| Title: |
Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis |
| Authors: |
Lefort, Mathilde; Sharmin, S.; Andersen, J.; Vukusic, S.; Casey, R.; Debouverie, M.; Edan, G.; Ciron, J.; Ruet, A.; de Sèze, J.; Maillart, E.; Zephir, H.; Labauge, Pierre; Defer, G.; Lebrun-Frenay, C.; Moreau, T.; Berger, E.; Clavelou, P.; Pelletier, J.; Stankoff, B.; Gout, O.; Thouvenot, Eric; Heinzlef, O.; Al-Khedr, A.; Bourre, B.; Casez, O.; Cabre, P.; Montcuquet, A.; Wahab, A.; Camdessanché, J.; Maurousset, A.; Ben Nasr, H.; Hankiewicz, K.; Pottier, C.; Maubeuge, N.; Dimitri-Boulos, D.; Nifle, C.; Laplaud, David-Axel; Horakova, D.; Havrdova, E.; Alroughani, R.; Izquierdo, G.; Eichau, S.; Ozakbas, S.; Patti, F.; Onofrj, M.; Lugaresi, A.; Terzi, M.; Grammond, P.; Grand'Maison, F; Yamout, B.; Prat, A.; Girard, M.; Duquette, P.; Boz, C.; Trojano, M.; Mccombe, P.; Slee, M.; Lechner-Scott, J.; Turkoglu, R.; Sola, P.; Ferraro, D.; Granella, F.; Shaygannejad, V.; Prevost, J.; Maimone, D.; Skibina, O.; Buzzard, K.; van Der Walt, A.; Karabudak, R.; van Wijmeersch, B.; Csepany, T.; Spitaleri, D.; Vucic, S.; Koch-Henriksen, N.; Sellebjerg, F.; Soerensen, P.; Hilt Christensen, C.; Rasmussen, P.; Jensen, M.; Frederiksen, J.; Bramow, S.; Mathiesen, H.; Schreiber, K.; Butzkueven, H.; Magyari, M.; Kalincik, T.; Leray, Emmanuelle |
| Contributors: |
Arènes: politique, santé publique, environnement, médias (ARENES); Université de Rennes (UR)-Institut d'Études Politiques IEP - Rennes-École des Hautes Études en Santé Publique (EHESP)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS); Recherche sur les services et le management en santé (RSMS); Université de Rennes (UR)-École des Hautes Études en Santé Publique (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Centre d'Investigation Clinique Rennes (CIC); Université de Rennes (UR)-Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou -Institut National de la Santé et de la Recherche Médicale (INSERM); École des Hautes Études en Santé Publique (EHESP); Département Méthodes quantitatives en santé publique (METIS); University of Melbourne; Copenhagen University Hospital Denmark = Københavns Universitetshospital Danmark (KUH); Hospices Civils de Lyon (HCL); Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Fondation Eugène Devic EDMUS; Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy); Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse); i-SEP (i-SEP); CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P)); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg; Hôpitaux Universitaires de Strasbourg (HUS)-Hôpitaux Universitaires de Strasbourg (HUS)-Hôpital de Hautepierre Strasbourg; Hôpitaux Universitaires de Strasbourg (HUS); CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier); Université de Montpellier (UM); Service de Neurologie CHU Caen; Université de Caen Normandie (UNICAEN); Normandie Université (NU)-Normandie Université (NU)-CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie (CHU Caen Normandie); Normandie Université (NU); Centre Hospitalier Universitaire de Nice (CHU Nice); Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon); Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon); Service Neurologie CHU Clermont-Ferrand; CHU Gabriel Montpied Clermont-Ferrand; CHU Clermont-Ferrand-CHU Clermont-Ferrand-Pôle Médecine interne, Neurologie, Neurochirurgie, Ophtalmologie CHU Clermont-Ferrand (MNDO); CHU Clermont-Ferrand-CHU Clermont-Ferrand; Hôpital de la Timone CHU - APHM (TIMONE); CHU Saint-Antoine AP-HP; Fondation Ophtalmologique Adolphe de Rothschild Paris; Service de Neurologie CHU Nimes (Pôle NIRR); Hôpital Universitaire Carémeau Nîmes (CHU Nîmes); Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes); Institut de Génomique Fonctionnelle (IGF); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM); CHI Poissy-Saint-Germain; CHU Amiens-Picardie; CHU Rouen; CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble (CHUGA); Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI); Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Monash University Melbourne; The Royal Melbourne Hospital; Université de Rennes (UR); Collectif de recherche handicap, autonomie et société inclusive (CoRHASI); OFSEP was supported by a grant provided by the French State and handled by the "Agence Nationale de la Recherche", within the framework of the "Investments for the Future" program, under the reference ANR-10-COHO-002, by the Eugène Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation. ML has recieved travel grant from ARSEP foundation for this project. The Clinical Outcomes Research unit at the University of Melbourne received funding from NHMRC (grant number 1140766, 1129789, and 1157717) to support this study. The MSBase Foundation is a not-for-profit organization that receives support from Biogen, Novartis, Merck, Roche, Teva Pharmaeutical Industries and Sanofi Genzyme. The Danish Multiple Sclerosis Registry did not receive any funding to collaborate in this study.; ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010) |
| Source: |
ISSN: 1471-2288 ; BMC Medical Research Methodology ; https://univ-rennes.hal.science/hal-03690493 ; BMC Medical Research Methodology, 2022, 22 (1), pp.155. ⟨10.1186/s12874-022-01623-8⟩. |
| Publisher Information: |
CCSD; BioMed Central |
| Publication Year: |
2022 |
| Collection: |
Université Jean Monnet – Saint-Etienne: HAL |
| Subject Terms: |
Causal contrasts; Censoring; Effectiveness; Indication bias; Multiple sclerosis; Positivity assumption; Propensity score; MESH: Fingolimod Hydrochloride; MESH: Humans; MESH: Multiple Sclerosis; Relapsing-Remitting; MESH: Natalizumab; MESH: Treatment Outcome; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35637426; PUBMED: 35637426; PUBMEDCENTRAL: PMC9150358; WOS: 000805581400002 |
| DOI: |
10.1186/s12874-022-01623-8 |
| Availability: |
https://univ-rennes.hal.science/hal-03690493; https://univ-rennes.hal.science/hal-03690493v1/document; https://univ-rennes.hal.science/hal-03690493v1/file/12874_2022_Article_1623.pdf; https://doi.org/10.1186/s12874-022-01623-8 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.D83DD3F9 |
| Database: |
BASE |