Response to Letter to the Editor: “Is High-Intensity Interval Training More Effective Than Moderate Continuous Training in Rehabilitation of Multiple Sclerosis: A Comprehensive Systematic Review and Meta-analysis”

Abstract

s insightful commentary on our systematic review and meta-analysis. First, because the reporting guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses that we followed during the study did not mandate the level of agreement between authors, 1 we did not include a quantitative assessment of author agreement. We acknowledge its importance for future studies to strengthen the reliability of findings. Second, the authors commented on the level of evidence supporting our results. Thus, we have implemented Grading of Recommendations , Assessment, Development, and Evaluations (GRADE) assessment to determine the level of evidence of results obtained in our review concerning the effect of high-intensity interval training versus moderate-intensity continuous training on people with multiple sclerosis. 2 We found that the level of evidence for cardiorespiratory functions was low. The evidence for fatigue and body composition domains (including lean tissue mass and fat percentage) was also low and very low, respectively. However , for all domains of cognitive functions, it was moderate. Lastly, there was low evidence regarding the effect of different exercise protocols on biomarker levels. Importantly, the level of evidence was downgraded because of participation of different multiple sclerosis phenotypes in each included study, which hinders the generalizability of the obtained results (indirectness domain of GRADE assessment). 3 In addition, there were several included studies with a small sample size, affecting the imprecision domain of GRADE assessment. Furthermore, we acknowledge the limited number of trials available. However, we ensured that this limitation was considered during protocol preparation because 2 studies are the minimum for conducting a meta-analysis. 4 Third, in our study we addressed risk-of-bias analysis by reporting the total score of each article using the Physiotherapy Evidence Database (PEDro) scale. Although a comprehensive assessment of publication bias was desirable, limitations in the number of studies included in the meta-analysis precluded the use of a funnel plot. Funnel plots are known to have limited power to detect asymmetry with <10 studies, making it difficult to distinguish true publication bias from chance findings. 5 Finally, as emphasized in the Study Limitations subsection of the Discussion section, conducting subgroup analyses based on Expanded Disability Status Scale was not feasible in our study because of insufficient data availability. 2 Additionally, most of the studies included in our review aggregated participants across the entire spectrum of Expanded Disability Status Scale scores within either the experimental or control group without accounting for the diverse disease subtypes such as relapse and remitting, primary progressive, or secondary progressive. This aggregation poses challenges for further subgroup analysis, particularly considering the lower prevalence of primary progressive and secondary progressive compared with that of remitting. The current study's conclusion is not definitive, primarily because of the limited quality of evidence stemming from the heterogeneous nature of training characteristics in high-intensity interval training and moderate-intensity continuous training across various studies. In conclusion, we are confident that our review adheres to rigorous methodology and presents relevant findings regarding the effects of different exercise modalities on individuals with MS. We appreciate the constructive feedback provided and will consider these points for future studies to enhance the quality and clarity of our work.