Methodological Considerations Regarding Heterogeneity and Statistical Modeling in “Effects on Exercise Tolerance and Functional Outcomes of Eccentric versus Concentric Aerobic Exercise in People with COPD” [Letter]

We read with great interest the systematic review and meta-analysis by Magunagoikoetxea-Comins et al regarding the comparative effects of eccentric (ECC) and concentric (CON) aerobic exercise in patients with COPD. 1 While the study addresses a clinically relevant gap in pulmonary rehabilitation, we would like to offer some methodological observations that may influence the interpretation of the reported effect sizes and the certainty of the conclusions.The authors state in their methodology that random-effects models would be employed to account for study heterogeneity.However, the forest plots are explicitly labelled as "IV, Fixed, 95% CI", indicating the use of fixed-effect inverse-variance models across outcomes.According to the Cochrane Handbook for Systematic Reviews of Interventions, the choice between fixed-effect and random-effects models is critical when heterogeneity is present.2 When I 2 values exceed 75%, as seen in this study for Heart Rate (I 2 = 93%), Dyspnea (I 2 = 89%), and Endurance Time (I 2 = 94%), the fixed-effect model tends to underestimate the standard error, leading to artificially narrow CIs and potentially inflated p-values.Applying a fixed-effect model under these conditions leads to "false precision," where a result appears highly significant despite substantial inconsistency across studies.3 To illustrate the potential impact of model choice, we contrasted the fixed-effect estimates reported by the authors with pooled effects re-estimated under random-effects assumptions (DerSimonian and Laird inverse-variance method) for each outcome using Review Manager (version 5.4, Cochrane Collaboration) software.For example, in Figure 3 of the article by Magunagoikoetxea-Comins et al, heart rate showed very high heterogeneity (I 2 = 93%): while the fixed-effect model suggested a significant reduction (MD -14.37 bpm [-18.24,-10.50], p