Comparison of Two Methods for Estimating MS-Related Mortality: The Excess Mortality vs. the Cause-Specific Frameworks
Fabien Rollot
(1, 2, 3)
,
Zoe Uhry
(4, 1)
,
Emmanuelle Dantony
(5, 1)
,
Sandra Vukusic
(1, 2, 3)
,
Marc Debouverie
(6, 7)
,
Emmanuelle Le Page
(8, 9)
,
Jonathan Ciron
(10, 11)
,
Aurélie Ruet
(12, 13)
,
Jerome de Seze
(14)
,
Helene Zephir
(15)
,
Pierre Labauge
(16)
,
Gilles Defer
(17)
,
Christine Lebrun-Frenay
(18)
,
Thibault Moreau
(19)
,
David Laplaud
(20, 21)
,
Eric Berger
(22)
,
Pierre Clavelou
(23, 24)
,
Jean Pelletier
(25)
,
Eric Thouvenot
(26, 27)
,
Olivier Heinzlef
(28)
,
Jean-Philippe Camdessanche
(29)
,
Mathieu Fauvernier
(5, 1, 30)
,
Laurent Remontet
(5, 1)
,
Emmanuelle Leray
(9, 31, 32, 33, 34, 35, 36, 37)
1
HCL -
Hospices Civils de Lyon
2 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
3 Fondation Eugène Devic EDMUS
4 Santé publique France - French National Public Health Agency [Saint-Maurice, France]
5 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
6 APEMAC - Adaptation, mesure et évaluation en santé. Approches interdisciplinaires
7 Service de neurologie [CHRU Nancy]
8 Service de Neurologie [CHU Rennes]
9 CIC - Centre d'Investigation Clinique [Rennes]
10 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
11 Département Neurologie [CHU Toulouse]
12 U1215 Inserm - UB - Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale
13 Service de neurologie [Bordeaux]
14 Centre d’Investigation Clinique Plurithématique (CIC - P) - CIC Strasbourg
15 LilNCog - Lille Neurosciences & Cognition - U 1172
16 CHU Montpellier
17 Service de Neurologie [CHU Caen]
18 Service de Neurologie [CHU Nice]
19 CHU Dijon
20 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
21 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
22 Service de Neurologie [CHRU Besançon]
23 Neuro-Dol - Neuro-Dol
24 Service Neurologie [CHU Clermont-Ferrand]
25 TIMONE - Hôpital de la Timone [CHU - APHM]
26 IGF - Institut de Génomique Fonctionnelle
27 Pôle NIRR - Service de Neurologie [CHU Nimes]
28 Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy]
29 Service de Neurologie [CHU de Saint-Étienne]
30 Service de Biostatistiques [Lyon]
31 REPERES - Recherche en Pharmaco-épidémiologie et Recours aux Soins
32 METIS - Département Méthodes quantitatives en santé publique
33 EHESP - École des Hautes Études en Santé Publique [EHESP]
34 UR - Université de Rennes
35 ARENES - Arènes: politique, santé publique, environnement, médias
36 CoRHASI - Collectif de recherche handicap, autonomie et société inclusive
37 RSMS - Recherche sur les services et le management en santé
2 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
3 Fondation Eugène Devic EDMUS
4 Santé publique France - French National Public Health Agency [Saint-Maurice, France]
5 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
6 APEMAC - Adaptation, mesure et évaluation en santé. Approches interdisciplinaires
7 Service de neurologie [CHRU Nancy]
8 Service de Neurologie [CHU Rennes]
9 CIC - Centre d'Investigation Clinique [Rennes]
10 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
11 Département Neurologie [CHU Toulouse]
12 U1215 Inserm - UB - Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale
13 Service de neurologie [Bordeaux]
14 Centre d’Investigation Clinique Plurithématique (CIC - P) - CIC Strasbourg
15 LilNCog - Lille Neurosciences & Cognition - U 1172
16 CHU Montpellier
17 Service de Neurologie [CHU Caen]
18 Service de Neurologie [CHU Nice]
19 CHU Dijon
20 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
21 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
22 Service de Neurologie [CHRU Besançon]
23 Neuro-Dol - Neuro-Dol
24 Service Neurologie [CHU Clermont-Ferrand]
25 TIMONE - Hôpital de la Timone [CHU - APHM]
26 IGF - Institut de Génomique Fonctionnelle
27 Pôle NIRR - Service de Neurologie [CHU Nimes]
28 Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy]
29 Service de Neurologie [CHU de Saint-Étienne]
30 Service de Biostatistiques [Lyon]
31 REPERES - Recherche en Pharmaco-épidémiologie et Recours aux Soins
32 METIS - Département Méthodes quantitatives en santé publique
33 EHESP - École des Hautes Études en Santé Publique [EHESP]
34 UR - Université de Rennes
