ABSTRACT

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 (SD_IR) approach. In the current article, we provide guidance on how to properly assess for IIRD using the SD_IR 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 SD_IR 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.