Decentralised clinical trials in multiple sclerosis research.

Randomised controlled trials (RCTs) play an important role in multiple sclerosis (MS) research, ensuring that new interventions are safe and efficacious before their introduction into clinical practice. Trials have been evolving to improve the robustness of their designs and the efficiency of their conduct. Advances in digital and mobile technologies in recent years have facilitated this process and the first RCTs with decentralised elements became possible. Decentralised clinical trials (DCTs) are conducted remotely, enabling participation of a more heterogeneous population who can participate in research activities from different locations and at their convenience. DCTs also rely on digital and mobile technologies which allows for more flexible and frequent assessments. While hospitals quickly adapted to e-health and telehealth assessments during the COVID-19 pandemic, the conduct of conventional RCTs was profoundly disrupted. In this paper, we review the existing evidence and gaps in knowledge in the design and conduct of DCTs in MS.

On performance of parametric and distribution-free models for zero-inflated and over-dispersed count responses.

Zero-inflated Poisson (ZIP) and negative binomial (ZINB) models are widely used to model zero-inflated count responses. These models extend the Poisson and negative binomial (NB) to address excessive zeros in the count response. By adding a degenerate distribution centered at 0 and interpreting it as describing a non-risk group in the population, the ZIP (ZINB) models a two-component population mixture. As in applications of Poisson and NB, the key difference between ZIP and ZINB is the allowance for overdispersion by the ZINB in its NB component in modeling the count response for the at-risk group. Overdispersion arising in practice too often does not follow the NB, and applications of ZINB to such data yield invalid inference. If sources of overdispersion are known, other parametric models may be used to directly model the overdispersion. Such models too are subject to assumed distributions. Further, this approach may not be applicable if information about the sources of overdispersion is unavailable. In this paper, we propose a distribution-free alternative and compare its performance with these popular parametric models as well as a moment-based approach proposed by Yu et al. [Statistics in Medicine 2013; 32: 2390-2405]. Like the generalized estimating equations, the proposed approach requires no elaborate distribution assumptions. Compared with the approach of Yu et al., it is more robust to overdispersed zero-inflated responses. We illustrate our approach with both simulated and real study data.