- Title
- Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis
- Creator
- Lefort, M.; Sharmin, S.; Maillart, E.; Zephir, H.; Labauge, P.; Defer, G.; Lebrun-Frenay, C.; Moreau, T.; Berger, E.; Clavelou, P.; Pelletier, J.; Stankoff, B.; Andersen, J. B.; Gout, O.; Lechner-Scott, J.; .,; Vukusic, S.; Casey, R.; Debouverie, M.; Edan, G.; Ciron, J.; Ruet, A.; De Sèze, J.
- Relation
- BMC Medical Research Methodology Vol. 22, no. 155
- Publisher Link
- http://dx.doi.org/10.1186/s12874-022-01623-8
- Publisher
- BioMed Central
- Resource Type
- journal article
- Date
- 2022
- Description
- 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.
- Subject
- effectiveness; multiple sclerosis; propensity score; indication bias; causal contrasts; censoring
- Identifier
- http://hdl.handle.net/1959.13/1486176
- Identifier
- uon:51798
- Identifier
- ISSN:1471-2288
- Rights
- © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
- Language
- eng
- Full Text
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