Avoiding Hysteron Proteron: Use of Meta-Analysis for Examining Exercise Response Variation
Precision exercise medicine is aimed at developing exercise programs to optimize benefit for particular groups of people by accounting for individual variability in genes, environment, and lifestyle. One of the most important topics, and a critical element in exercise-based cardiac rehabilitation (EBCR), is appropriate testing for true exercise-associated interindividual response differences (IIRD). IIRD has not historically been performed. Consequently, misdirected efforts and resources aimed at identifying possible moderators and mediators, including genetic interactions, can occur within the same study. Subsequent conduct of potentially unethical follow-up studies occurs because random and within-subject variation have not been properly assessed. In a previous article of the Journal, we provided guidance on how to properly assess for exercise-associated IIRD in original randomized controlled trials (RCTs) using the standard deviation of individual response (SDIR) approach. In the current article, we provide guidance on how to properly assess for IIRD using the SDIR approach based on meta-analyses of RCTs, given that it has been suggested that the use of meta-analysis to assess IIRD is preferable over such assessment within an original RCT. It is the hope that the guidance provided in this brief article will lead to wider adoption of the SDIR method for examining true IIRD in meta-analyses of RCTs in EBCR studies both retrospectively and prospectively. Adherence to the proposed method will help avoid false conclusions regarding potential moderators and mediators, including genetic interactions, as well as unneeded follow-up studies.ABSTRACT

Forest plot for treatment effect changes (exercise minus control) in V̇o2peak in mL·kg−1·min−1, ordered from smallest to largest reductions based on the inverse-variance heterogeneity model. The black squares represent study-level mean treatment effect changes in V̇o2peak in mL·kg−1·min−1 and the horizontal lines extending through the black squares represent the lower (left side) and upper (right side) 95% confidence interval (CI) for treatment effect changes. The middle of the black diamond represents the overall pooled mean treatment effect change in V̇o2peak in mL·kg−1·min−1 and the left and right sides of the diamond represent the lower and upper 95% CI for this change. The black vertical line extending through the diamond represents the overall pooled treatment effect change in V̇o2peak in mL·kg−1·min−1 and the vertical line to the left of the forest plot represents the zero point.
Contributor Notes
Conflicts of Interest and Source of Funding: None.