Efficient design and analysis of randomized controlled trials in rare neurological diseases: An example in Guillain-Barré syndrome

PloS One
Nikki van LeeuwenHester F Lingsma

Abstract

Randomized controlled trials (RCTs) pose specific challenges in rare and heterogeneous neurological diseases due to the small numbers of patients and heterogeneity in disease course. Two analytical approaches have been proposed to optimally handle these issues in RCTs: covariate adjustment and ordinal analysis. We investigated the potential gain in efficiency of these approaches in rare and heterogeneous neurological diseases, using Guillain-Barré syndrome (GBS) as an example. We analyzed two published GBS trials with primary outcome 'at least one grade improvement' on the GBS disability scale. We estimated the treatment effect using logistic regression models with and without adjustment for prognostic factors. The difference between the unadjusted and adjusted estimates was disentangled in imbalance (random differences in baseline covariates between treatment arms) and stratification (change of the estimate due to covariate adjustment). Second, we applied proportional odds regression, which exploits the ordinal nature of the GBS disability score. The standard error of the estimated treatment effect indicated the statistical efficiency. Both trials were slightly imbalanced with respect to baseline characteristics, which was cor...Continue Reading

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Citations

Nov 2, 2020·BMC Health Services Research·Marzyeh AminiUNKNOWN MR CLEAN Registry Investigators

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Software Mentioned

rms package
R
R Foundation for Statistical Computation

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