Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
Survivor bias and disease progression in observational cohorts in multiple sclerosis.
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Wessels Mark H J, de Jong Daan J, Barrantes-Cepas Mar, Jelgerhuis Julia R, van Lierop Zoë, van Daele Eline, Wojdała Anna L, Fuchs Tom A N, Bet Marloes M D A, van Nederpelt David R, Koubiyr Ismail, Steenwijk Martijn D, Vrenken Hugo, Moraal Bastiaan, Barkhof Frederik, Uitdehaag Bernard M J, Teunissen Charlotte E, Killestein Joep, Schoonheim Menno M, Strijbis Eva M M
Аннотация
BACKGROUND: Long-term studies on multiple sclerosis progression often face dropout, possibly among those with more aggressive disease, biasing the cohort.
OBJECTIVES: We assessed potential survivorship bias in a long-term observational multiple sclerosis cohort.
METHODS: Three hundred sixty-one patients with multiple sclerosis were followed for 10 years, with clinical assessments, blood biomarkers and magnetic resonance imaging at baseline, follow-up 1 and follow-up 2. Progression was defined as an Expanded Disability Status Scale increase. Dropout was analysed and predicted; estimated Expanded Disability Status Scale was calculated for dropouts to assess bias. Brain volumes were normalized.
RESULTS: One hundred and sixty-two patients with multiple sclerosis completed all follow-ups; 81 showed progression. Dropout rates were 97/361 at follow-up 1 and 102/264 at follow-up 2. Dropouts had worse Expanded Disability Status Scale, Nine-Hole Peg test, Timed 25-Foot Walk, lower brain volume and higher lesion volume before dropping out. Blood biomarkers did not differ. Main dropout predictors were higher baseline Expanded Disability Status Scale, lesion volume, worse Nine-Hole Peg test and shorter disease duration. Median estimated Expanded Disability Status Scale at follow-up 2 for dropouts was 5.5 versus 3.5 for non-dropouts.
DISCUSSION: Fewer than half completed the study. High lesion load and worse clinical status predicted dropout. This may cause underestimation of progression and reduced statistical power. Similar bias may affect other long-term studies in chronic diseases.
OBJECTIVES: We assessed potential survivorship bias in a long-term observational multiple sclerosis cohort.
METHODS: Three hundred sixty-one patients with multiple sclerosis were followed for 10 years, with clinical assessments, blood biomarkers and magnetic resonance imaging at baseline, follow-up 1 and follow-up 2. Progression was defined as an Expanded Disability Status Scale increase. Dropout was analysed and predicted; estimated Expanded Disability Status Scale was calculated for dropouts to assess bias. Brain volumes were normalized.
RESULTS: One hundred and sixty-two patients with multiple sclerosis completed all follow-ups; 81 showed progression. Dropout rates were 97/361 at follow-up 1 and 102/264 at follow-up 2. Dropouts had worse Expanded Disability Status Scale, Nine-Hole Peg test, Timed 25-Foot Walk, lower brain volume and higher lesion volume before dropping out. Blood biomarkers did not differ. Main dropout predictors were higher baseline Expanded Disability Status Scale, lesion volume, worse Nine-Hole Peg test and shorter disease duration. Median estimated Expanded Disability Status Scale at follow-up 2 for dropouts was 5.5 versus 3.5 for non-dropouts.
DISCUSSION: Fewer than half completed the study. High lesion load and worse clinical status predicted dropout. This may cause underestimation of progression and reduced statistical power. Similar bias may affect other long-term studies in chronic diseases.