Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis

Lefort, M.; Sharmin, S.; Andersen, J.; Vukusic, S.; Casey, R.; Debouverie, M.; Edan, G.; Ciron, J.; Ruet, A.; De Seze, J.; Maillart, E.; Zephir, H.; Labauge, P.; Defer, G.; Lebrun-Frenay, C.; Moreau, T.; Berger, E.; Clavelou, P.; Pelletier, J.; Stankoff, B.; Gout, O.; Thouvenot, E.; Heinzlef, O.; Al-Khedr, A.; Bourre, B.; Casez, O.; Cabre, P.; Montcuquet, A.; Wahab, A.; Camdessanche, J.; Maurousset, A.; Ben Nasr, H.; Hankiewicz, K.; Pottier, C.; Maubeuge, N.; Nifle, C.; Laplaud, D.; Horakova, D.; Dimitri-Boulos, 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, CAVİT; 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.; Christensen, C.; Rasmussen, P.; Jensen, M.; Frederiksen, J.; Bramow, S.; Mathiesen, H.; Schreiber, K.; Butzkueven, H.; Magyari, M.; Kalincik, T.; Leray, E.

doi:10.1186/s12874-022-01623-8

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis

Atıf İçin Kopyala

Lefort M., Sharmin S., Andersen J. B., Vukusic S., Casey R., Debouverie M., ...Daha Fazla

BMC MEDICAL RESEARCH METHODOLOGY, cilt.22, sa.1, 2022 (SCI-Expanded)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 22 Sayı: 1
Basım Tarihi: 2022
Doi Numarası: 10.1186/s12874-022-01623-8
Dergi Adı: BMC MEDICAL RESEARCH METHODOLOGY
Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CINAHL, EMBASE, MEDLINE, Directory of Open Access Journals
Anahtar Kelimeler: Effectiveness, Multiple sclerosis, Propensity score, Indication bias, Causal contrasts, Censoring, Positivity assumption, PROPENSITY-SCORE METHODS, PLACEBO-CONTROLLED TRIAL, ORAL FINGOLIMOD, INTERFERON, PERFORMANCE, MODELS
Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

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.