35 ARENES - Arènes: politique, santé publique, environnement, médias
36 CoRHASI - Collectif de recherche handicap, autonomie et société inclusive
37 RSMS - Recherche sur les services et le management en santé
Fabien Rollot
- Function : Author
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- ORCID : 0000-0002-5752-2331
Sandra Vukusic
- Function : Author
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- ORCID : 0000-0001-7337-7122
Marc Debouverie
- Function : Author
- PersonId : 1297074
- ORCID : 0000-0002-6659-6148
Emmanuelle Le Page
- Function : Author
- PersonId : 1034157
Jonathan Ciron
- Function : Author
- PersonId : 795646
- ORCID : 0000-0002-3386-6308
- IdRef : 137599021
Aurélie Ruet
- Function : Author
- PersonId : 1221381
- ORCID : 0000-0002-0020-8739
Helene Zephir
- Function : Author
- PersonId : 1297076
- ORCID : 0000-0003-4029-2012
Pierre Labauge
- Function : Author
- PersonId : 759958
- ORCID : 0000-0001-7759-8555
- IdRef : 059860367
Christine Lebrun-Frenay
- Function : Author
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- ORCID : 0000-0002-3713-2416
- IdRef : 074517929
Pierre Clavelou
- Function : Author
- PersonId : 1218179
- ORCID : 0000-0003-2363-9352
Jean Pelletier
- Function : Author
- PersonId : 756935
- ORCID : 0000-0001-9730-7567
- IdRef : 078804868
Eric Thouvenot
- Function : Author
- PersonId : 1037455
- IdHAL : ericthouvenot
- ORCID : 0000-0001-8671-7747
- IdRef : 094970920
Jean-Philippe Camdessanche
- Function : Author
- PersonId : 775005
- ORCID : 0000-0002-5282-6707
- IdRef : 124178316
Mathieu Fauvernier
- Function : Author
- PersonId : 1313493
- IdHAL : mathieufauvernier
- ORCID : 0000-0002-3809-8248
- IdRef : 240832841
Emmanuelle Leray
Connectez-vous pour contacter l'auteur
- Function : Correspondent author
- PersonId : 18386
- IdHAL : emmanuelle-leray
- ORCID : 0000-0001-8424-4499
- IdRef : 099858185
Connectez-vous pour contacter l'auteur
Abstract
Background and objectives - Determining whether multiple sclerosis (MS) causes death is challenging. Our objective was to contrast 2 frameworks to estimate probabilities of death attributed to MS (P) and other causes (P): the cause-specific framework (CSF), which requires the causes of death, and the excess mortality framework (EMF), which does not. Methods - We used data from the Observatoire Français de la Sclérose en Plaques (OFSEP, n = 37,524) and from a comparative subset where causes of death were available (4,004 women with relapsing-onset MS [R-MS]). In CSF, the probabilities were estimated using the Aalen-Johansen method. In EMF, they were estimated from the excess mortality hazard, which is the additional mortality among patients with MS as compared with the expected mortality in the matched general population. P values were estimated at 30 years of follow-up, (1) with both frameworks in the comparative subset, by age group at onset, and (2) with EMF only in the OFSEP population, by initial phenotype, sex, and age at onset. Results - In the comparative subset, the estimated 30-year P values were greater using EMF than CSF: 10.9% (95% CI 8.3-13.6) vs 8.7% (6.4-11.8) among the youngest and 20.4% (11.3-29.5) vs 16.2% (8.7-30.2) for the oldest groups, respectively. In the CSF, probabilities of death from unknown causes ranged from 1.5% (0.7-3.0) to 6.4% (2.5-16.4), and even after their reallocation, P values remained lower with CSF than with EMF. The estimated probabilities of being alive were close using the 2 frameworks, and the estimated P (EMF vs CSF) was 2.6% (2.5-2.6) vs 2.1% (1.2-3.9) and 18.1% (16.9-19.3) vs 26.4% (16.5-42.2), respectively, for the youngest and oldest groups. In the OFSEP population, the estimated 30-year P values ranged from 7.5% (6.4-8.7) to 24.0% (19.1-28.9) in patients with R-MS and from 25.4% (21.1-29.7) to 36.8% (28.3-45.3) in primary progressive patients, depending on sex and age. Discussion - EMF has the great advantage of not requiring death certificates, their quality being less than optimal. Conceptually, it also seems more relevant because it avoids having to state, for each individual, whether death was directly or indirectly caused by MS or whether it would have occurred anyway, which is especially difficult in such chronic diseases.