Evidence map›Paper›PMID 35637426›Full record

ArticleBMC medical research methodology2022

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 and 78 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medical research methodology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Observational
  4. Comparative efficacy of ofatumumabTherapeutic advances in neurological disorders · 2024
    Article
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

88 authors at 20 institutions in 14 countries.

M Lefort *Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U 1309, Univ Rennes, EHESP, CNRS, Inserm, Rennes, France.
S Sharmin *Department of Medicine, University of Melbourne, Melbourne, Australia.
J B Andersen *Department of Neurology, The Danish Multiple Sclerosis Registry, Copenhagen University Hospital, Rigshospitalet Glostrup, Denmark.
S VukusicService de Neurologie, Sclérose en Plaques, Pathologies de La Myéline Et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, 69677, Lyon/Bron, France.
R CaseyService de Neurologie, Sclérose en Plaques, Pathologies de La Myéline Et Neuro-Inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, 69677, Lyon/Bron, France.
M DebouverieCentre Hospitalier Régional Universitaire de Nancy, Hôpital Central, Service de neurologie, Nancy, France.
G EdanCentre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou, Service de neurologie, Rennes, France.
J CironCentre Hospitalier Universitaire de Toulouse, Hôpital Purpan, CRC-SEP, Département de neurologie, Toulouse, France.
A RuetCentre Hospitalier Universitaire de Bordeaux, Hôpital Pellegrin, Service de neurologie, Bordeaux, France.
J De SèzeService des maladies inflammatoires du système nerveux - neurologie, centre d'investigation clinique de Strasbourg, Hôpitaux Universitaire de Strasbourg, Hôpital de Hautepierre, INSERM 1434, Strasbourg, France.
E MaillartAssistance Publique Des Hôpitaux de Paris, Hôpital de La Pitié-Salpêtrière, Service de neurologie, Paris, France.
H ZephirCentre Hospitalier Universitaire de Lille, Hôpital Salengro, Service de neurologie D, Lille, France.
P LabaugeCentre Hospitalier Universitaire de Montpellier, Hôpital Gui de Chauliac, Service de neurologie, Montpellier, France.
G DeferCentre Hospitalier Universitaire de Caen Normandie, Hôpital Côte de Nacre, Service de neurologie, Caen, France.
C Lebrun-FrenayCentre Hospitalier Universitaire de Nice, UR2CA-URRIS,, Université Nice Côte d'Azur, Hôpital, Pasteur 2, Service de neurologie, Nice, France.
T MoreauCentre Hospitalier Universitaire Dijon Bourgogne, Hôpital François Mitterrand, Maladies Inflammatoires du Système Nerveux Et Neurologie Générale, Service de neurologie, Dijon, France.
E BergerCentre Hospitalier Régional Universitaire de Besançon, Hôpital Jean Minjoz, Service de neurologie, Besançon, France.
P ClavelouCentre Hospitalier Universitaire de Clermont-Ferrand, Hôpital Gabriel-Montpied, Service de neurologie, Clermont-Ferrand, France.
J PelletierService de Neurologie, Aix Marseille Univ, APHM, Hôpital de La Timone, Pôle de Neurosciences Cliniques, 13005, Marseille, France.
B StankoffAssistance Publique Des Hôpitaux de Paris, Hôpital Saint-Antoine, Service de neurologie, Paris, France.
O GoutFondation Adolphe de Rothschild de L'œil Et du Cerveau, Service de neurologie, Paris, France.
E ThouvenotCentre Hospitalier Universitaire de Nîmes, Hôpital Carémeau, Service de neurologie, Nîmes, France.
O HeinzlefCentre Hospitalier Intercommunal de Poissy Saint-Germain-en-Laye, Service de neurologie, Poissy, France.
A Al-KhedrCentre Hospitalier Universitaire d'Amiens Picardie, Site sud, Service de neurologie, Amiens, France.
B BourreRouen University Hospital, 76000, Rouen, France.
O CasezCentre Hospitalier Universitaire Grenoble-Alpes, Site nord, Service de neurologie, Grenoble/La Tronche, France.
P CabreCentre Hospitalier Universitaire de Martinique, Hôpital Pierre Zobda-Quitman, Service de neurologie, Fort-de-France, France.
A MontcuquetCentre Hospitalier Universitaire Limoges, Hôpital Dupuytren, Service de neurologie, Limoges, France.
A WahabAssistance Publique Des Hôpitaux de Paris, Hôpital Henri Mondor, Service de neurologie, Créteil, France.
J P CamdessanchéCentre Hospitalier Universitaire de Saint-Étienne, Hôpital Nord, Service de neurologie, Saint-Étienne, France.
A MauroussetCentre Hospitalier Régional Universitaire de Tours, Hôpital Bretonneau, Service de neurologie, Tours, France.
H Ben NasrCentre Hospitalier Sud Francilien, Service de neurologie, Corbeil-Essonnes, France.
K HankiewiczCentre Hospitalier de Saint-Denis, Hôpital Casanova, Service de neurologie, Saint-Denis, France.
C PottierCentre Hospitalier de Pontoise, Service de neurologie, Pontoise, France.
N MaubeugeCentre Hospitalier Universitaire de Poitiers, Site de La Milétrie, Service de neurologie, Poitiers, France.
D Dimitri-BoulosAssistance Publique Des Hôpitaux de Paris, Hôpital Bicêtre, Service de neurologie, Le Kremlin-Bicêtre, France.
C NifleCentre Hospitalier de Versailles, Hôpital André-Mignot, Service de neurologie, Le Chesnay, France.
D A LaplaudCHU de Nantes, Service de Neurologie & CIC015 INSERM, 44093, Nantes, France.
