A comparison of different ways of including baseline counts in negative binomial models for data from falls prevention trials

This is the author accepted manuscript. The final version is available from Wiley-VCH Verlag via the DOI in this record.A common design for a falls prevention trial is to assess falling at baseline, randomize participants into an intervention or control group, and ask them to record the number of falls they experience during a follow-up period of time. This paper addresses how best to include the baseline count in the analysis of the follow-up count of falls in Negative Binomial (NB) regression. We examine the performance of various approaches in simulated datasets where both counts are generated from a mixed Poisson distribution with shared random subject effect. Including the baseline count after log-transformation as a regressor in NB regression (NB-logged) or as an offset (NB-offset) resulted in greater power than including the untransformed baseline count (NB-unlogged). Cook and Wei's Conditional Negative Binomial (CNB) model replicates the underlying process generating the data. In our motivating dataset, a statistically significant intervention effect resulted from the NB-logged, NB-offset and CNB models, but not from NB-unlogged, and large, outlying baseline counts were overly influential in NB-unlogged but not in NB-logged. We conclude that there is little to lose by including the log-transformed baseline count in standard NB regression compared to CNB for moderate to larger sized datasets.Funding Information: National Institute for Health Research, Grant no. RDA/02/06/41; Care South West Peninsul

Sample size for comparing negative binomial rates in noninferiority and equivalence trials with unequal follow-up times

We derive the sample size formulae for comparing two negative binomial rates based on both the relative and absolute rate difference metrics in noninferiority and equivalence trials with unequal follow-up times, and establish an approximate relationship between the sample sizes required for the treatment comparison based on the two treatment effect metrics. The proposed method allows the dispersion parameter to vary by treatment groups. The accuracy of these methods is assessed by simulations. It is demonstrated that ignoring the between-subject variation in the follow-up time by setting the follow-up time for all individuals to be the mean follow-up time may greatly underestimate the required size, resulting in underpowered studies. Methods are provided for back-calculating the dispersion parameter based on the published summary results

Comprehensive evaluation of differential gene expression analysis methods for RNA-seq data

A large number of computational methods have been developed for analyzing differential gene expression in RNA-seq data. We describe a comprehensive evaluation of common methods using the SEQC benchmark dataset and ENCODE data. We consider a number of key features, including normalization, accuracy of differential expression detection and differential expression analysis when one condition has no detectable expression. We find significant differences among the methods, but note that array-based methods adapted to RNA-seq data perform comparably to methods designed for RNA-seq. Our results demonstrate that increasing the number of replicate samples significantly improves detection power over increased sequencing depth

Comparison of normalization and differential expression analyses using RNA-Seq data from 726 individual Drosophila melanogaster

Comparison of normalization methods across conditions. Boxplots show the differences in the coefficient of variation across flies in each genotype/sex/environment condition. (PDF 245 kb

Digital innovation in Multiple Sclerosis Management

Due to innovation in technology, a new type of patient has been created, the e-patient, characterized by the use of electronic communication tools and commitment to participate in their own care. The extent to which the world of digital health has changed during the COVID-19 pandemic has been widely recognized. Remote medicine has become part of the new normal for patients and clinicians, introducing innovative care delivery models that are likely to endure even if the pendulum swings back to some degree in a post-COVID age. The development of digital applications and remote communication technologies for patients with multiple sclerosis has increased rapidly in recent years. For patients, eHealth apps have been shown to improve outcomes and increase access to care, disease information, and support. For HCPs, eHealth technology may facilitate the assessment of clinical disability, analysis of lab and imaging data, and remote monitoring of patient symptoms, adverse events, and outcomes. It may allow time optimization and more timely intervention than is possible with scheduled face-to-face visits. The way we measure the impact of MS on daily life has remained relatively unchanged for decades, and is heavily reliant on clinic visits that may only occur once or twice each year.These benefits are important because multiple sclerosis requires ongoing monitoring, assessment, and management.The aim of this Special Issue is to cover the state of knowledge and expertise in the field of eHealth technology applied to multiple sclerosis, from clinical evaluation to patient education