/10.1186/s12874-022-01623-8
- Journal volume & issue
-
Vol. 22,
no. 1
pp. 1 – 14
Abstract
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.
Keywords