D HorakovaDepartment of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
E K HavrdovaDepartment of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
R AlroughaniDivision of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait.
G IzquierdoHospital Universitario Virgen Macarena, Seville, Spain.
S EichauHospital Universitario Virgen Macarena, Seville, Spain.
S OzakbasDokuz Eylul University, Konak/Izmir, Turkey.
F PattiGF Ingrassia Department, University of Catania, Catania, Italy.
M OnofrjDepartment of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio, Chieti, Italy.
A LugaresiDipartimento Di Scienze Biomediche E Neuromotorie, Università Di Bologna, Bologna, Italy.
M TerziMedical Faculty, 19 Mayis University, Samsun, Turkey.
P GrammondCISSS Chaudiere-Appalache, Levis, Canada.
F Grand'MaisonNeuro Rive-Sud, Longueuil, QC, Canada.
B YamoutNehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon.
A PratHopital Notre Dame, Montreal, Canada.
M GirardHopital Notre Dame, Montreal, Canada.
P DuquetteHopital Notre Dame, Montreal, Canada.
C BozKTU Medical Faculty Farabi Hospital, Trabzon, Turkey.
M TrojanoDepartment of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy.
P McCombeUniversity of Queensland, Brisbane, Australia.
M SleeFlinders University, Adelaide, Australia.
J Lechner-ScottSchool of Medicine and Public Health, University Newcastle, Newcastle, Australia.
R TurkogluHaydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
P SolaDepartment of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy.
D FerraroDepartment of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy.
F GranellaDepartment of Medicine and Surgery, University of Parma, Parma, Italy.
V ShaygannejadIsfahan University of Medical Sciences, Isfahan, Iran.
J PrevostCSSS Saint-Jérôme, Saint-Jerome, Canada.
D MaimoneGaribaldi Hospital, Catania, Italy.
O SkibinaMonash University, Melbourne, Australia.
K BuzzardMonash University, Melbourne, Australia.
A Van der WaltMonash University, Melbourne, Australia.
R KarabudakHacettepe University, Ankara, Turkey.
B Van WijmeerschRehabilitation and MS-Centre Overpelt and Hasselt University, Hasselt, Belgium.
T CsepanyDepartment of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
D SpitaleriAzienda Ospedaliera Di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy.
S VucicWestmead Hospital, Sydney, Australia.
N Koch-HenriksenDepartment of Clinical Epidemiology, Aarhus University Hospital Aarhus, Aarhus, Denmark.
F SellebjergDanish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, 2600, Glostrup, Denmark.
P S SoerensenDanish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, 2600, Glostrup, Denmark.
C C Hilt ChristensenDepartment of Neurology, Aalborg University Hospital, Multiple Sclerosis Unit, Aalborg, Denmark.
P V RasmussenAarhus University Hospital, Neurology, PJJ Boulevard, DK-8200, Aarhus N, Denmark.
M B JensenDepartment of Neurology, University Hospital of Northern Sealand, Copenhagen, Denmark.
J L FrederiksenDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
S BramowDanish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, 2600, Glostrup, Denmark.
H K MathiesenDepartment of Neurology, Copenhagen University Hospital Herlev, Copenhagen, Denmark.
K I SchreiberDanish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, 2600, Glostrup, Denmark.
H ButzkuevenCentral Clinical School, Monash University, Melbourne, Australia.
M Magyari *Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia.
T Kalincik *Department of Medicine, University of Melbourne, Melbourne, Australia. tomas.kalincik@unimelb.edu.au.
E Leray *Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U 1309, Univ Rennes, EHESP, CNRS, Inserm, Rennes, France. emmanuelle.leray@ehesp.fr.
Copenhagen University Hospital · DKHôpital Notre-Dame · CAInserm · FRMonash University · AUAarhus University Hospital · DKAzienda Ospedaliero-Universitaria di Modena · ITCharles University · CZHospices Civils de Lyon · FRHospital Universitario Virgen Macarena · ESThe Royal Melbourne Hospital · AUAalborg University Hospital · DKAmerican University of Beirut Medical Center · LBAmiri Hospital · KWAssistance Publique – Hôpitaux de Paris · FRAzienda Ospedaliera S.Giuseppe Moscati · ITBicêtre Hospital · FRBox Hill Hospital · AUCegep de Saint Jerome · CACentre Hospitalier Intercommunal de Poissy · FRCentre Hospitalier Régional et Universitaire de Nancy · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNatalizumab 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.

methodsData 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.

resultsOverall, 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.

conclusionsThis 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.

Indexed as

Multiple SclerosisMultiple Sclerosis, Relapsing-RemittingFingolimod HydrochlorideHumansNatalizumabTreatment OutcomeFingolimod HydrochlorideNatalizumabCausal contrastsCensoringEffectivenessIndication biasMultiple sclerosisPositivity assumptionPropensity score

Identifiers

PMID35637426
PMCPMC9150358
OpenAlexW4281628421

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.