Using instrumental variables to correct for bias in real-world cohort studies of the effects of disease-modifying treatment in MS.
Multiple sclerosis treatment
causal inference
instrumental variables
reverse causality
Journal
Multiple sclerosis (Houndmills, Basingstoke, England)
ISSN: 1477-0970
Titre abrégé: Mult Scler
Pays: England
ID NLM: 9509185
Informations de publication
Date de publication:
03 Oct 2023
03 Oct 2023
Historique:
medline:
3
10
2023
pubmed:
3
10
2023
entrez:
3
10
2023
Statut:
aheadofprint
Résumé
Estimating the effect of disease-modifying treatment of MS in observational studies is impaired by bias from unmeasured confounders, in particular indication bias. To show how instrumental variables (IVs) reduce bias. All patients with relapsing onset of MS 1996-2010, identified by the nationwide Danish Multiple Sclerosis Registry, were followed from onset. Exposure was treatment index throughout the first 12 years from onset, defined as a cumulative function of months without and with medium- or high-efficacy treatment, and outcomes were hazard ratios (HRs) per unit treatment index for sustained Expanded Disability Scale Score (EDSS) 4 and 6 adjusted for age at onset and sex, without and with an IV. We used the onset cohort (1996-2000; 2001-2005; 2006-2010) as an IV because treatment index increased across the cohorts. We included 6014 patients. With conventional Cox regression, HRs for EDSS 4 and 6 were 1.15 [95% CI: 1.13-1.18] and 1.17 [1.13-1.20] per unit treatment index. Only with IVs, we confirmed a beneficial effect of treatment with HRs of 0.86 [0.81-0.91] and 0.82 [0.74-0.90]. The use of IVs eliminates indication bias and confirms that treatment is effective in delaying disability. IVs could, under some circumstances, be an alternative to marginal structural models.
Sections du résumé
BACKGROUND
UNASSIGNED
Estimating the effect of disease-modifying treatment of MS in observational studies is impaired by bias from unmeasured confounders, in particular indication bias.
OBJECTIVE
UNASSIGNED
To show how instrumental variables (IVs) reduce bias.
METHODS
UNASSIGNED
All patients with relapsing onset of MS 1996-2010, identified by the nationwide Danish Multiple Sclerosis Registry, were followed from onset. Exposure was treatment index throughout the first 12 years from onset, defined as a cumulative function of months without and with medium- or high-efficacy treatment, and outcomes were hazard ratios (HRs) per unit treatment index for sustained Expanded Disability Scale Score (EDSS) 4 and 6 adjusted for age at onset and sex, without and with an IV. We used the onset cohort (1996-2000; 2001-2005; 2006-2010) as an IV because treatment index increased across the cohorts.
RESULTS
UNASSIGNED
We included 6014 patients. With conventional Cox regression, HRs for EDSS 4 and 6 were 1.15 [95% CI: 1.13-1.18] and 1.17 [1.13-1.20] per unit treatment index. Only with IVs, we confirmed a beneficial effect of treatment with HRs of 0.86 [0.81-0.91] and 0.82 [0.74-0.90].
CONCLUSION
UNASSIGNED
The use of IVs eliminates indication bias and confirms that treatment is effective in delaying disability. IVs could, under some circumstances, be an alternative to marginal structural models.
Identifiants
pubmed: 37787012
doi: 10.1177/13524585231201423
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
13524585231201423Déclaration de conflit d'intérêts
Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: N.K.-H. did not declare any competing interests. L.C.T did not declare any competing interests. M.M. has served in scientific advisory board for Sanofi, Novartis, and Merck and has received honoraria for lecturing from Biogen, Merck, Novartis, Roche, Genzyme, and Bristol Myers Squibb. P.S.S. has received personal compensation for serving on advisory boards for Biogen, Merck, Novartis, and Teva; was on steering committees or independent data monitoring boards in trials sponsored by Merck and Novartis; and has received speaker honoraria from Biogen, Merck, Teva, BMS/Celgene, and Novartis. No other disclosures were reported.