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Impact of Methodological Choices in Comparative Effectiveness Studies: Application in Natalizumab Versus Fingolimod Comparison Among Patients With Multiple Sclerosis Publisher Pubmed



Lefort M1, 2 ; Sharmin S3, 4 ; Andersen JB5 ; Vukusic S6, 7, 8 ; Casey R6, 7, 8, 9 ; Debouverie M10 ; Edan G11 ; Ciron J12 ; Ruet A13 ; De Seze J14 ; Maillart E15 ; Zephir H16 ; Labauge P17 ; Defer G18 Show All Authors
Authors
  1. Lefort M1, 2
  2. Sharmin S3, 4
  3. Andersen JB5
  4. Vukusic S6, 7, 8
  5. Casey R6, 7, 8, 9
  6. Debouverie M10
  7. Edan G11
  8. Ciron J12
  9. Ruet A13
  10. De Seze J14
  11. Maillart E15
  12. Zephir H16
  13. Labauge P17
  14. Defer G18
  15. Lebrunfrenay C19
  16. Moreau T20
  17. Berger E21
  18. Clavelou P22
  19. Pelletier J23
  20. Stankoff B24
  21. Gout O25
  22. Thouvenot E26
  23. Heinzlef O27
  24. Alkhedr A28
  25. Bourre B29
  26. Casez O30
  27. Cabre P31
  28. Montcuquet A32
  29. Wahab A33
  30. Camdessanche JP34
  31. Maurousset A35
  32. Ben Nasr H36
  33. Hankiewicz K37
  34. Pottier C38
  35. Maubeuge N39
  36. Dimitriboulos D40
  37. Nifle C41
  38. Laplaud DA42, 43
  39. Horakova D44
  40. Havrdova EK44
  41. Alroughani R45
  42. Izquierdo G46
  43. Eichau S46
  44. Ozakbas S47
  45. Patti F48, 49
  46. Onofrj M50
  47. Lugaresi A51, 52
  48. Terzi M53
  49. Grammond P54
  50. Grandmaison F55
  51. Yamout B56
  52. Prat A57, 58
  53. Girard M57, 58
  54. Duquette P57, 58
  55. Boz C59
  56. Trojano M60
  57. Mccombe P61, 62
  58. Slee M63
  59. Lechnerscott J64, 65
  60. Turkoglu R66
  61. Sola P67
  62. Ferraro D67
  63. Granella F68, 69
  64. Shaygannejad V70
  65. Prevost J71
  66. Maimone D72
  67. Skibina O73
  68. Buzzard K73
  69. Van Der Walt A73
  70. Karabudak R74
  71. Van Wijmeersch B75
  72. Csepany T76
  73. Spitaleri D77
  74. Vucic S78
  75. Kochhenriksen N79
  76. Sellebjerg F80
  77. Soerensen PS80
  78. Hilt Christensen CC81
  79. Rasmussen PV82
  80. Jensen MB83
  81. Frederiksen JL84
  82. Bramow S80
  83. Mathiesen HK85
  84. Schreiber KI80
  85. Butzkueven H86, 87, 88
  86. Magyari M4, 80
  87. Kalincik T3
  88. Leray E1, 2

Source: BMC Medical Research Methodology Published:2022


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. © 2022, The Author(s).
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