Beyond current research practice: Methodological considerations in MS rehabilitation research (is designing the perfect rehabilitation trial the Holy Grail or a Gordian knot?)

Abstract

Rehabilitation is an essential aspect of symptomatic and supportive treatment for people with multiple sclerosis (MS). The number of randomised controlled trials (RCTs) for rehabilitation interventions in MS has increased over the last two decades. The design, conduct and reporting quality of some of these trials could be improved. There are, however, some specific challenges that researchers face in conducting RCTs of rehabilitation interventions, which are often ‘complex interventions’. This paper explores some of the challenges of undertaking robust clinical trials in rehabilitation. We focus on issues related to (1) participant selection and sample size, (2) interventions – the ‘dose’, content, active ingredients, targeting, fidelity of delivery and treatment adherence, (3) control groups and (4) outcomes – choosing the right type, number, timing of outcomes, and the importance of defining a primary outcome and clinically important difference between groups. We believe that by following internationally accepted RCT guidelines, by developing a critical mass of MS rehabilitation ‘trialists’ through international collaboration and by continuing to critique, challenge, and develop RCT designs, we can exploit the potential of RCTs to answer important questions related to the effectiveness of rehabilitation interventions.

The MoXFo initiative – study design: Considerations related to study design and methodology in exercise research for people with multiple sclerosis

“…Most studies assess the intervention effects immediately after the intervention, which is typically where the largest effects are observed, and where the frequently observed 'wear off' effect during follow-up is avoided. 3 MS exercise-specific opportunities and challenges. A major challenge related to timing, which is particularly pertinent to long-term MS exercise studies, relates to adherence, as high adherence is a prerequisite for robust long-term data.…”

“…2 This paper outlines the work of the 'Study design and methodology' group of the MoXFo initiative, and addresses critical aspects and future directions when initially defining the research question of interest and subsequently designing the study and intervention. While previous work has discussed generic challenges when designing rehabilitation trials, 3 we provide a structured and concise synthesis of exercise-specific research opportunities, challenges and considerations when designing randomized controlled trials (RCT) in MS. To fully understand whether and how exercise interventions work, we acknowledge the importance of using a variety of research designs. In this paper, however, we will focus mainly on RCTs, given the superior research design when studying the efficacy or (cost-)effectiveness of interventions.…”

Decentralised clinical trials in multiple sclerosis research

“… 15 Therefore, the findings of RCTs are typically not generalisable, and trials of treatments in real-world populations and under usual clinical practice settings are required to test their effectiveness. 15 – 17 Trial designs are moving towards integrating efficacy and effectiveness studies to save time and cost. 15 DCTs can help reduce this efficacy–effectiveness gap by enabling the conduct of pragmatic trials on a larger number of participants with more heterogeneous demographic and clinical characteristics from different locations and practice settings.…”

Prioritizing progressive MS rehabilitation research: A call from the International Progressive MS Alliance

“…10,37 While these mechanistic studies vary in methodological quality, these inter-disciplinary collaborations provide a foundation for future work to inform the design of rehabilitation interventions. 38 We can learn valuable lessons from conditions such as stroke, where motor recovery trials have included the combination of pharmaceutical approaches with rehabilitation interventions and the incorporation of biological and behavioral recovery biomarkers (e.g. imaging measures of brain volume or white matter tracts) into rehabilitation trials.…”